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Sample records for tnf-alpha inhibitor infliximab

  1. Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation

    DEFF Research Database (Denmark)

    Milman, Nils; Andersen, Claus B.; Hansen, Annette

    2006-01-01

    quality of life. At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features...

  2. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies

    DEFF Research Database (Denmark)

    Svenson, M; Geborek, P; Saxne, T

    2007-01-01

    Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mouse-human IgG1/kappa antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we ...

  3. Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in monozygotic twins with a de novo CARD15 mutation

    DEFF Research Database (Denmark)

    Milman, Nils; Andersen, Claus B; Hansen, Annette

    2006-01-01

    Blau syndrome is a hereditary granulomatous disease caused by mutations in the CARD15 gene that is diagnosed in children of young age with exanthema/erythema, arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in Danish Caucasian monozygotic male twins, exhibiting...... a heterozygous de novo R334W mutation in codon 334 of CARD15. The patients were initially diagnosed as having sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started at 1 year of age, and were followed by uveitis at 7-10 years of age. There was no involvement of the lungs or other...... quality of life. At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic features...

  4. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies

    DEFF Research Database (Denmark)

    Svenson, M; Geborek, P; Saxne, T

    2007-01-01

    Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mouse-human IgG1/kappa antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we...... have compared different methods of assessing drug levels and anti-infliximab antibodies (Abs) and analysed the character of these Abs in sera of RA patients treated with infliximab for 1.5-18 months....

  5. The effect of infliximab, a monoclonal antibody against TNF-alpha, on disc herniation resorption - A randomized controlled study

    NARCIS (Netherlands)

    Autio, Reijo A.; Karppinen, Jaro; Niinimaki, Jaakko; Ojala, Risto; Veeger, Nic; Korhonen, Timo; Hurri, Heikki; Tervonen, Osmo

    2006-01-01

    Study Design. Randomized, controlled study. Objective. To evaluate the effect of infliximab on herniated nucleus pulposus (HNP) resorption. Summary of Background Data. Although the effects of tumor necrosis factor alpha (TNF-alpha) on HNP resorption are not fully understood, TNF-alpha appears to be

  6. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul

    2010-01-01

    with tumor necrosis factor-alpha (TNF alpha) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n = 32, and psoriatic arthritis, n = 17) initiating TNF alpha inhibitor therapy (infliximab, n = 38...

  7. Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

    Science.gov (United States)

    Merkac, Maja Ivartnik; Tomazic, Janez; Strle, Franc

    2015-12-01

    A 57-year-old woman, receiving TNF-alpha inhibitor adalimumab for psoriasis, presented with early Lyme neuroborreliosis (Bannwarth's syndrome). Discontinuation of adalimumab and 14-day therapy with ceftriaxone resulted in a smooth course and favorable outcome of Lyme borreliosis. This is the first report on Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

  8. Off-label use of TNF-alpha inhibitors in a dermatological university department

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2015-01-01

    (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF-alpha inhibitors. A total of 11 patients (9%) experienced severe adverse...

  9. The effect of a metalloproteinase inhibitor (GI5402) on tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors during human endotoxemia

    NARCIS (Netherlands)

    Dekkers, P. E.; Lauw, F. N.; ten Hove, T.; te Velde, A. A.; Lumley, P.; Becherer, D.; van Deventer, S. J.; van der Poll, T.

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is released from the cell surface by cleavage of pro-TNF-alpha by metalloproteinases (MPs). In cell cultures, inhibition of MPs has been found not only to reduce the release of TNF-alpha, but also to enhance the surface expression of TNF-alpha and TNF-alpha

  10. The discovery of novel tartrate-based TNF-[alpha] converting enzyme (TACE) inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rosner, Kristin E.; Guo, Zhuyan; Orth, Peter; Shipps, Jr., Gerald W.; Belanger, David B.; Chan, Tin Yau; Curran, Patrick J.; Dai, Chaoyang; Deng, Yongqi; Girijavallabhan, Vinay M.; Hong, Liwu; Lavey, Brian J.; Lee, Joe F.; Li, Dansu; Liu, Zhidan; Popovici-Muller, Janeta; Ting, Pauline C.; Vaccaro, Henry; Wang, Li; Wang, Tong; Yu, W.; Zhou, G.; Niu, X.; Sun, J.; Kozlowski, J.A.; Lundell, D.J.; Madison, V.; McKittrick, B.; Piwinski, J.J.; Shih, N.Y.; Siddiqui, M. Arshad; Strickland, Corey O. (SPRI)

    2010-09-17

    A novel series of TNF-{alpha} convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

  11. Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaB.

    Science.gov (United States)

    Allen-Hall, Lisa; Arnason, John T; Cano, Pablo; Lafrenie, Robert M

    2010-02-17

    Uncaria tomentosa, commonly known as Cat's Claw or Uña de gato, is a medicinal plant that has been shown to have effective anti-inflammatory activities. We have previously shown that treatment of monocyte-like THP-1 cells with Uncaria tomentosa inhibits the production of the pro-inflammatory cytokine TNF-alpha while augmenting the production of IL-1beta. Since TNF-alpha and IL-1beta are usually regulated similarly and share a number of common promoter elements, including NF-kappaB and AP-1, the ability of Uncaria tomentosa to differentially regulate these inflammatory cytokines is of particular interest. To determine the mechanism of action of Uncaria tomentosa, we investigated the effects of specific inhibitors of NF-kappaB on cellular responses including transcription factor activation using TransAM assays, the expression of cytokines as measured by ELISA, and cell survival as measured by changes in cell number following treatment. Treatment with Uncaria tomentosa inhibited the LPS-dependent activation of specific NF-kappaB and AP-1 components. In addition, treatment with Uncaria tomentosa enhanced cell death when NF-kappaB was inhibited. The ability of Uncaria tomentosa to inhibit TNF-alpha production was diminished when NF-kappaB activation was prevented by drugs that mask NF-kappaB subunit nuclear localization signals, while IL-1beta expression was unchanged. These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-kappaB-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-alpha therapies. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Association of the TNF-alpha G-308A polymorphism with TNF-inhibitor response in sarcoidosis

    NARCIS (Netherlands)

    Wijnen, P.A.; Cremers, J.P.; Nelemans, P.J.; Erckens, R.J.; Hoitsma, E.; Jansen, T.L.; Bekers, O.; Drent, M.

    2014-01-01

    Responsiveness to tumour necrosis factor (TNF) inhibitors has been associated with the TNF-alpha G-308A polymorphism in rheumatoid arthritis. The aim of this study was to examine the association between the presence of this polymorphism and the response to TNF inhibitors in patients with refractory

  13. Role of golimumab, a TNF-alpha inhibitor, in the treatment of the psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Melissa A Michelon

    2010-05-01

    Full Text Available Melissa A Michelon1, Alice B Gottlieb1,21Tufts University School of Medicine, 2Department of Dermatology, Tufts Medical Center, Boston, MA, USAAbstract: Psoriatic arthritis (PsA is an inflammatory arthritis that affects many psoriasis patients and can often have a debilitating disease progression. Golimumab is a new tumor necrosis factor (TNF antagonist recently approved by the FDA for controlling signs and symptoms of psoriatic arthritis. In a Phase III clinical trial in patients with PsA, patients receiving golimumab showed significant improvement in the signs and symptoms of disease. It was usually well tolerated, but adverse events generally occurred more in patients receiving golimumab compared to placebo. Golimumab has also recently shown efficacy in slowing structural damage in PsA. This new biologic therapy provides physicians with another option in the treatment of this inflammatory arthritis while offering patients certain advantages over other TNF antagonists.Keywords: golimumab, psoriatic arthritis, TNF-alpha inhibitor

  14. Pneumocystepneumoni ved behandling med infliximab

    DEFF Research Database (Denmark)

    Josephson, Maria Eklund; Kristensen, Lena Hagelskjaer; Andersen, Vibeke

    2008-01-01

    The treatment of ulcerative colitis has improved since the appearance of Tumor Necrosis Factor (TNF)-alpha inhibitors. However, the use of TNF-alpha inhibitors increases the risk of opportunistic infections. We describe two cases of Pneumocystis jiroveci pneumonia during infliximab therapy...... for active ulcerative colitis. They were successfully treated with sulfametoxazole/trimetroprim. High awareness of P. jiroveci pneumonia in patients who develop pulmonary symptoms with hypoxia during TNF-alpha modulator therapy is recommended....

  15. Re-evaluating osteoporosis and fracture risk in Crohn's disease patients in the era of TNF-alpha inhibitors.

    Science.gov (United States)

    Hakimian, Shahrad; Kheder, Joan; Arum, Seth; Cave, David R; Hyatt, Benjamin

    2018-02-01

    Patients with Crohn's disease (CD) are at increased risk for osteoporosis and fractures as compared to the general population. Recently, various cytokines including tumor necrosis factor (TNF)-alpha are found to play a major role in bone health. In this study, we aimed to gain a better understanding of the risk factors for osteoporosis and vitamin D deficiency in the era of TNF-alpha inhibitors. We conducted a retrospective review of 464 consecutive patients with CD in our GI clinic between 2008 and 2015. Statistical analysis was performed using the student t-test and chi-square test. CD patients treated with TNF-alpha inhibitors (TNF) and those who are anti-TNF naïve (NB) had similar rates of vitamin D deficiency, insufficiency and normal vitamin D-25-OH levels. Similarly, rates of osteoporosis (16% vs 18%), osteopenia (53% vs 57%) and normal bone density (31% vs 25%) were comparable between the TNF and NB groups respectively. However, Z-scores at the spine (-0.47 vs -0.05) were significantly lower in the TNF group (p = .03). Interestingly, rates of osteoporosis in the NB group were drastically different before and after age 60 (3.6% vs 30%) with no major difference in the TNF group (15% vs 18%). Bone density was positively correlated with BMI (Pearson's R = 0.39) and negatively correlated with age and smoking status (R= -0.25). TNF group patients were diagnosed with osteoporosis from an earlier age compared to NB group but with a smaller increase in osteoporosis after menopause. Further prospective studies are necessary to further determine the role of anti-TNF medications in osteoporosis.

  16. Effect of infliximab on the levels of TNF-alpha and TGF-beta in the whole blood cultures of irradiated patients.

    Directory of Open Access Journals (Sweden)

    Agnieszka Magrys

    2008-12-01

    Full Text Available TGF-beta is supposed to be the major cytokine responsible for post-radiation fibrosis of healthy tissues and actively modifies post-radiation changes. The growth of TGF-beta level induces the expression of collagen synthesis gene which triggers off the production of fibrosis of hyaline membranes. The main purpose of this study was to discover the way and methods of reducing post-radiation damage of normal tissues and provide an adequate scientific justification for using Infliximab as an effective radio protector in the neoplasm radiotherapy. A group of 97 patients were subjected to the experiment. Randomly selected patients were assigned to 3 groups according to the radiation exposure. The samples of whole blood were suspended in RPMI 1640 growth medium standardized according to the number of leukocytes. Two milliliters of whole blood was taken from each patient immediately before irradiation and 100 microl sample of the blood was placed in wells with 0.8 mg/ml of Infliximab or without the preparation. TGF-beta levels in blood culture without cA2 before irradiation showed continuous rise from 3978 to 8950 pg/ml at the 96th h. In the post irradiated group without cA2, a continuous growth was recorded till the 48th h (from 4758 to 13324 pg/ml at the 24th h and then a slight decline to 11950 pg/ml at 96th h, respectively. In the cultures with cA2, TGF-beta levels before irradiation showed also the peak value at the 48th h (from 4050 to 7340 pg/ml at the 48th h and then started to go down (6500 pg/ml at the 72nd h and 5720 pg/ml at the 96th h. In the post-irradiated group, during the first 6 hours, there was a growth from 4717 pg/ml to 7462 pg/ml, and then a paradoxical increase to 16885 pg/ml at the 12th h. From the 12th h the values started to decrease to 6895 pg/ml at the 96th h. The obtained results confirmed the hypothesis of decreasing the TGF-beta expression by inactivating TNF-alpha with a monoclonal antibody (Infliximab in the patients

  17. TNF-alpha inhibitor associated myelopathies: A neurological complication in patients with rheumatologic disorders.

    Science.gov (United States)

    Barreras, Paula; Mealy, Maureen A; Pardo, Carlos A

    2017-02-15

    Tumor necrosis factor-alpha inhibitors (TNFα-I) are biological agents used in the treatment of rheumatologic disorders. TNFα-I have been associated with demyelinating disorders mimicking multiple sclerosis. The goal of this report is to illustrate cases of myelopathy which developed during the use of TNFα-I. We describe the clinical, neuroimaging and laboratory features of 4 cases of myelopathy associated with TNFα-I. The mean period of TNFα-I exposure was 27 [12-36] months. Three of the four patients exhibited active inflammatory myelopathy as the spinal cord MRI lesions enhanced with gadolinium and CSF pleocytosis or oligoclonal bands were present. All patients had normal brain MRIs at the time of presentation. TNFα-I may play a role in the development of myelopathies in absence of brain involvement or other features of demyelinating disease. TNFα-I associated myelopathy should be considered in patients with history of treatment with TNFα-I who exhibit symptoms of myelopathy. Copyright © 2017. Published by Elsevier B.V.

  18. Fijiolides A and B, inhibitors of TNF-alpha-induced NFkappaB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis.

    Science.gov (United States)

    Nam, Sang-Jip; Gaudêncio, Susana P; Kauffman, Christopher A; Jensen, Paul R; Kondratyuk, Tamara P; Marler, Laura E; Pezzuto, John M; Fenical, William

    2010-06-25

    Fijiolide A, a potent inhibitor of TNF-alpha-induced NFkappaB activation, along with fijiolide B, were isolated from a marine-derived bacterium of the genus Nocardiopsis. The planar structures of fijiolides A (1) and B (2) were elucidated by interpretation of 2D NMR spectroscopic data, while the absolute configurations of these compounds were defined by interpretation of circular dichroism and 2D NMR data combined with application of the advanced Mosher's method. Fijiolides A and B are related to several recently isolated chloroaromatic compounds, which appear to be the Bergman cyclization products of enediyne precursors. Fijiolide A reduced TNF-alpha-induced NFkappaB activation by 70.3%, with an IC(50) value of 0.57 micro-M. Fijiolide B demonstrated less inhibition, only 46.5%, without dose dependence. The same pattern was also observed with quinone reductase (QR) activity: fijiolide A was found to induce quinone reductase-1 (QR1) with an induction ratio of 3.5 at a concentration of 20 microg/mL (28.4 microM). The concentration required to double the activity was 1.8 microM. Fijiolide B did not affect QR1 activity, indicating the importance of the nitrogen substitution pattern for biological activity. On the basis of these data, fijiolide A is viewed as a promising lead for more advanced anticancer testing.

  19. p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease.

    Science.gov (United States)

    Waetzig, Georg H; Seegert, Dirk; Rosenstiel, Philip; Nikolaus, Susanna; Schreiber, Stefan

    2002-05-15

    Inflammatory bowel diseases (IBD)--Crohn's disease and ulcerative colitis--are relapsing chronic inflammatory disorders which involve genetic, immunological, and environmental factors. The regulation of TNF-alpha, a key mediator in the inflammatory process in IBD, is interconnected with mitogen-activated protein kinase pathways. The aim of this study was to characterize the activity and expression of the four p38 subtypes (p38alpha-delta), c-Jun N-terminal kinases (JNKs), and the extracellular signal-regulated kinases (ERK)1/2 in the inflamed intestinal mucosa. Western blot analysis revealed that p38alpha, JNKs, and ERK1/2 were significantly activated in IBD, with p38alpha showing the most pronounced increase in kinase activity. Protein expression of p38 and JNK was only moderately altered in IBD patients compared with normal controls, whereas ERK1/2 protein was significantly down-regulated. Immunohistochemical analysis of inflamed mucosal biopsies localized the main expression of p38alpha to lamina propria macrophages and neutrophils. ELISA screening of the supernatants of Crohn's disease mucosal biopsy cultures showed that incubation with the p38 inhibitor SB 203580 significantly reduced secretion of TNF-alpha. In vivo inhibition of TNF-alpha by a single infusion of anti-TNF-alpha Ab (infliximab) resulted in a highly significant transient increase of p38alpha activity during the first 48 h after infusion. A significant infliximab-dependent p38alpha activation was also observed in THP-1 myelomonocytic cells. In human monocytes, infliximab enhanced TNF-alpha gene expression, which could be inhibited by SB 203580. In conclusion, p38alpha signaling is involved in the pathophysiology of IBD.

  20. Imbalance between HAT and HDAC activities in the PBMCs of patients with ankylosing spondylitis or rheumatoid arthritis and influence of HDAC inhibitors on TNF alpha production.

    Directory of Open Access Journals (Sweden)

    Eric Toussirot

    Full Text Available OBJECTIVE: Acetylation or deacetylation of histone proteins may modulate cytokine gene transcription such as TNF alpha (TNF. We evaluated the balance between histone deacetytlase (HDAC and histone acetyltransferase (HAT in patients with rheumatoid arthritis (RA or ankylosing spondylitis (AS compared to healthy controls (HC and determined the influence of HDAC inhibitors (trichostatin A -TSA- or Sirtinol -Sirt- on these enzymatic activities and on the PBMC production of TNF. METHODS: 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT and HDAC activities were measured on nuclear extracts from PBMC using colorimetric assays. Enzymatic activities were determined prior to and after ex vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture supernatants in the absence or presence of TSA or Sirt. RESULTS: HAT and HDAC activities were significantly reduced in AS, while these activities reached similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF production by PBMC was significantly down-regulated by Sirt in HC and AS patients. CONCLUSION: HAT and HDAC were disturbed in AS while no major changes were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and AS. An imbalance between HAT and HDAC activities might provide the rationale for the development of HDACi in the therapeutic approach to inflammatory rheumatic diseases.

  1. The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status

    Czech Academy of Sciences Publication Activity Database

    Kovaříková, Martina; Hofmanová, Jiřina; Souček, Karel; Kozubík, Alois

    2004-01-01

    Roč. 72, č. 1 (2004), s. 23-31 ISSN 0301-4681 R&D Projects: GA ČR GA525/01/0419; GA ČR GP524/02/P051; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : colon cancer * cell differentiation * TNF-alpha Subject RIV: BO - Biophysics Impact factor: 4.481, year: 2004

  2. Comparison of combination therapies in the treatment of rheumatoid arthritis: leflunomide-anti-TNF-alpha versus methotrexate-anti-TNF-alpha.

    Science.gov (United States)

    De Stefano, Renato; Frati, Elena; Nargi, Fernando; Baldi, Caterina; Menza, Luana; Hammoud, Mohammed; Galeazzi, Mauro

    2010-05-01

    To compare the efficacy and safety of leflunomide (LEF)-anti-TNF-alpha combination therapy to methotrexate (MTX)-anti-TNF-alpha combination therapy in a group of patients with active rheumatoid arthritis (RA). We have recruited 120 patients with RA with a high disease activity despite being treated with MTX (15 mg/week) or LEF (20 mg/die) for 3 months, without side effects. In each of these patients, therapy with either MTX or LEF was continued and randomly combined with an anti-TNF-alpha drug: etanercept, infliximab, or adalimumab. Patients were assessed at study entry and at 4, 12, and at 24 weeks. The efficacy endpoints included variations in the DAS28-ESR and the ACR20, ACR50, and ACR70 responses. At each visit, any side-effect was recorded. There were no statistically significant differences in the DAS28 variations and in the ACR responses between the two groups or among the six subgroups. The number of discontinuation due to the appearance of serious side effects was higher, but not statistically significant, in the LEF-anti-TNF-alpha group than in the MTX-anti-TNF-alpha group. Other adverse events that did not necessitate the discontinuation of therapy occurred much more frequently in patients treated with MTX than in those treated with LEF. Anti-TNF-alpha drugs can be used in combination not only with MTX, but also with LEF, with the same probability of achieving significant clinical improvement in RA patients and without a significantly greater risk of serious adverse events. In contrast, it seems that combination therapy with LEF-anti-TNF-alpha is more readily tolerated than combination therapy with MTX-anti-TNF-alpha.

  3. TNF-Alpha Inhibitors for Chronic Urticaria

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2013-01-01

    be effective and relatively safe treatment options in a significant proportion of patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom standard immunosuppressive drugs are ineffective or associated with unacceptable side effects.......Patients with severe chronic urticaria may not respond to antihistamines, and other systemic treatment options may either be ineffective or associated with unacceptable side effects. We present data on efficacy and safety of adalimumab and etanercept in 20 adult patients with chronic urticaria...

  4. Low-dose methotrexate - a therapeutical kick in TNF-alpha antagonist treatment for recalcitrant psoriasis vulgaris.

    Science.gov (United States)

    Wilsmann-Theis, Dagmar; Fronhoffs, Kristina; Ehler, Lin-Kristin; Wenzel, Joerg; Bieber, Thomas; Klingmueller, Karin

    2014-01-01

    In contrast to the treatment of rheumatoid arthritis, there are few data in psoriasis vulgaris regarding the efficacy of combining tumor necrosis factor (TNF)-alpha inhibitors and methotrexate (MTX). Indeed, combination of MTX with different TNF-alpha inhibitors may enhance the therapeutic effects and reduce side effects because of less dosage of the single agent. The present authors present five cases in which low-dose MTX combined with TNF-alpha inhibitors led to impressive improvement in Psoriasis Area and Severity Index scores. Here, the present authors initiated very low-dose MTX treatment in addition to existing TNF-alpha inhibitor therapy to exhaust current therapy and prevent premature change of the biologic. These observations support the concept of combined treatment in recalcitrant cases of psoriasis, which need a systemically lifelong treatment when both first-line and second-line monotherapies fail to provide sufficient clinical response. © 2013 Wiley Periodicals, Inc.

  5. Ubiquitous hazardous metal lead induces TNF-{alpha} in human phagocytic THP-1 cells: Primary role of ERK 1/2

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Mohd Imran [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Islam, Najmul [Department of Biochemistry, J.N Medical College, Aligarh Muslim University, Aligarh (India); Sahasrabuddhe, Amogh A. [Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow (India); Mahdi, Abbas Ali [Department of Biochemistry, C.S.M. Medical University, Lucknow (India); Siddiqui, Huma; Ashquin, Mohd [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Ahmad, Iqbal, E-mail: ahmadi@sify.com [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India)

    2011-05-15

    Induction of tumor necrosis factor-{alpha} (TNF-{alpha}) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-{alpha} is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-{alpha} induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-{alpha} m-RNA and protein secretion. Moreover, the stability of TNF-{alpha} m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-{alpha} m-RNA. However, SB 203580 partially inhibited production and stability of TNF-{alpha} m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-{alpha} m-RNA. Data tends to suggest that expression and stability of TNF-{alpha} induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

  6. Infliximab's influence on anastomotic strength and degree of inflammation in intestinal surgery in a rabbit model

    DEFF Research Database (Denmark)

    Frostberg, Erik; Ström, Petter; Gerke, Oke

    2014-01-01

    BACKGROUND: Infliximab, a TNF-alpha inhibitor, is a potent anti-inflammatory drug in the treatment of inflammatory bowel diseases. Recent studies have investigated the effect of infliximab treatment on postoperative complications such as anastomotic leakage, however, with conflicting results...... and conclusions. The purpose of this study was to investigate whether a single dose infliximab has an adverse effect on the anastomotic healing process, observed as reduced anastomotic breaking strength and histopathologically verified lower grade of inflammatory response, in the small intestine of a rabbit....... METHODS: Thirty New Zealand rabbits (median weight 2.5 kg) were allocated to treatment with an intravenous bolus of either 10 mg/kg infliximab (n = 15) or placebo (n = 15). One week later all rabbits underwent two separate end-to-end anastomoses in the jejunum under general anesthesia. At postoperative...

  7. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were...... there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin, However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear...... regression analysis adjusting for the effect of gender and body mass index. Furthermore, TNF-alpha, but not leptin, was positively correlated to sIL-2R and negatively correlated to IL-2 production. In conclusion, increased plasma levels of TNF-alpha in aging is associated with poor IL-2 production ex vivo...

  8. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  9. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were...... associated with leptin, circulating interleukin-2 receptors (sIL-2R), and phytohaemagglutinin (PHA) induced IL-2 production in whole blood in elderly humans. Circulating levels of TNF-alpha and sIL-2R were higher in elderly humans (N=42) compared to a young control group (N=37) whereas...... there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin, However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear...

  10. NF-kappaB is involved in SHetA2 circumvention of TNF-alpha resistance, but not induction of intrinsic apoptosis.

    Science.gov (United States)

    Chengedza, Shylet; Benbrook, Doris Mangiaracina

    2010-03-01

    Treatment of cancer with tumor necrosis factor-alpha (TNF-alpha) is hindered by resistance and toxicity. The flexible heteroarotinoid, SHetA2, sensitizes resistant ovarian cancer cells to TNF-alpha-induced extrinsic apoptosis, and also induces intrinsic apoptosis as a single agent. This study tested the hypothesis that nuclear factor-kappaB (NF-kappaB) is involved in SHetA2-regulated intrinsic and extrinsic apoptosis. SHetA2 inhibited basal and TNF-alpha-induced or hydrogen peroxide-induced NF-kappaB activity through counter-regulation of upstream kinase (IkappaB kinase) activity, inhibitor protein (IkappaB-alpha) phosphorylation, and p-65 NF-kappaB subunit nuclear translocation, but independently of reactive oxygen species generation. Ectopic over-expression of p-65, or treatment with TNF-alpha receptor 1 (TNFR1) small interfering RNA or a caspase-8 inhibitor, each attenuated synergistic apoptosis by SHetA2 and TNF-alpha, but did not affect intrinsic apoptosis caused by SHetA2. In conclusion, NF-kappaB repression is involved in SHetA2 circumvention of resistance to TNF-alpha-induced extrinsic apoptosis, but not in SHetA2 induction of intrinsic apoptosis.

  11. The TNF-alpha transgenic mouse model of inflammatory arthritis.

    Science.gov (United States)

    Li, Ping; Schwarz, Edward M

    2003-08-01

    Rheumatoid arthritis is a chronic inflammatory disorder that affects multiple peripheral joints. It is the most common form of inflammatory arthritis and is characterized by synovial hyperplasia, immune cell infiltration, cartilage destruction, and bone erosion. To gain insight into the etiology of the disease, a variety of animal models have been established. Twelve years ago George Kollias' laboratory generated a transgenic (Tg) mouse that over-expresses human TNF-alpha, and develops an erosive polyarthritis with many characteristics observed in rheumatoid arthritis patients. The phenotype of this mouse model validated the theory that TNF-alpha is at the apex of the pro-inflammatory cascade in rheumatoid arthritis, and foreshadowed the remarkable success of anti-TNF-alpha therapy that has transformed the effective management of this disease. As such, the TNF-Tg mice are very useful tools for dissecting the molecular mechanisms of the pathogenic process and evaluating the efficacy of novel therapeutic strategies for rheumatoid arthritis. In this review we (1) provide a brief summary of TNF-alpha biology and the role of this dominant cytokine in rheumatoid arthritis, (2) describe the various TNF-Tg models and their phenotypes, and (3) give examples of how this model has been used experimentally.

  12. Importance of TNF-alpha in the course of acute infection with Trypanosoma cruzi: influence of its inhibition by pentoxifylline treatment

    Directory of Open Access Journals (Sweden)

    Sonia G Andrade

    2008-02-01

    Full Text Available Infection of C3H/He mice with the Peruvian strain of Trypanosoma cruzi (Biodeme type I, Z2b, a macrophagotropic strain, determined severe parasitism of macrophages, necrosis of the spleen, and high host mortality. In the present study, pentoxifylline (PTX, an inhibitor of TNF-alpha was investigated on its action upon splenic necrosis, parasitemia and host survival. Immunohistochemical data suggested the importance of this cytokine in parasite destruction and decreasing of parasitemia, although paradoxically contributing to the high mortality of infected mice. Necrotic lesions involving several organs, specially the heart, in acute Chagas disease, are important aggravating factors, increasing cardiac morbidity. Advantage of inhibiting TNF-alpha action was herein investigated. Infected mice were divided into two groups: untreated (n = 24, and PTX treated mice (n = 25. PTX was administered in two daily doses of 30 mg/kg/bw, by intraperitoneal route. Normal controls either treated with PTX or saline were also included. Histopathology of the spleen and in situ immunolabeling of TNF-alpha, using anti-TNF-alpha monoclonal antibody, were performed. Necrotic areas were evaluated by morphometry. Mice treated with PTX showed a significant decrease of necrotic areas and diminution of TNF-alpha expression in spleen tissue, suggesting that PTX treatment could control TNF-alpha effects, and thus be used as an adjuvant in the treatment of acute Chagas' disease.

  13. Tumor necrosis factor alpha (TNF alpha) in human skin : A comparison of different antibodies for immunohistochemistry

    NARCIS (Netherlands)

    van der Laan, N; de Leij, LFMH; Buurman, W; Timens, W; ten Duis, HJ

    Conflicting results have been reported regarding the localization and presence of TNF alpha in normal human skin, To study TNF alpha expression, we tested a panel of antibodies directed against human TNF alpha, First, antibodies were tested for immunoreactivity on cytospots of isolated

  14. A role for the non-receptor tyrosine kinase ACK1 in TNF-alpha-mediated apoptosis and proliferation in human intestinal epithelial caco-2 cells.

    Science.gov (United States)

    Zhao, Xinmei; Lv, Chaolan; Chen, Shengbo; Zhi, Fachao

    2017-09-16

    The roles of tumor necrosis factor alpha (TNF-alpha) and its mediators in cellular processes related to intestinal diseases remain elusive. In this study, we aimed to determine the biological role of activated Cdc42-associated kinase 1 (ACK1) in TNF-alpha-mediated apoptosis and proliferation in Caco-2 cells. ACK1 expression was knocked down using ACK1-specific siRNAs, and ACK1 activity was disrupted using a small molecule ACK1 inhibitor. The Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (TUNEL) and the BrdU incorporation assays were used to measure apoptosis and cell proliferation, respectively. ACK1-specific siRNA and the pharmacological ACK1 inhibitor significantly abrogated the TNF-alpha-mediated anti-apoptotic effects and proliferation of Caco-2 cells. Interestingly, TNF-alpha activated ACK1 at tyrosine 284 (Tyr284), and the ErbB family of proteins was implicated in ACK1 activation in Caco-2 cells. ACK1-Tyr284 was required for protein kinase B (AKT) activation, and ACK1 signaling was mediated through recruiting and phosphorylating the down-stream adaptor protein AKT, which likely promoted cell proliferation in response to TNF-alpha. Moreover, ACK1 activated AKT and Src enhanced nuclear factor-кB (NF-кB) activity, suggesting a correlation between NF-кB signaling and TNF-alpha-mediated apoptosis in Caco-2 cells. Our results demonstrate that ACK1 plays an important role in modulating TNF-alpha-induced aberrant cell proliferation and apoptosis, mediated in part by ACK1 activation. ACK1 and its down-stream effectors may hold promise as therapeutic targets in the prevention and treatment of gastrointestinal cancers, in particular, those induced by chronic intestinal inflammation. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  15. Pentoxifylline inhibits tumor necrosis factor-alpha (TNF alpha)-induced T-lymphoma cell adhesion to endothelioma cells.

    Science.gov (United States)

    Weiss, J M; Vanscheidt, W; Pilarski, K A; Weyl, A; Peschen, M; Schöpf, E; Vestweber, D; Simon, J C

    1995-05-01

    Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms. Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-alpha (TNF alpha), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-dependent (10(-5)-10(-3) M) fashion. Selective incubation of either endothelioma cells or T-lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNF alpha stimulation. We questioned whether pentoxifylline suppressed T-lymphoma cell/endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNF alpha-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.

  16. B cell epitopes on infliximab identified by oligopeptide microarray with unprocessed patient sera.

    Science.gov (United States)

    Homann, Arne; Röckendorf, Niels; Kromminga, Arno; Frey, Andreas; Jappe, Uta

    2015-10-29

    Autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease are treated with TNF-alpha-blocking antibodies such as infliximab and adalimumab. A common side effect of therapeutic antibodies is the induction of anti-drug antibodies, which may reduce therapeutic efficacy. In order to reveal immunogenic epitopes on infliximab which are responsible for the adverse effects, sera from patients treated with infliximab were screened by ELISA for anti-infliximab antibodies. Sera containing high levels of anti-drug-antibodies (>1.25 µg/ml) were analyzed in an oligopeptide microarray system containing immobilized 15-meric oligopeptides from the infliximab amino acid sequence. Immunogenic infliximab IgG-epitopes were identified by infrared fluorescence scanning and comparison of infliximab-treated patients versus untreated controls. Six relevant epitopes on infliximab were recognized by the majority of all patient sera: 4 in the variable and 2 in the constant region. Three of the epitopes in the variable region are located in the TNF-alpha binding region of infliximab. The fourth epitope of the variable part of infliximab is located close to the TNF-alpha binding region and contains an N-glycosylation sequon. The sera positive for anti-infliximab antibodies do not contain antibodies against adalimumab as determined by ELISA. Thus, there is no infliximab-adalimumab cross-reactivity as determined by these systems. Our data shall contribute to a knowledge-based recommendation for a potentially necessary therapy switch from infliximab to another type of TNF-alpha-blocker. The characterization of immunogenic epitopes on therapeutic monoclonal antibodies using unprocessed patient sera shall lead to direct translational aspects for the development of less immunogenic therapeutic antibodies. Patients benefit from less adverse events and longer lasting drug effects.

  17. Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn's Disease: A Comparison of Effectiveness and Safety.

    Science.gov (United States)

    Liu, Jinan; Sylwestrzak, Gosia; Ruggieri, Alexander P; DeVries, Andrea

    2015-07-01

    In recent years, there have been a number of pharmacological innovations for Crohn's disease (CD), a difficult-to-treat condition, including new treatment philosophies (e.g., top-down therapy) and new therapeutic options in terms of the agent and the route of administration. Three anti-tumor necrosis factor (anti-TNF-alpha) agents are available for use among CD patients in the United States: infliximab, an intravenous agent, and adalimumab and certolizumab pegol, 2 newer subcutaneous products. Infliximab is considered the "gold standard" because it has the longest clinical experience, and adalimumab and certolizumab pegol have each gained significant market share. To examine differences in effectiveness and safety between currently available intravenous and subcutaneous anti-TNF-alpha agents used to treat patients with CD. Data for this retrospective, administrative claims analysis were obtained from pharmacy and medical claims from major U.S. health plans geographically dispersed across 14 states during 2007-2011. Patients had at least 1 ICD-9-CM diagnosis for CD, 6 months pre-index eligibility, and initiated anti-TNF-alpha therapy on the index date. Patients in each cohort were propensity score matched on pre-index demographics, clinical characteristics, and baseline health care use. During the post-index period, age-sex adjusted incidence rate ratios (IRRs) of CD-related symptoms, infections, cancers, and hepatic-related conditions were compared using Cox (PH) models. The matched cohorts included 515 patients in each group, with an average age of 39 years. Median follow-up was 17.5 months in the intravenous cohort and 17.7 months in the subcutaneous cohort. In terms of effectiveness outcomes, age-sex adjusted IRRs for the subcutaneous group, with the intravenous cohort as a reference, were as follows: 0.61 (95% CI = 0.32-1.18, P = 0.14) for anal fissures; 0.97 (95% CI = 0.72-1.30, P = 0.85) for abscess; 1.08 (95% CI = 0.79-1.04, P = 0

  18. Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position--308

    DEFF Research Database (Denmark)

    Skov, Lone; Allen, Michael H; Bang, Bo

    2003-01-01

    secretion of TNF-alpha has been identified in humans. We have therefore investigated the association of the --308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC (n=191) and health adults (n-107) were...... compared. For the TNF--308 polymorphism there was significant association between the genotype or allele frequencies and having BCC. To determine whether patients with a previous BCC had an increased capacity to secrete TNF-alpha, mononuclear cells were stimulated with lipopolysaccharide. Mononuclear cells...... from patients with a previous BCC (n=15) demonstrated a significantly increased release of TNF-alpha upon stimulation with lipopolysaccharide (Pcells age-matched control subjects (n=16). Further studies of other polymorphisms of the TNF-alpha gene associated...

  19. Detrimental roles of TNF-alpha in the antiphospholipid syndrome and de novo synthesis of antiphospholipid antibodies induced by biopharmaceuticals against TNF-alpha.

    Science.gov (United States)

    Bećarević, Mirjana

    2017-11-01

    Antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by arterial and/or venous thrombosis and/or recurrent pregnancy losses. Obstetric APS (OAPS) is considered as a distinct entity from vascular APS (VAPS). In the absence of any additional disease, APS is designated as primary (PAPS), while the term secondary APS (SAPS) is used when other diseases are associated. Catastrophic APS (CAPS) is characterized by the rapid development of multiple thrombosis in various vital organs. The presence of antiphospholipid antibodies (aPL Abs) is considered as a laboratory criterion for APS diagnosis. aPL Abs cause an increase in systemic and decidual TNF-alpha levels in experimental model of APS (eAPS), while paradoxically, administration of TNF-alpha blockers has been associated with de novo synthesis of aPL Abs in patients with various autoimmune diseases. While eAPS provides evidence for the fact that application of TNF-alpha blockers has beneficial effects, lack of randomized prospective studies is the main obstacle for consideration of TNF-alpha blockers administration as a therapeutic option not for all, but at least for selected cases of APS patients despite compelling evidence for detrimental roles of TNF-alpha for both VASP and OAPS. This article represents a review of previously published reports on detrimental roles of TNF-alpha in APS, reports on the application of anti-TNF-alpha agents in eAPS and articles that reported de novo synthesis of aPL Abs induced by biopharmaceuticals against TNF-alpha.

  20. Infliximab inhibits DNA repair in ultraviolet B-irradiated premalignant keratinocytes

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.; Wulf, Hans Chr.

    2008-01-01

    Anti-tumor necrosis factor-alpha (TNF alpha) approaches are increasingly used in the therapy of autoimmune diseases. One of the safety concerns is the potential enhancement of skin carcinogenesis. The aim of this study was to investigate if the TNF alpha neutralizing antibody, infliximab, directly...... affects the cell cycle and DNA repair in premalignant human keratinocytes after ultraviolet-B (UVB) irradiation. We found that infliximab-treated cells exhibited an enhanced G2/M cell cycle arrest and increased apoptosis after 10-20 mJ/cm(2) UVB. In spite of this, the level of cyclobutane pyrimidine...... dimers (CPD) in infliximab-treated cells was significantly increased at both 24 and 48 h after irradiation with 10 mJ/cm(2) UVB. As we have recently shown that protein kinase B/Akt is involved in the TNF alpha signalling pathway and promotes cell survival and skin carcinogenesis, we measured activatory...

  1. The acute effects of TNF-alpha on the isolated perfused rat liver.

    Science.gov (United States)

    Shattuck, K E; Grinnell, C D; Goldman, A S; Rassin, D K

    1996-02-01

    TNF-alpha mediates the hepatic response to sepsis by mechanisms which are not well understood. TNF-alpha is known to stimulate the hepatocellular uptake of specific amino acids in vivo; however, little is known about the direct effects of TNF-alpha on hepatic amino acid or glutathione homeostasis, which is a potential factor in the acute hepatic response to sepsis. Using the isolated perfused rat liver, we characterized the effects of TNF-alpha on the secretion of amino acids and glutathione into bile and perfusate. Livers taken from adult male Sprague-Dawley rats were perfused with TNF-alpha at a dose of 1 or 2 micrograms. Bile and perfusate were collected for the quantitation of amino acid and glutathione concentrations. Administration of 2 micrograms TNF-alpha resulted in significant increases in biliary and perfusate concentrations of branched chain, gluconeogenic, and total amino acids. TNF-alpha was also associated with dose-related increases in oxygen uptake, and greater biliary concentrations of glutathione. TNF-alpha has direct effects upon hepatic amino acid metabolism, which represent some of the early events involved in the mechanism of response to sepsis.

  2. Amelioration of psoriasis by anti-TNF-alpha RNAi in the xenograft transplantation model

    DEFF Research Database (Denmark)

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia

    2009-01-01

    (RNAi) are therapeutically relevant. To test this hypothesis the present study describes first the in vitro functional screening of a panel of short hairpin RNAs (shRNAs) targeting human TNF-alpha mRNA and, next, the transfer of the most potent TNF-alpha shRNA variant, as assessed in vitro, to human...

  3. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Nordgaard-Lassen, Inge; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    Ag-positive patients at the start of anti-TNF-alpha treatment. Before anti-TNF-alpha therapy, vaccination with 23-valent pneumococcal vaccine is recommended, and HBV vaccination may be considered in seronegative patients. Annual vaccination against seasonal influenza is recommended. Human papilloma virus vaccination...... should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis......These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel...

  4. The role of TNF alpha polymorphism and expression in susceptibility to nasal polyposis.

    Science.gov (United States)

    Zhang, Guimin; Zhang, Jinmei; Kuang, Manbao; Lin, Peng

    2018-02-01

    In this study, we first performed a meta-analysis to assess the role of single-nucleotide polymorphism (SNP) within tumor necrosis factor alpha (TNF alpha) gene and TNF alpha expression in the risk of nasal polyposis. STATA 12.0 software was utilized to conduct the Mantel-Haenszel statistics, Cohen statistics, Begg's test, Egger's tests and sensitivity analysis. We systemically carried out the database retrieval and initially identified 486 articles. After screening, 15 articles were included in our meta-analysis. For TNF alpha rs1800629 G/A SNP, compared with control group, an increased risk of nasal polyposis of case group was observed in the models of A vs. G [p (P value of association) = 0.009, OR (odds ratio) = 1.35], GA vs. GG (p = 0.001, OR = 1.69), GA+AA vs. GG (p = 0.010, OR = 1.47). The similar results were observed in Caucasian subgroup (p 1). For TNF alpha rs361525 G/A SNP, no significant difference between control and case group was detected (all p > 0.05). In addition, a significant difference exists between case and control groups in the meta-analyses of TNF alpha expression in nasal mucosal cells, secreted TNF alpha (p 1), but not serum TNF alpha (p = 0.090). The present meta-analysis revealed that TNF alpha rs1800629, increased TNF alpha expression and secretion of nasal mucosal cells were associated with an increased risk of nasal polyposis.

  5. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Lassen, Inge Nordgaard; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    Ag-positive patients at the start of anti-TNF-alpha treatment. Before anti-TNF-alpha therapy, vaccination with 23-valent pneumococcal vaccine is recommended, and HBV vaccination may be considered in seronegative patients. Annual vaccination against seasonal influenza is recommended. Human papilloma virus vaccination......-TNF-alpha agents. Screening should take place for both active tuberculosis and latent tuberculosis. Screening must evaluate the risk of hepatitis B exposure/infection and that of other viral infections such as human immunodeficiency virus (HIV) and varicella zoster virus (VZV). The assessment should include...

  6. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Lassen, Inge Nordgaard; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis......These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel...... disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti-TNF-alpha...

  7. New binding mode to TNF-alpha revealed by ubiquitin-based artificial binding protein.

    Directory of Open Access Journals (Sweden)

    Andreas Hoffmann

    Full Text Available A variety of approaches have been employed to generate binding proteins from non-antibody scaffolds. Utilizing a beta-sheet of the human ubiquitin for paratope creation we obtained binding proteins against tumor necrosis factor (TNF-alpha. The bioactive form of this validated pharmacological target protein is a non-covalently linked homo-trimer. This structural feature leads to the observation of a certain heterogeneity concerning the binding mode of TNF-alpha binding molecules, for instance in terms of monomer/trimer specificity. We analyzed a ubiquitin-based TNF-alpha binder, selected by ribosome display, with a particular focus on its mode of interaction. Using enzyme-linked immunosorbent assays, specific binding to TNF-alpha with nanomolar affinity was observed. In isothermal titration calorimetry we obtained comparable results regarding the affinity and detected an exothermic reaction with one ubiquitin-derived binding molecule binding one TNF-alpha trimer. Using NMR spectroscopy and other analytical methods the 1:3 stoichiometry could be confirmed. Detailed binding analysis showed that the interaction is affected by the detergent Tween-20. Previously, this phenomenon was reported only for one other type of alternative scaffold-derived binding proteins--designed ankyrin repeat proteins--without further investigation. As demonstrated by size exclusion chromatography and NMR spectroscopy, the presence of the detergent increases the association rate significantly. Since the special architecture of TNF-alpha is known to be modulated by detergents, the access to the recognized epitope is indicated to be restricted by conformational transitions within the target protein. Our results suggest that the ubiquitin-derived binding protein targets a new epitope on TNF-alpha, which differs from the epitopes recognized by TNF-alpha neutralizing antibodies.

  8. Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans

    DEFF Research Database (Denmark)

    Petersen, Anne Marie; Plomgaard, Peter; Fischer, Christian P

    2009-01-01

    Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. Objective: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover, via a 4 hours recombinant human TNF......-alpha infusion (rhTNF-alpha). We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibit synthesis. Subjects and Methods: Using a randomized controlled, crossover design post-absorptive healthy young males (n=8) were studied 2 hours under basal conditions followed by 4 hours infusion...... of either rhTNF-alpha (700 ng.m(-2).h(-1)) or 20% human albumin (Control) which was the vehicle of rhTNF-alpha. Systemic and skeletal muscle protein turnover were estimated by a combination of tracer dilution methodology (primed continuous infusion of L-[ring-(2)H5]phenylalanine and L-[(15)N...

  9. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

    Directory of Open Access Journals (Sweden)

    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  10. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Lassen, Inge Nordgaard; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X......-TNF-alpha agents. Screening should take place for both active tuberculosis and latent tuberculosis. Screening must evaluate the risk of hepatitis B exposure/infection and that of other viral infections such as human immunodeficiency virus (HIV) and varicella zoster virus (VZV). The assessment should include...... should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis...

  11. [Peripheral neuropathy during Infliximab therapy: a case study].

    Science.gov (United States)

    Zinebi, Ali; Akhouad, Youssef; Rkiouak, Adil; Reggad, Ahmed; Kasmy, Zohour; Boudlal, Mostafa; Rabhi, Monsef; Ennibi, Khalid; Chaari, Jilali

    2016-01-01

    Anti TNF alpha treatments are wide spectrum therapies. Multiple side effects have been reported in recent years, particularly peripheral neuropathies. We report a case of axonal neuropathy occurring three months after starting treatment with Infliximab. Our study focused on a 60-year old female patient treated for therapy-resistant hemorrhagic rectocolitis, requiring treatment with infliximab. Three months later, the patient had sensory axonal neuropathy. Etiologic assessment remained negative and dose reduction was accompanied by an improvement in symptoms. The time between initiation of treatment with Infliximab and the onset of clinical manifestations as well as improvement after dose reduction advocate the responsibility of infliximab in the occurrence of sensory neuropathy. Its management is not standardized and should be discussed case by case.

  12. Estimate of CRP and TNF-alpha level before and after periodontal ...

    African Journals Online (AJOL)

    Conclusion: It can be concluded from the study that there can be a possible causal relationship between pathogenesis of periodontal disease and CVD as inferred from the statistical significant outcome in the form of decreased inflammatory biomarkers after the periodontal treatment. Key words: CVD, CRP, TNF-alpha, ...

  13. A high plasma concentration of TNF-alpha is associated with dementia in centenarians

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Andersen-Ranberg, K.; Jeune, B.

    1999-01-01

    with both Alzheimer's disease and generalized atherosclerosis in the centenarians. The concentration of TNF-alpha was positively correlated with the concentrations of plasma IL-6, sTNFR-II, and CRP. No associations were found with increased leucocyte subsets or the body mass index. Conclusion. This study...

  14. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility.

    NARCIS (Netherlands)

    Horssen, R. van; Hagen, T.L.M. ten; Eggermont, A.M.M.

    2006-01-01

    Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The

  15. TNF-{alpha} mediates the stimulation of sclerostin expression in an estrogen-deficient condition

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beom-Jun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Bae, Sung Jin [Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Sun-Young; Lee, Young-Sun; Baek, Ji-Eun; Park, Sook-Young [Asan Institute for Life Sciences, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Seung Hun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Koh, Jung-Min, E-mail: jmkoh@amc.seoul.kr [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Kim, Ghi Su [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Estrogen deprivation stimulates the bony sclerostin levels with reversal by estrogen. Black-Right-Pointing-Pointer TNF-{alpha} increases the activity and expression of MEF2 in UMR-106 cells. Black-Right-Pointing-Pointer TNF-{alpha} blocker prevents the stimulation of bony sclerostin expression by ovariectomy. Black-Right-Pointing-Pointer No difference in bony sclerostin expression between sham-operated and ovariectomized nude mice. -- Abstract: Although recent clinical studies have suggested a possible role for sclerostin, a secreted Wnt antagonist, in the pathogenesis of postmenopausal osteoporosis, the detailed mechanisms how estrogen deficiency regulates sclerostin expression have not been well-elucidated. Bilateral ovariectomy or a sham operation in female C57BL/6 mice and BALB/c nude mice was performed when they were seven weeks of age. The C57BL/6 mice were intraperitoneally injected with phosphate-buffered serum (PBS), 5 {mu}g/kg {beta}-estradiol five times per week for three weeks, or 10 mg/kg TNF-{alpha} blocker three times per week for three weeks. Bony sclerostin expression was assessed by immunohistochemistry staining in their femurs. The activity and expression of myocyte enhancer factors 2 (MEF2), which is essential for the transcriptional activation of sclerostin, in rat UMR-106 osteosarcoma cells were determined by luciferase reporter assay and western blot analysis, respectively. Bony sclerostin expression was stimulated by estrogen deficiency and it was reversed by estradiol supplementation. When the UMR-106 cells were treated with well-known, estrogen-regulated cytokines, only TNF-{alpha}, but not IL-1 and IL-6, increased the MEF2 activity. Consistently, TNF-{alpha} also increased the nuclear MEF2 expression. Furthermore, the TNF-{alpha} blocker prevented the stimulation of bony sclerostin expression by ovariectomy. We also found that there was no difference in sclerostin expression between ovariectomized

  16. [Regulation of ursolic acid on TNF-alpha and collagen in silicotic rats].

    Science.gov (United States)

    Peng, Haibing; Cao, Fuyuan; Wang, Jianxing; Zhao, Xia; Han, Shuying

    2014-07-01

    To explore the regulation of ursolic acid on the expressions of TNF-alpha and collagen on Silicotic Rats. Seventy-five Wistar rats (class SPF) were divided into there groups according to the randomized block design, namely, control, model, ursolic acid groups with twenty-five rats in each group. SiO2 powders (250 mg/kg) were douched in the trachea of rat to make the silicotic model in model and ursolic acid groups. Ursolic acid (40 mg/kg) was injected into stomach cavity in ursolic acid group from the second day of SiO2, while the rats in control group were given sodium chloride in the same condition for 28 consecutive days. All rats were put to death on the 7th,14th and 28th day. TNF-alpha contents in serum were detected by ELISA. Total collagen contents in lung tissue were determined by hydroxyproline kits. Collagen I and III in lung tissue were investigated by western blot technique. After four weeks of intervention, the contents of TNF-alpha in serum of the model group had rised, showing statistically significant difference in each time compared to those of the control group (P Ursolic acid had depressant effect on the contents of TNF-alpha (P content of total collagen was significantly improved in model group (P ursolic acid depressed the expression of total collagen protein compared to those of the model group (P ursolic acid and model groups were similar with the total collagen. Ursolic acid could decrease the expressions of TNF-alpha and collagen in the process of silicosis fibrosis.

  17. TNF-alpha-308G>A polymorphism and the risk of familial CAD in a Pakistani population.

    Science.gov (United States)

    Hussain, Sabir; Iqbal, Tahir; Javed, Qamar

    2015-01-01

    A case-control and trio-families study was performed to establish a potential association between TNF-alpha gene promoter SNPs at -308 and -238, and occurrence of CAD in a Pakistani population. In the first phase, 150 patients and 150 controls were enrolled in the case-control association study. In the second phase, heritability of susceptible alleles was investigated from 88 trio-families with CAD affected offspring. Biochemical analysis of lipids and hs-CRP was carried out spectrophotometrically, while serum TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Genotyping of the TNF-alpha SNPs were determined by PCR-RFLP method. Elevated serum TNF-alpha and hs-CRP were observed from CAD vs. controls (PA polymorphism in case-control study revealed that the said SNP was significantly associated with the increased risk of CAD. The findings demonstrated a significant link between the TNF-alpha variant allele A at -308 and CAD (P=0.0035), whereas the -238 SNP was not associated with the disease. Haplotype A-G of the TNF-alpha gene at -308G>A and -238G>A showed higher frequency in the patient group compared with controls (PA polymorphism is associated with CAD in the study population. Furthermore, for the first time, we showed that the TNF-alpha-308A allele was significantly associated with the familial CAD in our high risk population. Copyright © 2014. Published by Elsevier Inc.

  18. Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

    Science.gov (United States)

    Kim, Sung-Jo

    2010-06-01

    In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

  19. Local delivery of soluble TNF-alpha receptor 1 gene reduces infarct size following ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Sugano, Masahiro; Hata, Tomoji; Tsuchida, Keiko; Suematsu, Nobuhiro; Oyama, Jun-Ichi; Satoh, Shinji; Makino, Naoki

    2004-11-01

    Apoptosis in the myocardium is linked to ischemia/reperfusion injury, and TNF-alpha induces apoptosis in cardiomyocytes. A significant amount of TNF-alpha is detected after ischemia and reperfusion. Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNF-alpha receptor 1 and is an antagonist to TNF-alpha. In the present study, we examined the effects of sTNFR1 on infarct size in acute myocardial infarction (AMI) following ischemia/reperfusion. Male Wistar rats were subjected to left coronary artery (LCA) ligation. After 30 min of LCA occlusion, the temporary ligature on the LCA was released and blood flow was restored. Immediately after reperfusion, a total of 200 microg of sTNFR1 or LacZ plasmid was injected into three different sites of the left ventricular wall. At 6 h, 1 and 2 days after reperfusion, the TNF-alpha bioactivity in the myocardium was significantly higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase in the TNF-alpha bioactivity. The sTNFR1 plasmid significantly reduced DNA fragmentation and caspase activity compared to the LacZ plasmid. Finally, the sTNFR1 expression-plasmid treatment significantly reduced the area of myocardial infarction at 2 days after ischemia/reperfusion compared to LacZ plasmid. In conclusion, the TNF-alpha bioactivity in the heart increased from the early stage of ischemia/reperfusion, and this increase was thought to contribute in part to the increased area of myocardial infarction. Suppression of TNF-alpha bioactivity with the sTNFR1 plasmid reduced the infarct size in AMI following ischemia and reperfusion.

  20. TNF-alpha promoter, Nod2 and toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin

    NARCIS (Netherlands)

    Schippers, Emile F.; van 't Veer, Cornelis; van Voorden, Sjaak; Martina, Cerithsa A. E.; le Cessie, Saskia; van Dissel, Jaap T.

    2004-01-01

    Humans exhibit substantial inter-individual differences in TNF-alpha production upon endotoxin stimulation. To determine to what extent the lipopolysaccharide-induced TNF-alpha production capacity in vivo and ex vivo is determined by polymorphisms in toll-like receptor-4 (TLR4), the TNF-alpha

  1. Leptin and TNF-alpha levels in patients with chronic obstructive pulmonary disease and their relationship to nutritional parameters.

    Science.gov (United States)

    Calikoglu, Mukadder; Sahin, Gulsah; Unlu, Ali; Ozturk, Candan; Tamer, Lülüfer; Ercan, Bahadir; Kanik, Arzu; Atik, Uğur

    2004-01-01

    Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. In humans, there was a strong correlation between leptin and nutritional parameters, such as body mass index (BMI) and fat mass (FM). Administration of recombinant leptin to OB/OB mice, which have a genetic defect in leptin production, reduces food intake, increases energy expenditure, and decreases body weight. It is suggested that increased levels of circulating leptin levels may contribute to anorexia and weight loss in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as TNF-alpha. This study aimed to detect serum leptin and TNF-alpha levels in COPD patients without weight loss during stable disease and acute exacerbation, and to investigate relationships between leptin, TNF-alpha and nutritional parameters at different stages of the disease. 26 stable COPD patients, 16 COPD patients with acute exacerbation and 15 control subjects participated in this study. To eliminate the effects of sex differences, all patients and controls were male. BMI, percent ideal body weight, percent FM, sum of skinfold thickness and serum leptin and TNF-alpha levels were measured in all participants. Leptin and TNF-alpha levels were measured by ELISA. Serum leptin and TNF-alpha levels were significantly higher in the patients experiencing exacerbation than in the stable patients and controls. Although leptin levels were lower and TNF-alpha levels were higher in the stable patient group than in the controls, these differences were not statistically different. Leptin levels were significantly correlated with the nutritional parameters in both control and stable groups. However, in patients with acute exacerbation, a correlation between leptin and nutritional parameters was not found. There was no significant relationship between TNF-alpha

  2. Roles of TNF-alpha and IgE in the late phase of contact hypersensitivity induced by trimellitic anhydride.

    Science.gov (United States)

    Chai, Ok Hee; Lee, Hern Ku; Lee, Yong Chul; Lee, Moo Sam; Han, Eui Hyeog; Kim, Hyoung Tae; Song, Chang Ho

    2005-10-31

    Trimellitic anhydride (TMA) is widely used industrially to make epoxy and alkyd resins, plasticizers and surfactants. The purpose of this study was to investigate whether contact hypersensitivity (CHS) is induced by repeated TMA challenge and the role of TNF-alpha and IgE in the TMA-induced CHS. The repetition of the challenge enlarged the extent of an early and a late phase of CHS in TNF-alpha+/+ (B6129SF2/J) and Balb/c mice. In the late phase of TMA-induced CHS, the peak of ear swelling responses by single challenge showed at 24 h after challenge, but the peak was observed at 8 h after repeated challenge. In the TNF-alpha knockout TNF-alpha-/- (B6;129S-Tnftm1Gk1) mice, the repetition of the TMA challenges enlarged the extent of the late phase of CHS, but less than those in TNF-alpha+/+ mice. Injection of anti-TNF-alpha antibody into the peritoneal cavity of Balb/c mice significantly decreased the extent of the late phase of CHS. Subcutaneous injection of anti-IgE antibody into Balb/c mice also decreased the extent of the late phase of CHS in dose-dependent manner. Histologically, infiltration of polymorphonuclear leukocytes and eosinophils was more pronounced in repeatedly TMA-challenged TNF-alpha+/+ and Balb/c mice than in the TNF-alpha-/- mice and anti-TNF-alpha or anti-IgE antibodies treated Balb/c mice. These results indicate that mice sensitized by TMA could possibly offer a useful model to study the mechanism of CHS, and TNF-alpha and IgE may act as potential modulators in the late phase of TMA-induced CHS. Neutralization of TNF-alpha and IgE by anti-TNF-alpha or anti-IgE antibodies may provide therapeutic tools for the treatment of TMA-induced CHS.

  3. Suppression of TNF-alpha production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines

    DEFF Research Database (Denmark)

    Yu, J.; Parlesak, Alexandr; Sauter, S.

    2006-01-01

    precursors or metabolites [phosphatidylcholine, choline, betaine, S-adenosylmethionine (SAM)] have a modulating effect on tumor necrosis factor alpha (TNF-alpha) production by endotoxin-stimulated human mononuclear leukocytes and whether SAM-dependent polyamines (spermidine, spermine) are mediators of SAM......-induced inhibition of TNF-alpha synthesis. Methionine and betaine had a moderate stimulatory effect on TNF-alpha production, whereas phosphatidylcholine (ID(50) 5.4 mM), SAM (ID(50) 131 microM), spermidine (ID(50) 4.5 microM) and spermine (ID(50) 3.9 microM) had a predominantly inhibitory effect. Putrescine did...

  4. [Effects of polydatin on ALT, AST, TNF-alpha, and COX-2 in sepsis model mice].

    Science.gov (United States)

    Li, Xiao-Hui; Wu, Meng-Jiao; Zhang, Li-Na; Zheng, Jia-Jia; Zhang, Li; Wan, Jing-Yuan

    2013-02-01

    To investigate the protective effects of polydatin on sepsis-induced acute liver injury (ALI) in mice, and to preliminarily study its mechanisms. The sepsis model was established using cecal ligation and puncture (CLP).A sham-operation control group was also set up. Polydatin (50, 100, and 300 mg/kg, respectively) was administrated to mice 1 h before CLP. The survival and liver injury were evaluated subsequently per 6 h after CLP. The survived mice were scarified 24 h later. The serum and the liver tissue sample were collected. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetric method. The content of tumor necrosis factor-alpha (TNF-alpha) was assayed by ELISA. The cyclooxygenase-2 (COX-2) expression in the liver tissue was detected by Western blot. The pathological changes of the hepatic tissue were analyzed by hematoxylin and eosin stain. The mortality of mice reached as high as 50% at 24 h after CLP. The biochemical indices and the pathological changes of the liver tissue showed obvious lesion. The success rate of modeling was 90%. Compared with the sham-operation control group, the serum ALT,AST activity, the TNF-alpha content, and the hepatic COX-2 protein expression markedly increased in the CLP group (P < 0.01). Polydatin improved the sepsis-induced mortality dose-dependently, inhibited increased ALT, AST activity and TNF-alpha, decreased the hepatic COX-2 protein expression, and attenuated the pathological injury of the liver (P < 0.05). Polydatin could effectively protect sepsis-induced ALI, which might be achieved possibly through inhibiting serum TNF-alpha production and hepatic COX-2 expression.

  5. TNF-alpha levels in tears: a novel biomarker to assess the degree of diabetic retinopathy.

    Science.gov (United States)

    Costagliola, C; Romano, V; De Tollis, M; Aceto, F; dell'Omo, R; Romano, M R; Pedicino, C; Semeraro, F

    2013-01-01

    We assess the level of tumour necrosis factor alpha (TNF-alpha) in tear fluids and other serum parameters associated with diabetes in different degrees of diabetic retinopathy. We have performed a prospective, nonrandomized, observational study. Study population consisted of 16 healthy subjects (controls) and 32 type 2 diabetic patients: 16 affected by proliferative diabetic retinopathy (PDR) and 16 with nonproliferative retinopathy (NDPR, background/preproliferative). Body mass index, urinary albumin, blood glucose, HbA1c, and tear levels of TNF-alpha were measured in all subjects. The value of glycaemia, microalbuminurea, and Body mass index in diabetic retinopathy groups were higher than those in control group (P < 0.05). Glycemia in NPDR: 6.6 mmol/L (range: 5.8-6.3); in PDR: 6.7 mmol/L (range: 6.1-7.2); in control: 5.7 mmol/L (range: 4.9-6.1); microalbuminurea in NPDR: 10.6 mg/L (range: 5.6-20); in PDR: 25.2 mg/L (range: 17-40); in control: 5.3 mg/L (range: 2.6-10); Body mass index in NPDR: 26 Kg/m(2) (range: 20.3-40); in PDR: 28 Kg/m(2) (range 20.3-52); in control: 21 Kg/m(2) (range 19-26). The TNF-alpha concentrations in tears increase with the severity of pathology and were lower in control group than in diabetic subjects. In the end, the level of TNF-alpha is highly correlated with severity of diabetic retinopathy and with nephropathy. Tear fluid collection may be a useful noninvasive method for the detection of proliferative diabetic retinopathy.

  6. A high plasma concentration of TNF-alpha is associated with dementia in centenarians

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Andersen-Ranberg, K.; Jeune, B.

    1999-01-01

    Background Inflammatory mechanisms and immune activation have been hypothesized to play a role in the pathogenesis of age-associated diseases such as dementia and atherosclerosis. The purpose of this study was to evaluate the plasma concentration of tumor necrosis factor (TNF)-alpha in a large co...... demonstrates that, even in apparently healthy subjects, age-associated immune activation indicated by raised levels of pro-inflammatory cytokines may reflect age-associated pathological processes that develop over decades.......Background Inflammatory mechanisms and immune activation have been hypothesized to play a role in the pathogenesis of age-associated diseases such as dementia and atherosclerosis. The purpose of this study was to evaluate the plasma concentration of tumor necrosis factor (TNF)-alpha in a large...... cohort of centenarians and to look for its possible associations with cognitive function, atherosclerosis, and general health status. Furthermore, we investigated whether the concentration of TNF-alpha was correlated with the blood concentration of leucocyte subsets or the plasma concentrations...

  7. TNF-alpha induced junctional modulation enhances response to radiation in Caco-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Yeonjoo; Ahn, Hyein; Park, Jina; Lee, Byungryong; Chung, Eunkyung [Hallym University, Seoul (Korea, Republic of); Yi, Jaeoun [KIRAMS, Seoul (Korea, Republic of)

    2007-10-15

    The Adhesion molecules mediated cell-cell and cell matrix interactions are essential for variety of physiological and pathological processes including maintenance of normal tissues integrity as well as tumor development and progression. Cell-cell interaction is initiated by interactions of tight junctional proteins with neighboring cells. Tight junctions govern the paracellular permeability of endothelial and epithelial cells. Aberrations of tight junction formation are an early and key event during vascular spread cancer and inflammation. TNF-alpha plays an important role in the intestinal inflammation by increase of intestinal epithelial tight junction permeability. It has been reported that TNF alpha- modulated intestinal epithelial tight junction barrier is mediated by myosin light-chain kinase protein expression through NFk-B activation. However, the alterations of tight junctional proteins involved in the TNF-alpha-induced increase of intestinal TJ permeability remain unclear. Claudin is essential to the formation and maintenance of tight junction (TJ) and has been identified 24 members so far. Claudin-1, 3, 4, 6, 10 and 16 have been shown altered in various cancers and they may have important roles in cell survival, motility, and invasion of cancer cells. However, the functions of these proteins in tumorigenesis and inflammation are still being elucidated.

  8. Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF.

    Science.gov (United States)

    Zou, Jing; Pyykkö, Ilmari; Sutinen, Päivi; Toppila, Esko

    2005-04-01

    Transcranial vibration was applied for seven animals at a frequency of 250 Hz for 15 min, and five animals were used as normal controls to investigate cellular and molecular mechanism linked to vibration-induced hearing loss in animal model. Compound action potential (CAP) thresholds were measured by round window niche electrode. The expression of tumour necrosis factor alpha (TNF-alpha) and its receptors (TNF R1, TNF R2), vascular endothelium growth factor (VEGF) and its receptors (VEGF R1, VEGF R2) were analysed by immunohistochemistry. Transcranial vibration caused expression of TNF-alpha, TNF R1 and TNF R2 in the cochlea and the expression of TNF R2 was stronger than that of TNF R1. Vibration also induced VEGF and VEGF R2 expression in the cochlea. The average immediate hearing loss was 62 dB and after three days still 48 dB. It is concluded that transcranial vibration as during temporal bone drilling produces cochlear shear stress that is connected with up-regulation of TNF-alpha and its receptors. Also VEGF and VEGF R2 are up-regulated. These responses may be linked to both the damage and repair process of the cochlea.

  9. Generation of TNF alpha, IFN gamma, IL-6, IL-4 and IL-10 in mouse serum from trichinellosis: effect of the anti-inflammatory compound 4-deoxypyridoxine (4-DPD).

    Science.gov (United States)

    Frydas, S; Karagouni, E; Dotsika, E; Reale, M; Barbacane, R C; Vlemmas, I; Anogianakis, G; Trakatellis, A; Conti, P

    1996-03-01

    Infections caused by the nematode Trichinella spiralis is characterized in the host by an inflammatory response with cytokine production. In these studies we have detected TNF alpha, IL-6, IFN gamma, IL-4 and IL-10 in the serum of 10 mice infected with T. spiralis. Moreover, we detected, for the first time, these cytokines in the serum of mice treated with 4-DPD, a potent antagonist of vitamin B6 coenzyme which has anti-inflammatory properties. 4-DPD was used at 100, 400, 800 micrograms/bolus for 20 days, starting one day before the infection. After 15 days of T. spiralis infection, TNF alpha reached a maximum level, while IL-6 was maximal after 7 days, IFN gamma at 20 days and IL-4 at 14 days. IL-10 was not affected by the T. spiralis infection. When the animals were treated with 4-DPD at the reported dosages and infected with T. spiralis the inhibition of TNF alpha and IL-6, were dose-dependent in the first 7 days while IL-4 was reduced only at 400-800 micrograms/bolus. 4-DPD-treated mice did not statistically (P > 0.05) affect the generation of IFN gamma. In healthy animals the production of cytokines were not measurable, just as it was in non-infected animals treated with 4-DPD. The increase of cytokines such as, TNF alpha and IL-6 may be related to the severity of the disease, boosting the host's resistance to the pathogen and inhibiting parasite survival. In addition, the augmentation of IL-4 production enhances T and B cells and macrophage responses and may stimulate T-cell antibody-mediated response to the pathogen. 4-DPD, an inhibitor of IL-1 and inflammatory reactions, proved to be most effective on TNF alpha and IL-6, which are mainly produced by macrophages.

  10. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha

    DEFF Research Database (Denmark)

    Czermak, B J; Sarma, V; Bless, N M

    1999-01-01

    Under a variety of conditions, alveolar macrophages can generate early response cytokines (TNF-alpha, IL-1), complement components, and chemotactic cytokines (chemokines). In the current studies, we determined the requirements for TNF-alpha and the complement activation product C5a in chemokine...... production in vitro and in vivo. Two rat CXC chemokines (macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC)) as well as three rat CC chemokines (MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1) were investigated. Chemokine generation in vitro.......v., and effects on chemokine levels in bronchoalveolar lavage fluids were quantitated by ELISA. Both in vitro and in vivo studies demonstrated the requirements for TNF-alpha and C5a for full generation of CXC and CC chemokines. In vitro and in vivo blockade of TNF-alpha or C5a resulted in significantly reduced...

  11. The treatment of disc herniation-induced sciatica with infliximab - One-year follow-up results of FIRST II, a randomized controlled trial

    NARCIS (Netherlands)

    Korhonen, Timo; Karppinen, Jaro; Paimela, Leena; Malmivaara, Antti; Lindgren, Karl-August; Bowman, Chris; Hammond, Anthony; Kirkham, Bruce; Jarvinen, Simo; Niinimaki, Jaakko; Veeger, Nic; Haapea, Marianne; Torkki, Markus; Tervonen, Osmo; Seitsalo, Seppo; Hurri, Heikki

    2006-01-01

    Study Design. A randomized controlled trial. Objectives. To evaluate the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), in patients with acute/subacute sciatica secondary to herniated disc. Summary of Background Data. The results of

  12. The treatment of disc herniation-induced sciatica with infliximab - Results of a randomized, controlled, 3-month follow-up study

    NARCIS (Netherlands)

    Korhonen, T; Karppinen, J; Paimela, L; Malmivaara, A; Lindgren, KA; Jarvinen, S; Niinimaki, J; Veeger, N; Seitsalo, S; Hurri, H

    2005-01-01

    Study Design. A randomized controlled trial. Objectives. To evaluate the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF)-alpha in a randomized controlled setting. Summary of Background Data. Recently, we obtained encouraging results in an open-label study of

  13. Thy-1 attenuates TNF-alpha-activated gene expression in mouse embryonic fibroblasts via Src family kinase.

    Directory of Open Access Journals (Sweden)

    Bin Shan

    Full Text Available Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-alpha. Our study demonstrates distinct profiles of TNF-alpha-activated gene expression in Thy-1 positive (Thy-1+ and negative (Thy-1- subsets of mouse embryonic fibroblasts (MEF. TNF-alpha induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1- MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1- MEFs significantly attenuated TNF-alpha-activated gene expression. Mechanistically, TNF-alpha activated Src family kinase (SFK only in Thy-1- MEFs. Blockade of SFK activation abrogated TNF-alpha-activated gene expression in Thy-1- MEFs, whereas restoration of SFK activation rescued the TNF-alpha response in Thy-1+ MEFs. Our findings suggest that Thy-1 down-regulates TNF-alpha-activated gene expression via interfering with SFK- and NF-kappaB-mediated transactivation. The current study provides a novel mechanistic insight to the distinct roles of fibroblast Thy-1 subsets in inflammation.

  14. Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor necrosis factor (TNF)-alpha induces significant tumor regression.

    Science.gov (United States)

    Wright, P; Zheng, C; Moyana, T; Xiang, J

    1998-01-01

    Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. VKCK is a murine myeloma cell line expressing the light chain of the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro transfection of VKCK cells with the AdV AdV5LacZ, which contains the marker gene beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of 1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units) resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000, transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36 ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture. The secretion peaks at day 3 and is diminished at day 6 following the viral infection. These transfected VKCK cells also became more immunogenic with enhanced expression of major histocompatibility complex class I antigen. Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha virus with a repeated booster resulted in significant VKCK tumor regression in immune-competent mice, but not in athymic nude mice with a mean tumor weight of 0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with AdV5LacZ and phosphate-buffered saline, respectively (P management of solid human tumors.

  15. Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene

    Energy Technology Data Exchange (ETDEWEB)

    Orlov, Sergey V., E-mail: serge@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Mogilenko, Denis A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Shavva, Vladimir S. [Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Dizhe, Ella B.; Ignatovich, Irina A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Perevozchikov, Andrej P., E-mail: app@iem.sp.ru [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation)

    2010-07-23

    Research highlights: {yields} TNF{alpha} stimulates the distal alternative promoter of human apoA-I gene. {yields} TNF{alpha} acts by weakening of promoter competition within apoA-I gene (promoter switching). {yields} MEK1/2 and nuclear receptors PPAR{alpha} and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1{beta} and TNF{alpha}. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNF{alpha}-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNF{alpha} on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNF{alpha} leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNF{alpha}. The MEK1/2-ERK1/2 cascade and nuclear receptors PPAR{alpha} and LXRs are important for TNF{alpha}-mediated apoA-I promoter switching.

  16. Neuropathie périphérique sous Infliximab: étude d'une observation ...

    African Journals Online (AJOL)

    Les traitements Anti TNF alpha sont de prescription de plus en plus large. Des événements secondaires multiples ont été rapportés ses dernières années, en particulier les neuropathies périphériques. Nous rapportons un cas de neuropathie axonale survenant trois mois après le début d'un traitement par Infliximab. Il s'agit ...

  17. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans

    DEFF Research Database (Denmark)

    Starkie, Rebecca; Ostrowski, Sisse Rye; Jauffred, Sune

    2003-01-01

    and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli...... exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced...

  18. Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

    Science.gov (United States)

    Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

    2004-01-16

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

  19. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower musc...... that cytokines are partly derived from this adipose tissue bed. Furthermore, TNF-alpha was related to lower ASM and BCM, suggesting that TNF-alpha contributes to sarcopenia in ageing....

  20. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2-diabetes

    DEFF Research Database (Denmark)

    Pedersen, M; Bruunsgaard, H; Weis, Nina Margrethe

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower musc...... that cytokines are partly derived from this adipose tissue bed. Furthermore, TNF-alpha was related to lower ASM and BCM, suggesting that TNF-alpha contributes to sarcopenia in ageing....

  1. Altered TNF-Alpha, Glucose, Insulin and Amino Acids in Islets Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.

    2001-01-01

    The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-1 17,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (pinsulin concentration was demonstrated in the LPS stimulated HARV culture (palterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  2. TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma.

    Science.gov (United States)

    Pilaro, A M; Taub, D D; McCormick, K L; Williams, H M; Sayers, T J; Fogler, W E; Wiltrout, R H

    1994-07-01

    Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four- to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions.

  3. Effects of pentoxifylline on TNF-alpha and lung histopathology in HCL-induced lung injury

    Directory of Open Access Journals (Sweden)

    Itamar Souza de Oliveira-Júnior

    2008-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of pentoxifylline on hydrochloric acid-induced lung lesions in rats subjected to mechanical ventilation. METHODS: Twenty male, adult Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group as follows: control-MV (mechanical ventilation, MV group; bilateral instillation of HCl (HCl group; bilateral instillation of HCl followed by pentoxifylline (50 mg/kg bw infusion (HCl+PTX group and pentoxifylline infusion followed by bilateral instillation of HCl (PTX+HCl group. At 20, 30, 90 and 180 min after treatments, the blood partial pressures of CO2 and O2 were measured. The animals were euthanized, and bronchoalveolar lavages were taken to determine the contents of total proteins, corticosterone and TNF-alpha. Samples of lung tissue were used for histomorphometric studies and determining the wet-to-dry (W/D lung weight ratio. RESULTS: In the MV group, rats had alveolar septal congestion, and, in the HCl group, a remarkable recruitment of neutrophils and macrophages into the alveoli was noticed; these events were reduced in the animals with PTX+HCl. The partial pressure of oxygen increased in PTX+HCl animals (121±5 mmHg as compared with the HCl (62±6 mmHg and HCl+PTX (67±3 mmHg groups within 30 minutes. TNF-alpha levels in bronchoalveolar lavage were significantly higher in the HCl group (458±50 pg/mL, reduced in the HCl+PTX group (329±45 pg/mL and lowest in the PTX+HCl group (229±41 pg/mL. The levels of corticosterone in bronchoalveolar lavage were significantly lower in the HCl (8±1.3 ng/mL and HCl+PTX group (16±2 ng/mL and were highest in the PTX+HCl (27±1.9 ng/mL. CONCLUSION: Pretreatment with PTX improves oxygenation, reduces TNF-alpha concentration and increases the concentration of corticosterone in bronchoalveolar lavage upon lung lesion induced by HCl.

  4. Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats.

    Science.gov (United States)

    Altintas, Nejat; Erboga, Mustafa; Aktas, Cevat; Bilir, Bulent; Aydin, Murat; Sengul, Aysun; Ates, Zehra; Topcu, Birol; Gurel, Ahmet

    2016-02-01

    We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I-BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II-control group, a single intra-tracheal saline was installed; III-IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV-IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-β, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-β, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate

  5. Infliximab: 12 years of experience

    Science.gov (United States)

    2011-01-01

    Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are immune-mediated conditions that share an inflammatory mechanism fuelled by excessive cytokines, particularly TNF. Control of inflammation and rapid suppression of cytokines are important in treating these diseases. With this understanding and the corresponding advent of TNF inhibitors, RA patients, AS patients and PsA patients have found more choices than ever before and have greater hope of sustained relief. As a widely used TNF inhibitor, infliximab has a deep and established record of efficacy and safety data. Extensive evidence - from randomised controlled clinical trials, large registries and postmarketing surveillance studies - shows that infliximab effectively treats the signs and symptoms, provides rapid and prolonged suppression of inflammation, prevents radiologically observable disease progression and offers an acceptable safety profile in RA, AS and PsA. In very recent studies, investigators have observed drug-free remission in some patients. Additionally, infliximab may interfere with rapidly progressing disease in RA by early addition to methotrexate in patients with signs of an aggressive course. Finally, infliximab has been shown to reduce PsA clinical manifestations such as nail involvement. With our current understanding, substantial data and increasing confidence regarding use in practice, infliximab can be considered a well-known drug in our continued campaign against inflammatory rheumatic diseases. PMID:21624181

  6. Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize Toward TNF alpha-Mediated Hepatotoxicity

    NARCIS (Netherlands)

    Fredriksson, Lisa; Wink, Steven; Herpers, Bram; Benedetti, Giulia; Hadi, Mackenzie; de Bont, Hans; Groothuis, Geny; Luijten, Mirjam; Danen, Erik; de Graauw, Marjo; Meerman, John; van de Water, Bob

    Drug-induced liver injury (DILI) is an important clinical problem. Here, we used a genomics approach to in detail investigate the hypothesis that critical drug-induced toxicity pathways act in synergy with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) to cause cell death of

  7. Differential role of TNF-alpha and IFN-gamma in the brain of rats with chronic relapsing autoimmune encephalomyelitis.

    Science.gov (United States)

    Tanuma, N; Shin, T; Kogure, K; Matsumoto, Y

    1999-04-01

    To elucidate the mechanisms of relapses of the clinical signs in experimental autoimmune encephalomyelitis (EAE), the cytokine profile of chronic relapsing EAE (CR-EAE) in rats was determined by competitive polymerase chain reaction (PCR). By immunization with guinea pig spinal cord homogenate and treatment with low-dose cyclosporin A (CsA), rats developed two attacks of EAE with remission in between. Cytokine analysis revealed that the level of TNF-alpha mRNA increased at the first and second attacks with transient disappearance at the remission phase. In contrast, the level of IFN-gamma mRNA was suppressed at the first attack by CsA and peaked at the second attack. Intraventricular administration of IFN-gamma prior to onset of disease signs induced more relapses, or a severe lethal form. In addition, the intraventricular injection of TNF-alpha caused the persistence of the clinical signs. These findings suggest that TNF-alpha contributes to the first and second attacks of CR-EAE, while IFN-gamma is not required for the first attack but is closely related to the relapse of the disease. With regard to anti-inflammatory cytokines, the levels of both TGF-beta1 and IL-10 mRNA at the second attack were higher than those at the first attack. Taken together, differential involvement of TNF-alpha and IFN-gamma is closely associated with the clinical features of CR-EAE.

  8. IGF-1 and ADMA Levels Are Inversely Correlated in Nondiabetic Ankylosing Spondylitis Patients Undergoing Anti-TNF-Alpha Therapy

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    2014-01-01

    Full Text Available Like rheumatoid arthritis, ankylosing spondylitis (AS is also an inflammatory disease associated with accelerated atherosclerosis and the presence of metabolic syndrome (MeS features. AS patients often display osteoporosis as well as new bone formation. Insulin-like growth factor 1 (IGF-1 is a protein involved in both inflammation and bone metabolism. In the present study we assessed whether disease activity, systemic inflammation, MeS features, adipokines, and biomarkers of endothelial activation were associated with IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3 levels in a series of 30 nondiabetic AS patients without CV disease undergoing TNF-α antagonist-infliximab therapy. All determinations were made in the fasting state, immediately before an infliximab infusion. Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA, an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r=-0.397; P=0.04. However, no significant association was found between IGF-1 and IGFBP-3 levels and disease activity, systemic inflammation, metabolic syndrome features, or adipokines. In conclusion, in nondiabetic patients with AS undergoing periodic anti-TNF-α therapy, IGF-1 and ADMA are inversely correlated.

  9. Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes

    Science.gov (United States)

    We evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339-treated hamsters, and whether CE inhibited the over-secretion of apoB48-induced by TNF-alpha in enterocytes in a 35S-labelling study. In vivo, oral treatment with C...

  10. Pre-operative use of anti-TNF-alpha agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz; Nielsen, J.; Qvist, N.

    2013-01-01

    BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-alpha) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-alpha agents on post-operative outcomes 30 and 6...

  11. NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P

    1989-01-01

    The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5...

  12. NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P

    1989-01-01

    The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5...

  13. The TNF-alpha system in heart failure and after heart transplantation : plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity

    NARCIS (Netherlands)

    van Riemsdijk-van Overbeeke, I C; Baan, C C; Niesters, H G; Hesse, C J; Loonen, E H; Balk, A H; Maat, A P; Weimar, W

    BACKGROUND: The two soluble tumour necrosis factor (TNF) receptors (sTNF-R1, sTNF-R2) can bind TNF-alpha, which is a cytokine with cardiodepressant properties. In heart failure and after heart transplantation, the TNF-alpha system is unbalanced, due to elevated levels of sTNF receptors. AIM: To

  14. Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

    Science.gov (United States)

    Shearer, W. T.; Reuben, J. M.; Mullington, J. M.; Price, N. J.; Lee, B. N.; Smith, E. O.; Szuba, M. P.; Van Dongen, H. P.; Dinges, D. F.

    2001-01-01

    BACKGROUND: The extent to which sleep loss may predispose astronauts to a state of altered immunity during extended space travel prompts evaluation with ground-based models. OBJECTIVE: We sought to measure plasma levels of selected cytokines and their receptors, including the putative sleep-regulation proteins soluble TNF-alpha receptor (sTNF-alpha R) I and IL-6, in human subjects undergoing 2 types of sleep deprivation during environmental confinement with performance demands. METHODS: Healthy adult men (n = 42) were randomized to schedules that varied in severity of sleep loss: 4 days (88 hours) of partial sleep deprivation (PSD) involving two 2-hour naps per day or 4 days of total sleep deprivation (TSD). Plasma samples were obtained every 6 hours across 5 days and analyzed by using enzyme-linked immunoassays for sTNF-alpha RI, sTNF-alpha RII, IL-6, soluble IL-2 receptor, IL-10, and TNF-alpha. RESULTS: Interactions between the effects of time and sleep deprivation level were detected for sTNF-alpha RI and IL-6 but not for sTNF-alpha RII, soluble IL-2 receptor, IL-10, and TNF-alpha. Relative to the PSD condition, subjects in the TSD condition had elevated plasma levels of sTNF-alpha RI on day 2 (P =.04), day 3 (P =.01), and across days 2 to 4 of sleep loss (P =.01) and elevated levels of IL-6 on day 4 (P =.04). CONCLUSIONS: Total sleep loss produced significant increases in plasma levels of sTNF-alpha RI and IL-6, messengers that connect the nervous, endocrine, and immune systems. These changes appeared to reflect elevations of the homeostatic drive for sleep because they occurred in TSD but not PSD, suggesting that naps may serve as the basis for a countermeasures approach to prolonged spaceflight.

  15. TNF-alpha inhibition prevents cognitive decline and maintains hippocampal BDNF levels in the unpredictable chronic mild stress rat model of depression.

    Science.gov (United States)

    Şahin, Tuğçe Demirtaş; Karson, Ayşe; Balcı, Fuat; Yazır, Yusufhan; Bayramgürler, Dilek; Utkan, Tijen

    2015-10-01

    Previous findings have shown that patients with depression express higher levels of proinflammatory cytokines such as TNF-α and IL-6. We have recently found that Infliximab (a TNF-α inhibitor) decreased anhedonia and despair-like behavior in the rat unpredictable chronic mild stress (UCMS) model of depression suggesting that inflammation might play an important role in depression. An increasing number of studies suggest that inflammation is also associated with cognitive impairments. The current study aimed to investigate the effect of UCMS on the cognitive performance of rats and their hippocampal BDNF levels and the effect of chronic Infliximab (5mg/kg/weekly, i.p.) treatment on these measures. Rats were subjected to different types of stressors daily for a period of 56 days to induce depression-like state. The UCMS resulted in impairments in spatial and emotional memory acquisition and retention with no effect on the level of locomotor activity. These behavioral effects of UCMS were accompanied by reduction in the level of BDNF in the CA1 and CA3 regions of the hippocampus. Chronic Infliximab treatment prevented the UCMS-induced cognitive impairments as well as the reduction in the levels of hippocampal brain-derived neurotrophic factor (BDNF). These results suggest that Infliximab improves the spatial and emotional memory impairments induced by chronic stress in rats likely through its effects on hippocampal function by modulating inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Elevated plasma levels of TNF-alpha and Interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders

    Directory of Open Access Journals (Sweden)

    Ellinghaus Peter

    2009-11-01

    Full Text Available Abstract Background Diabetes mellitus (DM has reached epidemic proportions and is an important risk factor for heart failure (HF. Left ventricular diastolic dysfunction (LVDD is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6 and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease. Methods We enrolled 41 consecutive patients (mean age 65+/-10 years submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes. Results Patients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline had significantly higher IL-6 (P = 0,001, TNF-alpha (P Conclusion This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

  17. TNF-alpha -308G>A polymorphism is associated with suicide attempts in major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Hong, Jin-Pyo; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

    2013-09-05

    Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) -308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 (IL-10) -1082A>G are associated with increased risk for suicide attempts in MDD. Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD. The GG genotype of the TNF-alpha -308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 -1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types. Limitations include a relatively small sample size and a cross-sectional design. TNF-alpha -308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha -308G>A influences suicide in MDD. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Butter feeding enhances TNF-alpha production from macrophages and lymphocyte adherence in murine small intestinal microvessels.

    Science.gov (United States)

    Fujiyama, Yoichi; Hokari, Ryota; Miura, Soichiro; Watanabe, Chikako; Komoto, Shunsuke; Oyama, Tokushige; Kurihara, Chie; Nagata, Hiroshi; Hibi, Toshifumi

    2007-11-01

    Dietary fat is known to modulate immune functions. Intake of an animal fat-rich diet has been linked to increased risk of inflammation; however, little is known about how animal fat ingestion directly affects intestinal immune function. The objective of this study was to assess the effect of butter feeding on lymphocyte migration in intestinal mucosa and the changes in adhesion molecules and cytokines involved in this effect. T-lymphocytes isolated from the spleen were fluorescence-labeled and injected into recipient mice. Butter was administered into the duodenum, and villus microvessels of the small intestinal mucosa were observed under an intravital microscope. mRNA expression of adhesion molecules and cytokines in the intestinal mucosa were determined by quantitative PCR. The effect of butter feeding on tumor necrosis factor (TNF)-alpha mRNA expression of intestinal macrophages was also determined. Intraluminal butter administration significantly increased lymphocyte adherence to intestinal microvessels accompanied by increases in expression levels of adhesion molecules ICAM-1, MAdCAM-1 and VCAM-1. This accumulation was significantly attenuated by anti-MAdCAM-1 and anti-ICAM-1 antibodies. Butter administration significantly increased TNF-alpha in the lamina proprial macrophages but not interleukin-6. Anti-TNF-alpha treatment attenuated the enhanced expression of adhesion molecules induced by butter administration. T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.

  19. Effect of laser phototherapy on the release of TNF-alpha and MMP-1 by endodontic sealer-stimulated macrophages.

    Science.gov (United States)

    Sousa, Lorena R; Cavalcanti, Bruno N; Marques, Márcia M

    2009-02-01

    Our aim was to analyze the effect of laser phototherapy on the secretory activity of macrophages activated by interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS), and stimulated by substances leached from an epoxy resin-based sealer (AH-Plus) and a calcium hydroxide-based sealer (Sealapex). Laser phototherapy can modulate the inflammatory process, improving wound healing. This type of therapy could be useful for modulating postoperative symptoms seen after endodontic treatment. Cytotoxicity was indirectly assessed by measuring mitochondrial activity. Macrophages were stimulated by the leached substances or not (controls), and the groups were then irradiated or not. The secretion of pro-inflammatory cytokines (TNF-alpha and MMP-1) was analyzed using ELISA. Two irradiations at 6-h intervals were done with an As-Ga-Al diode laser (780 nm, 70 mW, spot size 4.0 mm(2), 3 J/cm(2), for 1.5 sec) in contact mode. The sealers were non-cytotoxic to macrophages. The production of TNF-alpha was significantly decreased by laser phototherapy, regardless of experimental group. The level of secretion of MMP-1 was similar in all groups. Based on the conditions of this study we concluded that in activated macrophages, laser phototherapy impairs the secretion of the pro-inflammatory cytokine TNF-alpha, but has no influence on MMP-1 secretion.

  20. TNF-alpha rs1800629 polymorphism is not associated with HPV infection or cervical cancer in the Chinese population.

    Directory of Open Access Journals (Sweden)

    Ning Wang

    Full Text Available BACKGROUND: While HPV infection is the main cause of cervical cancer, genetic susceptibility to HPV infection is not well understood. Tumor necrosis factor alpha (TNF-alpha, involved in the defense against HPV infection, plays an important role in cervical cancer progression and regression. The aim of this study was to investigate the relationship between the TNF-alpha rs1800629 polymorphism and risk of HPV infection or cervical cancer. METHODS: Three groups were involved in this study of Chinese women. Group 1 consisted of 285 high risk HPV positive cervical cancer patients, Group 2, 225 high risk HPV positive patients without cervical cancer, and Group 3, 318 HPV negative women with no cervical cancer. Blood samples were obtained from all patients and genotyped by PCR-RLFP. Fifty randomly selected samples were further sequenced. RESULTS: The allele and genotype distributions of the TNF-alpha rs1800629 polymorphism were not significantly different between each of the groups (P>0.05. There are no significant relationship between rs1800629 polymorphism and high risk HPV infection (OR = 0.649, 95% CI: 0.253-1.670, P = 0.371, cervical cancer (OR = 0.993, 95% CI: 0.376-2.618, P = 0.988, or cervical cancer with HPV infection (OR = 0.663, 95% CI: 0.250-1.758, P = 0.409. CONCLUSIONS: We demonstrated that there is no association between TNF rs1800629 polymorphism and the HPV infection, or cervical cancer with HPV infection.

  1. [A study of frequency of TNF alpha gene with type 2 diabetes mellitus with chronic periodontitis].

    Science.gov (United States)

    Liu, Bo; Yu, Ning; Tan, Li-si; Liu, Jing-bo; Guo, Yan; Pan, Ya-ping

    2011-04-01

    To detect the frequency of TNF alpha gene in patients of type 2 diabetes mellitus with chronic periodontitis, periodontitis without any systemic diseases and healthy controls. The case series were consisted of 112 patients with moderate, severe type 2 diabetes mellitus with chronic periodontitis, 99 patients with moderate, severe periodontitis without any systemic disease, 50 age- and gender-matched subjects with healthy periodontal conditions were enrolled. Clinical parameters were measured and recorded including probing depth(PD), clinical attachment loss(CAL), bleeding index(BI), and tooth movement(TM). The polymorphism of TNF-α-308 genotype (TNF1/2) was examined after electrophoresis on agarose gel and ethidium bromide staining. The difference between the case and healthy groups was analysed by Chi-square test, the difference in clinical index among groups which had different allele was analyzed for ANOVA with SPSS13.0 software package. We divided DM and CP groups into moderate and severe groups. There were significant difference between severe DM group and severe, moderate CP group, moderate DM group and chronic periodontitis of severe,moderate group. The probing depth and clinical attachment loss of the patients who took TNF-α-308 allele II were significantly higher than the patients who took TNF-α-308 allele I in DM and CP group. TNF-α-308 allele II might increase the susceptivity of periodontitis in population. TNF-α-308 allele II may play an important role in synergistic reaction of periodontitis and type 2 diabetes.

  2. Different combinations of maternal and postnatal diet are reflected in changes of hepatic parenchyma and hepatic TNF-alpha expression in male rat offspring.

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    Kačarević, Željka Perić; Grgić, Anđela; Šnajder, Darija; Bijelić, Nikola; Belovari, Tatjana; Cvijanović, Olga; Blažičević, Valerija; Radić, Radivoje

    2017-09-01

    Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25.

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    Li, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Chang, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

    2015-12-15

    This study was to investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-κB in DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-κB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-κB expression of DCs. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF-κB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and NF-κB expression in DCs stimulated by TNF-alpha. These results demonstrate that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Terminal Galactosylation and Sialylation Switching on Membrane Glycoproteins upon TNF-Alpha-Induced Insulin Resistance in Adipocytes.

    Science.gov (United States)

    Parker, Benjamin L; Thaysen-Andersen, Morten; Fazakerley, Daniel J; Holliday, Mira; Packer, Nicolle H; James, David E

    2016-01-01

    Insulin resistance (IR) is a complex pathophysiological state that arises from both environmental and genetic perturbations and leads to a variety of diseases, including type-2 diabetes (T2D). Obesity is associated with enhanced adipose tissue inflammation, which may play a role in disease progression. Inflammation modulates protein glycosylation in a variety of cell types, and this has been associated with biological dysregulation. Here, we have examined the effects of an inflammatory insult on protein glycosylation in adipocytes. We performed quantitative N-glycome profiling of membrane proteins derived from mouse 3T3-L1 adipocytes that had been incubated with or without the proinflammatory cytokine TNF-alpha to induce IR. We identified the regulation of specific terminal N-glycan epitopes, including an increase in terminal di-galactose- and a decrease in biantennary alpha-2,3-sialoglycans. The altered N-glycosylation of TNF-alpha-treated adipocytes correlated with the regulation of specific glycosyltransferases, including the up-regulation of B4GalT5 and Ggta1 galactosyltransferases and down-regulation of ST3Gal6 sialyltransferase. Knockdown of B4GalT5 down-regulated the terminal di-galactose N-glycans, confirming the involvement of this enzyme in the TNF-alpha-regulated N-glycome. SILAC-based quantitative glycoproteomics of enriched N-glycopeptides with and without deglycosylation were used to identify the protein and glycosylation sites modified with these regulated N-glycans. The combined proteome and glycoproteome workflow provided a relative quantification of changes in protein abundance versus N-glycosylation occupancy versus site-specific N-glycans on a proteome-wide level. This revealed the modulation of N-glycosylation on specific proteins in IR, including those previously associated with insulin-stimulated GLUT4 trafficking to the plasma membrane. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Terminal Galactosylation and Sialylation Switching on Membrane Glycoproteins upon TNF-Alpha-Induced Insulin Resistance in Adipocytes*

    Science.gov (United States)

    Parker, Benjamin L.; Thaysen-Andersen, Morten; Fazakerley, Daniel J.; Holliday, Mira; Packer, Nicolle H.; James, David E.

    2016-01-01

    Insulin resistance (IR) is a complex pathophysiological state that arises from both environmental and genetic perturbations and leads to a variety of diseases, including type-2 diabetes (T2D). Obesity is associated with enhanced adipose tissue inflammation, which may play a role in disease progression. Inflammation modulates protein glycosylation in a variety of cell types, and this has been associated with biological dysregulation. Here, we have examined the effects of an inflammatory insult on protein glycosylation in adipocytes. We performed quantitative N-glycome profiling of membrane proteins derived from mouse 3T3-L1 adipocytes that had been incubated with or without the proinflammatory cytokine TNF-alpha to induce IR. We identified the regulation of specific terminal N-glycan epitopes, including an increase in terminal di-galactose- and a decrease in biantennary alpha-2,3-sialoglycans. The altered N-glycosylation of TNF-alpha-treated adipocytes correlated with the regulation of specific glycosyltransferases, including the up-regulation of B4GalT5 and Ggta1 galactosyltransferases and down-regulation of ST3Gal6 sialyltransferase. Knockdown of B4GalT5 down-regulated the terminal di-galactose N-glycans, confirming the involvement of this enzyme in the TNF-alpha-regulated N-glycome. SILAC-based quantitative glycoproteomics of enriched N-glycopeptides with and without deglycosylation were used to identify the protein and glycosylation sites modified with these regulated N-glycans. The combined proteome and glycoproteome workflow provided a relative quantification of changes in protein abundance versus N-glycosylation occupancy versus site-specific N-glycans on a proteome-wide level. This revealed the modulation of N-glycosylation on specific proteins in IR, including those previously associated with insulin-stimulated GLUT4 trafficking to the plasma membrane. PMID:26537798

  6. TNF-alpha and IL-6 synergistically inhibit ketogenesis from fatty acids and alpha-ketoisocaproate in isolated rat hepatocytes.

    Science.gov (United States)

    Pailla, K; Lim, S K; De Bandt, J P; Aussel, C; Giboudeau, J; Troupel, S; Cynober, L; Blonde-Cynober, F

    1998-01-01

    During sepsis, lipid metabolism is shunted toward triacylglycerol synthesis and hepatic lipogenesis. A decrease in ketogenesis from free fatty acids also is observed, probably mediated by cytokines involved in host response to infection. Whether such an inhibition of ketogenesis occurs with other ketone body precursors such as ketoacids is not known. The aim of this study was to determine the effects of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) on hepatic ketone body production from octanoic acid, a medium-chain fatty acid, and from alpha-ketoisocaproate (KIC), the ketoanalogue of leucine. The experiments were conducted in cultured hepatocytes isolated from 24-hour-fasted Sprague-Dawley rats. Hepatocyte monolayers were incubated for 6 hours, with either KIC or octanoic acid (1 mmol/L), in the presence of glucagon and TNF-alpha (25 micro/L) IL-6 (15 microg/L) and/or IL-6. Acetoacetate, beta-hydroxybutyrate, and free fatty acids were determined in culture medium by enzymatic methods and KIC was measured by high-performance liquid chromatography. KIC and octanoic acid uptake by hepatocytes was 79% and 92%, respectively, over 6 hours, and cytokines had no influence. However, TNF-alpha and IL-6 caused inhibition of ketogenesis from alpha-ketoisocaproate (5.6% +/- 2.3% and 4.4% +/- 3.0%, respectively), and from octanoic acid (7.9% +/- 2.9%, 5.7% +/- 3.2%, respectively). In addition, when the two cytokines were present together in the culture medium, the inhibition was enhanced (inhibition of ketogenesis from KIC: 14.0% +/- 4.8%; from octanoic acid: 11.6% +/- 3.4%). In our experimental conditions, cytokines mediate an inhibition of ketogenesis; this process could be explained by a direct effect of cytokines on metabolic pathways of octanoic acid and KIC oran indirect effect by modification of the mitochondrial redox state.

  7. TNF-alpha upregulates expression of BMP-2 and BMP-3 genes in the rat dental follicle--implications for tooth eruption.

    Science.gov (United States)

    Yao, Shaomian; Prpic, Veronica; Pan, Fenghui; Wise, Gary E

    2010-01-01

    The dental follicle appears to regulate both the alveolar bone resorption and bone formation needed for tooth eruption. Tumor necrosis factor-alpha (TNF-alpha) gene expression is maximally upregulated at postnatal day 9 in the rat dental follicle of the first mandibular molar, a time that correlates with rapid bone growth at the base of the tooth crypt, as well as a minor burst of osteoclastogenesis. TNF-alpha expression is correlated with the expression of bone morphogenetic protein-2 (BMP-2), a molecule expressed in the dental follicle that can promote bone formation. Because BMP-2 signaling may be augmented by bone morphogenetic protein-3 (BMP-3), our objective in this study was to determine if the dental follicle expresses BMP-3 and if TNF-alpha stimulates the dental follicle cells to express BMP-2 and BMP-3. Dental follicles were collected from different postnatal ages of rat pups. Dental follicle cells were incubated with TNF-alpha to study its dosage and time-course effects on gene expression of BMP-2 and BMP-3, as determined by real-time RT-PCR. Next, immunostaining was conducted to confirm if the protein was synthesized and ELISA of the conditioned medium was conducted to determine if BMP-2 was secreted. We found that BMP-3 expression is correlated with the expression of TNF-alpha in the dental follicle and TNF-alpha significantly increased BMP-2 and BMP-3 expression in vitro. Immunostaining and ELISA showed that BMP-2 and BMP-3 were synthesized and secreted. This study suggests that TNF-alpha can upregulate the expression of bone formation genes that may be needed for tooth eruption.

  8. Stabilization of the autoproteolysis of TNF-alpha converting enzyme (TACE) results in a novel crystal form suitable for structure-based drug design studies.

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    Ingram, Richard N; Orth, Peter; Strickland, Corey L; Le, Hung V; Madison, Vincent; Beyer, Brian M

    2006-04-01

    The crystallization of TNF-alpha converting enzyme (TACE) has been useful in understanding the structure-activity relationships of new chemical entities. However, the propensity of TACE to undergo autoproteolysis has made enzyme handling difficult and impeded the identification of inhibitor soakable crystal forms. The autoproteolysis of TACE was found to be specific (Y352-V353) and occurred within a flexible loop that is in close proximity to the P-side of the active site. The rate of autoproteolysis was found to be proportional to the concentration of TACE, suggesting a bimolecular reaction mechanism. A limited specificity study of the S(1)' subsite was conducted using surrogate peptides and suggested substitutions that would stabilize the proteolysis of the loop at positions Y352-V353. Two mutant proteases (V353G and V353S) were generated and proved to be highly resistant to autoproteolysis. The kinetics of the more resistant mutant (V353G) and wild-type TACE were compared and demonstrated virtually identical IC(50) values for a panel of competitive inhibitors. However, the k(cat)/K(m) of the mutant for a larger substrate (P6 - P(6)') was approximately 5-fold lower than that for the wild-type enzyme. Comparison of the complexed wild-type and mutant structures indicated a subtle shift in a peripheral P-side loop (comprising the mutation site) that may be involved in substrate binding/turnover and might explain the mild kinetic difference. The characterization of this stabilized form of TACE has yielded an enzyme with similar native kinetic properties and identified a novel crystal form that is suitable for inhibitor soaking and structure determination.

  9. Safety of TNF-α inhibitors during IBD pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Loftus, Edward V; Jess, Tine

    2013-01-01

    Tumor necrosis factor (TNF)-alpha inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome.......Tumor necrosis factor (TNF)-alpha inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome....

  10. Inflammatory bowel disease as a paradoxical effect of anti-TNF alpha therapy.

    Science.gov (United States)

    Iriarte, Ainara; Zaera, Celia; Bachiller-Corral, Javier; López-Sanromán, Antonio

    2017-02-01

    Anti-TNF-α therapies are used in the treatment of different inflammatory conditions, such as inflammatory bowel disease (IBD). However, paradoxical effects may occur during treatment. In other words, these drugs can induce or unmask diseases similar to those they were intended to treat. Etanercept is the main anti-TNF-α agent associated with the development of paradoxical IBD; this drug, moreover, has no proven usefulness in the treatment of the disease. This association, which is not coincidental and meets the criteria for a temporal causal association, is infrequent and is seen particularly in patients with spondyloarthritis. Restarting treatment with etanercept may induce new intestinal symptoms. There are no endoscopic, histopathologic or clinical differences between primary and secondary IBD, and both are diagnosed in the same way. The most frequent presentation is Crohn disease. When a paradoxical event occurs, etanercept is usually replaced with infliximab, which has not been associated with disease recurrence. Copyright © 2016 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  11. Role of TNF-alpha, IL-1beta and IL-6 in the local tissue damage induced by Bothrops asper snake venom: an experimental assessment in mice.

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    Chaves, Fernando; Teixeira, Catarina F P; Gutiérrez, José María

    2005-02-01

    The role of the cytokines TNF-alpha, IL-1beta and IL-6 in the acute local pathological effects induced by Bothrops asper snake venom was assessed in mice. Intramuscular injection of this venom induced increments in IL-1beta and IL-6 in muscle, but no elevations of TNF-alpha were detected. Pentoxifylline (PTX), a methylxanthine derivative that inhibits the synthesis of TNF-alpha, and antibodies against these three cytokines were used to assess the role of these cytokines in venom-induced effects. As a control, PTX pretreatment was effective at abrogating lethality and serum TNF-alpha increments in mice subjected to endotoxemia induced by injection of Escherichia coli lipopolysaccharide, although it did not affect the increment in IL-1beta and IL-6 in such endotoxic model. PTX failed to reduce lethality, hemorrhage, myonecrosis, dermonecrosis and edema induced by B. asper venom. Moreover, pretreatment with anti-cytokine antibodies was also ineffective at reducing venom-induced myonecrosis and hemorrhage. It is concluded that TNF-alpha, IL-1beta and IL-6 do not have a significant role in the pathogenesis of the acute local pathological effects induced by B. asper venom in mice, although this does not exclude the possibility that these cytokines play a role in other aspects of venom-induced local pathology, as well as in the reparative and regenerative responses that take place after the onset of tissue damage.

  12. Induction of apoptosis in murine clonal osteoblasts expressed by human T-cell leukemia virus type I tax by NF-kappa B and TNF-alpha.

    Science.gov (United States)

    Kitajima, I; Nakajima, T; Imamura, T; Takasaki, I; Kawahara, K; Okano, T; Tokioka, T; Soejima, Y; Abeyama, K; Maruyama, I

    1996-02-01

    We investigated the effects of various cytokines in the presence of human T-cell leukemia virus type I (HTLV-I) tax protein in murine clonal osteoblasts, MC3T3-E1 cells. Skeletal remodeling by osteoclasts and osteoblasts is coordinated by cytokines, which are activated by HTLV-I tax protein via nuclear factor-kappa B (NF-kappa B). MC3T3-E1 cells were cocultured with an irradiated HTLV-I-producing lymphocyte cell line, MT-2. After coculture, the tumor necrosis factor-alpha (TNF-alpha) level in the medium was markedly elevated during the 7 days of culture, and MC3T3-E1 cells underwent apoptotic cell death. Marked apoptosis was also observed in MC3T3-E1 cells treated with MT-2 culture medium and in HTLV-I tax-expressing MC3T3-E1 clones, which both expressed high levels of TNF-alpha. This apoptosis was prevented by treatment with neutralizing anti-TNF-alpha antibody (alpha TNF). HTLV-I tax protein and TNF-alpha induced activation of NF-kappa B in apoptotic MC3T3-E1 cells. Decreased NF-kappa B activation was observed in HTLV-I tax-expressing MC3T3-E1 cells treated with alpha TNF. Our results suggest that HTLV-I tax activated NF-kappa B and subsequently TNF-alpha, leading to apoptosis of osteoblasts.

  13. [The effect of isoflurane on the secretion of TNF-alpha and IL-1 beta from LPS-stimulated human peripheral blood monocytes].

    Science.gov (United States)

    Sato, W; Enzan, K; Masaki, Y; Kayaba, M; Suzuki, M

    1995-07-01

    The cytokines such as tumor necrosis factor and interleukin-1 secreted from macrophages/monocytes proved to play important roles in the pathogenesis of endotoxemia, severe pancreatitis and other surgical injuries. However, it is still unclear how inhalational anesthetic agents influence the secretion of these cytokines from macrophages/monocytes. We investigated the effects of isoflurane on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased after LPS stimulation and this increase was inhibited by isoflurane in dose-dependent fashion. The inhibitory action of isoflurane disappeared between 1 and 3 hours after stopping isoflurane inhalation. We concluded that isoflurane could inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes stimulated by LPS in a dose-dependent fashion and that the inhibitory action of isoflurane was reversible.

  14. Effects of TNF-alpha and leptin on weight loss in patients with stable chronic obstructive pulmonary disease.

    Science.gov (United States)

    Shin, Kyeong-Cheol; Chung, Jin Hong; Lee, Kwan Ho

    2007-12-01

    Weight loss is common in patients with chronic obstructive pulmonary disease (COPD). However, the mechanisms of this weight loss are still unclear. Sixty male patients with stable COPD and 45 healthy male controls participated in this study. The COPD patients were divided into two groups, that is, the emphysema and chronic bronchitis groups, by the transfer coefficient of carbon monoxide. The body composition, resting energy expenditure (REE), plasma leptin levels and serum tumor necrosis factor-alpha (TNF-alpha) were measured in all the study participants. The difference and correlation of these parameters were investigated between the two groups. Emphysematous patients were characterized by a lower body mass index (BMI) and fat-mass (FM) compared with the chronic bronchitis patients (p leptin levels, as corrected for the FM, were not different between the COPD patients and healthy controls (78.3 +/- 30.9 pg/mL/kg vs. 70.9 +/- 17.3 pg/mL/kg, respectively), and the plasma leptin levels, as adjusted for the FM, were also not different between the two groups of COPD patients. In the chronic bronchitis patients, the plasma leptin concentration was correlated with the BMI (r = 0.866, p COPD patients than those in the controls, but there was no statistical difference (10.7 +/- 18.6 pg/mL vs. 7.2 x 3.5 pg/mL, respectively, p0.05). The leptin concentration was well correlated with the BMI and %FM in the patients with chronic bronchitis and the leptin concentration was only correlated with the %FM (r = 0.450, p = 0.027) in emphysema patients. There was no correlation between the plasma leptin concentration, as adjusted for the fat mass, and the activity of the TNF-alpha system. The interaction of leptin and the activity of the TNF-alpha system in the pathogenesis of tissue depletion may not play an important role in chronic stable COPD patients.

  15. Beta-adrenergic receptor 1 selective antagonism inhibits norepinephrine-mediated TNF-alpha downregulation in experimental liver cirrhosis.

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    Pedro Zapater

    Full Text Available BACKGROUND: Bacterial translocation is a frequent event in cirrhosis leading to an increased inflammatory response. Splanchnic adrenergic system hyperactivation has been related with increased bacterial translocation. We aim at evaluating the interacting mechanism between hepatic norepinephrine and inflammation during liver damage in the presence of bacterial-DNA. ANIMALS AND METHODS: Forty-six mice were included in a 16-week protocol of CCl(4-induced cirrhosis. Laparotomies were performed at weeks 6, 10, 13 and 16. A second set of forty mice injected with a single intraperitoneal dose of CCl(4 was treated with saline, 6-hydroxidopamine, Nebivolol or Butoxamine. After 5 days, mice received E. coli-DNA intraperitoneally. Laparotomies were performed 24 hours later. Liver bacterial-DNA, norepinephrine, TNF-alpha, IL-6 and beta-adrenergic receptor levels were measured. RESULTS: Bacterial-DNA translocation was more frequent in CCl(4-treated animals compared with controls, and increased as fibrosis progressed. Liver norepinephrine and pro-inflammatory cytokines were significantly higher in mice with vs without bacterial-DNA (319.7 ± 120.6 vs 120.7 ± 68.6 pg/g for norepinephrine, 38.4 ± 6.1 vs 29.7 ± 4.2 pg/g for TNF-alpha, 41.8 ± 7.4 vs 28.7 ± 4.3 pg/g for IL-6. Only beta-adrenergic receptor-1 was significantly increased in treated vs control animals (34.6 ± 7.3 vs 12.5 ± 5.3, p=0.01 and correlated with TNF-alpha, IL-6 and norepinephrine hepatic levels in animals with bacterial-DNA. In the second set of mice, cytokine levels were increased in 6-hydroxidopamine and Nebivolol (beta-adrenergic receptor-1 antagonist treated mice compared with saline. Butoxamine (beta-adrenergic receptor-2 antagonist didn't inhibit liver norepinephrine modulation of pro-inflammatory cytokines. CONCLUSIONS: Beta-adrenergic receptor-1 mediates liver norepinephrine modulation of the pro-inflammatory response in CCl(4-treated mice with bacterial-DNA.

  16. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

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    Sonia Pellissier

    Full Text Available Crohn's disease (CD and irritable bowel syndrome (IBS involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls. The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients. The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI and depressive symptoms (CES-D. After 30 min of rest, ECG was recorded for heart rate variability (HRV analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05 was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05. No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

  17. TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Renno, T; Krakowski, M; Piccirillo, C

    1995-01-01

    , then coordinately dropped to background levels during remission. Analysis of cells isolated from the CNS of mice with acute EAE showed that the Th1 cytokines, IL-2 and IFN-gamma, were produced by infiltrating CD4+ T cells. In contrast, TNF-alpha was predominantly transcribed by non-T mononuclear CNS cells......, the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha m...

  18. Glucose-stimulated prehepatic insulin secretion is associated with circulating alanine, triglyceride, glucagon, lactate and TNF-alpha in patients with HIV-lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Pedersen, S B

    2006-01-01

    and ISREG0-10 min. Increased concentrations of the nonglucose insulin secretagogues triglyceride (+124%), alanine (+35%) and glucagon (+88%), and also lactate (+96%) and tumour necrosis factor (TNF)-alpha (+62%) were observed in the 10 LIPO patients with aberrations in FISR and ISREG0-10 min compared...... with the remaining HIV-infected patients (all Ptriglyceride, alanine, glucagon, lactate and TNF-alpha may be associated with alterations in the first-phase prehepatic insulin secretion response to intravenous glucose in normoglycaemic lipodystrophic HIV-infected patients....

  19. Are there any positive effects of TNF-alpha blockers on bone metabolism?

    Directory of Open Access Journals (Sweden)

    A. Sulli

    2011-09-01

    Full Text Available Secondary osteoporosis (OP is a well-recognized complication of rheumatoid arthritis (RA. Treatment with TNF-a blockers, might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular regions. Objective: To assess the influence of anti-TNF-a therapy, on bone metabolism in RA patients. 36 RA patients were treated with stable therapy of prednisone (7.5 mg/day and methotrexate (MTX=10 mg/week. Nine of these RA patients further received etanercept (25 mg, twice/weekly and eleven infliximab (3mg/kg on 0, 2, 6, and every 8 weeks thereafter. A control group included 16 RA patients only with stable therapy (some dosage of prednisone and MTX. Quantitative Ultrasound (QUS bone densitometry was obtained at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy. Bone mineral density (BMD of the hip and lumbar spine were performed with a densitometer ( Lunar Prodigy, GE, USA at baseline and after 12 months. Soluble bone turnover markers [osteocalcin (OC, bone alkaline phospatase (ALP deoxypyridinoline/creatinine ratio (Dpd/Cr and cross-linked N-telopeptide of type I collagen / creatinine ratio (NTx/Cr] were measured using ELISA tests. Results: AD-SoS values were found increased by +4.55% after 12 months of treatment in the RA patients treated with anti-TNF-a therapy. On the contrary, the Ad-SoS levels decreased by -4.48% during the same period in the control RA group. BMD increased by +3.64% at lumbar spine and +2.90% at the hip (both p<0.001 in TNF-a blockers-treated patients and decreased by -2.89% and -3.10% (both p<0.001, respectively at lumbar spine and at the hip in RA patients without anti-TNF-a therapy. In RA patients treated with TNF-a blockers, OC and bone ALP levels were found significantly increased (p<0.01 and Dpd/Cr or NTx/Cr levels were found significantly decreased (p<0.01 at 12 months when compared to baseline values. Conclusion: During 12

  20. Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE)

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2001-01-01

    . However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We herewith demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-alpha during EAE. Zn-MT-II treatment could also significantly reduce...... apoptotic cell death of neurons and oligodendrocytes during EAE, as judged by using TUNEL and immunoreactivity for cytochrome c and caspases 1 and 3. In contrast, the number of apoptotic lymphocytes and macrophages was less affected by Zn-MT-II treatment. The Zn-MT-II-induced decrease in proinflammatory...... cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE...

  1. Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Penkowa, Milena; Pedersen, Bente K

    2005-01-01

    Skeletal muscle is now recognized as an endocrine organ with the capacity to produce signal peptides in response to muscle contractions. Here we demonstrate that resting healthy human muscles express cytokines in a fiber type specific manner. Human muscle biopsies from seven healthy young males...... were obtained from m. triceps, m. quadriceps vastus lateralis and m. soleus. Type I fibers contributed (mean +/- SE) 24.0 +/- 2.5% in triceps of total fibers, 51.3 +/- 2.4% in vastus and 84.9 +/- 22% in soleus. As expected, differences in the fiber type composition were accompanied by marked...... differences between the three muscles with regard to MHC I and MHC IIa mRNA expression. Immunohistochemistry demonstrated that tumor necrosis factor (TNF)-alpha and interleukin (IL)-18 were solely expressed by type II fibers, whereas the expression of IL-6 was more prominent in type I compared to type II...

  2. Vaginal Smear TNF-alpha, IL18, TLR4, and GATA3 mRNA Levels Correlate with Local Inflammation

    Directory of Open Access Journals (Sweden)

    Olga Bourmenskaya

    2014-12-01

    Full Text Available Background: A molecular approach to estimation of local inflammatory response associated with dysbiotic conditions of the vagina is reported. This approach is based on immune response gene transcription levels measured by qPCR assay. Methods and Results: qPCR analysis of 24 immune response gene transcripts in vaginal smears was performed for 215 women with vaginitis and 95 healthy controls. The data were sorted by comparison to local inflammatory response profiles assessed by conventional methods. The local inflammatory response in the vagina is found to correlate with TNF-alpha, IL18, TLR4, and GATA3 transcript levels. Sensitivity and specificity of the approach, as validated in accordance with conventional clinical examination results, are 94.9% and 93.7%, respectively. Conclusions: The noninvasive diagnostic approach to vaginal pathology based solely on its molecular characterization may prove to be clinically relevant.

  3. Studies on the biological effects of ozone: 2. Induction of tumor necrosis factor (TNF-alpha) on human leucocytes

    Energy Technology Data Exchange (ETDEWEB)

    Paulesu, L.; Luzzi, E.; Bocci, V. (Institute of General Physiology, University of Siena (Italy))

    1991-10-01

    The effect of ozone as a probable inducer of tumor necrosis factor (TNF-alpha) has been investigated on human blood and on Ficoll-purified blood mononuclear cells (PBMC). Samples were exposed at different ozone concentrations ranging from 2.2 to 108 micrograms/ml and incubated at 37 degrees C in an 95% air-5% CO2 atmosphere. At predetermined times, all cell supernatants were tested for TNF activity and some PBMC cultures were examined for DNA synthesis. The authors have shown that ozone concentration is critical in terms of TNF production and of cell mitogenesis and that, owing to the presence of erythrocytes, higher ozone concentrations are required to be effective in blood than in PBMC. Because ozonization of blood is a procedure followed in several European countries for the treatment of viral diseases and tumors, the release of factors with antiviral and immunomodulatory activities by leukocytes may explain the mechanism of action of ozone and of autohemotherapy.

  4. Transferability of antibody pairs from ELISA to fiber optic surface plasmon resonance for infliximab detection

    Science.gov (United States)

    Van Stappen, Thomas; Lu, Jiadi; Bloemen, Maarten; Geukens, Nick; Spasic, Dragana; Delport, Filip; Verbiest, Thierry; Lammertyn, Jeroen; Gils, Ann

    2015-03-01

    Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine up-regulated in inflammatory bowel disease, rheumatoid arthritis and psoriasis. The introduction of anti-TNF drugs such as infliximab has revolutionized the treatment of these diseases. Recently, therapeutic drug monitoring (TDM) of infliximab has been introduced in clinical decision making to increase cost-efficiency. Nowadays, TDM is performed using radio-immunoassays, homogeneous mobility shift assays or ELISA. Unfortunately, these assays do not allow for in situ treatment optimization, because of the required sample transportation to centralized laboratories and the subsequent assay execution time. In this perspective, we evaluated the potential of fiber optic-surface plasmon resonance (FO-SPR). To achieve this goal, a panel of 55 monoclonal anti-infliximab antibodies (MA-IFX) was developed and characterized in-house, leading to the identification of nine different clusters. Based on this high diversity, 22 antibody pairs were selected and tested for their reactivity towards IFX, using one MA-IFX as capture and one MA-IFX for detection, in a sandwich type ELISA and FO-SPR. This study showed that the reactivity towards IFX of each antibody pair in ELISA is highly similar to its reactivity on FO-SPR, indicating that antibody pairs are easily transferable between both platforms. Given the fact that FO-SPR shows the potential for miniaturization and fast assay time, it can be considered a highly promising platform for on-site infliximab monitoring.

  5. Transient induction of E-selectin expression following TNF alpha-based isolated limb perfusion in melanoma and sarcoma patients is not tumor specific.

    NARCIS (Netherlands)

    Nooijen, P.T.G.A.; Eggermont, A.M.; Verbeek, M.M.; Schalkwijk, L.; Buurman, W.A.; de Waal, R.M.W.; Ruiter, D.J.

    1996-01-01

    Transient induction of E-selectin expression following TNF alpha-based isolated limb perfusion in melanoma and sarcoma patients is not tumor specific. Nooijen PT, Eggermont AM, Verbeek MM, Schalkwijk L, Buurman WA, de Waal RM, Ruiter DJ. Department of Pathology, University Hospital Nijmegen, The

  6. ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice.

    NARCIS (Netherlands)

    Selzner, N; Selzner, M; Odermatt, B; Tian, Y; Rooijen, van N.; Clavien, PA

    2003-01-01

    AIMS: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. METHODS: Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and

  7. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.

    Science.gov (United States)

    2005-10-01

    Guidelines have been compiled by The Joint Tuberculosis Committee of the British Thoracic Society to quantify the risks of reactivation of tuberculosis with anti-tumour necrosis factor alpha (anti-TNF-alpha) treatment. These guidelines are intended to inform respiratory physicians, gastroenterologists, rheumatologists and dermatologists, together with specialist nurses in those disciplines.

  8. Tumor necrosis factor-alpha (TNF-alpha) concentrations from whole blood cultures correlate with isolated peripheral blood mononuclear cell cultures

    Science.gov (United States)

    Many cellular immune assays are impractical because they require labor-intensive isolation of cells from their natural environment. The objectives of this study were to determine the relationship between cell culture supernatant TNF-alpha from isolated peripheral blood mononuclear cells (PBMC) and w...

  9. TNF{alpha} induced FOXP3-NF{kappa}B interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Qiang; Li, Weina; Zhang, Cun; Qin, Xin; Xue, Xiaochang; Li, Meng; Shu, Zhen; Xu, Tianjiao; Xu, Yujin; Wang, Weihua [The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Wei, E-mail: Zhangw90@fmmu.edu.cn [The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Yingqi, E-mail: Zhangyqh@fmmu.edu.cn [The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi' an 710032 (China)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer FOXP3 inhibition of cell proliferation is p21-dependent under basal conditions. Black-Right-Pointing-Pointer Inflammation induced by TNF{alpha} inhibits the tumor suppressor role of FOXP3. Black-Right-Pointing-Pointer Interaction between p65 and FOXP3 inhibits p21 transcription activation. -- Abstract: Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNF{alpha} mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNF{alpha} treatment. Molecularly, we found that TNF{alpha} induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.

  10. Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate

    DEFF Research Database (Denmark)

    Hengstman, G.J.; Bleecker, J.L. De; Feist, E.

    2008-01-01

    BACKGROUND/AIMS: To determine the efficacy of infliximab combined with weekly methotrexate in drug-naive recent-onset dermatomyositis and polymyositis. METHODS: A multicentre open-label controlled trial was conducted. Disease activity was assessed using patient's and physician's disease activity...

  11. The effect of cloricromene, a coumarine derivative, on leukocyte accumulation, myocardial necrosis and TNF-alpha production in myocardial ischaemia-reperfusion injury.

    Science.gov (United States)

    Squadrito, F; Altavilla, D; Zingarelli, B; Ioculano, M; Calapai, G; Campo, G M; Miceli, A; Prosdocimi, M; Caputi, A P

    1993-01-01

    The effects of cloricromene, a coumarine derivative, were studied in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 68 +/- 4%; necrotic area/total area = 48 +/- 3%) high serum creatinphosphokinase activity (Sham MI/R = 29 +/- 8 U/ml; MI/R = 205 +/- 11 U/ml) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation), in the area-at-risk (6.3 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (6.5 +/- 0.5 U x 10(-3)/g tissue). Furthermore, serum TNF-alpha was undetectable during the occlusion period, but upon the release of the coronary artery significantly increased. At the end of reperfusion, macrophage TNF-alpha was also enhanced. The administration of cloricromene (2 mg/kg, 5 minutes after the onset of reperfusion) significantly reduced myocardial injury (necrotic area/area-at-risk 30 +/- 1.3%; necrotic area/total area = 25 +/- 1.5) blunted the increase in serum creatinphosphokinase activity (92 +/- 5 U/ml) and lowered myeloperoxidase activity in area-at-risk (2.5 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (2.2 +/- 0.3 U x 10(-3)/g tissue) and decreased the serum and macrophage levels of TNF-alpha. These data indicate that cloricromene exerts beneficial effects on myocardial ischaemia/reperfusion injury. Finally, since we measured increased serum levels of TNF-alpha that were blunted by the cloricromene treatment, our data are consistent with an involvement of TNF-alpha in the reperfusion injury induced by myocardial ischaemia.

  12. Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet.

    Science.gov (United States)

    Cordero, Paul; Campion, Javier; Milagro, Fermin I; Goyenechea, Estibaliz; Steemburgo, Thais; Javierre, Biola M; Martinez, J Alfredo

    2011-09-01

    Obesity-associated adipose tissue enlargement is characterized by an enhanced proinflammatory status and an elevated secretion of adipokines such as leptin and cytokines such as tumor necrosis factor (TNF)-alpha. Among the different mechanisms that could underlie the interindividual differences in obesity, epigenetic regulation of gene expression has emerged as a potentially important determinant. Therefore, 27 obese women (age, 32-50 years; baseline body mass index, 34.4 ± 4.2 kg/m(2)) were prescribed an 8-week low-calorie diet, and epigenetic marks were assessed. Baseline and endpoint anthropometric parameters were measured, and blood samples were drawn. Genomic DNA and RNA from adipose tissue biopsies were isolated before and after the dietary intervention. Leptin and TNF-alpha promoter methylation were measured by MSP after bisulfite treatment, and gene expression was also analyzed. Obese women with a successful weight loss (≥5% of initial body weight, n=21) improved the lipid profile and fat mass percentage (-12%, p<0.05). Both systolic (-5%, p<0.05) and diastolic (-8%, p<0.01) blood pressures significantly decreased. At baseline, women with better response to the dietary intervention showed lower promoter methylation levels of leptin (-47%, p<0.05) and TNF-alpha (-39%, p=0.071) than the non-responder group (n=6), while no differences were found between responder and non-responder group in leptin and TNF-alpha gene expression analysis. These data suggest that leptin and TNF-alpha methylation levels could be used as epigenetic biomarkers concerning the response to a low-calorie diet. Indeed, methylation profile could help to predict the susceptibility to weight loss as well as some comorbidities such as hypertension or type 2 diabetes.

  13. NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

    Science.gov (United States)

    Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

    2016-03-01

    Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

  14. [TNF-alpha, C-reactive protein and serum adiponectin modified in infertile patients with insulin resistance].

    Science.gov (United States)

    Vital Reyes, Victor Saúl; López Alarcón, Mardya; Zavala Ortega, Isabel; Hinojosa Cruz, Juan Carlos; Téllez Velasco, Sergio; Gris Calvo, Judith

    2008-11-01

    Women's reproductive potential is closely related to nutritional status. Some of the molecules that participate in ovarian regulation are produced in the adipose tissue, and therefore their production is associated with adiposity. To determine serum leptin, adiponectin, C-reactive protein, interleukin-6, and tumor necrosis factor alpha in infertile women with or without insulin resistance; and to associate these molecules with adiposity. Thirty-one infertile women were included. Nutritional status was evaluated through clinical and biochemical parameters. Patients were stratified according with their body mass index and the presence of insulin resistance. For statistics, parametric analyses were conducted. The prevalence of overweight was 67.5%; high adiposity was present in 92.3% and central distribution of fat in 96.2% of studied women. Hypercholesterolemia was found in 32.3% of patients, hypertriglyceridemia in 25.8%, and 61.3% presented hyperinsulinemia. Overweight women presented lower adiponectin, and higher TNF-alpha and C-reactive protein concentrations, than those with normal body mass index (p dislipidemias, and IR was high in our population studied. We conclude that adiposity is closely associated with some of the molecules that participate in the reproductive process and that also regulate inflammatory responses.

  15. Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion

    Science.gov (United States)

    Wright, A. D.; Chapes, S. K.

    1999-01-01

    The mechanism of how superantigens function to activate cells has been linked to their ability to bind and cross-link the major histocompatibility complex class II (MHCII) molecule. Cells that lack the MHCII molecule also respond to superantigens, however, with much less efficiency. Therefore, the purpose of this study was to confirm that staphylococcal enterotoxin A (SEA) could bind the MHCI molecule and to test the hypothesis that cross-linking SEA bound to MHCII-deficient macrophages would induce a more robust cytokine response than without cross-linking. We used a capture enzyme-linked immunosorbent assay and an immunprecipitation assay to directly demonstrate that MHCI molecules bind SEA. Directly cross-linking MHCI using monoclonal antibodies or cross-linking bound SEA with an anti-SEA antibody or biotinylated SEA with avidin increased TNF-alpha and IL-6 secretion by MHCII(-/-) macrophages. The induction of a vigorous macrophage cytokine response by SEA/anti-SEA cross-linking of MHCI offers a mechanism to explain how MHCI could play an important role in superantigen-mediated pathogenesis. Copyright 1999 Academic Press.

  16. Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes.

    Science.gov (United States)

    Fragoulis, Athanassios; Laufs, Jendrik; Müller, Susanna; Soppa, Ulf; Siegl, Stephanie; Reiss, Lucy Kathleen; Tohidnezhad, Mersedeh; Rosen, Christian; Tenbrock, Klaus; Varoga, Deike; Lippross, Sebastian; Pufe, Thomas; Wruck, Christoph Jan

    2012-10-27

    Rheumatoid arthritis (RA) is characterized by progressive inflammation associated with rampantly proliferating synoviocytes and joint destruction due to oxidative stress. Recently, we described nuclear factor erythroid 2-related factor 2 (Nrf2) as a major requirement for limiting cartilage destruction. NF-κB and AP-1 are the main transcription factors triggering the inflammatory progression in RA. We used sulforaphane, an isothiocyanate, which is both an Nrf2 inducer and a NF-κB and AP-1 inhibitor. Cultured synoviocytes were stimulated with sulforaphane (SFN) with or without TNF-α pre-treatment. NF-κB, AP-1, and Nrf2 activation was investigated via dual luciferase reporter gene assays. Matrix metalloproteinases (MMPs) were measured via zymography and luminex technique. Cytokine levels were detected using ELISA. Cell viability, apoptosis and caspase activity were studied. Cell proliferation was analysed by real-time cell analysis. SFN treatment decreased inflammation and proliferation dose-dependently in TNF-α-stimulated synoviocytes. SFN did not reduce MMP-3 and MMP-9 activity or expression significantly. Interestingly, we demonstrated that SFN has opposing effects on naïve and TNF-α-stimulated synoviocytes. In naïve cells, SFN activated the cytoprotective transcription factor Nrf2. In marked contrast to this, SFN induced apoptosis in TNF-α-pre-stimulated synoviocytes. We were able to show that SFN treatment acts contrary on naïve and inflammatory synoviocytes. SFN induces the cytoprotective transcription factor Nrf2 in naïve synoviocytes, whereas it induces apoptosis in inflamed synoviocytes. These findings indicate that the use of sulforaphane might be considered as an adjunctive therapeutic strategy to combat inflammation, pannus formation, and cartilage destruction in RA.

  17. Correlation of Neopterin and TNF-alpha with Asymmetric Dimethylarginine in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Dedeh Yuniarty

    2011-12-01

    Full Text Available BACKGROUND: A large number of obesity in the community increases the incidence of Metabolic Syndrome (MetS that can increase the risks of heart disease, diabetes, and stroke. One of the possible causes of stroke is atherosclerosis. Atherosclerosis is initiated by the incidence of inflammation and endothelial dysfuction. Atherosclerosis is involved in an ongoing inflammatory response. At the beginning of atherosclerosis, when the endothel become inflamed, it expresses adhesion molecules  that attract monocytes. The monocytes then migrate into the intima due to endothelial dysfunction. Activation of macrophage occurs in the process of inflammation as the earliest type of lesion of atherosclerosis. In this study, monocyte/macrophage activation is marked by Neopterin. In other process of atherosclerosis, vascular nitric oxide (NO activity has a role as a potent endogenous vasodilator. In regulating the vascular tone, NO has a role to suppress vascular smooth muscle proliferation, inhibit platelet adhesion and aggregation, and interferes with the leukocyte-endothelial cell interaction. In MetS, hypercholesterolemia decreases NO activity. Asymmetric Dimethylarginine (ADMA has been characterized as an endogenous, competitive inhibitor of NO synthase. In this study, the incidence of endothelial dysfunction is marked by ADMA. The aim of this study was to discover the role of Neopterin in MetS patients by evaluating the correlation between Neopterin and ADMA in MetS through tumor necrosis factor (TNF-α or direct line. METHODS: The study was cross sectional on 64 males with MetS aged 30-65 years. The measurements of TNF-α concentrations was done, respectively. RESULTS: Neopterin concentration correlated with Log TNF-α concentration (r=0.311, p=0.012. There is no significant correlation between Neopterin and ADMA (r=0.012, p=0.930; ADMA and Log TNF-α (r=0.029, p=0.821. CONCLUSIONS: There is no significant correlation between Neopterin and ADMA through

  18. Ultrasound Doppler measurements predict success of treatment with anti-TNF-alpha drug in patients with rheumatoid arthritis: a prospective cohort study

    DEFF Research Database (Denmark)

    Ellegaard, Karen; Christensen, Robin Daniel Kjersgaard; Torp-Pedersen, Søren

    2011-01-01

    and HAQ, biochemical measures and 28-joint DAS (DAS28) were collected for all patients. The amount of USD signal in the synovium was quantified by measuring the percentage of colour pixels-the colour fraction (CF). Predictive validity for patients who remain on anti-TNF-alpha therapy after 1 year......Methods. Patients with RA in anti-TNF-alpha therapy were followed 1 year after therapy initiation. All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a USD examination, clinical examination including tender and swollen joint count, visual analogue scale (VAS) global...... was assessed for both USD measurements and other disease measures. Baseline values of disease measures of patients who remained on treatment after 1 year was compared with those who stopped therapy. Results. The study cohort consisted of 109 patients. In this study, the baseline CF was the only measure...

  19. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

    Science.gov (United States)

    Henness, Sheridan; van Thoor, Eveline; Ge, Qi; Armour, Carol L; Hughes, J Margaret; Ammit, Alaina J

    2006-06-01

    Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-alpha-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-alpha-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

  20. Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumatoid arthritis who discontinued infliximab because of side effects

    Science.gov (United States)

    Iannone, Florenzo; Trotta, Francesco; Monteccuco, Carlomaurizio; Giacomelli, Roberto; Galeazzi, Mauro; Matucci‐Cerinic, Marco; Ferri, Clodoveo; Cutolo, Maurizio; Bambara, Lisa Maria; Triolo, Giovanni; Ferraccioli, Gianfranco; Valentini, Gabriele; Lapadula, Giovanni

    2007-01-01

    Objective To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. Methods Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS‐44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. Results 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS‐44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). Conclusions Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) α inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFα blocker has been withdrawn because of adverse events. PMID:16837489

  1. The interaction of butyrate with TNF-alpha during differentiation and apoptosis of colon epithelial cells: Role of NF-kappaB activation

    Czech Academy of Sciences Publication Activity Database

    Hýžďalová, Martina; Hofmanová, Jiřina; Pacherník, J.; Vaculová, Alena; Kozubík, Alois

    2008-01-01

    Roč. 44, - (2008), s. 33-43 ISSN 1043-4666 R&D Projects: GA AV ČR(CZ) KJB500040508; GA AV ČR(CZ) 1QS500040507; GA ČR(CZ) GA524/07/1178 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : butyrate * TNF-alpha * differentiation Subject RIV: BO - Biophysics Impact factor: 2.214, year: 2008

  2. Immunostimulatory properties and enhanced TNF- {alpha} mediated cellular immunity for tumor therapy by C{sub 60}(OH){sub 20} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Liu Ying; Jiao Fang; Qiu Yang; Li Wei; Qu Ying; Tian Chixia; Li Yufeng; Bai Ru; Lao Fang; Zhao Yuliang; Chai Zhifang; ChenChunying, E-mail: zhaoyuliang@ihep.ac.c, E-mail: chenchy@nanoctr.c [CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190 (China); Key Laboratory for Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)

    2009-10-14

    Publications concerning the mechanism of biological activity, especially the immunological mechanism of C{sub 60}(OH){sub 20} nanoparticles, are relatively limited. However, the structure and characteristics of this carbon allotrope have been widely investigated. In this paper, we have demonstrated that water-soluble C{sub 60}(OH){sub 20} nanoparticles have an efficient anti-tumor activity in vivo, and show specific immunomodulatory effects to the immune cells, such as T cells and macrophages, both in vivo and in vitro. For example, C{sub 60}(OH){sub 20} nanoparticles can increase the production of T-helper cell type 1 (Th1) cytokines (IL-2, IFN- {gamma} and TNF-{alpha}), and decrease the production of Th2 cytokines (IL-4, IL-5 and IL-6) in serum samples. On the other hand, C{sub 60}(OH){sub 20} nanoparticles show almost no adverse effect to the viability of immune cells in vitro but stimulate the immune cells to release more cytokines, in particular TNF- {alpha}, which plays a key role in the cellular immune process to help eliminate abnormal cells. TNF- {alpha} production increased almost three-fold in treated T lymphocytes and macrophages. Accordingly, we conclude that C{sub 60}(OH){sub 20} nanoparticles have an efficient anti-tumor activity and this effect is associated with an increased CD{sub 4}{sup +}/CD{sub 8}{sup +} lymphocyte ratio and the enhancement of TNF- {alpha} production. The data suggest that C{sub 60}(OH){sub 20} nanoparticles can improve the immune response to help to scavenge and kill tumor cells.

  3. Discovery and SAR of hydantoin TACE inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wensheng; Guo, Zhuyan; Orth, Peter; Madison, Vincent; Chen, Lei; Dai, Chaoyang; Feltz, Robert J.; Girijavallabhan, Vinay M.; Kim, Seong Heon; Kozlowski, Joseph A.; Lavey, Brian J.; Li, Dansu; Lundell, Daniel; Niu, Xiaoda; Piwinski, John J.; Popovici-Muller, Janeta; Rizvi, Razia; Rosner, Kristin E.; Shankar, Bandarpalle B.; Shih, Neng-Yang; Siddiqui, M.A.; Sun, J.; Tong, L.; Umland, S.; Wong, M.K.; Yang, D.Y.; Zhou, G. (Merck)

    2010-09-03

    We disclose inhibitors of TNF-{alpha} converting enzyme (TACE) designed around a hydantoin zinc binding moiety. Crystal structures of inhibitors bound to TACE revealed monodentate coordination of the hydantoin to the zinc. SAR, X-ray, and modeling designs are described. To our knowledge, these are the first reported X-ray structures of TACE with a hydantoin zinc ligand.

  4. Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression if IL-1beta and TNF-alpha.

    Science.gov (United States)

    Allen-Hall, Lisa; Cano, Pablo; Arnason, John T; Rojas, Rosario; Lock, Olga; Lafrenie, Robert M

    2007-01-19

    Uncaria tomentosa, commonly known as cat's claw, is a medicinal plant native to Peru, which has been used for decades in the treatment of various inflammatory disorders. Uncaria tomentosa can be used as an antioxidant, has anti-apoptotic properties, and can enhance DNA repair, however it is best know for its anti-inflammatory properties. Treatment with Uncaria tomentosa extracts inhibits the production of the pro-inflammatory cytokine, TNF-alpha, which is a critical mediator of the immune response. In this paper, we showed that treatment of THP-1 monocyte-like cells with Uncaria tomentosa extracts inhibited the MAP kinase signaling pathway and altered cytokine expression. Using ELISA assays, we showed that treatment with Uncaria tomentosa extracts augmented LPS-dependent expression of IL-1beta by 2.4-fold, while inhibiting the LPS-dependent expression of TNF-alpha by 5.5-fold. We also showed that treatment of LPS-stimulated THP-1 cells with Uncaria tomentosa extracts blocked ERK1/2 and MEK1/2 phosphorylation in a dose-dependent manner. These data demonstrate that treatment of THP-1 cells with Uncaria tomentosa extracts has opposite effects on IL-1beta and TNF-alpha secretion, and that these changes may involve effects on the MAP kinase pathway.

  5. Differential striatal levels of TNF-alpha, NFkappaB p65 subunit and dopamine with chronic typical and atypical neuroleptic treatment: role in orofacial dyskinesia.

    Science.gov (United States)

    Bishnoi, Mahendra; Chopra, Kanwaljit; Kulkarni, Shrinivas K

    2008-08-01

    Long term use of typical neuroleptics such as haloperidol may be limited by unwanted motor side effects like tardive dyskinesia characterized by repetitive involuntary movements, involving the mouth, face and trunk. Atypical neuroleptics, such as clozapine and risperidone are devoid of these side effects. However the precise mechanisms of the neuronal toxicity induced by haloperidol are poorly understood. It is possible that typical and atypical antipsychotic differently affects neuronal survival and death and that these effects considerably contribute to the differences in the development of TD. The aim of the present study is to investigate the role of TNF-alpha and NFkappaB on the toxicity induced by chronic haloperidol administration in an animal model of tardive dyskinesia. Rats were treated for 21 days with: haloperidol (5 mg/kg), clozapine (5 and 10 mg/kg), risperidone (5 mg/kg) or saline. Orofacial dyskinetic movements and total locomotor activity was evaluated. Striatal levels of dopamine were measure by HPLC/ED whereas striatal levels of TNF-alpha and NFkappaB p65 subunit were measured by ELISA technique. Haloperidol increased orofacial dyskinetic movements and total locomotor activity (on day 22) (PClozapine and risperidone also increased the orofacial dyskinetic movements but that significantly less than haloperidol (Pclozapine and risperidone did not. Haloperidol but not clozapine and risperidone significantly increased the levels of TNF-alpha and NFkappaB p65 subunit (Pdyskinesia in rats, an animal model for human tardive dyskinesia.

  6. Vaccination with vif-deleted feline immunodeficiency virus provirus, GM-CSF, and TNF-alpha plasmids preserves global CD4 T lymphocyte function after challenge with FIV.

    Science.gov (United States)

    Maksaereekul, Saipiroon; Dubie, Robert A; Shen, Xiaoying; Kieu, Hung; Dean, Gregg A; Sparger, Ellen E

    2009-06-08

    Feline immunodeficiency virus (FIV) DNA vaccine approaches that included a vif-deleted FIV provirus (FIV-pPPRDeltavif) and feline cytokine expression plasmids were tested for immunogenicity and efficacy by immunization of specific pathogen free cats. Vaccine protocols included FIV-pPPRDeltavif plasmid alone; a combination of FIV-pPPRDeltavif DNA and feline granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha expression plasmids; or a combination of FIV-pPPRDeltavif and feline interleukin (IL)-15 plasmids. Cats immunized with FIV-pPPRDeltavif, GM-CSF and TNF-alpha plasmids demonstrated an increased frequency of FIV-specific T cell proliferation responses compared to other vaccine groups. Immunization with FIV-pPPRDeltavif and IL-15 plasmids was distinguished from other vaccine protocols by the induction of antiviral antibodies. Suppression of virus loads was not observed for any of the FIV-pPPRDeltavif DNA vaccine protocols after challenge with the FIV-PPR isolate. However, prior immunization with FIV-pPPRDeltavif, GM-CSF, and TNF-alpha plasmids resulted in preservation of CD4 T cell functions, including mitogen-induced cytokine expression and antigen-specific proliferation upon infection with FIV. These findings justify further examination of cytokine combinations as adjuvants for lentiviral DNA vaccines.

  7. Epigallocatechin-3-gallate inhibits secretion of TNF-alpha, IL-6 and IL-8 through the attenuation of ERK and NF-kappaB in HMC-1 cells.

    Science.gov (United States)

    Shin, Hye-Young; Kim, Sang-Hyun; Jeong, Hyun-Ja; Kim, Sang-Yong; Shin, Tae-Yong; Um, Jae-Young; Hong, Seung-Heon; Kim, Hyung-Min

    2007-01-01

    Epigallocatechin-3-gallate (EGCG) is a major form of tea catechin and has a variety of biological activities. In the present study, we investigated the effect of EGCG on the secretion of TNF-alpha, IL-6 and IL-8, as well as its possible mechanism of action by using the human mast cell line (HMC-1). EGCG was treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187). To investigate the effect of EGCG on PMA+A23187-stimulated HMC-1 cells, ELISA, Western blot analysis, electrophorectic mobility shift assay and luciferase assay were used in this study. EGCG (100 microM) inhibited PMA+A23187-induced TNF-alpha, IL-6 and IL-8 expression and production. EGCG inhibited the intracellular Ca(2+) level. EGCG attenuated PMA+A23187-induced NF-kappaB and extracellular signal-regulated kinase (ERK1/2) activation, but not that of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. EGCG inhibited the production of TNF-alpha, IL-6 and IL-8 through the inhibition of the intracellular Ca(2+) level, and of ERK1/2 and NF-kappaB activation. These results indicate that EGCG may be helpful in regulating mast-cell-mediated allergic inflammatory response.

  8. Comparative Efficacy and Acceptability of Anti-TNF-Alpha Therapy in Ankylosing Spondylitis: A Mixed-Treatments Comparison

    Directory of Open Access Journals (Sweden)

    Yehua Wang

    2016-09-01

    Full Text Available Background: Tumor necrosis factor α (TNFα antagonists, namely, golimumab, adalimumab, infliximab, etanercept and certolizumab have been prescribed to alleviate and treat ankylosing spondylitis (AS. However, the lack of comparative evidence does not enable us to make constructive recommendations particularly for AS patient populations. Methods: Eligible controlled trials regarding the above 5 anti-TNFα therapies were searched electronically through PubMed, Embase and Cochrane until April 1, 2015. Odds ratios (ORs were estimated and compared for efficacy (ASAS20, ASAS40, ASAS5/6 responses and ASAS partial remission and acceptability (serious adverse effects (SAE among the anti-TNFα reagents. Results: Totally, 25 trials with 2989 participants were incorporated in this mixed treatment comparison. All the 5 TNFα blockers achieved better ASAS20, ASAS40, ASAS5/6 and ASAS-PR responses than the placebo. Furthermore, there was no significant distinction existed among inter-drug comparisons, except that unfavorable effects induced by certolizumab seemed to be less severe than those by etanercept (OR = 0.22, 95% CI: 0.05-0.93. Apart from that, etanercept was estimated to arrive at the most favorable ASAS20 response (90.6% and SAE (83.6%, while infliximab seemed to accomplish the best ASAS40 (83.6% and ASAS-PR responses (77.3%. In addition, adalimumab was estimated to rank the highest ASAS5/6 response (75.0%. Conclusions: Etanercept, infliximab and adalimumab might be prioritized among the commonly recognized 5 anti-TNFα therapies specific for AS patients, though existing evidence did not suffice to confirm significant superiority among the above 5 anti-TNFα reagent.

  9. Etanercept, a TNF-alpha binding agent, is ineffective in the prevention of post-ERCP pancreatitis in canines.

    Science.gov (United States)

    Buscaglia, Jonathan M; Simons, Brian W; Prosser, Brent J; Ruben, Dawn S; Giday, Samuel A; Magno, Priscilla; Clarke, John O; Shin, Eun Ji; Kalloo, Anthony N; Kantsevoy, Sergey V; Gabrielson, Kathleen L; Jagannath, Sanjay B

    2008-07-10

    The incidence of post-ERCP pancreatitis is 1-22%. It continues to be a difficult problem for endoscopist and patient. Uncovering an agent that may be used to prevent its occurrence is critical. The aim of our study was to investigate the role of etanercept in the prevention of post-ERCP pancreatitis. Endoscopic retrograde pancreatography (ERP)-induced injury was performed in dogs using a previously established endoscopic model of post-ERCP pancreatitis. Eight study dogs underwent ERP: 4 were pre-treated with etanercept one day before the procedure and 4 were untreated. In addition, three control dogs not undergoing ERP were also studied. Serum levels of amylase, lipase, and TNF-alpha, as well as the ratio of urinary trypsinogen activation peptide (TAP) and urinary creatinine, were measured before and after ERP. Necropsy was performed on post-operative day 5. All pancreatic specimens were graded by two blinded pathologists according to a validated scoring system. Eight study dogs developed mild to moderate clinical pancreatitis with hyperamylasemia (11,538+/-4,065 U/L vs. 701+/-157 U/L; post-ERP peak levels vs. baseline values: Pdogs compared to control dogs (6.16+/-1.85 vs. 1.06+/-0.49; P=0.001). There were escalating total injury scores concordant with more elaborate methods of endoscopically-induced injury although the trend did not reach the statistical significance (P=0.223). When comparing untreated to etanercept-treated dogs, there were no significant differences in serum amylase levels (P=0.903), serum lipase levels (P=0.771), TAP/creatinine urinary ratio (P=0.912), and pancreatic injury score (P=0.324). Etanercept is ineffective in prevention of mild to moderate post-ERCP pancreatitis in canines. ERP-induced pancreatic injury can be used as a reliable animal model for studies investigating therapy and prevention of post-ERCP pancreatitis.

  10. Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males

    Directory of Open Access Journals (Sweden)

    Rimbach Gerald

    2011-05-01

    Full Text Available Abstract Background Human paraoxonase 1 (PON1 is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G, a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results. Findings To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the PON1 polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers. Conclusions Our findings support the hypothesis that the common PON1 R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.

  11. In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of 99mtechnetium stannous colloid but do not affect neutrophil uptake

    International Nuclear Information System (INIS)

    Ramsay, Stuart C.; Maggs, Jacqueline; Powell, Kellie; Barnes, Jodie; Ketheesan, Natkunam

    2006-01-01

    Introduction: 99m Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. Methods: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. Results: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. Conclusions: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of

  12. Bilateral muscle fiber and nerve influences by TNF-alpha in response to unilateral muscle overuse - studies on TNF receptor expressions.

    Science.gov (United States)

    Renström, Lina; Stål, Per; Song, Yafeng; Forsgren, Sture

    2017-11-28

    TNF-alpha is suggested to be involved in muscle damage and muscle inflammation (myositis). In order to evaluate whether TNF-alpha is involved in the myositis that occurs in response to muscle overuse, the aim was to examine the expression patterns of TNF receptors in this condition. A rabbit muscle overuse model leading to myositis in the soleus muscle was used. The expression patterns of the two TNF receptors Tumor Necrosis Factor Receptor type 1 (TNFR1) and Tumor Necrosis Factor Receptor type 2 (TNFR2) were investigated. In situ hybridization and immunofluorescence were utilized. Immunostainings for desmin, NK-1R and CD31 were made in parallel. Immunoreactions (IR) for TNF receptors were clearly observed in white blood cells, fibroblasts and vessel walls, and most interestingly also in muscle fibers and nerve fascicles in the myositis muscles. There were very restricted reactions for these in the muscles of controls. The upregulation of TNF receptors was for all types of structures seen for both the experimental side and the contralateral nonexperimental side. TNF receptor expressing muscle fibers were present in myositis muscles. They can be related to attempts for reparation/regeneration, as evidenced from results of parallel stainings. Necrotic muscle fibers displayed TNFR1 mRNA and TNFR2 immunoreaction (IR) in the invading white blood cells. In myositis muscles, TNFR1 IR was observed in both axons and Schwann cells while TNFR2 IR was observed in Schwann cells. Such observations were very rarely made for control animals. The findings suggest that there is a pronounced involvement of TNF-alpha in the developing myositis process. Attempts for reparation of the muscle tissue seem to occur via both TNFR1 and TNFR2. As the myositis process also occurs in the nonexperimental side and as TNF receptors are confined to nerve fascicles bilaterally it can be asked whether TNF-alpha is involved in the spreading of the myositis process to the contralateral side via the

  13. In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of {sup 99m}technetium stannous colloid but do not affect neutrophil uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ramsay, Stuart C. [Townsville Nuclear Medicine, Mater Hospital, Pimlico, Queensland 4812 (Australia) and School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia)]. E-mail: stuart.ramsay1@jcu.edu.au; Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Powell, Kellie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia); Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia)

    2006-07-15

    Introduction: {sup 99m}Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. Methods: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. Results: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. Conclusions: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects

  14. [Disseminated tuberculosis following infliximab therapy for Crohn disease: a case report].

    Science.gov (United States)

    Bouchentouf, R; Yasser, Z; Aitbenasser, M A

    2014-12-01

    Anti-tumor necrosis factor (TNF) therapy has been the major advance in the treatment of inflammatory bowel disease, especially Crohn's disease. But there is a higher risk of infections, especially tuberculosis (TB), in patients treated with anti-TNFα. The authors report a case of disseminated tuberculosis with the following features: pulmonary tuberculosis, left supra clavicular cervical and meditational lymphadenopathy, bilateral pleural effusion, peritoneal and splenic involvement. This disseminated tuberculosis was observed in a 39-year-old woman who was treated by infliximab for refractory Crohn's disease. The evolution with antituberculosis drugs was fatal, the death of the patient was due to hepatic encephalitis. The physicians should always be aware in the use of TNF-alpha blockers according to guidelines. Its recommended to realize a complete pretherapeutic assessment and it is necessary to follow-up the patients to detect possible reactivation of latent tuberculosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

    DEFF Research Database (Denmark)

    Jinquan, T; Frydenberg, Jane; Mukaida, N

    1995-01-01

    receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene...

  16. Antibodies to Infliximab and Adalimumab in Patients with Rheumatoid Arthritis in Clinical Remission

    DEFF Research Database (Denmark)

    Eng, Grith P; Bendtzen, Klaus; Bliddal, Henning

    2015-01-01

    Objective. To investigate if antibodies towards biological TNF-α inhibitors (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in clinical remission and to relate any anti-TNFi Abs to circulating level of TNF-α inhibitor (TNFi). Methods. Patients with RA, treated with infliximab....../44 patients (18%) treated with infliximab and 1/49 patients (2%) treated with adalimumab (p = 0.012). In the former group, anti-TNFi Abs corresponded with low levels of TNFi (p = 0.048). Anti-TNFi Ab-positive patients had shorter disease duration at initiation of TNFi therapy (p = 0.023) but were similar...... for the rest of the compared parameters. Conclusions. In RA patients in clinical remission, anti-TNFi Abs occur frequently in patients treated with infliximab, while they occur rarely in patients treated with adalimumab. Presence of anti-infliximab Abs is accompanied by low or undetectable levels of infliximab...

  17. [Effects of electro-warmed needle of inner-Mongolian medicine on serum TNF-alpha, ACTH and corticosterone contents in fatigue rats].

    Science.gov (United States)

    Chen, Ying-song; Lu, Jun; Su-Chao, Lu-men; Wu, Qi-zhu; Tu, Ya; Agula

    2008-08-01

    To observe the effect of electro-warmed needle (EWN, of Inner-Mongolian medicine) on fatigue rats' behavior, hypothalamic-pituitary-adrenocortex (HPA) axis activity and immune system so as to reveal its neuro-endocrino-immune mechanism. Male SD rats were randomized into control (n=20), model (n=20) and EWN (n=19) groups. Fatigue model was established by forcing the rat to swim in a water pool till exhaustion, once daily, continuously for 21 days. "Dinghui" (central spot over the bregmatic bone) and "Xinxue" (the center of the depression beneath the 7th thoracic vertebra) were punctured with silver needles which were warmed electrically by using a MLY-I Electrical Needle-warming Apparatus, once every 3 days, 7 sessions altogether. On the 21st day of modeling, swim-exhaustion duration (SED), and immobility time and struggle times in tail suspension test were measured. Twenty-four hours after the last swim, the rats' serum TNF-alpha, ACTH an corticosterone contents were detected by enzyme linked immunosorbent assay (ELISA). Compared with control group SED, immobility time and struggle times in tail suspension test in model group decreased, increased and lowered respectively and significantly (P 0.05). Compared with control group, serum TNF-alpha, ACTH and corticosterone contents in model group increased significantly (P < 0.01), while in comparison with model group, the 3 indexes of EWN group were significantly lower (P < 0.01, 0.05). EWN treatment can reduce fatigue-induced increase of serum TNF-alpha, ACTH and corticosterone levels, and raise motor ability, suggesting a favorable regulation of HPA axis and immune function after EWN and improvement of fatigue in fatigue

  18. Alcohol depletes coenzyme-Q(10) associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells.

    Science.gov (United States)

    Vidyashankar, Satyakumar; Nandakumar, Krishna S; Patki, Pralhad S

    2012-12-08

    Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP(450) 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP(450) 2E1. The results showed that ethanol at 100mM concentration caused 40% cytotoxicity at 72h as determined by MTT assay. The incorporation of labeled [2-(14)C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24h incubation, whereas incorporation of labeled [2-(14)C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q(10) which is detrimental for cell viability. But vitamin E (10mM) could partially restore coenzyme-Q(10) and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained intact. Alanine amino transferase activity was increased by 4.85 folds in cells treated with ethanol confirming hepatocyte damage. Hence, it is inferred that ethanol induced cytotoxicity in HepG2 cells due to coenzyme-Q(10) depletion and increased TNF-alpha secretion. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Ascorbic acid pre-treated quartz stimulates TNF-alpha release in RAW 264.7 murine macrophages through ROS production and membrane lipid peroxidation.

    Science.gov (United States)

    Scarfì, Sonia; Magnone, Mirko; Ferraris, Chiara; Pozzolini, Marina; Benvenuto, Federica; Benatti, Umberto; Giovine, Marco

    2009-03-19

    Inhalation of crystalline silica induces a pulmonary fibrotic degeneration called silicosis caused by the inability of alveolar macrophages to dissolve the crystalline structure of phagocytosed quartz particles. Ascorbic acid is capable of partially dissolving quartz crystals, leading to an increase of soluble silica concentration and to the generation of new radical sites on the quartz surface. The reaction is specific for the crystalline forms of silica. It has been already demonstrated an increased cytotoxicity and stronger induction of pro-inflammatory cyclooxygenase-2 (COX-2) by ascorbic acid pre-treated quartz (QA) compared to untreated quartz (Q) in the murine macrophage cell line RAW 264.7. Taking advantage of the enhanced macrophage response to QA as compared to Q particles, we investigated the first steps of cell activation and the contribution of early signals generated directly from the plasma membrane to the production of TNF-alpha, a cytokine that activates both inflammatory and fibrogenic pathways. Here we demonstrate that TNF-alpha mRNA synthesis and protein secretion are significantly increased in RAW 264.7 macrophages challenged with QA as compared to Q particles, and that the enhanced response is due to an increase of intracellular ROS. Plasma membrane-particle contact, in the absence of phagocytosis, is sufficient to trigger TNF-alpha production through a mechanism involving membrane lipid peroxidation and this appears to be even more detrimental to macrophage survival than particle phagocytosis itself. Taken together these data suggest that an impairment of pulmonary macrophage phagocytosis, i.e. in the case of alcoholic subjects, could potentiate lung disease in silica-exposed individuals.

  20. Alcohol depletes coenzyme-Q10 associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells

    International Nuclear Information System (INIS)

    Vidyashankar, Satyakumar; Nandakumar, Krishna S.; Patki, Pralhad S.

    2012-01-01

    Highlights: ► Ethanol induced cytotoxicity in HepG2 cells in absence of lipogenesis. ► Ethanol inhibited HMG-CoA reductase activity. ► Ethanol induced HMG-CoA reductase inhibition is due to decreased cell viability. ► Incubation with mevalonate could not increase the cholesterol. ► Cytotoxicity brought about by CoQ10 depletion and increased TNF-alpha. -- Abstract: Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP 450 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP 450 2E1. The results showed that ethanol at 100 mM concentration caused 40% cytotoxicity at 72 h as determined by MTT assay. The incorporation of labeled [2- 14 C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24 h incubation, whereas incorporation of labeled [2- 14 C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q 10 which is detrimental for cell viability. But vitamin E (10 mM) could partially restore coenzyme-Q 10 and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained

  1. Efficacy of treatment intensification with adalimumab, etanercept and infliximab in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Eng, Grith; Stoltenberg, Michael B; Szkudlarek, Marcin

    2013-01-01

    To summarize the empirical evidence regarding the effect of treatment intensification on clinical outcomes in patients with rheumatoid arthritis treated with one of the TNF-α-inhibitors, adalimumab, etanercept or infliximab.......To summarize the empirical evidence regarding the effect of treatment intensification on clinical outcomes in patients with rheumatoid arthritis treated with one of the TNF-α-inhibitors, adalimumab, etanercept or infliximab....

  2. Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists

    Directory of Open Access Journals (Sweden)

    Urbano PCM

    2014-07-01

    Full Text Available Paulo César Martins Urbano,1 Vanete Thomaz Soccol,1 Valderilio Feijó Azevedo2 1Biotechnology and Bioprocess Engineering Program, Federal University of Parana, Curitiba, Parana, Brazil; 2Hospital de Clínicas, Federal University of Parana, Curitiba, Parana, Brazil Abstract: Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-α (tumor necrosis factor-α raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products. This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-α antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF-κB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-α antagonists which should be submitted to regulatory agencies for evaluation. Keywords: anti-TNF drugs, rheumatoid arthritis, apoptosis, NF-κB, FLIP

  3. Legionella pneumoni hos patienter, der er i behandling med infliximab

    DEFF Research Database (Denmark)

    Vinter, Hanne; Nielsen, Henrik Ib

    2009-01-01

    Therapy with tumour necrosis factor-alfa inhibitors is widely used in various inflammatory disorders, but adverse events from severe infections with intracellular pathogens may occur. We describe two cases of severe pulmonary legionellosis in patients treated with infliximab for Crohn's disease...

  4. [The effect of polyester vascular prostheses on synthesis TNF-alpha, IFN-gamma and NO by human peripheral blood leukocytes--in vitro].

    Science.gov (United States)

    Zywicka, Bogusława; Czarny, Anna; Zaczyńska, Ewa; Pielka, Stanisław; Solski, Leszek

    2005-01-01

    Vascular prostheses produced on the basis of polyester are today commonly used in vascular surgery. To improve their biofuncionality special technologies are used, among them double knit and hydrophile feature enrichment. These modifications could cause the local activation of leukocytes to produce the mediators of inflammatory reaction, which in turn leads to hyperplasia of endothelium and other dangerous complications. In our study we used two kinds of polyester prostheses: double velour knitted hydrophilic Dallon H and standard double velour knitted prosthesis Dallon as control. The aim of this work was to compare in vitro the levels of cytokines TNF-alpha, interferon (IFN) and nitric oxide (NO) found in the supernatants of human blood leukocyte cultures after stimulation by both these above-mentioned vascular prostheses materials which are designed for use in direct blood contact. Tested implant materials Dallon H had no influence on synthesis of production of IFN, TNF-alpha and NO by human blood leukocytes. These results allow to made the initial selection of biomaterials before their in vivo evaluation.

  5. Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women.

    Science.gov (United States)

    Tsiotra, P C; Tsigos, C; Yfanti, E; Anastasiou, E; Vikentiou, M; Psarra, K; Papasteriades, C; Raptis, S A

    2007-10-01

    Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMIwomen (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (pDM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (pDM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

  6. Elaidic acid sustains LPS and TNF-alpha induced ICAM-1 and VCAM-I expression on human bone marrow endothelial cells (HBMEC).

    Science.gov (United States)

    Sanadgol, Nima; Mostafaie, Ali; Bahrami, Gholamreza; Mansouri, Kamran; Ghanbari, Fariba; Bidmeshkipour, Ali

    2010-08-01

    Elaidic acid, the predominant trans-fatty acid in industrially hydrogenated oils, exists on high levels in Iranian hydrogenated oils and margarines. This study was undertaken to investigate the effect of elaidic acid and its cis-counterpart oleic acid on expression of ICAM-1 and VCAM-1 on human bone marrow endothelial cells (HBMECs). HBMEC were pre-treated with TNF-alpha or LPS for induction of the adhesion molecules expression, and then treated with elaidic acid or oleic acid. Soluble and cell associated forms of ICAM-1 and VCAM-1 were quantified by ELISA and Western blot. Our findings indicated that oleic acid suppresses VCAM-1 and ICAM-1 expression on HBMEC near to the basal level. Conversely, elaidic acid maintained the level of VCAM-1 and ICAM-1 up-regulated by TNF-alpha or LPS. It is suggested that elaidic acid could keep the HBMEC at the stimulated phenotype. These findings provide further support on the detrimental effects of elaidic acid in promotion and induction of cardiovascular diseases (CVD). 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

    Science.gov (United States)

    Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

    2011-01-01

    We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

  8. TNF-alpha impairs the S-G2/M cell cycle checkpoint and cyclobutane pyrimidine dimer repair in premalignant skin cells: Role of the PI3K-Akt pathway

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.; Calay, D.

    2008-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is induced by UVB radiation and has been implicated in the early stages of skin carcinogenesis. Here, we show that in normal keratinocytes and the transformed keratinocyte cell lines, HaCaT and A431, TNF-alpha stimulates protein kinase B/Akt, which results...... cycling. TNF-alpha enhanced apoptosis less potently and did not increase the level of CPD or stimulate cell cycle progression in normal keratinocytes. Our data suggest that TNF-alpha overrides the G2/M checkpoint in premalignant skin cells and allows for some cells containing unrepaired CPD to enter...... in activation of the survival complex mTORC1 (mammalian target of rapamycin complex 1) and inhibition of the proapoptotic proteins Bad and Fox03a. In UVB-irradiated HaCaT cells (10-20 mJ cm(-2)), TNF-alpha increased the proportion of cycling cells and enhanced the rate of apoptosis. A significantly higher...

  9. Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation

    NARCIS (Netherlands)

    de Vries, Mirjam K.; Wolbink, Gerrit Jan; Stapel, Steven O.; de Vrieze, Henk; van Denderen, J. Christiaan; Dijkmans, Ben A. C.; Aarden, Lucien A.; van der Horst-Bruinsma, Irene E.

    2007-01-01

    OBJECTIVES: Correlation of serum trough infliximab levels and antibodies to infliximab (anti-infliximab) with clinical response in ankylosing spondylitis. METHODS: In accordance with the international ASsessment in Ankylosing Spondylitis (ASAS) consensus statement, patients were treated with

  10. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  11. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  12. Serum IL-4, IL-12 and TNF-alpha in malaria: a comparative study associating cytokine responses with severity of disease from the Coastal Districts of Odisha.

    Science.gov (United States)

    Sarangi, Anshuman; Mohapatra, P C; Dalai, R K; Sarangi, Ashok Kumar

    2014-06-01

    We investigated the role of IL-4, IL-12 and TNF-alpha in clinically well-defined groups of Plasmodium falciparum and vivax (Pf & Pv) infected patients belonging to Group I (++), Group II (+++) and Group III (++++). On the basis of hematological parameters, hyperparasitaemia, and evidence of neurological involvement, three different levels of severity were selected attributing a score from Group I (++) to Group III (++++). In each group 16 patients each of P. falciparum and P. vivax malaria were studied. As a control group for cytokine determination 30 healthy volunteers were included in the study. Serum samples were analyzed for IL-12, IL-4 and TNF-alpha using (ELISA) obtained commercially (Ray Biotech). Hb levels of Pf and Pv patients were 8 ± 1.94, 7.6 ± 1.64 g/dl and 3.6 ± 1.23 and 10.1 ± 1.21, 9.4 ± 1.43 and 7.1 ± 0.98 g/dl. Serum iron levels of Pf and Pv patients were 85.86 ± 0.86, 81.10 ± 0.70 and 70.1 ± 0.73 and 99.47 ± 0.85, 96.67 ± 1.13 and 91.7 ± 2.65 mg/dl. TNF-alpha levels of Pf and Pv patients were 155 ± 23.66, 307.5 ± 111.87 and 955 ± 261.32 and 72 ± 9.93, 140.88 ± 23.11 and 469.37 ± 416.99 pg/ml. IL-12 levels of Pf and Pv patients were 117.5 ± 8.16, 160.63 ± 20.81 and 293.13 ± 94.64 and 75.7 ± 9.25, 112.9 ± 12.05 and 200 ± 53.78 pg/ml. IL-4 levels of Pf and Pv patients were 3.7 ± 0.11, 3.2 ± 0.13 and 2.3 ± 0.63 and 5.33 ± 1.08, 4.8 ± 0.16 and 3.9 ± 0.48 pg/ml. In the control group the values of TNF-alpha, IL-12 and IL-4 were 42.9 ± 13.5, 49.8 ± 11.59 and 6.06 ± 1.32 pg/ml respectively. Cytokines and poor oxygen delivery should not be viewed as alternative theories of malarial disease pathophysiology instead poor oxygen delivery is one of the consequences of excessive release of inflammatory cytokines which is further augmented by the present work.

  13. Inhibitory effects of the flavonoids isolated from Waltheria indica on the production of NO, TNF-alpha and IL-12 in activated macrophages.

    Science.gov (United States)

    Rao, Yerra Koteswara; Fang, Shih-Hua; Tzeng, Yew-Min

    2005-05-01

    Three flavonoids were isolated from the whole plants of Waltheria indica and biological properties investigated. On the basis of their spectroscopic data, these compounds were identified as (-)-epicatechin, quercetin, and tiliroside. These flavonoids significantly and dose-dependently inhibited the production of the inflammatory mediator nitric oxide (NO), and the cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-12), in lipopolysaccharide (LPS) and interferon (IFN)-gamma activated murine peritoneal macrophages, without displaying cytotoxicity. The order of inhibitory activity was quercetin>tiliroside>(-)-epicatechin. Furthermore, peritoneal macrophages were pre-activated with LPS/IFN-gamma for 24 h, and the inhibitory effects of the above mentioned isolates on the production of NO were determined after a further 24 h, to address the possible mechanisms of their action. The present study supports the use of W. indica for the treatment of inflammatory diseases in traditional medicine.

  14. Effects of a melanogenic bicyclic monoterpene diol on cell cycle, p53, TNF-alpha, and PGE2 are distinct from those of UVB.

    Science.gov (United States)

    Kraus, Eliyahu; Galvin, Jason W; Boumakis, Stavroula; Boamah, Ernest K; Canning, Matthew T; Yarosh, Daniel B; Brown, David A

    2003-12-01

    Bicyclic monoterpene (BMT) diols are small-molecule compounds that mimic ultraviolet radiation (UVR) by inducing melanogenesis. The objective of this study was to compare the effects of 2,2-dimethyl-3-propanyldiol-norbornane (AGI-1140), a novel BMT diol, and ultraviolet B (UVB) on additional cellular responses. S91 mouse melanoma cells were treated with a range of concentrations of AGI-1140, and examined for induction of melanogenesis and nitric oxide (NO). The effect of AGI-1140 on dendrite outgrowth from human melanocytes was examined by quantitative microscopy. The effect of AGI-1140 and UVB on phosphorylation of p53 serine 15 in human keratinocytes was examined by Western blotting, while the release of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) was determined by enzyme-linked immunosorbent assay. The effects of AGI-1140 and UVB on cell cycle arrest of human melanocytes, keratinocytes, fibroblasts, and endothelial cells were compared using fluorescence-activated cell sorting. Similar to UVB, AGI-1140 induced both melanogenesis and NO in melanoma cells. AGI-1140 also induced dendrite outgrowth from melanocytes, indicative of differentiation. However, whereas UVB induced G2 cell cycle arrest with phosphorylation of p53 at serine 15, AGI-1140 induced G1 cell cycle arrest without this phosphorylation. Additionally, unlike UVB, AGI-1140 did not increase the secretion of TNF-alpha or PGE2, mediators of UVB-induced immunosuppressive and inflammatory responses in the skin that may contribute to carcinogenesis. This study shows that melanogenesis can be induced by AGI-1140 without many of the deleterious effects associated with UVB.

  15. Does Dietary Deoxynivalenol Modulate the Acute Phase Reaction in Endotoxaemic Pigs?—Lessons from Clinical Signs, White Blood Cell Counts, and TNF-Alpha

    Directory of Open Access Journals (Sweden)

    Tanja Tesch

    2015-12-01

    Full Text Available We studied the interaction between deoxynivalenol (DON-feeding and a subsequent pre- and post-hepatic immune stimulus with the hypothesis that the liver differently mediates the acute phase reaction (APR in pigs. Barrows (n = 44 were divided into a DON-(4.59 mg DON/kg feed and a control-diet group, surgically equipped with permanent catheters pre- (V. portae hepatis and post-hepatic (V. jugularis interna and infused either with 0.9% NaCl or LPS (7.5 µg/kg BW. Thus, combination of diet (CON vs. DON and infusion (CON vs. LPS, jugular vs. portal created six groups: CON_CONjug.-CONpor., CON_CONjug.-LPSpor., CON_LPSjug.-CONpor., DON_CONjug.-CONpor., DON_CONjug.-LPSpor., DON_LPSjug.-CONpor.. Blood samples were taken at −30, 15, 30, 45, 60, 75, 90, 120, 150, 180 min relative to infusion and analyzed for leukocytes and TNF-alpha. Concurrently, clinical signs were scored and body temperature measured during the same period. LPS as such induced a dramatic rise in TNF-alpha (p < 0.001, hyperthermia (p < 0.01, and severe leukopenia (p < 0.001. In CON-fed pigs, an earlier return to physiological base levels was observed for the clinical complex, starting at 120 min post infusionem (p < 0.05 and persisting until 180 min. DON_LPSjug.-CONpor. resulted in a lower temperature rise (p = 0.08 compared to CON_LPSjug.-CONpor.. In conclusion, APR resulting from a post-hepatic immune stimulus was altered by chronic DON-feeding.

  16. Infliximab dependency in children with Crohn's disease

    DEFF Research Database (Denmark)

    Duricova, D; Pedersen, N; Lenicek, M

    2009-01-01

    BACKGROUND: Recently, infliximab dependency has been described. AIM: To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000-2006 and to describe clinical and genetic predictors of long-term infliximab response. METHODS: A phenotype model of infliximab....../partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24-22.55; OR 6.7, 95% CI: 1.67-26.61). No association was found with studied...... polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders (P = 0.0002). CONCLUSIONS: Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior...

  17. Expression of TNF-alpha and IL-6 in HMC-1 cells treated with bisphenol A is attenuated by plant-originating glycoprotein (75 kDa) by blocking p38 MAPK.

    Science.gov (United States)

    Lee, Jin; Lim, Kye-Taek

    2010-07-01

    Bisphenol A (BPA) is known as an estrogen-mimic environmental hormone which has the ability to indirectly stimulate the production of allergic inflammation-related cytokines. Cudrania tricuspidata Bureau (CTB) has been used in Korean folk medicine for a long time. In order to determine the inhibitory effect of a glycoprotein (CTB glycoprotein, 75 kDa) isolated from CTB fruits on the activities of allergic inflammation-related cytokines (TNF-alpha and IL-6) caused by BPA, we evaluated the activities of protein kinase C (PKC), p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor (NF)-kappaB, and inflammation-related cytokine (TNF-alpha and IL-6) in the BPA-induced HMC-1 cells using immunoblot analysis and RT-PCR. The results obtained from this study revealed that CTB glycoprotein (100 microg/ml) inhibits the translocation of PKC from cytosol to the membrane, the phosphorylation of p38 MAPK, the activation of NF-kappaB, and the expression levels of TNF-alpha and IL-6. Taken together, the results in this study suggest that CTB glycoprotein inhibits the expression of allergic inflammation-related cytokines (TNF-alpha and IL-6) by blocking NF-kappaB and p38 kinase in BPA-induced HMC-1 cells.

  18. Infliximab-induced intertriginous psoriasis in patient with Crohn's desease

    Directory of Open Access Journals (Sweden)

    Federica Mola

    2011-10-01

    Full Text Available Tumor necrosis factor-α (TNFα inhibition is an effective treatment of moderate-to-severe psoriasis and other diseases (rheumatoid arthritis, ankylosing spondylitis, psoriasis or Crohn’s disease. We report a case of a 32- years-old patient affected by Crohn’s disease since the age of 25 who started infliximab infusion after four years of treatment with prednisone and azathioprine per os without improvement. After the fifth infusion of infliximab, he developed a form of intertriginous psoriasis which was approached with topical steroid cream. The patient never presented psoriasis in the past. New onset of psoriasis in patients without history for skin diseases (as in our case is a quite uncommon complication of TNFα inhibitor therapy. The increased production of IFNα during TNFα inhibitor therapy is a possible pathophysiologic explanation for this paradoxical effect of the anti-TNFα.

  19. Effects of Anti-TNF Alpha Drugs on Disability in Patients with Rheumatoid Arthritis: Long-Term Real-Life Data from the Lorhen Registry

    Directory of Open Access Journals (Sweden)

    Matteo Filippini

    2014-01-01

    Full Text Available This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years.

  20. Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    2014-01-01

    Full Text Available Objective. TRAIL is a potential biomarker of cardiovascular (CV disease. Ankylosing spondylitis (AS is a chronic inflammatory disease associated with metabolic syndrome (MeS and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

  1. New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and NO and TNF-alpha production in LPS-stimulated RAW264.7 cells.

    Science.gov (United States)

    Jin, Hui Zi; Lee, Dongho; Lee, Jeong Hyung; Lee, Kyeong; Hong, Young-Soo; Choung, Dong-Ho; Kim, Young Ho; Lee, Jung Joon

    2006-01-01

    A bioassay-guided isolation of an ethyl acetate-soluble extract of the aerial parts of Inula britannica var. chinensis (Rupr.) Regel, using an in vitro NF-kappaB reporter gene assay, led to the isolation of four new sesquiterpene dimers bearing a norbornene moiety, inulanolides A-D, and three known sesquiterpenes, 1,6alpha-dihydroxyeriolanolide, 1-acetoxy-6alpha-hydroxyeriolanolide, and eupatolide. The structures of the new compounds were elucidated by spectroscopic methods. Among these compounds, inulanolides B and D and eupatolide, exhibited potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50 values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent with their inhibitory effect on NF-kappaB activation, compounds and also strongly inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 microM.

  2. Infliximab Biosimilar (CT-P13; Infliximab-dyyb): A Review in Autoimmune Inflammatory Diseases.

    Science.gov (United States)

    Blair, Hannah A; Deeks, Emma D

    2016-10-01

    Infliximab biosimilar (CT-P13/infliximab-dyyb; Remsima ® , Inflectra ® ) is approved in several countries for use in all indications for which reference infliximab (Remicade ® ) is approved, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, psoriasis, Crohn's disease, and ulcerative colitis. Clinical data contributing to the EU approval of infliximab biosimilar were obtained from two pivotal double-blind clinical trials in patients with AS (PLANETAS) or RA (PLANETRA). Infliximab biosimilar demonstrated equivalence to reference infliximab in terms of its pharmacokinetic profile in patients with AS, patients with RA, and in healthy volunteers, and in terms of its efficacy in patients with RA. Clinical response rates in patients with RA or AS were maintained over the longer term (up to 102 weeks). In addition, the efficacy of infliximab biosimilar in patients with RA or Crohn's disease and ulcerative colitis [i.e. inflammatory bowel disease (IBD)] has been demonstrated in the real-world setting. Infliximab biosimilar was generally well tolerated, with a tolerability profile similar to that of reference infliximab. Switching from reference infliximab to infliximab biosimilar had no detrimental effect on efficacy, safety, or immunogenicity compared with continuous infliximab biosimilar therapy, according to the extensions of PLANETAS and PLANETRA, and real-world data in IBD. Current evidence therefore suggests that infliximab biosimilar is a useful alternative to reference infliximab in patients with autoimmune inflammatory diseases.

  3. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH

  4. Cut-off levels and diagnostic accuracy of infliximab trough levels and anti-infliximab antibodies in Crohn's disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Bendtzen, Klaus; Brynskov, Jørn

    2011-01-01

    Reasons for infliximab failure in Crohn's disease and ulcerative colitis are debated. Serum levels of infliximab and anti-infliximab antibodies have been associated with loss of response. We aimed at determining cut-off levels for infliximab and anti-infliximab antibody concentrations associated...

  5. Disseminated nocardiosis in a patient on infliximab and methylprednisolone for treatment-resistant Sweet's syndrome.

    Science.gov (United States)

    Drone, Elizabeth R; McCrory, Allison L; Lane, Natalie; Fiala, Katherine

    2014-07-01

    A 62-year-old white man with a 10-year history of treatment-refractory Sweet's syndrome was admitted to the hospital with the onset of purpuric lesions. Methylprednisolone and infliximab were administered. Our patient developed disseminated Nocardia infection and eventually succumbed. Opportunistic infections such as Nocardia have been associated with infliximab and other tumour necrosis factor (TNF)-α inhibitors. The astute clinician should be aware of the risk of rare opportunistic infections, particularly in patients on TNF-α inhibitors and systemic corticosteroids.

  6. Guidelines for treatment with infliximab for Crohn's disease

    NARCIS (Netherlands)

    Hommes, D. W.; Oldenburg, B.; van Bodegraven, A. A.; van Hogezand, R. A.; de Jong, D. J.; Romberg-Camps, M. J. L.; van der Woude, J.; Dijkstra, G.

    2006-01-01

    Infliximab is an accepted induction and maintenance treatment for patients with Crohn's disease. The effectiveness of infliximab has been demonstrated for both active luminal disease and for enterocutaneous fistulisation. In addition, infliximab can be administered for extraintestinal symptoms of

  7. Guidelines for treatment with infliximab for Crohn's disease.

    NARCIS (Netherlands)

    Hommes, D.W.; Oldenburg, B.; Bodegraven, A.A; Hogezand, R.A. van; Jong, D.J. de; Romberg-Camps, M.; Woude, J. van der; Dijkstra, G.

    2006-01-01

    Infliximab is an accepted induction and maintenance treatment for patients with Crohn's disease. The effectiveness of infliximab has been demonstrated for both active luminal disease and for enterocutaneous fistulisation. In addition, infliximab can be administered for extraintestinal symptoms of

  8. Diverging mechanisms for TNF-alpha receptors in normal mouse brains and in functional recovery after injury: From gene to behavior.

    Science.gov (United States)

    Quintana, Albert; Molinero, Amalia; Florit, Sergi; Manso, Yasmina; Comes, Gemma; Carrasco, Javier; Giralt, Mercedes; Borup, Rehannah; Nielsen, Finn Cilius; Campbell, Iain L; Penkowa, Milena; Hidalgo, Juan

    2007-09-01

    Cytokines, such as tumour necrosis factor (TNF)-alpha and lymphotoxin-alpha, have been described widely to play important roles in the brain in physiologic conditions and after traumatic injury. However, the exact mechanisms involved in their function have not been fully elucidated. We give some insight on their role by using animals lacking either Type 1 receptor (TNFR1KO) or Type 2 (TNFR2KO) and their controls (C57Bl/6). Both TNFR1KO and to a greater extent TNFR2KO mice showed increased exploration/activity neurobehavioral traits in the hole board test, such as rearings, head dippings, and ambulations, compared with wild-type mice, suggesting an inhibitory role of TNFR1/TNFR2 signaling. In contrast, no significant differences were observed in the elevated plus maze test, ruling out a major role of these receptors in the control of anxiety. We next evaluated the response to a freeze injury to the somatosensorial cortex. The effect of the cryolesion on motor function was evaluated with the horizontal ladder beam test, and the results showed that both TNFR1KO and TNFR2KO mice made fewer errors, suggesting a detrimental role for TNFR1/TNFR2 signaling for coping with brain damage. Expression of approximately 22600 genes was analyzed using an Affymetrix chip (MOE430A) at 0 (unlesioned), 1, or 4 days post-lesion in the three strains. The results show a unique and major role of both TNF receptors on the pattern of gene expression elicited by the injury but also in normal conditions, and suggest that blocking of TNFR1/TNFR2 receptors may be beneficial after a traumatic brain injury. (c) 2007 Wiley-Liss, Inc.

  9. Gingival crevicular fluid and serum levels of APRIL, BAFF and TNF-alpha in rheumatoid arthritis and osteoporosis patients with periodontal disease.

    Science.gov (United States)

    Gümüş, Pinar; Buduneli, Eralp; Biyikoğlu, Başak; Aksu, Kenan; Saraç, Fulden; Buduneli, Nurcan; Lappin, David F

    2013-10-01

    This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and compare this to differences between TNF-alpha levels in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy women with periodontal disease (SH). Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. APRIL, BAFF and TNF-α levels were determined by ELISA. Statistical analysis was performed using multivariate analysis, ANOVA and Spearman correlation. Pocket depths differed in site-specific comparisons, but otherwise clinical measurements were similar in the three study groups. Multivariate least squares regression ANOVA adjusted for age and for plaque index indicated that total amounts of TNF-α and concentrations of TNF-α, BAFF and APRIL were significantly greater in the RA patients than in the SH group (p<0.05), and GCF concentrations of BAFF were greater in OPR patients than in SH. Serum TNF-α and BAFF were significantly higher in the RA group compared to SH (p<0.05) and serum TNF-α was greater in RA than in OPR (p<0.05). APRIL and BAFF correlated with RANKL levels in GCF and serum (p<0.05). Despite long-term usage of anti-inflammatory drugs in the RA and OPR patients, increased TNF-family cytokines, might suggest that these patients have a propensity to overproduce these inflammatory mediators but whether this results from greater disease activity or contribute to greater disease activity remains moot. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases

    Science.gov (United States)

    2011-01-01

    Introduction A proportion of patients receiving infliximab have antibodies toward infliximab (ATI), which are associated with increased risk of infusion reaction and reduced response to treatment. We studied the association of infliximab concentration at treatment initiation and development of ATI as well as the association of the presence of ATI and maintenance of infliximab. Methods All patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving infliximab beginning in December 2005 were retrospectively followed until January 2009 or until infliximab discontinuation. Trough serum infliximab and ATI concentrations were measured at each visit. The patients were separated into two groups: ATIpos if ATI were detected at least once during the follow-up period and ATIneg otherwise. Repeated measures analysis of variance was used to study the association of infliximab concentration at treatment initiation and the development of ATI. Maintenance of infliximab in the two groups was studied by using Kaplan-Meier curves. Results We included 108 patients: 17 with RA and 91 with SpA. ATI were detected in 21 patients (19%). The median time to ATI detection after initiation of infliximab was 3.7 months (1.7 to 26.0 months). For both RA and SpA patients, trough infliximab concentration during the initiation period was significantly lower for ATIpos than ATIneg patients. RA patients showed maintenance of infliximab at a median of 19.5 months (5.0 to 31.0 months) and 12.0 months (2.0 to 24.0 months) for ATIneg and ATIpos groups, respectively (P = 0.08). SpA patients showed infliximab maintenance at a median of 16.0 months (3.0 to 34.0 months) and 9.5 months (3.0 to 39.0 months) for ATIneg and ATIpos groups, respectively (P = 0.20). Among SpA patients, those who were being treated concomitantly with methotrexate had a lower risk of developing ATI than patients not taking methotrexate (0 of 14 patients (0%) vs. 25 of 77 patients (32%); P = 0.03). Conclusions High

  11. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems.

    Science.gov (United States)

    Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

    2009-06-26

    Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-alpha in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-alpha and oleic acid treated cells was evaluated using flow cytometry. PPAR-gamma translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-alpha inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-alpha and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Oleic acid was found to

  12. Treatment persistence during therapeutic sequences with adalimumab and infliximab in the treatment of Crohn's disease

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    Carlos Taxonera

    Full Text Available Background and aim: Tumor necrosis factor (TNF inhibitors have demonstrated efficacy and safety in the treatment Crohn's disease (CD. However, the loss of response over time means that they are usually used sequentially. The aim of this study was to compare treatment persistence with different sequences of TNF inhibitors in patients with active luminal CD. Methods: A Markov model (3-month cycles was developed to simulate the therapeutic sequences of beginning biological treatment with infliximab or adalimumab, with a time horizon of three years. Each state of the model represented treatment (induction, standard dose or escalated dose with each TNF inhibitor or the state without biological treatment. The transition probabilities between states were determined by the clinical response to TNF inhibitors obtained from the literature. The likelihood of discontinuation due to adverse effects was also considered. Results: After three years, the percentage of CD patients receiving infliximab and adalimumab as a first TNF inhibitor that remained in treatment was 52.8% and 59.3% (p = 0.1 respectively. Median time to discontinuation of the standard dose was 26.26 months in patients who started with adalimumab and 24.39 months in patients who started with infliximab. Conclusion: In the model, there were no significant differences in persistence after three years with the initial drug among patients with active luminal CD starting treatment with infliximab or adalimumab.

  13. Prospective comparison of preference and efficacy of adalimumab and infliximab for treating ulcerative colitis naive to antitumor necrosis factor therapy.

    Science.gov (United States)

    Mizoshita, Tsutomu; Katano, Takahito; Tanida, Satoshi; Hirano, Atsuyuki; Miyaki, Tomokatsu; Ozeki, Keiji; Suzuki, Yuka; Sugimura, Naomi; Kataoka, Hiromi; Joh, Takashi

    2017-08-01

    There have been few reports on 2 tumor necrosis factor alpha inhibitors, infliximab and adalimumab, with respect to patient preference and efficacy in ulcerative colitis (UC).We used questionnaires to evaluate the preference and reasons for drug choice between infliximab and adalimumab in UC patients naive to antitumor necrosis factor alpha therapy. We also analyzed the efficacy of infliximab and adalimumab prospectively and endoscopically before treatment and at 14 and 54 weeks.Of the 25 UC patients, infliximab and adalimumab were chosen by 10 (40%) and 15 (60%), respectively. Patients who favored infliximab considered "fear of syringes" (7/10, 70%) as the most important influencing factor, whereas patients who favored adalimumab considered "ease of administration" (10/15, 66.7%) and "time required for therapy" (10/15, 66.7%) as the most important factors. There were no statistical differences in remission induction and maintenance between the infliximab and adalimumab groups with regard to response, remission, mucosal healing, steroid-free, and steroid-free remission rates at weeks 14 and 54.The efficacy of adalimumab in remission induction and maintenance was equivalent to that of infliximab in UC patients naive to antitumor necrosis factor alpha therapy in this prospective study, but more patients preferred adalimumab.

  14. Infliximab dosing patterns in a sample of patients with Crohn's disease: results from a medical chart review.

    Science.gov (United States)

    Tkacz, Joseph; Lofland, Jennifer H; Vanderpoel, Julie; Ruetsch, Charles

    2014-04-01

    Infliximab, a monoclonal antibody tumor necrosis factor-alpha inhibitor, is an effective therapy that is indicated for the treatment of patients with Crohn's disease. Although dose escalation from 5 mg/kg to 10 mg/kg is allowed according to the prescribing label of infliximab, conflicting results exist regarding the rate at which this escalation may occur, which may affect payers and providers. The goal of this exploratory study was to characterize and quantify the rate of infliximab dose escalation in a sample of patients with Crohn's disease. Administrative claims data from patients with Crohn's disease in a large mid-Atlantic managed care organization were collected and used to target and recruit providers into a chart review study of infliximab dosing. Data from the charts of 161 patients with Crohn's disease who were receiving infliximab between 2006 and 2010 were extracted. Patients were grouped into an infliximab dose-escalation group or a dose-stable group based on these data. The evidence of any infliximab dose ≥7.5 mg/kg or evidence of a mean maintenance interval of 42 days or less resulted in the placement of a patient in the dose-escalation group, with the balance of patients comprising the stable-dose group. A total of 925 infliximab infusions were captured from 161 patients. Of the 161 patients identified, 110 had at least 4 infusions, and 4 had missing data; therefore, only 106 (66%) patients were qualified for the final infliximab dosing analysis. A total of 18 (17%) of these patients had evidence of infliximab dose escalation (dose-escalation group), and the remaining 88 (83%) patients had a consistent 5-mg/kg dose and schedule (stable-dose group). Of the 18 patients in the dose-escalation group, 9 (50%) had a decrease in maintenance interval, whereas 12 (66.7%) patients had an increase in their dosage. A total of 3 (16.7%) patients had both an increase in dose and a reduction in maintenance interval. Infliximab has been shown to be a cost

  15. Infliximab maintenance therapy for fistulizing Crohn's disease

    NARCIS (Netherlands)

    Sands, Bruce E.; Anderson, Frank H.; Bernstein, Charles N.; Chey, William Y.; Feagan, Brian G.; Fedorak, Richard N.; Kamm, Michael A.; Korzenik, Joshua R.; Lashner, Bret A.; Onken, Jane E.; Rachmilewitz, Daniel; Rutgeerts, Paul; Wild, Gary; Wolf, Douglas C.; Marsters, Paul A.; Travers, Suzanne B.; Blank, Marion A.; van Deventer, Sander J.

    2004-01-01

    Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. We performed a multicenter, double-blind,

  16. Efficacy of adalimumab in sarcoidosis patients who developed intolerance to infliximab.

    Science.gov (United States)

    Crommelin, Heleen A; van der Burg, Leone M; Vorselaars, Adriane D M; Drent, Marjolein; van Moorsel, Coline H M; Rijkers, Ger T; Deneer, Vera H M; Grutters, Jan C

    2016-06-01

    Tumor necrosis factor-alpha (TNF-α) inhibitors are regarded as the third-line therapy in sarcoidosis, the first choice generally being infliximab. To date, data regarding response to adalimumab in sarcoidosis patients intolerant to infliximab are lacking. The objective of this retrospective observational study was to establish if adalimumab could achieve stabilization or improvement of the disease in refractory sarcoidosis patients who developed intolerance to infliximab. Sarcoidosis patients referred to St Antonius Interstitial Lung Diseases Center of Excellence, Nieuwegein, The Netherlands, between January 2008 and April 2015 who switched from infliximab to adalimumab were included. Changes in organ function, inflammatory biomarker levels, and adverse events were retrieved from medical records. Out of 142 infliximab treated patients, 18 (13%) had to discontinue treatment due to antibody formation or severe adverse events and switched to adalimumab therapy. Organ function improved in 7 patients (39%), was stable in 6 patients (33%), and worsened in 5 patients (28%) after 12 months of treatment or after 6 months if evaluation after 12 months was not available (n = 4). In none of the patients biomarker levels of soluble interleukin-2 receptor (sIL-2R) deteriorated. Median decrease in sIL-2R was 3614 pg/mL. Most reported adverse event was infection (n = 10). Adalimumab is an effective alternative for patients intolerant to infliximab. The switch to adalimumab achieved clinical improvement in 39% and stabilization in 33% of patients intolerant to infliximab. Further research is needed to develop guidelines on how to use adalimumab for sarcoidosis in terms of dosing regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Impaired CD40L signaling is a cause of defective IL-12 and TNF-alpha production in Sézary syndrome: circumvention by hexameric soluble CD40L.

    Science.gov (United States)

    French, Lars E; Huard, Bertrand; Wysocka, Maria; Shane, Ryan; Contassot, Emmanuel; Arrighi, Jean-François; Piguet, Vincent; Calderara, Silvio; Rook, Alain H

    2005-01-01

    Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma characterized by peripheral blood involvement, impaired cell-mediated immunity, and T-helper 1 (TH1) cytokine production. To understand the mechanism of these defects, we studied the expression and function of CD40L in peripheral blood mononuclear cells (PBMCs) of patients with SzS. We found that PBMCs of patients with SzS have a defect in interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production upon anti-CD3 stimulation and that tumor CD4+ T lymphocytes have a specific defect in CD40L induction after anti-CD3 ligation in vitro. This defect may explain the poor IL-12 production, because IL-12 production by anti-CD3-stimulated PBMCs was dependent on CD40L in healthy donors. The observed defect in tumor cell CD40L expression appears to be due to inappropriate T-cell signaling upon CD3 ligation, because expression of other T-cell activation antigens such as CD25, and to a lesser extent CD69, are also impaired on tumor cells. Importantly however, the inability of SzS PBMCs to appropriately produce IL-12 and TNF-alpha could be restored by recombinant hexameric CD40L. Taken together, our results demonstrate that impaired IL-12 and TNF-alpha production in SzS is associated with defective CD4+ T lymphocyte CD40L induction and indicate that CD40L may have therapeutic potential in SzS.

  18. Selected immunological changes in patients with Goeckerman's therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University, Hradec Kralove (Czech Republic). Faculty of Medicine

    2006-07-01

    Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation.

  19. Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis

    Directory of Open Access Journals (Sweden)

    Richard Hariman

    2016-01-01

    Full Text Available Eosinophilic fasciitis (EF is a rare disorder involving chronic inflammation of the fascia and connective tissue surrounding muscles, nerves, and blood vessels. While its pathogenesis is not entirely understood, this disorder is thought to be autoimmune or allergic in nature. We present here a case of a 59-year-old male who developed peripheral eosinophilia and subsequent eosinophilic fasciitis during treatment with infliximab. To our knowledge, eosinophilic fasciitis has not been previously described in patients during treatment with an inhibitor of tumor necrosis factor α.

  20. Phosphatidylserine-dependent anti-prothrombin antibodies (aPS/PT) in infliximab-treated patients with inflammatory bowel diseases.

    Science.gov (United States)

    Malíčková, Karin; Ďuricová, Dana; Bortlík, Martin; Janatková, Ivana; Zima, Tomáš; Lukáš, Milan

    2013-04-01

    To (1) examine the occurrence and concentrations of aPS/PT and aPL in inflammatory bowel disease (IBD) patients at the beginning of and during anti-TNF-alpha therapy with infliximab; (2) investigate the link of the aPS/PT and aPL presence with antibodies to infliximab (ATI) formation; and (3) examine possible clinical consequences of aPS/PT and/or aPL positivity in IBD patients. Thirty (30) IBD patients treated with infliximab were analyzed regarding aPS/PT, aPL, and ATI antibody serum levels by standardized ELISAs at treatment weeks 2 (W2) and 14 (W14). At W2, 40 % of infliximab-treated patients had elevated aPS/PT and 16.7 % had elevated aPL serum levels. At W14, the proportion of aPS/PT-positive sera decreased to 16.6 %, whereas aPL distribution remained unchanged. Moreover, concentrations of aPS/PT have shown significant differences at W2 (16.64 [10.06; 33.06] U for IgG and 18.46 [9.18; 32.48] U for IgM) and at W14 (8.24 [2.78; 19.82] U for IgG and 8.57 [5.55; 26.82] U for IgM), p = 0.009 and p = 0.003, respectively. In ATI-positive samples, aPS/PT IgG were more frequent (p = 0.001 for W2 and p = 0.003 for W14), whereas aPS/PT IgM and aPL IgG/IgM did not show such association. Higher concentrations of aPS/PT IgG and IgM were found in IBD patients at the beginning of the biological treatment period compared to the maintenance treatment period. Moreover, aPS/PT IgG were more frequent in ATI-positive individuals, which was not observed in aPL. We speculate that there is a relationship between the aPS/PT and the severity of inflammation and auto-aggressive processes in IBD.

  1. Chemioxyexcitation (delta pO2/ROS)-dependent release of IL-1 beta, IL-6 and TNF-alpha: evidence of cytokines as oxygen-sensitive mediators in the alveolar epithelium.

    Science.gov (United States)

    Haddad, J J; Safieh-Garabedian, B; Saadé, N E; Kanaan, S A; Land, S C

    2001-02-07

    The signalling mechanisms in oxidative stress mediated by cytokines in the perinatal alveolar epithelium are not well known. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the profile of cytokines in response to ascending Deltap O(2)regimen (oxyexcitation). The peak of TNF-alpha (4 h) preceded IL-1beta and IL-6 (6-9 h), indicating a positive feedback autocrine loop confirmed by exogenous rmTNF-alpha. Reactive oxygen species (ROS) induced a dose-dependent release of cytokines, an effect specifically obliterated by selective antioxidants of the hydroxyl radical (*OH) and superoxide anion (O(2)-). Actinomycin and cycloheximide blocked the induced production of cytokines, implicating transcriptional and translational control. Whilst the dismutating enzymes superoxide dismutase (SOD) and catalase were ineffective in reducing ROS-induced cytokines, MnP, a cell-permeating SOD mimetic, abrogated xanthine/xanthine oxidase-dependent cytokine release. Desferrioxamine mesylate, which inhibits the iron-catalysed generation of *OH via the Fenton reaction, exhibited a mild effect on the release of cytokines. Dynamic variation in alveolar p O(2)constitutes a potential signalling mechanism within the perinatal lung allowing upregulation of cytokines in an ROS-dependent manner. Copyright 2001 Academic Press.

  2. Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in pediatric patients treated for psoriasis with the Goeckerman regimen

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University of Prague, Hradec Kralove (Czech Republic). Faculty of Medicine

    2007-11-15

    Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

  3. Disseminated nocardiosis in a patient on infliximab and methylprednisolone for treatment-resistant Sweet′s syndrome

    Directory of Open Access Journals (Sweden)

    Elizabeth R Drone

    2014-01-01

    Full Text Available A 62-year-old white man with a 10-year history of treatment-refractory Sweet′s syndrome was admitted to the hospital with the onset of purpuric lesions. Methylprednisolone and infliximab were administered. Our patient developed disseminated Nocardia infection and eventually succumbed. Opportunistic infections such as Nocardia have been associated with infliximab and other tumour necrosis factor (TNF-α inhibitors. The astute clinician should be aware of the risk of rare opportunistic infections, particularly in patients on TNF-α inhibitors and systemic corticosteroids.

  4. Low Dose Infliximab for Prevention of Postoperative Recurrence of Crohn’s Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab

    Science.gov (United States)

    Sorrentino, Dario; Marino, Marco; Dassopoulos, Themistocles; Zarifi, Dimitra; Del Bianco, Tiziana

    2015-01-01

    Objective In patients with postoperative recurrence of Crohn’s disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses. Design Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn’s Disease Activity Index infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn’s disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy. Results Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively pInfliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects. Conclusions Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment. PMID:26670274

  5. Mucosal healing of Crohn's disease in a patient with concurrent systemic lupus erythematosus using infliximab.

    Science.gov (United States)

    Kagaya, Yuka; Sakamoto, Hirotsugu; Yano, Tomonori; Sunada, Keijiro; Lefor, Alan Kawarai; Niki, Toshiro; Yamamoto, Hironori

    2017-06-01

    We describe a patient with Crohn's disease (CD) concurrent with systemic lupus erythematosus (SLE). Continuous prednisolone and cyclosporine treatment resulted in no recurrent symptoms. However, diarrhea, vomiting, and fever occurred for approximately 3 months. A colonoscopy was then performed, which showed a discontinuous cobblestone appearance and longitudinal ulcers extending from the sigmoid colon to the descending colon and distal ileum. A biopsy revealed a noncaseating granulomatous lesion in the colonic mucosa. These findings led to a diagnosis of CD concurrent with SLE. We first attempted treatment with a full elemental diet, mesalazine, and azathioprine, in that order. However, as there was no improvement in inflammation, we started infliximab, a tumor necrosis factor-alpha inhibitor. Transanal double-balloon enteroscopy performed 4 months after starting infliximab showed mucosal healing, suggesting that infliximab was effective. There are few reports of treating patients with CD concurrent with SLE using a tumor necrosis factor-alpha inhibitor. We report our experience with a patient who had mucosal healing with infliximab and review the literature.

  6. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

    Directory of Open Access Journals (Sweden)

    Natalia P. Machado

    2013-09-01

    Full Text Available OBJECTIVE: We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy. METHODS: A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05. RESULTS: After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%, parasitic (23.5%, fungal (20.6% and viral (8.8% agents. CONCLUSION: The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab.

  7. INFLIXIMAB IN TREATMENT OF REFRACTORY JUVENILE ARTHRITIS

    Directory of Open Access Journals (Sweden)

    I.P. Nikishina

    2010-01-01

    Full Text Available Inclusion to the clinical practice of genetically engineered biological medications opens new opportunities in treatment of juvenile arthritis. The article summarizes an experience of treatment of juvenile arthritis with infliximab in children’s department of Scientific Center of Rheumatology, Russian Academy of Medical Sciences. The analysis included 55 patients (16 children had systemic type, 23 — polyarticular type of juvenile arthritis, and 16 patients had juvenile spondylarthritis, treated with infliximab in 2002–2009 years. Infliximab was administrated in patients with high activity of the disease refractory to the modern basic therapy. Patients received intravenous infliximab 3–5 mg/kg daily according to the standard scheme (on 0, 2, 6 weeks and further every 8 weeks. Therapy with this drug was estimated as effective (improvement on 30% and more according ACRpedi in 80% of patients: 16% achieved ACR30, 29% — ACR50, 26% — ACR70, and 9% — ACR90. Unfavorable effects (infusion reactions were detected in 16% of cases. Infections, including one case of disseminated tuberculosis, developed in 20% of patients. Thus, treatment with infliximab is effective and has good «risk–benefit» ratio in treatment of patients with refractory juvenile arthritis. Key words: children, juvenile arthritis, infliximab, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(1:142-149

  8. A Study Investigating the Association of Dermatological and Infusion Reactions to Infliximab and Infliximab Trough Levels

    Directory of Open Access Journals (Sweden)

    Vivian Wai-Mei Huang

    2015-01-01

    Full Text Available BACKGROUND: Although infliximab is an effective therapy for inflammatory bowel disease (IBD, it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs and infliximab trough levels (ITLs exists.

  9. Comparison of Techniques for Monitoring Infliximab and Antibodies Against Infliximab in Crohn's Disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Ainsworth, Mark A; Tovey, Michael

    2013-01-01

    Several techniques are used to measure infliximab (IFX) and anti-IFX antibodies (Abs) in Crohn's disease. The aim of this study was to compare different assays for this purpose.......Several techniques are used to measure infliximab (IFX) and anti-IFX antibodies (Abs) in Crohn's disease. The aim of this study was to compare different assays for this purpose....

  10. Psoríase moderada a grave tratada com infliximabe em 53 pacientes: perfil dos pacientes, eficácia e efeitos adversos Moderate to severe psoriasis treated with infliximab - 53 patients: patients profile, efficacy and adverse effects

    Directory of Open Access Journals (Sweden)

    Artur Antonio Duarte

    2011-04-01

    TNF-alpha. Infliximab neutralizes the biological activity of TNF-alpha. Adverse reactions that occur during infusion or up to 24 hours afterwards are referred to as acute reactions. Delayed reactions are those occurring between 24 hours and 14 days after an infusion. OBJECTIVE: To evaluate the profile of patients with moderate to severe psoriasis that is resistant to conventional treatment, and to assess adverse reactions to infliximab. METHODS: Fifty-three patients, 40 men and 13 women, were treated with infliximab. The dose used was 5 mg/kg in weeks 0, 2 and 6 (induction phase, followed by maintenance therapy every 8 weeks. RESULTS: Of the 53 patients, 6 participated only in the induction phase. These patients reached Psoriasis Area Severity Index (PASI of 90-100 and opted to discontinue treatment. Forty-seven patients continued therapy with the drug for at least 2-3 years. Of these, 55.3% (n=26 experienced some type of adverse event. Acute adverse events were recorded in 34% of the patients and delayed adverse events in 36.1%. The prevalence of comorbidities was 57.4%. CONCLUSION: In the present study, infliximab was found to constitute a safe and effective form of therapy. Of the comorbidities recorded in the patients in this study, obesity was associated with a delayed and less effective response to treatment. When adequately monitored, neither acute nor delayed adverse events require discontinuation of therapy, since they do not represent an uncontrolled risk to the patient.

  11. Outcomes After Primary Infliximab Treatment Failure in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Buhl, Sine; Steenholdt, Casper; Rasmussen, Maria

    2017-01-01

    primary infliximab treatment failure, the majority of patients (n = 51, 63%) had inflammatory bowel disease-related surgery (Crohn's disease n = 19, 58%; ulcerative colitis n = 32, 67%; P = 0.49). There was a markedly increased risk of surgery in patients with primary infliximab treatment failure...... treated with infliximab as first-line anti-tumor necrosis factor treatment at a tertiary center. Primary infliximab treatment failure was defined as no clinical improvement during infliximab induction therapy resulting in discontinuation of infliximab therapy. RESULTS: A total of 560 patients (Crohn...... as compared to initial responders: odds ratio 6.3 (3.8-10.6), P disease 1 year after primary infliximab treatment failure. CONCLUSIONS: Primary infliximab treatment failure is associated with poor outcome including high risk...

  12. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter

    2010-01-01

    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  13. An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase I clinical trial using a novel oral anti-TNF alpha-based therapy.

    Science.gov (United States)

    Almon, Einat; Khoury, Tawfik; Drori, Ariel; Gingis-Velitski, Svetlana; Alon, Sari; Chertkoff, Raul; Mushkat, Mordechai; Shaaltiel, Yoseph; Ilan, Yaron

    2017-07-01

    An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants. Subjects were followed for safety parameters and for an effect on T lymphocytes subsets and cytokine levels. An oral administration of PRX-106 was safe and well tolerated. The PK study showed that PRX106 is not absorbed. No effect on white blood cells and lymphocytes counts were noted. A dose dependent effect was noted on systemic lymphocytes. The oral administration of all three dosages was associated with an increase in CD4+CD25+ and CD8+CD25+ subset of suppressor lymphocytes. A marked increase in CD4+CD25+FoxP3 regulatory T cells was noted in the 8mg treated group. In addition, NKT regulatory cells, CD3+CD69+ and CD4+CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed. An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation. The PRX-106 may provide a safe orally administered effective anti-TNF alpha-based immune therapy for inflammatory bowel diseases and non-alcoholic steatohepatitis, as well as other autoimmune, TNF-mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

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    John S Cho

    2009-09-01

    Full Text Available The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

  15. Inhibitors

    Science.gov (United States)

    ... Icon View public health webinars on blood disorders Inhibitors Language: English (US) Español (Spanish) Recommend on Facebook ... because treatment of bleeds becomes less effective. About Inhibitors People with hemophilia, and many with VWD type ...

  16. Biosimilar infliximab use in paediatric IBD.

    Science.gov (United States)

    Richmond, Lisa; Curtis, Lee; Garrick, Victoria; Rogers, Pam; Wilson, Michelle; Tayler, Rachel; Henderson, Paul; Hansen, Richard; Wilson, David C; Russell, Richard K

    2018-01-01

    Biosimilar infliximab became available in the UK in 2015. Paediatric experience to date on its use is limited. We prospectively evaluated the safety and efficacy of biosimilar infliximab (Remsima) in two paediatric gastroenterology networks in patients with inflammatory bowel disease. Prospective clinical data were collected from laboratory reports, electronic patient records and case notes of 40 patients starting Remsima for the first time. Disease activity scores together with blood and stool biomarkers were used to assess response. Our data set highlights that Remsima was associated with a significant clinical and biochemical improvement (pinfliximab is as effective as originator infliximab and its use is associated with significant cost savings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Enhanced CCR9 expression levels in psoriatic skin are associated with poor clinical outcome to infliximab treatment.

    Science.gov (United States)

    Koga, Aiko; Kajihara, Ikko; Yamada, Saori; Makino, Katsunari; Ichihara, Asako; Aoi, Jun; Makino, Takamitsu; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu

    2016-05-01

    Infliximab is an anti-tumor necrosis factor (TNF)-α antibody drug that suppresses TNF-α and its associated inflammatory responses. Although infliximab therapy generally results in a 75% or greater improvement in the Psoriasis Area and Severity Index from baseline in psoriasis patients, there is the heterogeneity of therapeutic efficacy in psoriasis patients among patients of a similar PASI baseline score. However, there are few published reports about the predictors of the clinical response among psoriasis patients who undergo biologic therapies. We thus evaluated the possible existence of biologic markers that would indicate poor prognosis of infliximab using skin biopsy specimens. This was because we assumed that the inhibitors for upregulated chemokine/chemokine receptors in non-responders may have the ability to reduce the occurrence of psoriatic eruptions. PCR array analyses identified that the levels of various chemokines and chemokine receptors were increased in non-responders in comparison to responders. Immunohistochemical analyses revealed that upregulation of the CCR9 protein levels was not associated with the pretherapeutic PASI score, but with poor response to infliximab. Our results indicated that the expression levels of CCR9 in lesional skin may be a useful biologic marker of the clinical efficacy of infliximab therapy in psoriasis patients. © 2015 Japanese Dermatological Association.

  18. Remission induction by Raising the dose of Remicade in RA (RRRR study: Rationale and study protocol for a randomized controlled trial comparing for sustained clinical remission after discontinuation of infliximab in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Koji Oba

    2017-12-01

    Full Text Available Infliximab, an inhibitor of TNF-α, is one of the most widely used biological disease-modifying antirheumatic drugs. Recent studies indicated that baseline serum TNF-α could be considered as a key indicator for optimal dosing of infliximab for RA treatment to achieve the clinical response and its sustained remission. The Remission induction by Raising the dose of Remicade in RA (RRRR study is an open-label, parallel group, multicenter randomized controlled trial to compare the proportions of clinical remission based on the simplified disease activity index (SDAI after 1 year of treatment and its sustained remission rate after another 1 year between the investigational treatment strategy (for which the dose of infliximab was chosen based on the baseline serum TNF and the standard strategy of 3 mg/kg per 8 weeks of infliximab administration in infliximab-naïve patients with RA showing an inadequate response to MTX. The primary endpoint is the proportion of patients who kept discontinuation of infliximab 1 year after discontinued infliximab at the time of 54 weeks after the first administration of infliximab. The secondary endpoints are the proportion of clinical remission based on SDAI and changes in SDAI from baseline at each time point, other clinical parameters, quality of life measures and adverse events. Target sample size of randomized patients is 400 patients in total. The main results of the RRRR study are expected to be published at the end of 2017.

  19. Infliximab in Russian clinical practice

    Directory of Open Access Journals (Sweden)

    G V Lukina

    2012-01-01

    Full Text Available The study of infliximab began (INF in Russia in 2001. It was the first genetically engineered biological agent (GEBA registered in our country to treat patients with rheumatoid arthritis (RA. With the advent of infliximab, a Russian biological rheumatoid arthritis therapy registry started its work. In October 2005, it was set up on the basis of GEBA centers founded in the leading rheumatology clinics of Russia. Objective: to generalize the Russian experience in using INF (its efficacy, tolerance, and side effects in patients with RA in real clinical practice within the framework of a multicenter observational study. Subjects and methods. The register included patients with a valid diagnosis of RA in whom INF treatment was first started. The main indication for this was previous basic therapy failure. This investigation analyzed 396 patients receiving INF therapy. Prior to INF administration, all the patients were examined to identify whether they had possible latent tuberculosis, by applying chest X-ray study and Mantoux test. The European League Against Rheumatism criteria were used to evaluate the efficiency of INF therapy. The relationship between the therapeutic effects of the drug and its cumulative dose was specially used. The trend in X-ray progression was estimated using the Sharp method modified by van der Heijde. INF was given in a dose of 3 mg/kg by the classical regimen: at 0, 2, and 6 weeks, then every 8 weeks. The main assessment periods were at 22 and 46—54 weeks. Results. Analysis of the data of real clinical practice in Russia demonstrates that the use of INF in RA patients with the inadequate effect of traditional disease-modifying antirheumatic drugs (DMARDs is able to cause a rapid and pronounced reduction in disease activity. There is significant evidence that the IFN-treated patients with RA had also suppressed bone destruction. INF treatment for early RA gives rise to remissions more frequently in the early stage of

  20. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial.

    Science.gov (United States)

    Jørgensen, Kristin K; Olsen, Inge C; Goll, Guro L; Lorentzen, Merete; Bolstad, Nils; Haavardsholm, Espen A; Lundin, Knut E A; Mørk, Cato; Jahnsen, Jørgen; Kvien, Tore K

    2017-06-10

    TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up. Adult patients on stable treatment with infliximab originator treated in a hospital setting for at least 6 months were eligible for participation. Patients with informed consent were randomised in a 1:1 ratio to either continued infliximab originator or to switch to CT-P13 treatment, with unchanged dosing regimen. Data were collected at infusion visits in 40 Norwegian study centres. Patients, assessors, and patient care providers were masked to treatment allocation. The primary endpoint was disease worsening during 52-week follow-up. 394 patients in the primary per-protocol set were needed to show a non-inferiority margin of 15%, assuming 30% disease worsening in each group. This trial is registered with ClinicalTrials.gov, number NCT02148640. Between Oct 24, 2014, and July 8, 2015, 482 patients were enrolled and randomised (241 to infliximab originator, 241 to CT-P13 group; one patient was excluded from the full analysis and safety set for CT-P13) and 408 were included in the per-protocol set (202 in the infliximab originator group and 206 in the CT-P13 group). 155 (32%) patients in the full analysis set had Crohn's disease, 93 (19%) had ulcerative colitis, 91 (19%) had spondyloarthritis, 77 (16%) had rheumatoid arthritis, 30 (6%) had psoriatic arthritis, and 35 (7%) had chronic plaque psoriasis. Disease worsening occurred in 53 (26%) patients in the infliximab originator group and 61 (30%) patients in the CT-P13 group (per-protocol set; adjusted treatment difference -4·4%, 95% CI -12·7 to 3·9). The

  1. Clonorchis sinensis excretory/secretory products promote the secretion of TNF-alpha in the mouse intrahepatic biliary epithelial cells via Toll-like receptor 4.

    Science.gov (United States)

    Yan, Chao; Wang, Yan-Hong; Yu, Qian; Cheng, Xiao-Dan; Zhang, Bei-Bei; Li, Bo; Zhang, Bo; Tang, Ren-Xian; Zheng, Kui-Yang

    2015-10-24

    Toll-like receptor 4 (TLR4), as one of the most important pathogen pattern recognitions (PPRs) plays a central role in elicitation of innate immunity and mediation of adaptive responses against foreign antigens. However, little is known of the roles of TLR4 in the immune responses of biliary epithelial cells (BECs) induced by Clonorchis sinensis, a parasite of significance in human health. In the present study, the primary mouse intrahepatic biliary epithelial cells (MIBECs) were pre-treated with TLR4 inhibitor peptide or control peptide and then stimulated by excretory/secretory products (ESP) of C. sinensis, respectively. The expressions of TLR4 and relative cytokines were determined using western blot and a bead-based analytic detection system, respectively. The results showed that ESP of C. sinensis significantly increased the expression of TLR4 which promoted the expression of MyD88 and NF-κB in BECs; the levels of TNF-α but not IL-6 from MIBECs stimulated by ESP alone were also considerably increased, compared with the group of the medium stimulated. However, the concentration of TNF-α was significantly decreased when MIBECs were pre-treated with TLR4 inhibitor. In addition, ESP could depress the level of IL-6 in MIBECs which was elevated by LPS. Our data for the first time demonstrate that ESP of C. sinensis can potently induce secretion of pro-inflammatory cytokines via TLR4 in MIBECs, which suggests that TLR4 plays an important role in host defenses against C. sinensis and the pathogenesis of clonorchiasis.

  2. Infliximab eye drops treatment in corneal neovascularization.

    Science.gov (United States)

    Voiculescu, O B; Voinea, L M

    2015-01-01

    Corneal neovascularization is a serious condition that may arise secondary to chemical burns, ischemia, infection, trauma, and inflammation and represents a major cause of blindness. This study investigated the efficacy of topical application of infliximab [tumor necrosis factor-a (TNF-a) monoclonal antibody] in the treatment of corneal neovascularization in the rabbit model.

  3. Infliximab-Related Infusion Reactions: Systematic Review

    Science.gov (United States)

    Ron, Yulia; Kivity, Shmuel; Ben-Horin, Shomron; Israeli, Eran; Fraser, Gerald M.; Dotan, Iris; Chowers, Yehuda; Confino-Cohen, Ronit; Weiss, Batia

    2015-01-01

    Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms. PMID:26092578

  4. Infliximab for the treatment of ulcerative colitis

    NARCIS (Netherlands)

    Eshuis, Emma J.; Bemelman, Willem A.; Stokkers, Pieter C. F.

    2009-01-01

    Infliximab (IFX), an anti-TNF biologic agent, has been demonstrated to offer benefits for the treatment of autoimmune disorders, such as rheumatoid arthritis and Crohn's disease. Several trials have also investigated the efficacy of IFX for the treatment of ulcerative colitis (UC). IFX was found to

  5. Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Wolbink, G. J.; Voskuyl, A. E.; Lems, W. F.; de Groot, E.; Nurmohamed, M. T.; Tak, P. P.; Dijkmans, B. A. C.; Aarden, L.

    2005-01-01

    Objective: To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). Methods: Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab

  6. Antibodies to Infliximab Are Associated with Lower Infliximab Levels and Increased Likelihood of Surgery in Pediatric IBD

    Science.gov (United States)

    Zitomersky, Naamah L.; Atkinson, Benjamin J.; Fournier, Kerri; Mitchell, Paul D.; Stern, Julia Bender; Butler, Michael C.; Ashworth, Lori; Hauenstein, Scott; Heiner, Linda; Chuang, Emil; Singh, Sharat; Bousvaros, Athos

    2017-01-01

    Background Adult studies suggest antibodies to infliximab (ATI) correlate with loss of response in inflammatory bowel disease but pediatric data are limited. Methods We conducted a cross-sectional study of trough infliximab levels and ATI in 134 pediatric and young adult patients receiving infliximab. At the time serum was obtained demographics, disease phenotype, duration of infliximab therapy, use of combination therapy (methotrexate or 6-mercaptopurine with infliximab), and surgery were recorded. Results Assays were performed on 134 subjects currently receiving infliximab (85 male; mean age, 17.3 ± 4.3 years; 114 Crohn’s disease and 20 ulcerative colitis). Infliximab use ranged from 12 days to 12 years: median 2.0 (interquartile range [1.1–4.3]) years. Twenty-seven of 134 (20%) patients had ATI ≥5 U/mL. Of patients with ATI ≥5 U/mL, 59% had infliximab levels infliximab infusions. Sixty percent who underwent surgery had ATI ≥12 U/mL; in contrast, only 8% of patients who did not undergo surgery had ATI ≥12 U/mL (P = 0.01). At the time of serum sampling, 50 (37%) patients were receiving combination therapy, compared with 84 (63%) on infliximab alone. Combination therapy at the time of serum sampling did not correlate with either increase infliximab levels or lower ATI compared with infliximab monotherapy. However, prior immunomodulator use was associated with lower antibody levels (P = 0.007). Conclusions ATI correlates with reduction in infliximab level and a higher risk of surgery in patients with inflammatory bowel disease. PMID:25569737

  7. The first trimester human trophoblast cell line ACH-3P: a novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations--TNF-alpha stimulates MMP15 expression.

    Science.gov (United States)

    Hiden, Ursula; Wadsack, Christian; Prutsch, Nicole; Gauster, Martin; Weiss, Ursula; Frank, Hans-Georg; Schmitz, Ulrike; Fast-Hirsch, Christa; Hengstschläger, Markus; Pötgens, Andy; Rüben, Angela; Knöfler, Martin; Haslinger, Peter; Huppertz, Berthold; Bilban, Martin; Kaufmann, Peter; Desoye, Gernot

    2007-12-19

    The trophoblast compartment of the placenta comprises various subpopulations with distinct functions. They interact among each other by secreted signals thus forming autocrine or paracrine regulatory loops. We established a first trimester trophoblast cell line (ACH-3P) by fusion of primary human first trimester trophoblasts (week 12 of gestation) with a human choriocarcinoma cell line (AC1-1). Expression of trophoblast markers (cytokeratin-7, integrins, matrix metalloproteinases), invasion abilities and transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology, cytogenetics and doubling time was similar to the parental AC1-1 cells. The different subpopulations of trophoblasts e.g., villous and extravillous trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger expression of extravillous trophoblast markers. Higher expression of insulin-like growth factor II receptor and human chorionic gonadotropin represents the basis for the known autocrine stimulation of extravillous trophoblasts. We conclude that ACH-3P represent a tool to investigate interaction of syngeneic trophoblast subpopulations. These cells are particularly suited for studies into autocrine and paracrine regulation of various aspects of trophoblast function. As an example a novel effect of TNF-alpha on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.

  8. A Novel Strategy for TNF-Alpha Production by 2-APB Induced Downregulated SOCE and Upregulated HSP70 in O. tsutsugamushi-Infected Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Ching-Ying Wu

    Full Text Available Orientia (O. tsutsugamushi-induced scrub typhus is endemic across many regions of Asia and the Western Pacific, where an estimated 1 million cases occur each year; the majority of patients infected with O. tsutsugamushi end up with a cytokine storm from a severe inflammatory response. Previous reports have indicated that blocking tumor necrosis factor (TNF-α reduced cell injury from a cytokine storm. Since TNF-α production is known to be associated with intracellular Ca2+ elevation, we examined the effect of store-operated Ca2+ entry (SOCE inhibitors on TNF-α production in O. tsutsugamushi-infected macrophages. We found that 2-aminoethoxydiphenyl borate (2-APB, but not SKF96365, facilitates the suppression of Ca2+ mobilization via the interruption of Orai1 expression in O. tsutsugamushi-infected macrophages. Due to the decrease of Ca2+ elevation, the expression of TNF-α and its release from macrophages was repressed by 2-APB. In addition, a novel role of 2-APB was found in macrophages that causes the upregulation of heat shock protein 70 (HSP70 expression associated with ERK activation; upregulated TNF-α production in the case of knockdown HSP70 was inhibited with 2-APB treatment. Furthermore, elevated HSP70 formation unexpectedly did not help the cell survival of O. tsutsugamushi-infected macrophages. In conclusion, the parallelism between downregulated Ca2+ mobilization via SOCE and upregulated HSP70 after treatment with 2-APB against TNF-α production was found to efficiently attenuate an O. tsutsugamushi-induced severe inflammatory response.

  9. Does smoking reduce infliximab's effectiveness against Crohn's disease?

    Science.gov (United States)

    Narula, Neeraj; Fedorak, Richard N

    2009-02-01

    Crohn's disease (CD) is an idiopathic inflammatory bowel disease and has no known cure. CD symptoms are treated using an array of medicines, including biological agents such as infliximab. However, infliximab therapy is expensive; therefore, identifying variables that can help predict response to infliximab is worthwhile. The present article reviews the impact of tobacco smoking on the efficacy of infliximab in CD. Earlier studies have speculated that smoking has a negative effect on the response to infliximab in CD, but the current literature is largely unable to identify a significant relationship between the two. Although smoking is known to have a negative effect on the course of CD, as well as other organ systems, presently, a CD patient's smoking status should not influence treatment decisions regarding infliximab therapy.

  10. TNF-alpha promotes lymphangiogenesis and lymphatic metastasis of gallbladder cancer through the ERK1/2/AP-1/VEGF-D pathway

    International Nuclear Information System (INIS)

    Hong, HaiJie; Jiang, Lei; Lin, YanFei; He, CaiLong; Zhu, GuangWei; Du, Qiang; Wang, XiaoQian; She, FeiFei; Chen, YanLing

    2016-01-01

    Tumor necrosis factor-alpha (TNF-α), a key player in cancer-related inflammation, was recently demonstrated to be involved in the lymphatic metastasis of gallbladder cancer (GBC). Vascular endothelial growth factor D (VEGF-D) is a key lymphangiogenic factor that is associated with lymphangiogenesis and lymph node metastasis in GBC. However, whether VEGF-D is involved in TNF-α-induced lymphatic metastasis of GBC remains undetermined. The expression of VEGF-D in patient specimens was detected by immunohistochemistry and the relationship between VEGF-D in the tissue and TNF-α in the bile of the matching patients was analyzed. The VEGF-D mRNA and protein levels after treatment with exogenous TNF-α in NOZ, GBC-SD and SGC-996 cell lines were measured by real-time PCR and ELISA. The promoter activity and transcriptional regulation of VEGF-D were analyzed with the relative luciferase reporter assay, mutant constructs, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, RNA interference and Western blotting. Inhibitors of JNK, p38 MAPK and ERK1/2 were used to explore the upstream signaling effector of AP-1. We used lentiviral vector expressing a VEGF-D shRNA construct to knockdown VEGF-D gene in NOZ and GBC-SD cells. The role of the TNF-α-VEGF-D axis in the tube formation of human dermal lymphatic endothelial cells (HDLECs) was determined using a three-dimensional coculture system. The role of the TNF-α - VEGF-D axis in lymphangiogenesis and lymph node metastasis was studied via animal experiment. TNF-α levels in the bile of GBC patients were positively correlated with VEGF-D expression in the clinical specimens. TNF-α can upregulate the protein expression and promoter activity of VEGF-D through the ERK1/2 - AP-1 pathway. Moreover, TNF-α can promote tube formation of HDLECs, lymphangiogenesis and lymph node metastasis of GBC by upregulation of VEGF-D in vitro and in vivo. Taken together, our data suggest that TNF-α can promote

  11. A study investigating the association of dermatological and infusion reactions to infliximab and infliximab trough levels.

    Science.gov (United States)

    Huang, Vivian; Dhami, Neil; Fedorak, Darryl; Prosser, Connie; Shalapay, Carol; Kroeker, Karen I; Halloran, Brendan P; Dieleman, Levinus A; Fedorak, Richard N

    2015-01-01

    Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists. To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab. Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients' records were reviewed for dermatological and infusion reactions to infliximab. One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg⁄mL [interquartile range (IQR) 2.0 μg⁄mL to 13.3 μg⁄mL] versus 6.6 μg⁄mL [IQR 3.2 μg⁄mL to 12.7 μg⁄mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg⁄mL [IQR 0.1 μg⁄mL to 5.7 μg⁄mL]) was lower than that of patients who experienced no such AEs (6.6 μg⁄mL [IQR 3.2 μg⁄mL to 12.7 μg⁄mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg⁄mL [IQR 8.8 μg⁄mL to 17.4 μg⁄mL]; P<0.001). One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events.

  12. Effectiveness of infliximab after adalimumab failure in Crohn's disease.

    Science.gov (United States)

    Chaparro, María; Andreu, Montserrat; Barreiro-de Acosta, Manuel; García-Planella, Esther; Ricart, Elena; Domènech, Eugeni; Esteve, María; Merino, Olga; Nos, Pilar; Peñalva, Mireia; Gisbert, Javier P

    2012-10-07

    To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure. A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

  13. Treatment of psoriasis: focus on clinic-based management with infliximab.

    Science.gov (United States)

    de Eusebio, Esther; Armario-Hita, José Carlos; de Miquel, Víctor Alegre

    2014-02-01

    Psoriasis is a disabling chronic inflammatory condition of the skin and joints that typically requires long-term treatment. Recommended treatments for psoriasis include a wide range of topical and systemic options, from topical agents and targeted phototherapy for mild psoriasis to traditional systemic agents such as methotrexate, cyclosporine and acitretin for more serious disease. The introduction of targeted biological agents such as T-cell-modulating agents, tumor necrosis factor α (TNFα) antagonists and interleukin (IL)-12 and IL-23 inhibitors has provided new choices for the management of psoriasis and psoriatic arthritis that may offer better long-term efficacy and tolerability than traditional approaches. Most biological agents are administered by subcutaneous injection. Infliximab, a TNFα antagonist, is the only biological agent approved for psoriasis that is administered by intravenous infusion, in the setting of hospital-based or specialized infusion center-based clinics. Infliximab allows weight-based dosing and may offer more rapid disease control than other biological agents, with significant improvements seen as early as 1 week after treatment initiation. This article gives an overview of psoriasis management, focusing on clinic-based infusion therapy with infliximab.

  14. A study investigating the association of dermatological and infusion reactions to infliximab and infliximab trough levels

    Science.gov (United States)

    Huang, Vivian Wai-Mei; Dhami, Neil; Fedorak, Darryl; Prosser, Connie; Shalapay, Carol; Kroeker, Karen Ivy; Halloran, Brendan Phillip; Dieleman, Levinus Albert; Fedorak, Richard Neil

    2015-01-01

    BACKGROUND: Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists. OBJECTIVES: To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab. METHODS: Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients’ records were reviewed for dermatological and infusion reactions to infliximab. RESULTS: One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg/mL [interquartile range (IQR) 2.0 μg/mL to 13.3 μg/mL] versus 6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg/mL [IQR 0.1 μg/mL to 5.7 μg/mL]) was lower than that of patients who experienced no such AEs (6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg/mL [IQR 8.8 μg/mL to 17.4 μg/mL]; Pinfliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events. PMID:25706572

  15. Infliximab-induced autoantibodies: a multicenter study.

    Science.gov (United States)

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  16. [Gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukins 2, 4 and 6 (IL-2, IL-4, IL-6) in cervical-uterine cells of intraepithelial neoplasia: a preliminary report].

    Science.gov (United States)

    Pardo-Govea, Tatiana; Callejas, Diana; Núñez-Troconis, José; Araujo, Mary; Costa, Luciana; Pons, Héctor; Delgado, Mariela; Monsalve, Francisca

    2005-03-01

    The purpose of this work was to determine the expression of type Th1 cytokines: IL-2 and IFNgamma, and Th2: IL-4 and IL-6, as well as TNF-alpha in patients with precancerous lesions of the uterine cervix and their relationship with the human papiloma virus (HPV). 30 patients with precancerous lesions (NIC 1: 70%, NIC 2: 16.7% and NIC 3: 1.3%) and 9 normal controls were studied. A clinical history, gynecological evaluation, cytology and an uterine biopsy were carried out in each patient and control. PCR was used for the diagnosis of HPV. IFN-gamma expression (positive cells/field) was increased in patients with NIC (5.06 +/- 4.7 vs 0 in the control group; p < 0.05). TNFa was a little higher in pathologycal tissues than in the controls (5.23 +/- 3.63 vs 1.55 +/- 2.65; p < 0.05). IL-2 was higher in pathologycal cases than in the controls (8.73 +/- 5.23 vs 0.33 +/- 1, p < 0.05). IL-4 were expressed in both, patients and controls (6.53 +/- 5.23 vs 5.77 +/- 7.32). IL-6 was also higher in patients (4.63 +/- 3.34 vs 0.77 +/- 2.33; p < 0.05). When the HPV status was considered, only IFN-gamma (p < 0.05) and IL-2 (p < 0.05) were significantly higher in HPV positive patients (n = 4) compared to controls. When HPV+ patients were compared with HPV- patients, only IFNgamma was significant (11.5 +/- 5 vs 4.07 +/- 3.8; p < 0.05). In conclusion, Type Th1 immune response prevails in patients with precancerous lesions, whether they are HPV positive or not.

  17. Good response to infliximab in rheumatoid arthritis following failure of interleukin-1 receptor antagonist.

    Science.gov (United States)

    Bao, Jun; Yue, Tao; Li, Ting; He, Dong-Yi; Bao, Yi-Xiao

    2016-04-01

    To evaluate the efficacy of tumor necrosis factor inhibitor infliximab in patients with rheumatoid arthritis (RA) who were disease-resistant to recombinant human interleukin-1 receptor antagonist (IL-1Ra). A total of 104 patients with active RA despite methotrexate (MTX) treatment were enrolled in the open trial. Among them, 27 IL-1Ra nonresponders 'Switchers' and 51 biologic-naive patients 'Naivers' received an infusion of 3 mg/kg infliximab at weeks 0, 2, 6 and 14, combined with concurrent MTX therapy, while the other 26 patients who had never received any biologics 'Controls' continued MTX monotherapy. Clinical outcomes and safety were assessed at weeks 0, 2 and every 4 weeks thereafter for 18 weeks with the American College of Rheumatology (ACR) core set criteria, the Disease Activity Score in 28 joints, and records of adverse events (AEs) and abnormal laboratory findings. At week 18, an ACR20 response was achieved in 56% of Switchers and 61% of Naivers, compared with 23% of Controls (P = 0.0013 and 0.0126, respectively). Compared with Controls, both Switchers and Naivers achieved a significant improvement in tender-joint count, swollen-joint count, patient's assessment of pain, patient's and physician's global assessment of disease activity, erythrocyte sedimentation rate and C-reactive protein. Switchers even achieved a greater benefit from health assessment questionnaire (HAQ) scores than Naivers. Infliximab was well tolerated, with a similar incidence of AEs across all study groups. Switching from IL-1Ra to infliximab is effective in improving disease activity and maintaining joint function. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  18. Engineering N-terminal domain of tissue inhibitor of metalloproteinase (TIMP)-3 to be a better inhibitor against tumour necrosis factor-alpha-converting enzyme.

    Science.gov (United States)

    Lee, Meng-Huee; Verma, Vandana; Maskos, Klaus; Nath, Deepa; Knäuper, Vera; Dodds, Philippa; Amour, Augustin; Murphy, Gillian

    2002-01-01

    We previously reported that full-length tissue inhibitor of metalloproteinase-3 (TIMP-3) and its N-terminal domain form (N-TIMP-3) displayed equal binding affinity for tissue necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE). Based on the computer graphic of TACE docked with a TIMP-3 model, we created a number of N-TIMP-3 mutants that showed significant improvement in TACE inhibition. Our strategy was to select those N-TIMP-3 residues that were believed to be in actual contact with the active-site pockets of TACE and mutate them to amino acids of a better-fitting nature. The activities of these mutants were examined by measuring their binding affinities (K(app)(i)) and association rates (k(on)) against TACE. Nearly all mutants at position Thr-2 exhibited slightly impaired affinity as well as association rate constants. On the other hand, some Ser-4 mutants displayed a remarkable increase in their binding tightness with TACE. In fact, the binding affinities of several mutants were less than 60 pM, beyond the sensitivity limits of fluorimetric assays. Further studies on cell-based processing of pro-TNF-alpha demonstrated that wild-type N-TIMP-3 and one of its tight-binding mutants, Ser-4Met, were capable of inhibiting the proteolytic shedding of TNF-alpha. Furthermore, the Ser-4Met mutant was also significantly more active (P<0.05) than the wild-type N-TIMP-3 in its cellular inhibition. Comparison of N-TIMP-3 and full-length TIMP-3 revealed that, despite their identical TACE-interaction kinetics, the latter was nearly 10 times more efficient in the inhibition of TNF-alpha shedding, with concomitant implications for the importance of the TIMP-3 C-terminal domain in vivo. PMID:11988096

  19. Infliximab stability after reconstitution, dilution, and storage under refrigeration.

    Science.gov (United States)

    Beer, Paul M; Wong, Susan J; Schartman, Jerome P; Kulas, Karen E; Hartman, Coby L; Giganti, Monica; Falk, Naomi S

    2010-01-01

    The purpose of this study was to investigate the stability of reconstituted infliximab solutions and determine whether infliximab is suitable for compounding for potential intravitreal use. Infliximab was reconstituted, and the solution was aliquoted and stored refrigerated. On each day of testing, an aliquot was serially diluted to concentrations ranging from 50,000 pg/mL to 69 pg/mL. Each dilution was assayed by microsphere immunoassay daily for 5 days and weekly for a total of 6 weeks. The outcome measure was median fluorescence intensity measured by dual laser flow analysis of fluorochrome-labeled secondary antibodies to infliximab bound to tumor necrosis factor-alpha-coated microspheres. There was an increasing median fluorescence intensity for increasing infliximab concentration in a sigmoidal dose-response curve with a variable slope that was equivalent for each time point. Each respective concentration of infliximab showed nearly equivalent median fluorescence intensity for every time point over the 6-week period. The authors found that the immunoreactivity of 2 different concentrations of infliximab stored at 4 degrees C over a 6-week period remained stable. Infliximab is suitable for compounding and could be a cost-effective intravitreal medication for use in clinical practice if further study supports its safety and efficacy.

  20. Infliximab (Remicade), a new biological treatment for Crohn's disease

    NARCIS (Netherlands)

    D'Haens, G. R.

    1999-01-01

    Tumour necrosis factor plays a pivotal role in Crohn's disease intestinal inflammation. Blocking this cytokine by means of the chimeric monoclonal antibody infliximab has led to a rapid reduction in mucosal inflammation. More than 65% of refractory Crohn's disease patients treated with infliximab

  1. Extensive preclinical evaluation of an infliximab biosimilar candidate.

    Science.gov (United States)

    Velasco-Velázquez, M A; Salinas-Jazmín, N; Hisaki-Itaya, E; Cobos-Puc, L; Xolalpa, W; González, G; Tenorio-Calvo, A; Piña-Lara, N; Juárez-Bayardo, L C; Flores-Ortiz, L F; Medina-Rivero, E; Pérez, N O; Pérez-Tapia, S M

    2017-05-01

    Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis

    Science.gov (United States)

    Ternant, David; Ducourau, Emilie; Perdriger, Aleth; Corondan, Anca; Le Goff, Benoît; Devauchelle-Pensec, Valérie; Solau-Gervais, Elisabeth; Watier, Hervé; Goupille, Philippe; Paintaud, Gilles; Mulleman, Denis

    2014-01-01

    Aims Infliximab, an anti-tumour necrosis factor-α monoclonal antibody, is indicated in rheumatoid arthritis (RA). Our objective was to evaluate the influence of the sources of infliximab pharmacokinetic variability in RA. Methods Eighty-four patients treated with infliximab for RA were included in a prospective noncomparative study. They were analysed between two consecutive infliximab infusions. Infliximab concentrations were measured before the infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next infusion. Infliximab concentrations were described using a two-compartment population pharmacokinetic model. Results The mean (interindividual standard deviation) estimated central volume of distribution was 2.3 l (36%) and systemic clearance was 0.019 l h−1 (37%). The central volume of distribution increased with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance increased with pre-infusion C-reactive protein concentration by 20%, varying from 3 to 14 mg l−1, and was decreased by 30% when methotrexate was coadministered. Conclusions The influence of methotrexate and inflammation on infliximab clearance suggests that individual adjustment of infliximab doses according to disease activity may be useful in RA. PMID:24354889

  3. Infusion reactions during infliximab treatment are not associated with IgE anti-infliximab antibodies

    NARCIS (Netherlands)

    van Schie, Karin A.; Ooijevaar-de Heer, Pleuni; Kruithof, Simone; Plasencia, Chamaida; Jurado, Teresa; Pascual Salcedo, Dora; Brandse, Johannan F.; D'Haens, Geert Ram; Wolbink, Gerrit Jan; Rispens, Theo

    2017-01-01

    Controversy exists on the role of IgE antidrug antibodies (IgE-ADA) in infusion reactions (IR) on infliximab treatment, partly due to the lack of a positive control used for assay validation. We sought to (1) develop a robust assay to measure IgE-ADA, including a positive control, (2) determine the

  4. Effects of infliximab retreatment after consecutive discontinuation of infliximab and adalimumab in refractory Crohn's disease

    NARCIS (Netherlands)

    Brandse, Johannan F.; Peters, Charlotte P.; Gecse, Krisztina B.; Eshuis, Emma J.; Jansen, Jeroen M.; Tuynman, Hans A.; Löwenberg, Mark; Ponsioen, Cyriel Y.; van den Brink, Gijs R.; Dʼhaens, Geert R.

    2014-01-01

    Switches between anti-tumor necrosis factor agents in the treatment of Crohn's disease (CD) occur in case of treatment failure, intolerance, or patient preference. No data are currently available on the usefulness of a second infliximab treatment after earlier discontinuation and previous switch to

  5. Infusion reactions during infliximab treatment are not associated with IgE anti-infliximab antibodies.

    Science.gov (United States)

    van Schie, Karin A; Ooijevaar-De Heer, Pleuni; Kruithof, Simone; Plasencia, Chamaida; Jurado, Teresa; Pascual Salcedo, Dora; Brandse, Johannan F; d'Haens, Geert Ram; Wolbink, Gerrit Jan; Rispens, Theo

    2017-07-01

    Controversy exists on the role of IgE antidrug antibodies (IgE-ADA) in infusion reactions (IR) on infliximab treatment, partly due to the lack of a positive control used for assay validation. We sought to (1) develop a robust assay to measure IgE-ADA, including a positive control, (2) determine the association between IgE-ADA and IR and (3) determine the incidence of IgE-ADA in infliximab treated patients. A recombinant human IgE anti-infliximab monoclonal antibody was developed as standard and positive control. With this antibody, we set up a novel robust assay to measure IgE-ADA. IgE-ADA was determined in three retrospective cohorts (n=159) containing IR+ (n=37) and IR- (n=39), and longitudinal sera of 83 spondyloarthritis. IgE-ADA was found in 0/39 IR-, whereas 4/37 (11%) IR+ showed low levels (0.1-0.3 IU/mL, below the 0.35 IU/mL threshold associated with elevated risk of allergic symptoms). All patients who were IgE-ADA positive also had (very) high IgG-ADA levels. The incidence of IgE-ADA in patients with infliximab-treated spondyloarthritis was estimated at less than approximately 1%. IgE-ADA is rarely detected in infliximab-treated patients. Moreover, the absence of IgE-ADA in the majority of IR+ patients suggests that IgE-ADA is not associated with infusion reactions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Infliximab dependency in pediatric Crohn's disease: Long-term follow-up of an unselected cohort

    OpenAIRE

    Ridder, Lissy; Rings, Edmond; Damen, Gerard; Kneepkens, Frank; Schweizer, J.; Kokke, Freddy; Benninga, Marc; Norbruis, Obbe; Hoekstra, Hans; Gijsbers, Carolien; Escher, Johanna

    2008-01-01

    textabstractBackground: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD patients initially responding to infliximab therapy. Methods: All pediatric patients treated with infliximab by pediatric gastroenterologists in the Netherlands because of severe luminal o...

  7. Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS), and clinical and magnetic resonance imaging measures of disease activity in a 1 year follow-up study of patients with axial spondyloarthritis treated with TNF-{alpha} inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne J; Sørensen, Inge J; Hermann, Kay-Geert A

    2010-01-01

    OBJECTIVES: To investigate construct validity and responsiveness of the novel ankylosing spondylitis disease activity score (ASDAS) in patients with spondyloarthritis (SpA). METHODS: In a 46 weeks prospective, longitudinal multi-center study of 60 SpA patients (80% men, median age 40 years (range...

  8. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF alpha inhibitors

    DEFF Research Database (Denmark)

    Pedersen, S.J.; Hetland, M.L.; Sørensen, Inge Juul

    2010-01-01

    excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 mu g/l (14-572) vs. 43 (20-184)), and MMP-3 (43 mu g/l (9.1-401) vs. 16 (2.5-47), p a parts per thousand currency signa......Euro parts per thousand 0.001), whereas total aggrecan was lower (662 mu g/l (223-2,219) vs. 816 (399-2,190),p a parts per thousand currency signaEuro parts per thousand 0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p a parts per thousand currency signa......Euro parts per thousand 0.03) in clinical responders (n = 24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p a parts per thousand currency signaEuro parts per thousand 0.02) in non-responders (n = 13). The study demonstrated changes of plasma IL-6...

  9. Imaging and serum analysis of immune complex formation of radiolabelled infliximab and anti-infliximab in responders and non-responders to therapy for rheumatoid arthritis

    NARCIS (Netherlands)

    van der Laken, C. J.; Voskuyl, A. E.; Roos, J. C.; Stigter van Walsum, M.; de Groot, E. R.; Wolbink, G.; Dijkmans, B. A. C.; Aarden, L. A.

    2007-01-01

    BACKGROUND: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the

  10. Infliximab and complications after colectomy in patients with ulcerative colitis

    DEFF Research Database (Denmark)

    Bregnbak, David; Mortensen, Christian; Bendtsen, Flemming

    2012-01-01

    Infliximab treatment may increase the risk of subsequent postoperative complications in patients with ulcerative colitis. The main purpose of the present study therefore was to assess postoperative complications in patients who have undergone colectomy for ulcerative colitis with and without...

  11. Infliximab-induced intertriginous psoriasis in patient with Crohn's disease

    OpenAIRE

    Mola, Federica; Motolese, Alberico

    2011-01-01

    Tumor necrosis factor-α (TNFα) inhibition is an effective treatment of moderate-to-severe psoriasis and other diseases (rheumatoid arthritis, ankylosing spondylitis, psoriasis or Crohn’s disease). We report a case of a 32- years-old patient affected by Crohn’s disease since the age of 25 who started infliximab infusion after four years of treatment with prednisone and azathioprine per os without improvement. After the fifth infusion of infliximab, he developed a form of intertriginous psorias...

  12. EFFECTIVENESS OF INFLIXIMAB IN PATIENTS WITH JUVENILE ANKYLOSING SPONDYLARTHRITIS

    Directory of Open Access Journals (Sweden)

    A.L. Kozlova

    2009-01-01

    Full Text Available The objective of open-labeled study was estimation of effectiveness and safety of infliximab — monoclonal antibodies to tumor necrosis factor (TNF - in treatment of 48 patients with juvenile ankylosing spondylarthritis. Duration of observation was 6 weeks — 1,5 years. Anticytokine treatment was administrated on the ground of therapy with immunosuppressive agents in 96% of patients. Infliximab was administrated in median dose 7,4 ± 3,7 mg/kg of body weight by standard scheme (0–2–6 — week and further every 8 weeks intravenously. Results of a trial showed that infliximab has evident anti-inflammatory effect. Treatment with infliximab provided development of remission of articular syndrome, decreasing and normalization of laboratory indices of activity of disease, the rate of disability, and increasing of quality of life in 84% of patients. Effect of this medication was registered after first infusion and continued during all period of follow up. Adverse effects included transfusion reactions: fever, head ache, nausea/vomiting in 10% of patients, allergic arthritis — in 2% of patients. Thus, treatment of infliximab is pathogenetically grounded, effective and safe in patients with juvenile ankylosing spondylarthritis.Key words: children, juvenile ankylosing spondylarthritis, infliximab, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(2:20-26

  13. Primary and secondary nonresponse to infliximab: mechanisms and countermeasures.

    Science.gov (United States)

    Wong, Uni; Cross, Raymond K

    2017-10-01

    Primary and secondary non-response to infliximab are common in patients with inflammatory bowel disease and remain a management challenge in clinical practice. Areas covered: This article describes the epidemiology, mechanisms and risk factors for primary and secondary nonresponse to infliximab in patients with inflammatory bowel disease. Data on proactive and reactive therapeutic drug monitoring are examined in this review. An algorithm for evaluation and management of non-response to infliximab is provided. Preventative measures are also discussed. Relevant articles were identified after a literature search using PubMed. Search terms included 'infliximab', 'loss of response', 'immunogenicity', and 'drug monitoring'. References of identified articles were also reviewed to identify additional references. Expert opinion: A common cause for primary and secondary non-response include inadequate dosing of infliximab; inadequate dosing can be identified through assessment of drug and anti-drug antibody levels. Therapeutic drug monitoring should be done in patients losing response to infliximab. Use of drug monitoring proactively is still under debate.

  14. Dramatic response to infliximab in refractory neurosarcoidosis

    Directory of Open Access Journals (Sweden)

    Chintamaneni Sreekanth

    2010-01-01

    Full Text Available Sarcoidosis is a systemic disease characterized by noncaseating granulomas in the involved organs. Neurologic manifestations involving the central and/or peripheral nervous system occur in about 5% of patients. Neurosarcoidosis is often refractory to conventional treatment and therefore more effective treatment options are needed. While the etiology of the disease is still unknown, there is now a better understanding of its pathogenesis on a molecular level. It is clear that tumor necrosis factor-α (TNFα plays a pivotal role in the development of the granulomas and it is believed to be a key cytokine involved in the pathogenesis of the disease. Taking advantage of this better understanding of disease pathogenesis, anti-TNFα agents are being increasingly used to treat refractory sarcoidosis. We report a patient with refractory neurosarcoidosis who showed dramatic improvement in the clinical and radiological manifestations following treatment with infliximab; he suffered a relapse upon discontinuation of the medication.

  15. Previous infliximab therapy and postoperative complications after proctocolectomy with ileum pouch anal anastomosis

    NARCIS (Netherlands)

    Eshuis, Emma J.; Al Saady, Rana L.; Stokkers, Pieter C. F.; Ponsioen, Cyriel Y.; Tanis, Pieter J.; Bemelman, Willem A.

    2013-01-01

    It is unclear whether infliximab treatment induces increased complication rates after surgery for ulcerative colitis. Aim was to compare complication rates after pouch surgery in refractory ulcerative colitis patients with versus without previous infliximab therapy. We performed a retrospective

  16. Rat hepatocyte invasion by Listeria monocytogenes and analysis of TNF-alpha role in apoptosis Invasão de hepatócitos de rato por Listeria monocytogenes e análise do papel do TNF-alfa na apoptose

    Directory of Open Access Journals (Sweden)

    Sânia Alves dos Santos

    2005-04-01

    Full Text Available Listeria monocytogenes, etiological agent of severe human foodborne infection, uses sophisticated mechanisms of entry into host cytoplasm and manipulation of the cellular cytoskeleton, resulting in cell death. The host cells and bacteria interaction may result in cytokine production as Tumor Necrosis Factor (TNF alpha. Hepatocytes have potential to produce pro-inflammatory cytokines as TNF-alpha when invaded by bacteria. In the present work we showed the behavior of hepatocytes invaded by L. monocytogenes by microscopic analysis, determination of TNF-alpha production by bioassay and analysis of the apoptosis through TUNEL technique. The presence of bacterium, in ratios that ranged from 5 to 50,000 bacteria per cell, induced the rupture of cellular monolayers. We observed the presence of internalized bacteria in the first hour of incubation by electronic microscopy. The levels of TNF-alpha increased from first hour of incubation to sixth hour, ranging from 0 to 3749 pg/mL. After seven and eight hours of incubation non-significant TNF-alpha levels decrease occurred, indicating possible saturation of cellular receptors. Thus, the quantity of TNF-alpha produced by hepatocytes was dependent of the incubation time, as well as of the proportion between bacteria and cells. The apoptosis rate increased in direct form with the incubation time (1 h to 8 + 24 h, ranging from 0 to 43%, as well as with the bacteria : cells ratio. These results show the ability of hepatocyte invasion by non-hemolytic L. monocytogenes, and the main consequences of this phenomenon were the release of TNF-alpha by hepatocytes and the induction of apoptosis. We speculate that hepatocytes use apoptosis induced by TNF-alpha for release bacteria to extracellular medium. This phenomenon may facilitate the bacteria destruction by the immune system.Listeria monocytogenes, agente etiológico de infecção grave de origem alimentar, utiliza mecanismos sofisticados de entrada no citoplasma

  17. Infliximab-associated alveolitis after treatment for severe left-sided ulcerative colitis.

    LENUS (Irish Health Repository)

    Veerappan, Sundaram G

    2012-02-01

    Here we describe a patient with ulcerative colitis who developed alveolitis after infliximab therapy. With earlier case reports of development of alveolitis in rheumatoid arthritis patients after infliximab infusion, the temporal relationship between the infliximab therapy and the development of alveolitis in this case, raises the possibility that the two might be causally related. With an increasing trend towards treating moderate to severely active ulcerative colitis patients with infliximab as a rescue therapy, clinicians should be aware of this potentially serious complication.

  18. Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study

    Science.gov (United States)

    2012-01-01

    Background To get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort study Methods In a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis. Results 147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (5 mg/L). Interestingly also in RA patients with DAS28 ≤ 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels. Conclusions Low (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in

  19. Infliximab Biosimilars in the Treatment of Inflammatory Bowel Diseases: A Systematic Review.

    Science.gov (United States)

    Radin, Massimo; Sciascia, Savino; Roccatello, Dario; Cuadrado, Maria Jose

    2017-02-01

    Biological therapies represent a fundamental innovation for the management of inflammatory bowel diseases (IBD). However, many biological originators have reached, or are about to reach, patent expiry and long-term therapy costs have become progressively unsustainable. CT-P13, a biosimilar of the anti-tumor necrosis factor (anti-TNF) monoclonal antibody infliximab, might represent a significant alternative to its originator, with the potential to decrease medical care costs and, therefore, become available to a large number of patients. In this systematic review, we analyzed the data from available clinical trials that recently investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in naïve patients and in patients who switched from its originator infliximab, focusing on clinical efficacy, safety and immunogenicity. A detailed literature search was developed a priori to identify articles that investigated the validity of indication extrapolation of CT-P13 for the treatment of IBD in TNF inhibitor treatment-naïve patients and in patients who switched from the originator infliximab. This was applied to Ovid MEDLINE, In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus for content from 2012 to September 2016. We based our review on the available data from 11 studies that included a total of 1007 IBD patients: 570 patients suffering from Crohn's disease (294 switched and 276 naïve), 435 patients suffering from ulcerative colitis (127 switched and 308 naïve), and two IBD unclassified patients (switched). Overall, no significant difference in efficacy and safety between the originator infliximab and its biosimilar CT-P13 was observed. When assessing the safety of CT-P13, we found that 9.2% of patients experienced adverse effects (4.1% infusion-related reactions and 4.3% infections). The analyzed studies did not report a significant difference in terms of efficacy, safety and

  20. The Tolerability and Efficacy of Rapid Infliximab Infusions in Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Qazi, Taha; Shah, Bhavesh; El-Dib, Mohammed; Farraye, Francis A

    2016-02-01

    Few studies have assessed the loss of efficacy or patient and caregiver satisfaction with rapid infliximab infusions. The aim of this study is to assess the tolerability, loss of efficacy and to describe the impact on resource utilization and patient satisfaction in rapid infliximab infusions. Subjects with inflammatory bowel disease receiving rapid infliximab infusions were included in the study. Subjects received maintenance infusions from June 2011 to June 2013. Incidence of adverse reactions and the total number of rapid infliximab infusions were recorded. Efficacy was compared to published studies evaluating the long-term efficacy of infliximab infusions. Patient satisfaction was addressed through a survey following the implementation of the rapid infusion protocol. Seventy-five subjects with IBD were included in the study. Five hundred and twenty-two rapid infliximab infusions were provided to patients. There were no acute or delayed infusion reactions. Ten subjects (13 %) required either a dose escalation or interval adjustment between infliximab infusions. A majority of patients reported increased satisfaction with 1-h infliximab infusions, and 97 % of surveyed patients opted to continue rapid infusions. The rapid infliximab infusion protocol increased infusion unit efficiency by increasing capacity by 15 %. Cost savings in the elimination of nursing time translated to approximately $108,150 savings at our institution. Rapid infliximab infusions do not appear to increase the risk of loss of response compared to historical studies of long-term infliximab efficiency. A rapid infliximab infusion protocol improved efficiency in our infusion unit and increased patient and nursing satisfaction.

  1. The infliximab biosimilar in the treatment of moderate to severe plaque psoriasis.

    Science.gov (United States)

    Dapavo, Paolo; Vujic, Igor; Fierro, Maria Teresa; Quaglino, Pietro; Sanlorenzo, Martina

    2016-10-01

    The infliximab originator's patent recently expired, leading to the production of biosimilar versions of the drug. The biosimilars' efficacy was not tested on patients with psoriasis but most regulatory authorities approved their use in psoriasis because of an extrapolation of data from studies conducted in other diseases. We sought to describe the use of the infliximab biosimilar (Remsima; CT-P13) in patients with psoriasis. Objective (Psoriasis Area and Severity Index) and subjective (visual analog pain scale) measurements of disease activity were collected in 2 cohorts of patients with moderate to severe plaque psoriasis: cohort 1 patients switched from the infliximab originator to the infliximab biosimilar; and cohort 2 patients were infliximab-naïve and started on the infliximab biosimilar. We observed no changes of Psoriasis Area and Severity Index and visual analog pain scale scores in 30 patients who switched from the infliximab originator to the biosimilar. Four of 5 infliximab-naïve patients who started infliximab biosimilar treatment achieved 75% improvement or better from baseline Psoriasis Area and Severity Index score at the end of the induction phase. Number of patients and length of follow-up was limited. Patients with psoriasis taking infliximab originator treatment can switch to the infliximab biosimilar without experiencing a significant change in clinical response or additional adverse events. The use of the infliximab biosimilar could reduce the growing pressure on health care budgets. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease.

    Science.gov (United States)

    de Bruyn, Jessica R; Becker, Marte A; Steenkamer, Jessica; Wildenberg, Manon E; Meijer, Sybren L; Buskens, Christianne J; Bemelman, Willem A; Löwenberg, Mark; Ponsioen, Cyriel Y; van den Brink, Gijs R; D'Haens, Geert R

    2018-01-01

    Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. In a previous trial, patients with ileocecal Crohn's disease were randomized to either immediate ileocecal resection or medical treatment with Infliximab. In case of insufficient response to Infliximab, the latter underwent secondary ileocecal resection. We compared specimens from those patients undergoing immediate resection (Infliximab naïve, n = 20) to those who failed Infliximab therapy (n = 20). Infliximab naïve and Infliximab failure patients had similar severity of inflammation when assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D'Haens-score, median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin depositions were increased in patients previously exposed to Infliximab compared to patients naïve to Infliximab. On mRNA level, procollagen peptidase showed significantly more mucosal mRNA expression in Crohn's disease patients who failed Infliximab. Infliximab responders showed no increase of this marker after 4 weeks of successful Infliximab treatment. Failure to Infliximab therapy is associated with subclinical fibrosis in Crohn's disease.

  3. Comparison of infliximab drug measurement across three commercially available ELISA kits.

    Science.gov (United States)

    Lee, Monique Wei Meng; Connor, Susan; Ng, Watson; Toong, Catherine Mei-Ling

    2016-10-01

    The monitoring of infliximab drug levels aids in the management of several autoimmune diseases, notably inflammatory bowel disease. Several commercial kits are now available and approved by the Therapeutic Goods Administration (TGA) for the measurement of infliximab levels, but there have been limited verification or comparison studies to date. Finding an assay that most accurately measures infliximab is essential for optimal drug titration and patient management. We performed this study to compare the performance of the Grifols Promonitor, Theradiag Lisatracker and R-Biopharm Ridascreen enzyme linked immunosorbent assay (ELISA) kits. Preparations of serum containing known concentrations of infliximab were assayed using each kit, including in the presence of interference from anti-infliximab antibodies, autoantibodies and other biological agents. The Lisatracker kit provided the most accurate determination of infliximab drug levels, however it yielded false positive results at low concentrations of infliximab. The average coefficients of variation (CVs) for the kits were 8% for Lisatracker, 5% for Ridascreen and 11% for Grifols. Infliximab measurements across all kits were affected by interference from antibodies to infliximab (ATI). This study identified the Lisatracker kit as the most accurate in quantifying infliximab levels, although it was limited by false positive results at low concentrations of infliximab as well as interference from ATI. This has important implications for the monitoring and management of patients receiving infliximab therapy. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  4. Infliximab dependency in pediatric Crohn's disease : Long-term follow-up of an unselected cohort

    NARCIS (Netherlands)

    de Ridder, Lissy; Rings, Edmond H. H. M.; Damen, Gerard M.; Kneepkens, C. M. Frank; Schweizer, Joachim J.; Kokke, Freddy T. M.; Benninga, Marc A.; Norbruis, Obbe F.; Hoekstra, J. Hans; Gijsbers, Carolien F. M.; Escher, Johanna C.

    Background: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD

  5. Infliximab dependency in pediatric Crohn's disease: Long-term follow-up of an unselected cohort

    NARCIS (Netherlands)

    L. de Ridder (Lissy); E.H.H.M. Rings (Edmond); G.M. Damen (Gerard); C.M.F. Kneepkens (Frank); J. Schweizer; F.T.M. Kokke (Freddy); M.A. Benninga (Marc); O.F. Norbruis (Obbe); J.H. Hoekstra (Hans); C.F.M. Gijsbers (Carolien); J.C. Escher (Johanna)

    2008-01-01

    textabstractBackground: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in

  6. Infliximab dependency in pediatric Crohn's disease: long-term follow-up of an unselected cohort

    NARCIS (Netherlands)

    de Ridder, Lissy; Rings, Edmond H. H. M.; Damen, Gerard M.; Kneepkens, C. M. Frank; Schweizer, Joachim J.; Kokke, Freddy T. M.; Benninga, Marc A.; Norbruis, Obbe F.; Hoekstra, J. Hans; Gijsbers, Carolien F. M.; Escher, Johanna C.

    2008-01-01

    BACKGROUND: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD

  7. Infliximab dependency in pediatric Crohn's disease: long-term follow-up of an unselected cohort.

    NARCIS (Netherlands)

    Ridder, L.; Rings, E.H.; Damen, G.M.; Kneepkens, C.M.; Schweizer, J.J.; Kokke, F.T.; Benninga, M.A.; Norbruis, O.F.; Hoekstra, J.H.; Gijsbers, C.F.M.; Escher, J.C.

    2008-01-01

    BACKGROUND: Infliximab is effective for induction and maintenance of remission in Crohn's disease. It is unknown how long patients should be kept on infliximab therapy. The primary aim of this study was to assess duration of effective maintenance therapy and infliximab dependency in pediatric CD

  8. Review article: dose optimisation of infliximab for acute severe ulcerative colitis

    NARCIS (Netherlands)

    Hindryckx, P.; Novak, G.; Vande Casteele, N.; Laukens, D.; Parker, C.; Shackelton, L. M.; Narula, N.; Khanna, R.; Dulai, P.; Levesque, B. G.; Sandborn, W. J.; D'Haens, G.; Feagan, B. G.; Jairath, V.

    2017-01-01

    Although optimal medical management of acute severe ulcerative colitis (UC) is ill-defined, infliximab has become a standard of care. Accumulating evidence suggests an increased rate of infliximab clearance in patients with acute severe UC and a reduced colectomy rate with an intensified infliximab

  9. Changes in Body Mass Index and Lipid Profile in Psoriatic Patients After Treatment With Standard Protocol of Infliximab.

    Science.gov (United States)

    Ehsani, Amir Houshang; Mortazavi, Hossein; Balighi, Kamran; Hosseini, Mahboubeh Sadat; Azizpour, Arghavan; Hejazi, Seyyedeh Pardis; Goodarzi, Azadeh; Darvari, Seyyedeh Bahareh

    2016-09-01

    Psoriasis is a chronic and inflammatory dermatologic disease. Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial. Regarding frequent use of infliximab in psoriasis, and the hypothesis that anti TNF-α treatment may increase Body Mass Index (BMI) and alter lipid profile in these patients, the aim of this study was to assess changes in BMI and Lipid Profile and level of leptin in Psoriatic Patients under Treatment of Standard Protocol of Infliximab in a 24 week period. This study was accomplished as a before-after study. Twenty-seven psoriatic patients were included, and standard infliximab therapy was applied. All patients underwent 3 times of blood collection and in each session; LDL, HDL, Total Cholesterol, Triglycerides, Leptin, and PASI score were measured at the start of the study and at the 12th and 24th week of follow-up. Twenty-five patients consisted of 18 (72%) male and 7 (28%) female subjects were evaluated. The mean age of the patients was 36.91±13.31 years. PASI score demonstrated significant decrease after 24 weeks; however, BMI and HDL and leptin showed a significant increase during treatment. Significant negative correlation was seen between Leptin and PASI score changes (r=0.331, P=0.042). HDL and BMI had the most correlations with leptin (positive correlation) and PASI score (negative correlation). Results demonstrated a dramatic decrease in PASI, increase in BMI and HDL and increased in leptin; somewhat correlated to each other. These results suggest that patients taking infliximab should take more care of their weight and lipid profile, while on treatment.

  10. Prediction of successful dose reduction or discontinuation of adalimumab, etanercept, or infliximab in rheumatoid arthritis patients using serum drug levels and antidrug antibody measurement.

    Science.gov (United States)

    Bouman, Cam; van Herwaarden, N; van den Hoogen, Fhj; van der Maas, A; van den Bemt, Bjf; den Broeder, A A

    2017-06-01

    To evaluate if TNF inhibitor serum drug levels (DL) or anti-drug antibodies (ADAb) can predict successful dose reduction (in patients with high DL) or discontinuation (in patients with no/low DL or ADAb) in rheumatoid arthritis (RA) patients. RA patients that were using adalimumab (n = 42), etanercept (n = 76) or infliximab (n = 51) and were doing well, were tapered until discontinuation or flare (1-1.5 year follow up). Random timed DL for adalimumab and etanercept and trough DL for infliximab were measured before dose reduction: Receiver-Operator-Curves (ROC) analyses with optimal cut-off DL were determined. No predictive value of adalimumab and infliximab DL for all outcomes were found, except for an inverse association of lower etanercept DL and higher chance for successful dose reduction (Area Under the Curve (AUC) 0.36, 95% CI 0.23-0.49; cut-off 7.8). ADAb were infrequent and not predictive of successful discontinuation. No predictive value of baseline adalimumab, etanercept and infliximab DL or ADAb for successful dose reduction or discontinuation in RA was found in this context, with the possible exception of high adalimumab trough levels for successful dose reduction.

  11. Infliximab in the treatment of plaque type psoriasis

    Directory of Open Access Journals (Sweden)

    Rosita Saraceno

    2009-04-01

    Full Text Available Rosita Saraceno, Andrea Saggini, Lucia Pietroleonardo, Sergio ChimentiDepartment of Dermatology, University of Rome Tor Vergata, Rome, Viale Oxford 81, Rome, ItalyAbstract: Psoriasis is a chronic and immunomediated skin disease characterized by erythematous scaly plaques. Psoriasis affects approximately 1% to 3% of the Caucasian population. Tumor necrosis factor alpha (TNF-α is a proinflammatory cytokine that plays a critical role in the pathogenesis of psoriasis. Infliximab is an anti-TNF-α drug widely used for the treatment of plaque type psoriasis and psoriatic arthritis. Controlled clinical trials demonstrated that infliximab is characterized by a high degree of clinical response in moderate to severe plaque psoriasis. Moreover infliximab showed rapid efficacy in nail psoriasis which represents a therapeutic challenge for dermatologists and a relevant source of distress for patients with plaque psoriasis. This anti-TNF-α has an encouraging safety profile, especially as long as physicians are watchful in prevention and early diagnosis of infections and infuse reactions. The efficacy, tolerability and safety profiles suggest infliximab as a suitable anti-psoriatic drug in the long-term treatment of a chronic disease such as plaque-type psoriasis.Keywords: psoriasis, nail psoriasis, infliximab, long-term treatment

  12. Use of infliximab and anti-infliximab antibody measurements to evaluate and optimize efficacy and safety of infliximab maintenance therapy in Crohn's disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper

    2013-01-01

    Infliximab (IFX) is a therapeutic monoclonal antibody (Ab) against TNF-α, which is used to induce and maintain remission in patients with moderate to severe Crohn's disease. Despite its effectiveness, approximately one third of patients experience primary treatment failure, and another one third...

  13. Interleukin-10 does not mediate the inhibitory effect of PDE-4 inhibitors and other cAMP-elevating drugs on lipopolysaccharide-induced tumors necrosis factor-alpha generation from human peripheral blood monocytes.

    Science.gov (United States)

    Seldon, P M; Barnes, P J; Giembycz, M A

    1998-01-01

    Lipopolysaccharide (LPS)-induced liver injury in mice and LPS-induced tumor necrosis factor-alpha (TNF-alpha) generation by murine macrophages and hepatocytes are suppressed markedly by agents that elevate intracellular cAMP. Phosphodiesterase (PDE)-4 inhibitors, beta 2-adrenoceptor agonists, and E-series prostaglandins also attenuate the induction of the TNF-alpha gene in human monocytes in response to bacterial LPS. The mechanism of action of cAMP is unclear, but in the mouse, is believed to involve the generation of this anti-inflammatory cytokine, interleukin-10 (IL-10). In this article, we describe the results of studies designed to determine the extent to which IL-10 contributes to the suppression of TNF-alpha generation from LPS-stimulated human monocytes evoked by 8-bromo cyclic AMP (8-Br-cAMP), rolipram, salbutamol, and prostaglandin E2 (PGE2). LPS evoked a time- and concentration-dependent generation of TNF-alpha (t1/2 = 4.5 h; EC50 = 273 pg/mL), which was inhibited by exogenous human recombinant (h) IL-10 (IC50 = 124 pg/mL), and by rolipram (EC50 = 420 nM), 8-Br-cAMP (EC50 = 77 (microM), PGE2 (EC50 = 15 nM) and salbutamol (EC50 = 20 nM). In addition, 8-Br-cAMP, PGE2; and salbutamol (but not rolipram) augmented significantly LPS-induced IL-10 production (two-to-fivefold) under identical experimental conditions. Pretreatment of monocytes with an anti-IL-10 monoclonal antibody (MAb) that abolished the inhibitory action of a maximally effective concentration of exogenous hrIL-10, failed to attenuate the inhibitory effect of rolipram, PGE2, salbutamol, and 8-Br-cAMP. Anti-IL-10 was similarly inactive when the number of monocytes seeded was increased from 0.5 to 4 x 10(6)/mL or when measurements were made at 42 h post-LPS, a time when the concentration of IL-10 released was maximal. Collectively, these data suggest that in contrast to murine hepatocytes and macrophages, IL-10 does not mediate the inhibitory effect of cAMP-elevating drugs on TNF-alpha

  14. Infliximab dependency is related to decreased surgical rates in adult Crohn's disease patients

    DEFF Research Database (Denmark)

    Pedersen, N.; Duricova, D.; Lenicek, M.

    2010-01-01

    Background Infliximab dependency in children with Crohn's disease (CD) has recently been described and found to be associated with a decreased surgery rate. Aim To assess infliximab dependency of adult CD patients, evaluate the impact on surgery, and search for possible clinical and genetic...... predictors. Methods Two hundred and forty-five CD patients treated with infliximab were included from Danish and Czech Crohn Colitis Database (1999-2006). Infliximab response was assessed as immediate outcome, 1 month after infliximab start: complete, partial, and no response. Three months outcome, after...

  15. Stabilization of Bilateral Progressive Rheumatoid Corneal Melt with Infliximab

    Directory of Open Access Journals (Sweden)

    Sheelah F. Antao

    2012-01-01

    Results. A patient with rheumatoid arthritis presented with bilateral PUK following a 2-month history of ocular discomfort and redness. His systemic prednisolone (PDN and methotrexate (MTX were increased and, despite an initial favorable response, bilateral recurrent corneal perforations ensued. Both eyes underwent cyanoacrylate glue repair, amniotic membrane transplantation (AMT, and penetrating keratoplasty (PKP. Recurrence of the disease and bilateral perforations of the second PKP in both eyes prompted administration of intravenous infliximab immediately after the fourth PKP. The disease activity rapidly settled in both eyes, and at eighteen-month followup, after 12 infliximab infusions, the PUK remains quiescent with no further graft thinning or perforation. Conclusion. Infliximab can be used to arrest the progression of severe bilateral rheumatoid PUK in cases that are refractory to conventional treatment.

  16. Long-term outcomes of refractory neurosarcoidosis treated with infliximab.

    Science.gov (United States)

    Cohen Aubart, Fleur; Bouvry, Diane; Galanaud, Damien; Dehais, Caroline; Mathey, Guillaume; Psimaras, Dimitri; Haroche, Julien; Pottier, Corinne; Hie, Miguel; Mathian, Alexis; Devilliers, Hervé; Nunes, Hilario; Valeyre, Dominique; Amoura, Zahir

    2017-05-01

    Central nervous system localizations of sarcoidosis may be refractory to conventional treatment such as steroids and immunosuppressive drugs. Infliximab, a TNF-α antagonist chimeric antibody, has been shown to be effective for treatment of these localizations. The aim of this study was to evaluate the efficacy and safety, in particular the long-term outcomes, of the use of infliximab for the treatment of neurosarcoidosis. We retrospectively reviewed medical records of patients with neurosarcoidosis who had been treated with infliximab between 2009 and 2015. All patients had histologically proven non-caseating granulomas. Eighteen patients with histologically proven sarcoidosis were included in this study. All had neurological involvement consisting of meningeal (n = 16), cerebral (n = 10), spinal cord (n = 6), and/or optic nerve (n = 5) involvement. Sixteen patients had previously received at least one immunosuppressive drug in addition to corticosteroids, including cyclophosphamide in 11 patients. All patients received treatment with infliximab (3-7.5 mg/kg) associated with corticosteroids (n = 18), low-dose methotrexate (n = 15), azathioprine (n = 2), or mycophenolate (n = 1). Sixteen out of 18 patients improved clinically (initial median modified Rankin scale score of 3, final median score of 1; p infliximab, six patients obtained complete remission (33%), ten attained partial remission (56%), and two had stable disease (11%). The median follow-up time was 20 months (range 6-93). Nine patients relapsed during follow-up (50%). Eight patients developed toxic side effects and seven of these side effects were infectious events. Infliximab is an efficacious treatment of refractory neurosarcoidosis. However, relapses frequently occurred during follow-up.

  17. Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood.

    Science.gov (United States)

    Pott, Gregory B; Chan, Edward D; Dinarello, Charles A; Shapiro, Leland

    2009-05-01

    Several observations suggest endogenous suppressors of inflammatory mediators are present in human blood. alpha-1-Antitrypsin (AAT) is the most abundant serine protease inhibitor in blood, and AAT possesses anti-inflammatory activity in vitro and in vivo. Here, we show that in vitro stimulation of whole blood from persons with a genetic AAT deficiency resulted in enhanced cytokine production compared with blood from healthy subjects. Using whole blood from healthy subjects, dilution of blood with RPMI tissue-culture medium, followed by incubation for 18 h, increased spontaneous production of IL-8, TNF-alpha, IL-1 beta, and IL-1R antagonist (IL-1Ra) significantly, compared with undiluted blood. Dilution-induced cytokine production suggested the presence of one or more circulating inhibitors of cytokine synthesis present in blood. Serially diluting blood with tissue-culture medium in the presence of cytokine stimulation with heat-killed Staphylococcus epidermidis (S. epi) resulted in 1.2- to 55-fold increases in cytokine production compared with S. epi stimulation alone. Diluting blood with autologous plasma did not increase the production of IL-8, TNF-alpha, IL-1 beta, or IL-1Ra, suggesting that the endogenous, inhibitory activity of blood resided in plasma. In whole blood, diluted and stimulated with S. epi, exogenous AAT inhibited IL-8, IL-6, TNF-alpha, and IL-1 beta significantly but did not suppress induction of the anti-inflammatory cytokines IL-1Ra and IL-10. These ex vivo and in vitro observations suggest that endogenous AAT in blood contributes to the suppression of proinflammatory cytokine synthesis.

  18. Fatal miliary Coccidioidomycosis in a patient receiving infliximab therapy: a case report

    Directory of Open Access Journals (Sweden)

    Rogan Mark P

    2007-09-01

    Full Text Available Abstract A 78-year-old white male from Iowa in the United States of America receiving the anti- tumor necrois factor (TNF agent infliximab therapy for rheumatoid arthritis developed a cheek ulcer which failed to respond to empiric antibiotic therapy. He subsequently presented with progressive respiratory failure from miliary coccidioidomycosis which proved fatal. The patient vacationed in Arizona 6 months previously and likely contracted the organism there as Iowa is not an endemic area for coccidioidomycosis. Respiratory failure from miliary infiltration is an uncommon presentation of coccidioidomycosis. Physicians should be aware of the importance of travel history and potential for life-threatening coccidioidomycosis in patients receiving tumor necrosis factor inhibitors.

  19. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 May Help Downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70 in the Neurogenic Bladder of Spinal Cord Injured Patient with Urinary Tract Infections: A Two-Case Study

    Directory of Open Access Journals (Sweden)

    Kingsley C. Anukam

    2009-01-01

    Full Text Available The management of urinary tract infection (UTI in individuals with spinal cord injury (SCI continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P=.015 in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

  20. Infliximab en pacientes con enfermedad ocular inflamatoria, refractarios a DARMES

    Directory of Open Access Journals (Sweden)

    Elmer R. García-Salazar

    2013-07-01

    Full Text Available Se describe la experiencia con infliximab (anticuerpo monoclonal con una potente acción antiinflamatoria en el tratamiento de enfermedades oculares inflamatorias secundarias a patologías reumáticas y refractarias a drogas antirreumáticas modificadoras de la enfermedad (DARMES. Se evaluó el caso de una paciente de 50 años con artritis reumatoide (AR de fondo activo y una paciente de 37 años con vasculitis anticuerpos anticitoplasma de neutrófilos especifico para mieloperoxidasa (ANCA MPO sin compromiso de órgano noble, ambas con escleritis bilateral y perforación con prolapso de iris del ojo izquierdo. Ellas recibieron infliximab EV en dosis de 3 a 5 mg/kg/dosis, según el esquema, a las 0, 2, 6 y 8 semanas. Infliximab resultó eficaz y seguro para el tratamiento de escleritis asociada a AR y vasculitis ANCA MPO positivo, refractaria a tratamiento con DARMES y corticoides en dosis altas. Los injertos de tejido esclerocorneal evolucionaron favorablemente con infliximab.

  1. Potential role of infliximab therapy in twelve Libyan patients with ...

    African Journals Online (AJOL)

    Potential role of infliximab therapy in twelve Libyan patients with Behçet's disease. E Basma, T Rajab, M Amani, E Borhan, B Gamal, M Eshabani. Abstract. Background: The blocking of tumour necrosis factor-α (TNF-α) with the socalled anti TNF-α agents has turned into the most important tool in the management of a variety ...

  2. Infliximab (Revellex(R)): a promise fulfilled?: medicine in practice ...

    African Journals Online (AJOL)

    Infliximab (Revellex(R)): a promise fulfilled?: medicine in practice. JP Wright. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners ...

  3. Changing Infliximab Prescription Patterns in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Larsen, Lone; Drewes, Asbjørn Mohr; Broberg, Marie Christine Hede

    2018-01-01

    Background: Long-term data on real life use of infliximab (IFX) for inflammatory bowel disease (IBD) are lacking. We studied prescription patterns during the first 16 years following marketing authorization. Methods: In a population-based cohort from the North Denmark Region, all IBD patients...

  4. Low Indeterminate Rates Associated With Use of the QuantiFERON-TB Gold In-Tube Test in Children With Inflammatory Bowel Disease on Long-term Infliximab.

    Science.gov (United States)

    Vortia, Eugene; Uko, Victor E; Yen-Lieberman, Belinda; Frawley, Jill; Worley, Sarah E; Danziger-Isakov, Lara; Kaplan, Barbara; Mahajan, Lori

    2018-03-19

    Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term treatment with TNF-α inhibitors. The objective of this study was to assess the proportion of indeterminate results for the QuantiFERON-TB Gold In-Tube in children with inflammatory bowel disease (IBD) on long-term infliximab treatment and to evaluate the range of interferon-γ responses to mitogen. A single-center prospective study of children 5 to 19 years of age with IBD on long-term infliximab treatment (>3 months). Each child was assessed for tuberculosis exposure risk and had blood drawn for the QuantiFERON-TB Gold In-Tube. Data on the range of interferon-γ responses and final QuantiFERON-TB Gold In-Tube test results were collected. Ninety-three children were included, with a median age of 16 years. The median total duration of infliximab therapy was 34 months (range, 3-119 months). The QuantiFERON-TB Gold In-Tube was indeterminate in 1 patient (1.1%), positive in 2 patients, and negative in 90 patients. The maximum interferon-γ response to mitogen (10 IU/mL) was observed in 82 patients (88%), with only 1 patient having an inadequate response. The proportion of indeterminate results was significantly lower than the prospectively hypothesized rate of 8%, based on prior studies in nonimmunosuppressed patients (P = 0.004). Pediatric patients with IBD on long-term treatment with infliximab had an adequate interferon-γ response to mitogen and a low indeterminate rate when assessed with the QuantiFERON-TB Gold In-Tube test. This study demonstrates a robust interferon gamma response to phytohemagglutinin stimulation in a pediatric population on long-term therapy with infliximab. The QuantiFERON-TB Gold In-Tube test may therefore be useful as a periodic

  5. Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Glintborg, Bente; Gudbjornsson, Bjorn; Krogh, Niels Steen

    2014-01-01

    OBJECTIVE: The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care. METHODS: We conducted an observational cohort study based on the nationwide Danish Rheumato......OBJECTIVE: The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care. METHODS: We conducted an observational cohort study based on the nationwide Danish...... Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P drug survival than...... Icelandic patients (1183 vs 483 days). In univariate analyses stratified by country, time until dose escalation, response rates, drug survival and 1-year's disease activity were independent of starting dose. Drug survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In clinical...

  6. Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy.

    Science.gov (United States)

    Huang, Vivian W; Prosser, Connie; Kroeker, Karen I; Wang, Haili; Shalapay, Carol; Dhami, Neil; Fedorak, Darryl K; Halloran, Brendan; Dieleman, Levinus A; Goodman, Karen J; Fedorak, Richard N

    2015-06-01

    Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD. Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission. A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 μg/g, median ITLs 7.3 μg/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197-0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536-1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254-0.742) and objective remission (AUC = 0.773; 95% CI, 0.622-0.924). Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy.

  7. Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Svenson, Morten; Bendtzen, Klaus

    2012-01-01

    A 61 year old woman with active luminal Crohn's disease was successfully treated with infliximab induction therapy followed by 5 infusions every 8 weeks. However, symptoms returned in the weeks preceding the 7th and 8th infusions. The 9th infusion was therefore given only 4 weeks after the 8th...... infusion, but an acute severe anaphylactoid reaction occurred immediately after start of the infusion. Anti-infliximab IgG antibody concentration was high (100 U/ml) prior to the 8th infusion and up to 1 year after infliximab discontinuation (81 U/ml). Anti-infliximab IgE antibodies were not found......, and the anti-infliximab antibodies did not cross react with adalimumab. One week after the anaphylactoid reaction to infliximab, adalimumab therapy was initiated. Twelve days after the first adalimumab administration (80 mg), a delayed hypersensitivity reaction occurred. This was likely caused by rapidly...

  8. Clinical Use and Mechanisms of Infliximab Treatment on Inflammatory Bowel Disease: A Recent Update

    Science.gov (United States)

    Guo, Yuan; Lu, Nonghua; Bai, Aiping

    2013-01-01

    The pathogenesis and treatment of inflammatory bowel disease (IBD) have been recently advanced, while it is still challenged with high morbidity and poor prognosis. Infliximab, a monoclonal antibody of tumor necrosis factor (TNF), has emerged as an efficient treatment with many clinical benefits such as quick disease activity reduction and IBD patient life quality improvement. However, the biological effects of infliximab on IBD need to be elucidated. This paper reviewed the clinical use and recently advanced biological action of infliximab on IBD. By forming the stable complex with the soluble or the membrane form of TNF in fluid environment or on cell surface of immune cell, fibroblast, endothelium, and epithelium, infliximab quenches TNF activity and performs the important biological actions which lead to amelioration and remission of immune responses. The mechanisms of infliximab treatment for IBD were intensively discussed. The recent advances on two topics including predictors and side effects of infliximab treatment were also reviewed. PMID:23484133

  9. Infliximab dependency in a national cohort of children with Crohn's disease

    DEFF Research Database (Denmark)

    Wever, Anne Vibeke; Riis, Lene; Vind, Ida

    2006-01-01

    AIM: The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohn's disease (CD) treated in Denmark from 1999 to 2003. MATERIAL AND METHODS: The National Danish Crohn Colitis Database of infliximab was used...... to identify all Danish CD patients treated at pediatric departments with infliximab. The clinical outcome was assessed by pattern recognition of the disease course 30 days after the first infliximab infusion and 90 days after intended end of treatment. RESULTS: During a 3 year period, infliximab was given...... to 24 CD patients (9 male/15 female) aged median 15.4 (range 9.8-18.6) years with a median disease duration of 26 (range 0.7-93) months and a median number of infusions of 6 (range 2-11). Five milligrams of infliximab per kilogram infusions were given intravenously. Immediate response was as follows: 8...

  10. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease.

    Science.gov (United States)

    Yarur, A J; Kanagala, V; Stein, D J; Czul, F; Quintero, M A; Agrawal, D; Patel, A; Best, K; Fox, C; Idstein, K; Abreu, M T

    2017-04-01

    Infliximab has been found to be efficacious in the treatment of fistulas in the setting of Crohn's disease, even though some patients do not benefit from therapy. To assess the correlation between perianal fistula healing and trough levels of infliximab. In this cross-sectional study, we identified patients with Crohn's disease who had perianal fistulas and were treated with infliximab for at least 24 weeks. We excluded patients who underwent a faecal diversion procedure or proctectomy. Predictive variables included demographics, disease phenotype, disease activity, infliximab levels, anti-infliximab antibodies. The primary outcome was fistula healing defined as the absence of drainage. The secondary outcome was complete fistula closure and mucosal healing. 117 patients were included. Patients with fistula healing had significantly higher median serum infliximab levels when compared to those with active fistulas [15.8 vs. 4.4 μg/mL, respectively (P infliximab levels. The AUC for the association between fistula healing and infliximab levels was 0.82 (P infliximab levels and fistula closure was 0.69 (P = 0.014). Patients with anti-infliximab antibodies had a lower chance of achieving fistula healing (OR: 0.04 [95%CI: 0.005-0.3], P infliximab levels and rates of fistula healing. Achieving infliximab levels ≥10.1 mcg/mL in patients with Crohn's disease and perianal fistulas may improve outcomes as part of a treat-to-target strategy. © 2017 John Wiley & Sons Ltd.

  11. Characteristics and outcomes of rheumatoid arthritis patients who started biosimilar infliximab.

    Science.gov (United States)

    Sung, Yoon-Kyoung; Cho, Soo-Kyung; Kim, Dam; Won, Soyoung; Choi, Chan-Bum; Bang, So-Young; Hong, Seung-Jae; Kim, Hyoun Ah; Koh, Eun-Mi; Lee, Hye-Soon; Suh, Chang-Hee; Yoo, Dae-Hyun; Bae, Sang-Cheol

    2017-06-01

    To compare the characteristics of rheumatoid arthritis (RA) patients receiving either biosimilar or originator infliximab and to identify the effectiveness and safety of biosimilar infliximab in RA patients in real-world practice. RA patients who started either biosimilar or originator infliximab were selected using the prospective biologic disease-modifying anti-rheumatic drugs (DMARDs) registry: BIOlogics Pharmacoepidemiologic StudY (BIOPSY). Baseline characteristics of the two groups were compared, and short-term treatment outcomes, including DAS28-ESR and HAQ-DI scores, were compared after initiation of biosimilar or originator infliximab. The drug retention rates of the two groups were also compared. A total of 100 RA patients, 55 biosimilar, and 45 originator infliximab users were included in this analysis. Baseline characteristics of age, disease duration, and previous or current medications were similar in the two groups. Baseline DAS28-ESR was higher in the originator infliximab group (6.3 ± 1.1 vs. 5.8 ± 1.1, p = 0.02). The early DAS28-ESR remission rates observed 7.9 ± 1.8 months after starting biosimilar and originator infliximab were 15.0 and 25.0%, respectively (p = 0.47). The change in HAQ-DI did not differ between the two groups (0.4 ± 0.7 vs. 0.4 ± 0.8, p = 0.94). Patients treated with biosimilar infliximab in clinical practice had lower disease activity at the start of treatment than those receiving originator infliximab. Biosimilar infliximab was well-tolerated, safe, and of similar clinical effectiveness to originator infliximab. Larger number of patient and longer follow-up data will be needed to confirm the effectiveness and safety of biosimilar infliximab in clinical practice.

  12. Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Medine Cumhur Cüre

    2016-10-01

    Full Text Available Background: Cisplatin (Cis is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α. Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. Aims: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. Study Design: Animal experimentation. Methods: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg. In the CIN group, a single dose of infliximab (7 mg/kg was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg was administered. All rats were sacrificed five days after Cis injection. Results: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein than those of the control (278.7±62.1 pg/mg protein, p=0.003 and CIN groups (239.0±64.2 pg/mg protein, p=0.013. The Cis group was found to have high carbonic anhydrase (CA-II and low carbamoyl phosphate synthetase-1 (CPS-1 levels. Aspartate transaminase (AST and alanine transaminase (ALT levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. Conclusion: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and

  13. Infliximab Dependency in a National Cohort of Children with Crohn's Disease

    DEFF Research Database (Denmark)

    Wewer, Anne Vibeke; Riis, L; Vind, Ida

    2006-01-01

    AIM: The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohn's disease (CD) treated in Denmark from 1999 to 2003. MATERIAL AND METHODS: The National Danish Crohn Colitis Database of infliximab was used...... of symptoms requiring reinfusions of infliximab to regain CR or PR, and 6 (25%) had NR. Six (25%) patients needed surgery during or after treatment with infliximab. Side effects were seen in four (17%) patients. No serious events were noted. CONCLUSION: Seventy-one percent of the children appeared to benefit...

  14. Infliximab dependency in a national cohort of children with Crohn's disease

    DEFF Research Database (Denmark)

    Wever, Anne Vibeke; Riis, Lene; Vind, Ida

    2006-01-01

    AIM: The aim was to evaluate the pattern of responsiveness and to monitor side effects of episodic administration of infliximab in children with active Crohn's disease (CD) treated in Denmark from 1999 to 2003. MATERIAL AND METHODS: The National Danish Crohn Colitis Database of infliximab was used...... of symptoms requiring reinfusions of infliximab to regain CR or PR, and 6 (25%) had NR. Six (25%) patients needed surgery during or after treatment with infliximab. Side effects were seen in four (17%) patients. No serious events were noted. CONCLUSION: Seventy-one percent of the children appeared to benefit...

  15. Infliximab-Induced Hypothyroidism: A Novel Case and Postulations concerning the Mechanism

    Directory of Open Access Journals (Sweden)

    Brett Cerniglia

    2013-01-01

    Full Text Available We report a patient with cutaneous sarcoidosis who developed hypothyroidism following 17 months of infliximab therapy. To our knowledge, this is the first reported case of hypothyroidism following infliximab administration. While it is possible that the patient’s hypothyroidism was unrelated to the use of infliximab, the time course and lack of alternative explanations make such an association plausible. We postulate that hypothyroidism in this patient may have been related to the development of autoantibodies to infliximab that triggered the development of an autoimmune thyroiditis. Regardless of the mechanism, we would encourage clinicians to keep the potential mechanisms of TNF- in mind when treating patients with TNF- antagonist medications.

  16. Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats.

    Science.gov (United States)

    Ozer, Erdem Kamil; Goktas, Mustafa Tugrul; Kilinc, Ibrahim; Toker, Aysun; Bariskaner, Hulagu; Ugurluoglu, Ceyhan; Iskit, Alper Bektas

    2017-07-01

    Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.

  17. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of infliximab encapsulated in liposomes.

    Science.gov (United States)

    Zhang, Rui; Qian, Jiang; Li, Xiaofeng; Yuan, Yifei

    2017-12-01

    To evaluate the safety and efficacy of intravitreal injection of liposomes encapsulating infliximab in experimental autoimmune uveoretinitis (EAU) rats. Liposomes containing infliximab were prepared and characterised for mean particle size, entrapment efficiency, polydispersity index (PDI) and zeta potential. In vitro release profile and the stability of infliximab-lip were evaluated. EAU rats were intravitreally injected with saline, infliximab, infliximab-lip or unloaded liposomes. Clinical signs and ocular histological sections were graded. Infliximab concentrations were determined with competitive ELISA. Safety of the intravitreal injections was evaluated by electroretinography (ERG) and histopathological examination. Retinal biodistribution and clearance of rhodamine-conjugated liposomes containing infliximab were evaluated with a laser scanning confocal microscope. The mean particle size of infliximab liposomes was 351.3±58 nm and entrapment efficiency was 90.65%±2.68%. PDI and zeta potential of infliximab liposomes were 0.386 and -20.8±9.78 mV, respectively. Stability test data showed that the infliximab-lip was stable for 60 days at room temperature. In EAU rats, intravitreal injection of infliximab and infliximab-lip greatly reduced intraocular inflammation determined by clinical scores and histopathological analyses (n=4). The mean concentrations of infliximab decreased quickly in infliximab injection group and were lower than those in infliximab-lip injection group (n=4 eyes, pinfliximab-lip in ERG (n=4 rats, p>0.05) and histopathological sections compared with normal rats. Confocal microscopy showed that fluorescent liposomes were observed in almost every layer of the retina and remained detectable for >30 days after injection. Intravitreal injection of liposomal infliximab can prolong the persistence of the drug in vitreous body and demonstrated a satisfactory safety and significant therapeutic potentials in EAU. The use of biodegradable

  18. Direct effect of infliximab on intestinal mucosa sustains mucosal healing: exploring new mechanisms of action.

    Science.gov (United States)

    Petito, Valentina; Lopetuso, Loris Riccardo; Arena, Vincenzo; Stigliano, Egidio; Boninsegna, Alma; Bibbò, Stefano; Poscia, Andrea; Alfieri, Sergio; Rosa, Fausto; Amato, Arianna; Cammarota, Giovanni; Papa, Alfredo; Sgambato, Alessandro; Gasbarrini, Antonio; Scaldaferri, Franco

    2016-04-01

    Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level. To assess the role of infliximab on intestinal mucosa and whether it contributes to mucosal healing. Human colonic mucosal biopsies were incubated with or without infliximab. Cultured biopsies were evaluated for histological staining, CD68, CD3, E-cadherin and phospho-extracellular signal-regulated kinases (ERK) expression, and apoptosis. A scratch assay and MTT assay were performed with Caco2 cells in the presence of infliximab and/or tumour necrosis factor (TNF)-α or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-α and infliximab alone or in association. Infliximab-treated biopsies displayed a better histological appearance, reduced inflammation with an increase of E-cadherin, phospho-ERK and apoptosis. Supernatants showed lower TNF-α, IL-17, IL-6 and IL-8 concentration, with an increase in fibroblast-growth-factor. Motility at scratch assay and proliferation at MTT assay of Caco2 cells displayed differential modulation by TNF-α and infliximab, directly or through supernatants of human intestinal fibroblasts and human peripheral blood mononuclear cells exposed to them. Infliximab contributes to the mucosal healing process by acting directly at an intestinal mucosal level; infliximab indirectly affects epithelial cell migration and proliferation by acting on both fibroblasts and leukocytes. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective, observational study of patients treated with infliximab for ankylosing spondylitis

    Science.gov (United States)

    Rahman, Proton; Choquette, Denis; Bensen, William G; Khraishi, Majed; Chow, Andrew; Zummer, Michel; Shaikh, Saeed; Sheriff, Maqbool; Dixit, Sanjay; Sholter, Dalton; Psaradellis, Eliofotisti; Sampalis, John S; Letourneau, Vincent; Lehman, Allen J; Nantel, François; Rampakakis, Emmanouil; Otawa, Susan; Shawi, May

    2016-01-01

    factor-α inhibitors. Conclusions Characteristics of patients with AS at infliximab initiation changed over time towards lower disease activity and shorter disease duration. Infliximab treatment significantly reduced disease activity independent of treatment initiation year, although patients enrolled in recent years achieved lower disease activity over 48 months. Trial registration number NCT00741793. PMID:27048632

  20. Estratégia de troca entre agentes anti-TNF-alfa não melhora a capacidade funcional em pacientes com artrite reumatoide de longa evolução Switching between anti-TNF-alpha agents does not improve functional capacity in patients with long-standing and active rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Maria Roberta Melo P Soares

    2012-02-01

    Full Text Available OBJETIVOS: Avaliar a resposta clínica após a estratégia de troca entre agentes antifator de necrose tumoral alfa (anti-TNF-alfa em pacientes com artrite reumatoide (AR. PACIENTES E MÉTODOS: Foram incluídos 99 pacientes com diagnóstico de AR (American College of Rheumatology, 1987, em uso de terapia anti-TNF-alfa, para avaliação da resposta terapêutica após 24 semanas. A estratégia de troca foi feita se, após 12 a 24 semanas, houvesse relato de evento adverso sério (T: toxicidade ou se não ocorresse redução maior que 0,6 do índice de atividade da doença (DAS28 inicial (RI: resposta inadequada. Nesse último caso, o paciente foi considerado como falência primária (FP. Falência secundária (FS foi definida se houvesse perda de resposta após melhora inicial. Remissão (DAS28 0,2 do questionário de avaliação da saúde (HAQ inicial] foram avaliadas por análise de regressão linear. P OBJECTIVES: To assess clinical response after switching between anti-tumor necrosis factor-alpha (anti-TNF-alpha agents in patients with rheumatoid arthritis (RA. PATIENTS AND METHODS: This study included 99 patients diagnosed with RA American College of Rheumatology, 1987, on anti-TNF-alpha therapy, to assess the therapeutic response after 24 weeks. Switching was performed if, after 12 to 24 weeks, a severe adverse event was reported (toxicity: T or if no reduction greater than 0.6 in the initial Disease Activity Score 28 (DAS28 occurred (inadequate response: IR. In case of IR, the patient was considered as primary failure (PF. Secondary failure (SF was defined as loss of response after initial improvement. Remission (DAS28 0.2] were assessed by use of linear regression analysis. The significance level adopted was P < 0.05. RESULTS: Switching was performed in 39 (39.4% patients, especially due to PF (24.3%, SF (35.1% and T (40.5%. The retention rate of the first agent was 60.1%, and the mean time for switching was 14.2 ± 10.9 months. After

  1. Polyarthritis flare in patient with ankylosing spondylitis treated with infliximab

    Directory of Open Access Journals (Sweden)

    E. Filippucci

    2011-06-01

    Full Text Available Over the last ten years, the treatment of seronegative spondyloarthropathies has changed dramatically with the introduction of the anti-tumor necrosis factor alpha (TNFα agents. Nevertheless, there is a growing number of studies describing several adverse reactions in patients treated with biological agents. In the present report we describe the case of a 22-year-old male patient with ankylosing spondylitis who developed a “paradoxic” adverse reaction, while receiving infliximab.

  2. Infliximab therapy in pediatric Crohn’s disease: a review

    Directory of Open Access Journals (Sweden)

    Kalyan Ray Parashette

    2010-06-01

    Full Text Available Kalyan Ray Parashette1, Raghavendra Charan Makam2, Carmen Cuffari31Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA, USA; 3Division of Pediatric Gastroenterology, The Johns Hopkins Children’s Center, Baltimore, MD, USAAbstract: Anti-tumor necrosis factor alpha (TNF-α therapy has re-defined our treatment paradigms in managing patients with Crohn’s disease (CD and ulcerative colitis. Although the ACCENT studies showed proven efficacy in the induction and maintenance of disease remission in adult patients with moderate to severe CD, the pediatric experience was instrumental in bringing forth the notion of “top-down” therapy to improve overall clinical response while reducing the risk of complications resulting from long-standing active disease. Infliximab has proven efficacy in the induction and maintenance of disease remission in children and adolescents with CD. In an open-labeled study of 112 pediatric patients with moderate to severe CD, 58% achieved clinical remission on induction of infliximab (5 mg/kg therapy. Among those patients who achieved disease remission, 56% maintained disease remission on maintenance (5 mg/kg every 8 weeks therapy. Longitudinal follow-up studies have also shown that responsiveness to infliximab therapy also correlates well with reduced rates of hospitalization, and surgery for complication of long-standing active disease, including stricture and fistulae formation. Moreover, these children have also been shown to improve overall growth while maintaining an effective disease remission. The pediatric experience has been instructive in suggesting that the early introduction of anti-TNF-α therapy may perhaps alter the natural history of CD in children, an observation that has stimulated a great deal of interest among gastroenterologists who care for adult patients with CD.Keywords: Crohn’s disease

  3. Het ontstaan van immuuncomplexen van infliximab en anti-infliximab als een verklaring voor het falen van infliximabtherapie bij reumatoïde artritis: observationeel onderzoek bij 4 patiënten

    NARCIS (Netherlands)

    van der Laken, C. J.; Voskuyl, A. E.; Roos, J. C.; Stigter van Walsum, M.; de Groot, E. R.; Wolbink, G. J.; Dijkmans, B. A. C.; Aarden, L. A.

    2008-01-01

    OBJECTIVE: To investigate the in vivo mechanism of non-responding to infliximab treatment of patients with rheumatoid arthritis (RA) and the role of anti-infliximab antibodies by using radiolabeled infliximab. DESIGN: Descriptive and comparative study. METHOD: Two responding and two non-responding

  4. In vitro inhibition of enterobacteria-reactive CD4+Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Mangano, K.; Sardesai, N.; D'Alcamo, M.

    2008-01-01

    VGX-1027 is an isozaxoline compound that has recently been found to primarily target the function of murine macrophages but not of T cells, inhibiting secretion of tumor necrosis factor (TNF)-alpha in response to different Toll-like receptor agonists in vitro and in vivo. The well-defined role of...

  5. Infliximab for treating sarcoidosis patients, Portuguese experience

    Directory of Open Access Journals (Sweden)

    M. Aguiar

    2011-03-01

    Full Text Available Despite aggressive treatment, sarcoidosis may be debilitating and progressive. The role of tumor necrosis factor (TNF ap in the genesis of granulomas is ambiguous. It has proved to be critical in the formation and maintenance of granulomatous inflammation and its antagonist, Infl iximab, has therefore been used with success in the treatment of patients with sarcoidosis. There are, however, reports of onset of sarcoidosis in patients treated for other conditions and where there had been no outbursts before submission to this therapy. We used Infl iximab in the treatment of patients with sarcoidosis who either had not responded to corticosteroids and other conventional drugs or had developed unacceptable side effects to these drugs. The initial dose was 5 mg/kg body weight and subsequent doses were given at weeks 2, 4 and then every other 8 weeks for a total period of one year. We treated ten patients with biopsy proven sarcoidosis, five men and five women, with a mean age of 47.1 years ranging from 28 to 63 years of age. Three patients had severe neurological symptoms, two had hepatic cirrhosis, one had granulomatous inflammation of the lachrymal gland and had already undergone repeated surgery, one had extensive pulmonary involvement (stage III, one had disfiguring lupus pernio and two presented disabling cutaneous nodules. Eight patients had more than one organ with evidence of disease. All patients were submitted to at least seven infusions of Infliximab. In four patients the dosage of corticosteroids or other immunosuppressive drugs was suspended, in three the dosage was reduced and in one, corticosteroids were added to the Infl iximab therapy. In five of the patients there was an important improvement. One of the patients with neurological symptoms displayed a complete recovery, while another had significant improvement of vision deficit enabling her to read again. Two patients withdrew from therapy, one due to lack of improvement of

  6. Inflammatory Bowel Disease Patients Are Frequently Nonadherent to Scheduled Induction and Maintenance Infliximab Therapy: A Canadian Cohort Study

    Directory of Open Access Journals (Sweden)

    Christopher Ma

    2015-01-01

    Full Text Available BACKGROUND: Adherence to maintenance medication regimens in inflammatory bowel disease patients has traditionally been poor. Although infliximab has demonstrated efficacy in inducing and maintaining disease remission, adherence to regularly scheduled infliximab infusions is required to maintain therapeutic trough drug levels and prevent the development of anti-infliximab antibodies.

  7. Tolerability of Shortened Infliximab Infusion Times in Patients With Inflammatory Bowel Diseases : A Single-Center Cohort Study

    NARCIS (Netherlands)

    Breynaert, Christine; Ferrante, Marc; Fidder, Herma; Van Steen, Kristel; Noman, Maja; Ballet, Vera; Vermeire, Severine; Rutgeerts, Paul; Van Assche, Gert

    OBJECTIVES: Scheduled maintenance therapy with infliximab decreases the risk of infusion reactions. Many centers have accelerated infusion times to 1 h in selected patients who tolerate 5 mg/kg infliximab infusions. The aim of this study was to compare the tolerability of 1-h and 2-h infliximab

  8. Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study.

    NARCIS (Netherlands)

    Bemt, B.J.F van den; Broeder, A. den; Snijders, G.F.; Hekster, Y.A.; Riel, P.L.C.M. van; Benraad, B.; Wolbink, G.J.; Hoogen, F.H.J. van den

    2008-01-01

    OBJECTIVES: In clinical trials only a small subset of patients with rheumatoid arthritis (RA) benefits from higher than standard dose of infliximab (>3 mg/kg/8 weeks). However, dose escalation of infliximab is frequently applied in clinical practice. Individual adjustment of infliximab treatment

  9. A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis

    NARCIS (Netherlands)

    Hommes, Daan W.; Erkelens, Willemien; Ponsioen, Cyriel; Stokkers, Pieter; Rauws, Erik; van der Spek, Mirjam; ten Kate, Fiebo; van Deventer, Sander J.

    2008-01-01

    GOALS: To evaluate the safety and efficacy of infliximab in patients with primary sclerosing cholangitis. STUDY: In this double-blind, placebo-controlled study, 24 patients with primary sclerosing cholangitis were screened and randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg) or

  10. The Immunogenicity of Branded and Biosimilar Infliximab in Rheumatoid Arthritis According to Th9-Related Responses

    Directory of Open Access Journals (Sweden)

    Rossella Talotta

    2017-10-01

    Full Text Available Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in T-helper-9 (Th9 percentages induced by an in vitro stimulation test. Methods: Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis (RA outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded infliximab inadequate responders and 10 healthy controls were cultured, with or without 50 μg/mL of infliximab originator (Remicade® or 50 μg/mL of infliximab biosimilar (Remsima® for 18 h. Th9 lymphocytes were identified by means of flow cytometry as PU.1 and IRF4-expressing, IL-9-secreting CD4+ T cells. Furthermore, the markers CCR7 and CD45RA were used to distinguish naïve from memory IL-9 producer cells. Results: Under unstimulated conditions, the drug-free RA patients had the highest percentages of Th9 lymphocytes. Following stimulation with branded infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7+, CD45RA− (central memory and CCR7−, CD45RA− (effector memory cells significantly increased in the group of inadequate responders, but no significant variation was observed after exposure to the biosimilar of infliximab. Conclusions: Th9 cells seem to be involved in the immune response to the epitopes of branded, but not biosimilar, infliximab, and this may depend on the recall and stimulation of both central and effector memory cells.

  11. As Infliximab Use for Ulcerative Colitis Has Increased, so Has the Rate of Surgical Resection.

    Science.gov (United States)

    Kin, Cindy; Kate Bundorf, M

    2017-07-01

    Infliximab was approved for ulcerative colitis in 2005 after randomized trials showed it reduced the risk of colectomy. Its effect on population-level surgery rates is unknown. Our aim is to assess the impact of infliximab approval for ulcerative colitis on surgical intervention. Retrospective review of a private insurance claims database (2002 to 2013) was performed of patients aged 18-64 diagnosed with ulcerative colitis and with 2 years of follow-up. Outcome measures were infliximab treatment and surgical resection. Multivariable logistic regression used independent variables of time period of diagnosis, age, gender, comorbidities, and insurance type. The cohort included 58,681 patients. Age, gender, and comorbidities were comparable across time periods. Patients diagnosed in the post-infliximab period had greater odds of undergoing infliximab treatment within the first year of diagnosis than those in the pre-infliximab era (OR = 2.88, p infliximab period (OR 1.5, p infliximab for ulcerative colitis has, as expected, increased since its approval, but so has the risk of surgery. Thus, the introduction of biologic therapy has not decreased the risk for surgery for this patient population.

  12. The duration of effect of infliximab maintenance treatment in paediatric Crohn's disease is limited

    NARCIS (Netherlands)

    de Bie, C. I.; Kindermann, A.; Kokke, F. T. M.; Damen, G. M.; Kneepkens, C. M. F.; van Rheenen, P. F.; Schweizer, J. J.; Hoekstra, J. H.; Norbruis, O. F.; Ten, W. E. Tjon A.; Vreugdenhil, A. C.; Deckers-Kocken, J. M.; Gijsbers, C. F. M.; Escher, J. C.; de Ridder, L.; Hummel, T.

    2011-01-01

    P>Background Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). Aim To evaluate the long-term efficacy of infliximab treatment in paediatric CD. Methods In this observational, multicentre study, all paediatric CD

  13. Re-activation of bovine tuberculosis in a patient treated with infliximab

    DEFF Research Database (Denmark)

    Larsen, Mette Vang; Thomsen, V Ø; Sørensen, Inge Juul

    2008-01-01

    before initiation of treatment with infliximab. The tuberculin skin test (TST) was negative, chest radiography was normal and she had no known risk factors for TB. After 4 months of treatment with infliximab, the patient developed ascites caused by Mycobacterium bovis. The TST was repeatedly negative...

  14. Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis

    Science.gov (United States)

    Ternant, David; Mulleman, Denis; Lauféron, Francine; Vignault, Céline; Ducourau, Emilie; Wendling, Daniel; Goupille, Philippe; Paintaud, Gilles

    2012-01-01

    AIMS Infliximab, an anti-tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients. METHODS Twenty-six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg−1 infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two-compartment model with first-order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve. RESULTS A total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day−1 (22%) and intercompartment clearance = 2.3 l day−1. Methotrexate influenced neither pharmacokinetic nor BASDAI variability. CONCLUSIONS Using the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis. PMID:21692827

  15. Infliximab and adalimumab drug levels in Crohn's disease: contrasting associations with disease activity and influencing factors.

    Science.gov (United States)

    Ward, M G; Warner, B; Unsworth, N; Chuah, S-W; Brownclarke, C; Shieh, S; Parkes, M; Sanderson, J D; Arkir, Z; Reynolds, J; Gibson, P R; Irving, P M

    2017-07-01

    Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab. To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels. We performed a cross-sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey-Bradshaw index, C-reactive protein and faecal calprotectin. 6-tioguanine nucleotide (TGN) concentrations were measured in patients treated with thiopurines. A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (P=.081) and biochemical remission (P=.003) and faecal calprotectin normalisation (Pinfliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels. Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels. © 2017 John Wiley & Sons Ltd.

  16. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    OBJECTIVE: Approximately 30% of patients with depression fail to respond to a selective serotonin reuptake inhibitor (SSRI). Few studies have attempted to define these patients from a biological perspective. Studies suggest that overall patients with depression show increased production of proinflammatory cytokines. We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant. METHODS: Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in DSM-1V major depressives who were SSRI resistant, in formerly SSRI resistant patients currently euthymic and in healthy controls. RESULTS: Patients with SSRI-resistant depression had significantly higher production of the pro-inflammatory cytokines IL-6 (p=0.01) and TNF-alpha (p=0.004) compared to normal controls. Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group. Anti-inflammatory cytokine levels did not differ across the 3 groups. CONCLUSION: Suppression of proinflammatory cytokines does not occur in depressed patients who fail to respond to SSRIs and is necessary for clinical recovery.

  17. Anti-infliximab antibodies are already detectable in most patients with rheumatoid arthritis halfway through an infusioncycle: an open-label pharmacokinetic cohort study

    NARCIS (Netherlands)

    Bemt, B.J.F van den; Broeder, A. den; Wolbink, G.J.; Hekster, Y.A.; Riel, P.L. van; Benraad, B.; Hoogen, F.H.J. van den

    2011-01-01

    BACKGROUND: This study in patients with rheumatoid arthritis (RA) treated with infliximab describes prospectively the course of (anti)infliximab levels within an infusioncycle to assess at what moment patients develop low/no infliximab trough levels and/or detectable anti-infliximab levels. METHODS:

  18. Synergistic induction of CX3CL1 by TNF alpha and IFN gamma in osteoblasts from rheumatoid arthritis: involvement of NF-kappa B and STAT-1 signaling pathways

    Directory of Open Access Journals (Sweden)

    Kuninobu Wakabayashi

    2008-10-01

    Full Text Available Takeo Isozaki, Tsuyoshi Kasama, Ryo Takahashi, Tsuyoshi Odai, Kuninobu Wakabayashi, Hirohito Kanemitsu, Kyoko Nohtomi, Hiroko T Takeuchi, Satoshi Matsukura, Masakazu TezukaDivision of Rheumatology, Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan, and the Department of Orthopedics, Denencyofu Central Hospital, Tokyo, JapanAbstract: To explore the regulation of CX3CL1 in inflammatory bone diseases, CX3CL1 expression by osteoblasts (OB was examined. Human OB isolated from rheumatoid arthritis (RA patients, osteoarthritis patients, and normal individuals were incubated in the presence of cytokines. Soluble CX3CL1 levels were determined with an enzyme-linked immunosorbent assay. Expression of CX3CL1 mRNA was examined using quantitative real-time polymerase chain reaction. Although tumor necrosis factor (TNF-α or interferon (IFN-γ alone RA OB induced negligible CX3CL1 secretion, the combination of TNF-α and IFN-γ induced dramatic increases in both soluble CX3CL1 protein and mRNA transcripts. This synergistic effect was more pronounced in OB from RA than in OB from either osteoarthritis or normal individuals. The expression of CX3CL1 was markedly reduced by specific inhibitors of the nuclear factor-κB (NF-κB or STAT-1 transcription factor. These findings suggest that osteoblasts are an important cellular source of CX3CL1 and may play roles in inflammatory bone/joint diseases.Keywords: osteoblast, CX3CL1, chemokine, NF-κB, STAT-1

  19. Knowledge of Fecal Calprotectin and Infliximab Trough Levels Alters Clinical Decision-making for IBD Outpatients on Maintenance Infliximab Therapy

    Science.gov (United States)

    Prosser, Connie; Kroeker, Karen I.; Wang, Haili; Shalapay, Carol; Dhami, Neil; Fedorak, Darryl K.; Halloran, Brendan; Dieleman, Levinus A.; Goodman, Karen J.; Fedorak, Richard N.

    2015-01-01

    Background: Infliximab is an effective therapy for inflammatory bowel disease (IBD). However, more than 50% of patients lose response. Empiric dose intensification is not effective for all patients because not all patients have objective disease activity or subtherapeutic drug level. The aim was to determine how an objective marker of disease activity or therapeutic drug monitoring affects clinical decisions regarding maintenance infliximab therapy in outpatients with IBD. Methods: Consecutive patients with IBD on maintenance infliximab therapy were invited to participate by providing preinfusion stool and blood samples. Fecal calprotectin (FCP) and infliximab trough levels (ITLs) were measured by enzyme linked immunosorbent assay. Three decisions were compared: (1) actual clinical decision, (2) algorithmic FCP or ITL decisions, and (3) expert panel decision based on (a) clinical data, (b) clinical data plus FCP, and (c) clinical data plus FCP plus ITL. In secondary analysis, Receiver-operating curves were used to assess the ability of FCP and ITL in predicting clinical disease activity or remission. Results: A total of 36 sets of blood and stool were available for analysis; median FCP 191.5 μg/g, median ITLs 7.3 μg/mL. The actual clinical decision differed from the hypothetical decision in 47.2% (FCP algorithm); 69.4% (ITL algorithm); 25.0% (expert panel clinical decision); 44.4% (expert panel clinical plus FCP); 58.3% (expert panel clinical plus FCP plus ITL) cases. FCP predicted clinical relapse (area under the curve [AUC] = 0.417; 95% confidence interval [CI], 0.197–0.641) and subtherapeutic ITL (AUC = 0.774; 95% CI, 0.536–1.000). ITL predicted clinical remission (AUC = 0.498; 95% CI, 0.254–0.742) and objective remission (AUC = 0.773; 95% CI, 0.622–0.924). Conclusions: Using FCP and ITLs in addition to clinical data results in an increased number of decisions to optimize management in outpatients with IBD on stable maintenance infliximab therapy. PMID

  20. Outcome Following Infliximab Therapy for Pediatric Patients Hospitalized with Refractory Colitis-Predominant Inflammatory Bowel Disease

    Science.gov (United States)

    Falaiye, Tolulope O.; Mitchell, Keisha R.; Lu, Zengqi; Saville, Benjamin R.; Horst, Sara N.; Moulton, Dedrick E.; Schwartz, David A.; Wilson, Keith T.; Rosen, Michael J.

    2013-01-01

    Objectives While randomized trials demonstrated efficacy of infliximab for both pediatric Crohn’s disease (CD) and ulcerative colitis (UC), few patients in these studies exhibited colitis requiring hospitalization. The aims of this study were to determine the rate of subsequent infliximab failure and dose escalation in pediatric patients started on infliximab during hospitalization for colitis-predominant IBD, and to identify potential predictors of these endpoints. Methods Single center retrospective cohort study of patients admitted from 2005 to 2010 with Crohn’s colitis, UC, or IBD-unspecified (IBD-U) and initiated on infliximab. Results We identified 29 patients (12 Crohn’s colitis, 15 UC, and 2 IBD-U; median age 14 years) with a median follow-up of 923 days. 18 patients (62%) required infliximab dose escalation (increased dose or decreased infusion interval). Infliximab failure occurred in 18 patients (62%), due to ineffectiveness in 12 (67%) and adverse reactions in 6 (33%). 12 patients (41%) underwent colectomy. Subsequent need for infliximab dose escalation was associated with lower body mass index (BMI) z-score (P=0.01), lower serum albumin (P=0.03), and higher ESR (P=0.002) at baseline. ESR predicted subsequent infliximab dose escalation with an area under the curve of 0.89 (95% CI 0.72–1.00) and a sensitivity and specificity at a cutoff of 38 mm/hr of 0.79 (95% CI 0.49–0.95) and 0.88 (95% CI 0.47–0.99), respectively. Conclusions Most hospitalized pediatric patients with colitis treated with infliximab require early dose escalation and fail the drug long term. Low BMI and albumin, and high ESR may identify patients who would benefit from a higher infliximab starting dose. PMID:24048170

  1. Clinical relevance and inter-test reliability of anti-infliximab antibodies and infliximab trough levels in patients with inflammatory bowel disease.

    Science.gov (United States)

    Guiotto, Cristina; Daperno, Marco; Frigerio, Francesco; Vizzini, Margherita; Cerruti, Roberta; Ercole, Elena; Cosimato, Maurizio; Lavagna, Alessandro; Germano, Laura; Migliardi, Marco; Rocca, Rodolfo

    2016-02-01

    Treatment with infliximab is a common option for inflammatory bowel disease (IBD) patients. Therapeutic drug monitoring could improve treatment management. To test inter-test reliability of two commercially available diagnostic kits for infliximab trough levels and infliximab antibodies, and their association with treatment outcomes. 86 IBD outpatients on infliximab maintenance treatment were enrolled in a prospective cross-sectional study, 115 samples were available for inter-test reliability. Inter-test agreement was good both for trough levels (concordance correlation coefficient 0.78, weighted κ 0.60, Sperman's ρ 0.937) and for infliximab antibodies (weighted κ 0.79) measurement, when comparing Promonitor and ImmunDiagnostik kits. According to manufacturers' cut-off values, trough levels were classified as undetectable (17%), low (21%) or in range (63%). The only significant associations were: mucosal healing (p=0.026; OR 6.50), infliximab antibody status (p=0.0015; OR 0.031) and adverse events (p=0.009; OR 0.115). Higher trough levels were observed among patients on concomitant steroid/immunosuppressive therapy and among patients with dose-intensification. Infliximab antibodies were significantly associated to treatment-related adverse events (p=0.0003, OR 30.42), and to lower trough levels, but not to other clinical variables. The two tests performed equally well. Infliximab antibodies were associated to adverse events, while trough levels were not associated to treatment outcomes. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  2. Inflammatory bowel disease patients are frequently nonadherent to scheduled induction and maintenance infliximab therapy: A Canadian cohort study.

    Science.gov (United States)

    Ma, Christopher; Evaschesen, Chad J; Gracias, Grenvil; Huang, Vivian W; Fedorak, Darryl K; Kroeker, Karen I; Dieleman, Levinus A; Halloran, Brendan P; Fedorak, Richard N

    2015-01-01

    Adherence to maintenance medication regimens in inflammatory bowel disease patients has traditionally been poor. Although infliximab has demonstrated efficacy in inducing and maintaining disease remission, adherence to regularly scheduled infliximab infusions is required to maintain therapeutic trough drug levels and prevent the development of anti-infliximab antibodies. To characterize patient adherence to regularly scheduled induction and maintenance infliximab infusions. A retrospective cohort study was conducted evaluating adult outpatients with Crohn disease or ulcerative colitis on an induction or maintenance regimen of regularly scheduled infliximab from 2008 to 2010 at the University of Alberta (Edmonton, Alberta). Nonadherence was defined by a discrepancy of >72 h between the scheduled date of infusion and the actual date of administration. Patients were defined as nonadherent if they received 1 week late. While three-quarters of patients are adherent to infliximab induction therapy, fewer than one-third remained adherent to their scheduled maintenance infliximab regimen.

  3. Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

    Science.gov (United States)

    Ehrenpreis, Eli D

    2017-12-01

    Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

  4. Infliximab en pacientes con enfermedad ocular inflamatoria, refractarios a DARMES

    OpenAIRE

    Elmer R. García-Salazar; Henry Terrazas; Javier Gonzales; Miguel Fernández

    2013-01-01

    Se describe la experiencia con infliximab (anticuerpo monoclonal con una potente acción antiinflamatoria) en el tratamiento de enfermedades oculares inflamatorias secundarias a patologías reumáticas y refractarias a drogas antirreumáticas modificadoras de la enfermedad (DARMES). Se evaluó el caso de una paciente de 50 años con artritis reumatoide (AR) de fondo activo y una paciente de 37 años con vasculitis anticuerpos anticitoplasma de neutrófilos especifico para mieloperoxidasa (ANCA MPO) s...

  5. Management of inflammatory bowel disease in poor responders to infliximab

    Science.gov (United States)

    Guerra, Iván; Bermejo, Fernando

    2014-01-01

    Infliximab (IFX) is an effective treatment for inducing and maintaining response in Crohn’s disease and ulcerative colitis patients. Some patients present lack of response or loss of response to IFX during maintenance therapy. Empirical management with combination therapy with an immunomodulator, IFX dose escalation, or switching IFX for another antitumor necrosis factor-α drug, mainly adalimumab, is common in clinical practice. Selecting the best choice with the help of serum drug concentrations and trough IFX antibody concentrations could be a very interesting approach. In addition to surgery, a broad spectrum of new drugs has been tested and could expand treatment options in the near future. PMID:25258548

  6. Long-term safety and efficacy of infliximab for the treatment of ankylosing spondylitis

    Science.gov (United States)

    Elalouf, Ofir; Elkayam, Ori

    2015-01-01

    The introduction of TNFα blockers has revolutionized the treatment of ankylosing spondylitis (AS). The objectives of this review are to summarize the most up-to-date data on long-term efficacy and safety of infliximab in AS, with special emphasis on axial and extra-articular disease, predictors of response, and radiological response. The general consensus of this literature search was that infliximab is highly efficacious in the treatment of AS. Most studies have demonstrated good clinical outcomes after 3 years of treatment, as measured by Spondyloarthritis International Society response in 75%–85% of treated AS patients. Reports on the long-term effects of infliximab as documented by radiological findings, however, are controversial. While some studies reported a similar progression rate as that of the historical OASIS cohort, others have suggested that infliximab may halt new bone formation. The long-term safety of infliximab is well known, mainly from data stored in national registries. While it has been suggested that side effects of infliximab may be fewer in AS compared to rheumatoid arthritis, data on this issue are sparse, with most of the information on long-term safety pertaining to rheumatoid arthritis. It can however be concluded that the long-term efficacy of infliximab is apparently maintained in AS and with an acceptable safety profile. PMID:26640380

  7. Higher order structures of Adalimumab, Infliximab and their complexes with TNFα revealed by electron microscopy.

    Science.gov (United States)

    Tran, Bich Ngoc; Chan, Siew Leong; Ng, Chloe; Shi, Jian; Correia, Ivan; Radziejewski, Czeslaw; Matsudaira, Paul

    2017-12-01

    Adalimumab and Infliximab are recombinant IgG1 monoclonal antibodies (mAbs) that bind and neutralize human tumor necrosis factor alpha (TNFα). TNFα forms a stable homotrimer with unique surface-exposed sites for Adalimumab, Infliximab, and TNF receptor binding. Here, we report the structures of Adalimumab-TNFα and Infliximab-TNFα complexes modeled from negative stain EM and cryo-EM images. EM images reveal complex structures consisting of 1:1, 1:2, 2:2, and 3:2 complexes of Adalimumab-TNFα and Infliximab-TNFα. The 2:2 complex structures of Adalimumab-TNFα and Infliximab-TNFα show diamond-shaped profiles and the 2D class averages reveal distinct orientations of the Fab domains, indicating different binding modes by Adalimumab and Infliximab to TNFα. After separation by size exclusion chromatography and analysis by negative stain EM, the 3:2 complexes of Adalimumab-TNFα or Infliximab-TNFα complexes are more complicated but retain features recognized in the 2:2 complexes. Preliminary cryo-EM analysis of 3:2 Adalimumab-TNFα complex generated a low-resolution density consistent with a TNFα trimer bound with three Fab domains from three individual antibody molecules, while each antibody molecule binds to two molecules of TNFα trimer. The Fc domains are not visible in the reconstruction. These results show the two mAbs form structurally distinct complexes with TNFα. © 2017 The Protein Society.

  8. Use of Electronic Health Record Tools to Facilitate and Audit Infliximab Prescribing.

    Science.gov (United States)

    Sharpless, Bethany R; Del Rosario, Fernando; Molle-Rios, Zarela; Hilmas, Elora

    2018-01-01

    The objective of this project was to assess a pediatric institution's use of infliximab and develop and evaluate electronic health record tools to improve safety and efficiency of infliximab ordering through auditing and improved communication. Best use of infliximab was defined through a literature review, analysis of baseline use of infliximab at our institution, and distribution and analysis of a national survey. Auditing and order communication were optimized through implementation of mandatory indications in the infliximab orderable and creation of an interactive flowsheet that collects discrete and free-text data. The value of the implemented electronic health record tools was assessed at the conclusion of the project. Baseline analysis determined that 93.8% of orders were dosed appropriately according to the findings of a literature review. After implementation of the flowsheet and indications, the time to perform an audit of use was reduced from 60 minutes to 5 minutes per month. Four months post implementation, data were entered by 60% of the pediatric gastroenterologists at our institution on 15.3% of all encounters for infliximab. Users were surveyed on the value of the tools, with 100% planning to continue using the workflow, and 82% stating the tools frequently improve the efficiency and safety of infliximab prescribing. Creation of a standard workflow by using an interactive flowsheet has improved auditing ability and facilitated the communication of important order information surrounding infliximab. Providers and pharmacists feel these tools improve the safety and efficiency of infliximab ordering, and auditing data reveal that the tools are being used.

  9. Long-Term Outcome of Patients with Ulcerative Colitis and Primary Non-response to Infliximab.

    Science.gov (United States)

    Papamichael, Konstantinos; Rivals-Lerebours, Oliviane; Billiet, Thomas; Vande Casteele, Niels; Gils, Ann; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul J; Mantzaris, Gerassimos J; Peyrin-Biroulet, Laurent; Vermeire, Severine

    2016-09-01

    We studied the long-term outcome of patients with ulcerative colitis [UC] and primary non response [PNR] to infliximab and searched for predictors of colectomy in these patients. This retrospective, multi-centre study included UC patients from three European referral centres, with PNR to infliximab defined as a lack of clinical improvement after the induction therapy, leading to drug discontinuation. Relapse, for patients who continued on biologicals after PNR to infliximab, was defined as drug discontinuation for PNR, loss of response, or serious adverse event. Serum infliximab concentrations at Weeks 2 and 6 were evaluated using an enzyme-linked immunosorbent assay [ELISA] developed in house. The study population consisted of 99 anti-tumour necrosis factor [TNF]-naïve patients with UC and PNR to infliximab. At the end of follow-up (median: 3.2 [interquartile range 1-6.3] years), 55 [55.6%] of these patients underwent colectomy. Multiple Cox regression analysis identified acute severe UC (hazard ratio [HR]: 24; 95% confidence interval [CI]: 2.5-231; p = 0.006], baseline C-reactive protein [CRP] > 5mg/l [HR: 11; 95% CI: 2.1-58.8; p = 0.005], baseline albumin infliximab concentration at Week 2 infliximab, there was a marginally higher cumulative probability for relapse in patients switching to another anti-TNF agent compared with those swapping to vedolizumab [p logrank = 0.08]. About half of UC patients with PNR to infliximab will undergo colectomy. Patients with severe inflammation and low serum infliximab concetrations during the induction phase are at greatest risk. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. IMPORTANCE OF MEASURING LEVELS OF INFLIXIMAB IN PATIENTS TREATING INFLAMMATORY BOWEL DISEASE IN A BRAZILIAN COHORT.

    Science.gov (United States)

    Kampa, Katia Cristina; Morsoletto, Daphne Benatti Gonçalves; Loures, Marcela Rocha; Pissaia, Alcindo; Nones, Rodrigo Bremer; Ivantes, Cláudia Alexandra Pontes

    2017-12-01

    Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases. In such pathologies, there is an increased production of alpha tumor necrosis factor (TNF-α). Patients, in whom the conventional immunosuppressant treatment fails, require the use of immunobiological therapy, such as anti-TNF-α, a monoclonal antibody. Infliximab is an anti-TNF-α drug, a chimerical immunoglobulin, with a murine component, which is responsible for the generation of immunogenicity against the drug and formation of anti-TNF-α antibodies. The presence of anti-drug antibodies may be responsible for adverse events and reduction of the drug's effectiveness. Patients with inflammatory bowel diseases undergoing therapy with biological medication, such as infliximab, can relapse overtime and this may not be translated into clinical symptoms. Thus, there is a need for a method to evaluate the efficacy of the drug, through the measurement of serum infliximab levels, as well as antibodies research. This study aimed to measure serum infliximab levels and anti-infliximab antibodies in patients with inflammatory bowel diseases post-induction phase and during maintenance therapy, and describe the therapeutic modifications that took place based on the serum levels results. It was a retrospective study, that included forty-five patients, with a total of 63 samples of infliximab measurement. Twenty-one patients had an adequate infliximab serum level, 31 had subtherapeutic levels and 11 had supratherapeutic levels. Seven patients had their medication suspended due to therapeutic failure or high levels of antibodies to infliximab. In conclusion, only a third of the patients had adequate infliximab levels and 36% presented with subtherapeutic levels at the end of the induction phase. Therapy optimization occurred based in about 46% of the samples results, demonstrating the importance of having this tool to help the clinical handling of patients with inflammatory bowel diseases ongoing

  11. Infliximab for ipilimumab-induced colitis: A series of 13 patients.

    Science.gov (United States)

    Hillock, Nadine T; Heard, Sharryn; Kichenadasse, Ganessan; Hill, Catherine L; Andrews, Jane

    2017-10-01

    To review the outcomes of metastatic melanoma patients treated with infliximab for severe steroid-refractory colitis secondary to ipilimumab therapy. Immune-related colitis is a known potential adverse effect of ipilimumab, that causes significant morbidity and extended hospital stays. There are limited outcome data for patients treated with infliximab for ipilimumab-induced colitis refractory to corticosteroids. Management guidelines have been developed based on case study evidence only. A retrospective review of all patients administered infliximab for ipilimumab-induced colitis at South Australian public hospitals between October 2011 and April 2015. Resolution of colitis/diarrhea, duration of hospital stay, dosage regimen of infliximab used (single dose vs multiple dose) and surgical intervention if required. Between October 2011 and April 2015, 106 patients were dispensed ipilimumab from South Australian public hospitals for the treatment of metastatic melanoma. Thirteen were administered infliximab for severe, steroid-refractory colitis secondary to ipilimumab. Sixty-two percent received a single dose of infliximab only. Four patients achieved resolution of colitis symptoms at 1 month postinfliximab. Thirty-three percent required surgical intervention despite treatment with infliximab. One patient declined surgery and subsequently died due to bowel perforation. The average number of overnight bed days due to colitis was 27. This series of patients with severe ipilimumab-induced colitis suggests that despite treatment with infliximab a high proportion of patients do not achieve resolution of symptoms. Review of these cases has highlighted the absence of evidence-based guidelines to treat severe, steroid refractory colitis secondary to ipilimumab. Further prospective studies may clarify the role of infliximab for the treatment of ipilimumab-induced colitis. © 2016 John Wiley & Sons Australia, Ltd.

  12. The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease.

    Science.gov (United States)

    Seow, C H; Leung, Y; Vande Casteele, N; Ehteshami Afshar, E; Tanyingoh, D; Bindra, G; Stewart, M J; Beck, P L; Kaplan, G G; Ghosh, S; Panaccione, R

    2017-05-01

    Transplacental transfer of infliximab and adalimumab results in detectable drug levels in the cord blood and infant. To determine if pregnancy influenced the pharmacokinetics of anti-TNF agents in women with inflammatory bowel disease. Twenty-five women from the University of Calgary inflammatory bowel disease(IBD) pregnancy clinic on maintenance infliximab or adalimumab were recruited prospectively with serum bio-banking performed each trimester. Infliximab trough and adalimumab steady-state levels were the outcomes of interest and were analysed using the ANSER infliximab and adalimumab assays. Multivariate linear mixed-effects models were constructed to assess infliximab and adalimumab drug levels during pregnancy adjusting for the clinical covariates of albumin, BMI and CRP. Fifteen women (eight Crohn's disease, seven ulcerative colitis) received infliximab and 10 women with 11 pregnancies were treated with adalimumab. Median age was 29.6 years (IQR: 27.6-31.2 years). Median disease duration was 9.2 years (IQR: 3.16-15.0 years). Median trough infliximab concentrations were 8.50 μg/mL (IQR: 7.23-10.07 μg/mL), 10.31 μg/mL (IQR: 7.66-15.63 μg/mL) and 21.02 μg/mL (IQR: 16.01-26.70 μg/mL) at trimesters 1, 2 and 3 respectively. Significant changes in albumin and BMI (P 0.05) were documented throughout pregnancy. After adjusting for albumin, BMI and CRP, infliximab trough levels increased during pregnancy, by 4.2 μg/mL per trimester (P = 0.02), while adalimumab drug levels remained stable (P > 0.05). Infliximab levels rise during pregnancy, whereas adalimumab levels remain stable after accounting for changes in albumin, BMI and CRP. Therapeutic drug monitoring in the second trimester may be useful in guiding dosing in the third trimester. © 2017 John Wiley & Sons Ltd.

  13. Successful treatment of PASH syndrome with infliximab, cyclosporine and dapsone.

    Science.gov (United States)

    Staub, J; Pfannschmidt, N; Strohal, R; Braun-Falco, M; Lohse, P; Goerdt, S; Leverkus, M

    2015-11-01

    The group of autoinflammatory syndromes associated with Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis are poorly defined and difficult to control with currently available treatment modalities. We describe a patient with PASH syndrome and report about the successful multimodal treatment with infliximab, cyclosporine, and dapsone. A review of the available literature to date about this group of autoinflammatory diseases was performed. We performed genetic analysis for PSTPIP1 mutations associated with PAPA syndrome. A 22-year-old woman presented to our department with pyoderma gangrenosum, concomitant acne, and suppurative hidradenitis. She had previously been treated unsuccessfully with etanercept, adalimumab, fumaric acid and the IL-1 receptor antagonist (IL-1RA) anakinra without prolonged remission. Treatment with intravenous infliximab in combination with cyclosporine and dapsone lead to sudden and prolonged improvement of the clinical symptoms that we classified as PASH syndrome. We review the literature about this group of diseases and report the third case of PASH syndrome to date. PASH syndrome and associated diseases should be considered whenever hidradenitis suppurativa is found in association with pyoderma gangrenosum. We provide a systematic overview about PASH syndrome and suggest a novel multimodal therapeutic regimen beyond isolated inhibition of TNF or IL-1. © 2014 European Academy of Dermatology and Venereology.

  14. Infliximab therapy for Crohn’s disease in the presence of chronic hepatitis C infection - Reply

    Directory of Open Access Journals (Sweden)

    M. Galeazzi

    2011-09-01

    Full Text Available Il trattamento del morbo di Crohn con infliximab rappresenta una importante terapia nei pazienti con la forma fistolizzata della malattia, refrattaria al trattamento con farmaci convenzionali. Tuttavia esistono preoccupazioni nell’usare questo farmaco in pazienti con concomitante infezione cronica da HCV. Tali preoccupazioni sono determinate dal rischio teorico di un accelerato scompenso epatico dovuto all’effetto immunomodulante dell’Infliximab. Noi descriviamo il caso di un paziente affetto da morbo di Crohn e concomitante infezione attiva da epatite C sottoposto a terapia con Infliximab che non ha mostrato alcun peggioramento della funzionalità epatica e dei livelli di carica virale testati con PCR.

  15. A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide.

    Science.gov (United States)

    Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

    2015-01-01

    Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma.

  16. Infliximab dependency is related to decreased surgical rates in adult Crohn's disease patients

    DEFF Research Database (Denmark)

    Pedersen, N.; Duricova, D.; Lenicek, M.

    2010-01-01

    last intended infusion: prolonged response (maintenance of complete/partial response), infliximab dependency (relapse requiring repeated infusions to regain complete/partial response or need of infliximab > 12 months to sustain response). Results Forty-seven percent obtained prolonged response, 29...... on maintenance versus on demand regime was 33 and 31%, respectively (P = 0.63). No relevant clinical or genetic predictors were identified. Conclusion The infliximab dependency response seems to be equivalent to the prolonged response in adult CD patients when comparing surgery rates. Eur J Gastroenterol Hepatol...

  17. Effect of acupuncture on TNF-alpha, IL-1b and IL-10 concentrations in the peritoneal exudates of carrageenan-induced peritonitis in rats Efeito da acupuntura sobre a concentração de TNF-alfa, IL-1b e IL-10 no exsudato peritoneal de ratos com peritonite induzida por carragenina

    Directory of Open Access Journals (Sweden)

    Márcia Valéria Rizzo Scognamillo-Szabó

    2005-02-01

    Full Text Available Acupuncture is an ancient and empirical therapeutic procedure known by its efficacy in the treatment of pain. However, the influence of acupuncture on inflammatory process is still poorly understood and additional research is needed. In this work, we investigated the mechanism of action of manual acupuncture on the inhibition of neutrophil migration to the peritoneal cavity induced by the inflammatory stimulus carrageenan in Wistar rats. Previous results from our laboratory showed that this anti-inflammatory effect is not due to endogenous corticoid release. Furthermore, the concentration of IL-1b, but not of TNF-alpha or IL-10 in the carrageenan-induced exudates was reduced in the acupuncture group. Further research will be needed to elucidate the mechanisms involved in the anti-inflammatory action of acupuncture as described here.A acupuntura é método terapêutico milenar reconhecido por sua eficácia no tratamento da dor, porém seu efeito sobre processos inflamatórios é ainda pouco conhecido e maiores estudos são necessários. Neste trabalho, é investigado o mecanismo de ação da acupuntura manual sobre a inibição na migração de neutrófilos para a cavidade peritoneal induzida por carragenina em ratos Wistar. Resultados prévios indicam que esse efeito antiinflamatório não depende de hormônios corticóides. Entretanto, as concentrações de IL-1b no exsudato induzido por carragenina foram reduzidas pelo tratamento com acupuntura. Por outro lado os níveis de TNF-alfa e IL-10 não foram afetados pelo tratamento. Mais pesquisas poderão elucidar os mecanismos envolvidos na ação antiinflamatória da acupuntura.

  18. Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis

    Science.gov (United States)

    Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Tatsuki, Yoshihiko; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao

    2011-01-01

    Objectives To investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA). Methods Patients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high). Results In TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab. PMID:21478189

  19. Tumor necrosis factor inhibitors in pediatric asthma.

    Science.gov (United States)

    Gjurow, Daniela; Grzelewski, Tomasz; Sobocińska, Agnieszka; Stelmach, Iwona

    2009-06-01

    Asthma is the most common pulmonary disease in children worldwide. As its prevalence significantly increases from 30% to 50% every 10 years it seems that finding the exact form of treatment is crucial to achieve a long-term-benefit effect. Sometimes it appears hard, especially in case of difficult and severe asthma when a standard therapy is not sufficient. The success of omalizumab inspired further studies which turned the spotlight on other pro-inflammatory cytokines such as TNF-alpha. After the success of anti-TNF-alpha therapy in many other inflammatory diseases such as for instance Crohn's Disease and Rheumatoid Arthritis, there appeared several trials discussing the usage of anti-TNF agents in asthma. The first wave of enthusiasm over positive results in treating asthma patients was blunted by other researches which challenged the benefit of anti-TNF-alpha in asthma. What is more, they warned about serious problems and adverse events related to that kind of treatment. These results hindered further investigation, especially in case of children's population, because of the ambiguity as far as the risks and benefits of the treatment were concerned. Nevertheless, the research on anti-TNF-alpha and asthma underlined a significant polymorphism in asthma phenotypes. It seems likely that a therapy with anti-TNF-alpha should be limited to a small subgroup of patients with a specific phenotype manifested by an increased TNF axis. The purpose of this review article is to discuss some recent patents in anti-TNF-alpha therapy.

  20. Inflammatory bowel disease patients are frequently nonadherent to scheduled induction and maintenance infliximab therapy: A Canadian cohort study

    Science.gov (United States)

    Ma, Christopher; Evaschesen, Chad J; Gracias, Grenvil; Huang, Vivian W; Fedorak, Darryl K; Kroeker, Karen I; Dieleman, Levinus A; Halloran, Brendan P; Fedorak, Richard N

    2015-01-01

    BACKGROUND: Adherence to maintenance medication regimens in inflammatory bowel disease patients has traditionally been poor. Although infliximab has demonstrated efficacy in inducing and maintaining disease remission, adherence to regularly scheduled infliximab infusions is required to maintain therapeutic trough drug levels and prevent the development of anti-infliximab antibodies. OBJECTIVES: To characterize patient adherence to regularly scheduled induction and maintenance infliximab infusions. METHODS: A retrospective cohort study was conducted evaluating adult outpatients with Crohn disease or ulcerative colitis on an induction or maintenance regimen of regularly scheduled infliximab from 2008 to 2010 at the University of Alberta (Edmonton, Alberta). Nonadherence was defined by a discrepancy of >72 h between the scheduled date of infusion and the actual date of administration. Patients were defined as nonadherent if they received infliximab infusions per schedule. RESULTS: A total of 215 patients (173 Crohn disease, 42 ulcerative colitis) met the inclusion criteria. Patients received a median of 12.0 infliximab infusions (interquartile range 7.0 to 13.0) during the study period; 412 induction and 1837 maintenance infliximab infusions were administered. Of 140 patients, 109 (77.9%) were adherent to their infliximab induction regimen, while 68 of 215 (31.6%) were adherent to their infliximab maintenance regimen. One hundred ninety-eight of 215 (92.1%) patients received at least one delayed maintenance infliximab infusion and 20 (10.1%) received maintenance infusions, on average, >1 week late. CONCLUSIONS: While three-quarters of patients are adherent to infliximab induction therapy, fewer than one-third remained adherent to their scheduled maintenance infliximab regimen. PMID:26069894

  1. Prognostic factors for long-term infliximab treatment in Crohn's disease patients: a 20-year single centre experience.

    Science.gov (United States)

    Billiet, T; Cleynen, I; Ballet, V; Ferrante, M; Van Assche, G; Gils, A; Vermeire, S

    2016-10-01

    The long-term efficacy of infliximab in patients with Crohn's disease is suboptimal. To study prognostic factors for real-life long-term effcacy of infliximab in Crohn's disease. All consecutive Crohn's disease patients treated with infliximab at a tertiary centre were retrospectively analysed. Only patients who received scheduled infliximab maintenance treatment were considered. Patient- and disease-related factors were used to identify independent predictors of infliximab failure-free survival using Cox proportional hazards regression. Of 1031 patients with Crohn's disease, 261 were eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4-4.7] years, and 65 (24.9%) patients experienced infliximab failure. Estimated 5-year infliximab failure-free survival was 65.9% (95% CI 58.3-73.5). Multivariate Cox regression identified disease duration ≥1 year (HR 2.5 (95% CI 1.2-5.2), P = 0.02), L1 disease location [HR 2.0 (1.1-3.5), P = 0.02], prior anti-TNF use [HR 2.3 (1.1-4.8), P = 0.03], haemoglobin infliximab failure-free survival. Stratifying patients into risk groups resulted in estimated 3-year infliximab failure-free survival rates ranging from 95.3% (94.2-96.4) to 26.3% (8.6-44.0) depending on the number of risk factors (P = 8 × 10(-13) ). This study identified several easy to obtain predictors of infliximab failure in patients with Crohn's disease, and these are in line with previous reports. Those with a high-risk profile for infliximab failure in whom infliximab initiation is considered, should be treated as early as possible making use of therapeutic drug monitoring. © 2016 John Wiley & Sons Ltd.

  2. Tumour necrosis factor inhibitor treatment and occurrence of anterior uveitis in ankylosing spondylitis

    DEFF Research Database (Denmark)

    Lie, Elisabeth; Lindström, Ulf; Zverkova-Sandström, Tatiana

    2017-01-01

    OBJECTIVES: Tumour necrosis factor-α inhibitor (TNFi) treatment has been shown to reduce the rates of anterior uveitis (AU) in patients with ankylosing spondylitis (AS). Our objective was to compare the effect of adalimumab (ADA), etanercept (ETN) and infliximab (IFX) on AU occurrence in AS, using...

  3. Predictors of response to infliximab in patients with fistulizing Crohn's disease Factores predictivos de respuesta a infliximab en pacientes con enfermedad de Crohn fistulizante

    Directory of Open Access Journals (Sweden)

    M. Luna-Chadid

    2004-06-01

    Full Text Available Objective: to evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. Methods: consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. Results: 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (% rates (partial/complete depending on fistula location were: enterocutaneous (25/68%, perianal (35/60%, rectovaginal (36/64%, and enterovesical (20/40%. None of the studied variables (including concomitant immunosuppressive therapy correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21% depending on the dose of infliximab was: first dose (5.6%, second (7.4%, and third (11.1%. Conclusions: infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.Objetivo: evaluar la eficacia e identificar los factores predictivos de respuesta al tratamiento con infliximab en la enfermedad de Crohn fistulizante. Métodos: se realizó un estudio prospectivo en pacientes con enfermedad de Crohn fistulizante que recibían tratamiento con infliximab. La respuesta parcial se definió como una reducción del 50% o más de la línea base en el número de fístulas que drenan. La respuesta completa se definió como el cierre de todas las fístulas. Se evaluó la influencia de diferentes variables sobre la

  4. Association of -308 TNF-alpha promoter polymorphism with viral ...

    African Journals Online (AJOL)

    2012-06-02

    Jun 2, 2012 ... Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. Science. 1998;279(5349):389-393. 10. Bergamini A, Faggioli E, Bolacchi F, et al. Enhanced production of tumor necrosis factor-alpha and interleukin-6 due to prolonged response to lipopolysaccharide in human macrophages ...

  5. Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    2015-01-01

    Full Text Available Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week. During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started.

  6. Polimorfismo del TNF-alpha en autoinmunidad y tuberculosis.

    Directory of Open Access Journals (Sweden)

    Paula A. Correa

    2004-06-01

    Full Text Available El factor de necrosis tumoral alfa (TNF-a está incriminado tanto en enfermedades autoinmunes como en infecciosas. En el presente estudio se examinó el polimorfismo de la región promotora -308 del gen del TNF-a en enfermedades autoinmunes [lupus eritematoso sistémico (LES, artritis reumatoidea (AR, síndrome de Sjögren primario (SSp] y en tuberculosis. La genotipificación del polimorfismo -308 del TNF-a se realizó en ADN de pacientes con AR (N=165, LES (N=118, SSp (N=67, tuberculosis (N=138 y controles sanos (N=419, mediante reacción en cadena de la polimerasa con polimorfismos en los tamaños de los fragmentos de restricción (PCR-RFLP. El alelo TNF2 se asoció con la AR (OR=1,6; IC95% 1,2-2,3, p=0,008, el LES (OR=2,3; IC95% 1,6-3,3, p

  7. Health Care Resource Use and Costs for Crohn’s Disease before and after Infliximab Therapy

    Directory of Open Access Journals (Sweden)

    Dustin E Loomes

    2011-01-01

    Full Text Available BACKGROUND: Infliximab therapy in patients with Crohn’s disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study.

  8. Clinical Experience with Infliximab for Crohn’s Disease: The First 100 Patients in Edmonton, Alberta

    Directory of Open Access Journals (Sweden)

    Clifford Sample

    2002-01-01

    Full Text Available OBJECTIVE: To determine whether the clinical efficacy and safety of infliximab in diverse clinical referral practices was similar to that seen in the randomized, controlled clinical trials.

  9. Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis

    DEFF Research Database (Denmark)

    Sjöberg, Mats; Walch, Andrea; Meshkat, Mina

    2012-01-01

    Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives.......Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives....

  10. Real-life treatment paradigms show infliximab is cost-effective for management of ulcerative colitis.

    Science.gov (United States)

    Ung, Victoria; Thanh, Nguyen Xuan; Wong, Karen; Kroeker, Karen I; Lee, Thomas; Wang, Haili; Ohinmaa, Arto; Jacobs, Philip; Fedorak, Richard N

    2014-11-01

    Infliximab is effective for induction and maintenance of response in patients with moderate to moderately severe ulcerative colitis. Previous cost analyses of infliximab treatment for ulcerative colitis used models of colectomy vs infliximab and response rates derived from early clinical trials. In real life, therapeutic options are more complex; patients frequently choose to remain in an unwell state rather than undergo colectomy, and rates of response to infliximab are generally higher than those reported from clinical trials. We evaluate the real-life cost-effectiveness of infliximab for treatment of ulcerative colitis where infliximab was readily available compared with not available, causing patients to remain in unwell states. We constructed a Markov model to simulate disease progression of patients with moderate or moderately severe ulcerative colitis who depended on corticosteroids and/or did not respond to thiopurine therapy. Utility scores and transition probabilities between health states were determined by using data from randomized controlled trials and real-life rates published by expert inflammatory bowel disease centers. Health care costs were obtained from the Ontario Case Costing Initiative and the Alberta Health Schedule of Medical Benefits documents. The incremental cost-effectiveness ratios for infliximab treatment of ulcerative colitis were $79,000 and $64,000 per quality-adjusted life year, compared with ongoing medical therapy, at 5-year and 10-year treatment time horizons, respectively. By using real-life response rates and patients' preference to avoid colectomy, infliximab therapy is a cost-effective strategy at a willingness-to-pay threshold of $80,000 for treatment of ulcerative colitis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Health care resource use and costs in Crohn's disease before and after infliximab therapy.

    Science.gov (United States)

    Loomes, Dustin E; Teshima, Christopher; Jacobs, Philip; Fedorak, Richard N

    2011-09-01

    Infliximab therapy in patients with Crohn's disease decreases resource use; however, the overall impact on health-related expenditures is unclear, especially beyond one year of study. A retrospective analysis of economic data one and two years before and after infliximab therapy was performed using patients who served as their own controls. Total health care resource use and direct health care costs were compared for patients with or without fistulae. Patients with one (n=66) and two (n=39) years of economic data before and after infliximab treatment had their resource use and direct health care costs estimated. In the year following initiation of infliximab therapy, there were significant decreases in health care use, reflected in total hospital days (495 to 155 [P<0.05]), inpatient colonoscopies (46 to 24 [P<0.05]), outpatient colonoscopies (58 to 33 [P<0.05]) and major surgeries (10 to 2 [P<0.05]). Direct health care costs of inpatient costs for luminal (-$1,747 [P<0.05]) and fistulizing disease (-$2,530 [P<0.05]), major surgeries (-$1240 [P<0.05]) and outpatient colonoscopies (-$184 [P<0.05]) were also significantly reduced before and after infliximab therapy. Total direct health care costs, including the drug cost of infliximab, increased ($21,416 [P<0.05]). In general, the trends in health care costs analyzed over four consecutive years paralleled the two consecutive-year analysis.  Infliximab therapy in patients with Crohn's disease resulted in a significant decrease in both resource use and health care costs, but an increase in total direct health care costs once the cost of infliximab was added.

  12. Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

    Science.gov (United States)

    Eser, Alexander; Primas, Christian; Reinisch, Sieglinde; Vogelsang, Harald; Novacek, Gottfried; Mould, Diane R; Reinisch, Walter

    2018-01-30

    Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab. © 2018, The American College of Clinical Pharmacology.

  13. Infliximab for the treatment of CNS sarcoidosis: A multi-institutional series.

    Science.gov (United States)

    Gelfand, Jeffrey M; Bradshaw, Michael J; Stern, Barney J; Clifford, David B; Wang, Yunxia; Cho, Tracey A; Koth, Laura L; Hauser, Stephen L; Dierkhising, Jason; Vu, NgocHanh; Sriram, Subramaniam; Moses, Harold; Bagnato, Francesca; Kaufmann, Jeffrey A; Ammah, Deidre J; Yohannes, Tsion H; Hamblin, Mark J; Venna, Nagagopal; Green, Ari J; Pawate, Siddharama

    2017-11-14

    To describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α. Investigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes. Of 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24-71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4-8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location. Most patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments. This study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses. © 2017 American Academy of Neurology.

  14. Appropriate infliximab infusion dosage and monitoring: results of a panel meeting of rheumatologists, dermatologists and gastroenterologists

    Science.gov (United States)

    de Vries, Hilbert S; van Oijen, Martijn G H; Driessen, Rieke J B; de Jong, Elke M G J; Creemers, Marjonne C W; Kievit, Wietske; de Jong, Dirk J

    2011-01-01

    AIMS Infliximab, an anti-TNF biologic agent, is currently indicated and reimbursed for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis. Development of national and international guidelines for rheumatology, gastroenterology and dermatology, was mostly based on clinical studies and expert opinion. The aim of this study was to compare available guidelines and local protocols for rheumatology, dermatology and gastroenterology, regarding dosage of infliximab, synergy of infliximab with concomitant medication and monitoring of vital signs during infliximab administration, for achieving optimal care. METHODS Current international, national and local guidelines on the use of infliximab were reviewed and compared, differences and shortcomings were identified, and optimal treatment schedules discussed during a meeting (July 2008) of clinical experts and researchers from three departments of a Dutch university hospital. RESULTS Recommended dosages of infliximab are not equal for different indications. Loss of response to infliximab is a common problem encountered within the three medical specialties, but indications for adjustments in treatment schedules are lacking in all of the guidelines. Monitoring of vital signs (blood pressure, pulse, temperature) during infusion with infliximab is common practice and recommended by some guidelines. Routine measurement of vital signs is not of any value in predicting or recognizing acute infusion reactions, in our experience, and this is confirmed by literature on inflammatory bowel disease. CONCLUSION Different indications encompass different dosing schedules. National and internal guidelines do not provide advice regarding loss of response. Routine measurement of vital signs during infusion is not valuable in detecting acute infusion reactions and should only be performed in case of an acute infusion reaction. These topics need to

  15. Circulating Biomarkers for Predicting Infliximab Response in Rheumatoid Arthritis: A Systematic Bioinformatics Analysis.

    Science.gov (United States)

    Huang, Qiu-Lan; Zhou, Fu-Jiang; Wu, Cheng-Bin; Xu, Chao; Qian, Wen-Ying; Fan, De-Ping; Cai, Xu-Shan

    2017-04-17

    BACKGROUND Infliximab shows good efficacy in treating refractory rheumatoid arthritis (RA). However, many patients responded poorly and related studies were inconsistent in predictive biomarkers. This study aimed to identify circulating biomarkers for predicting infliximab response in RA. MATERIAL AND METHODS Public databases of Gene Expression Omnibus (GEO) and ArrayExpress were searched for related microarray datasets, focused on the response to infliximab in RA. All peripheral blood samples were collected before infliximab treatment and gene expression profiles were measured using microarray. Differential genes associated with infliximab efficacy were analyzed. The genes recognized by half of the datasets were regarded as candidate biomarkers and validated by prospective datasets. RESULTS Eight microarray datasets were identified with 374 blood samples of RA patients, among which 191 (51.1%) were diagnosed as non-responders in the subsequent infliximab treatment. Five genes (FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1) were associated with the efficacy and recognized by half of the datasets. The 5-gene model showed a good predictive power in random- and prospective-designed studies, with AUC (area under receiver operating characteristic [ROC] curve)=0.963 and 1.000, and it was also applicable at the early phase of treatment (at week 2) for predicting the response at week 14 (AUC=1.000). In the placebo group, the model failed to predict the response (AUC=0.697), indicating the model's specificity in infliximab treatment. CONCLUSIONS The model of FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1 in peripheral blood is useful for efficiently predicting the response to infliximab treatment in rheumatoid arthritis.

  16. EFFECTIVENESS OF INFLIXIMAB IN PATIENT WITH SYSTEMIC TYPE OF JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.S. Zholobova

    2011-01-01

    Full Text Available The article presents the case report of a child with juvenile rheumatoid arthritis, systemic type. The efficacy of infliximab (Remicade in treatment of systemic types of juvenile rheumatoid arthritis (JRA is analyzed. Treatment of JRA with high doses of prednisolone is inacceptable due to the risk of severe adverse events.Key words: juvenile rheumatoid arthritis, systemic type, infliximab, prednisolone, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (2: 201–204

  17. Need for infliximab dose intensification in Crohn’s disease and ulcerative colitis

    Science.gov (United States)

    Taxonera, Carlos; Olivares, David; Mendoza, Juan L; Díaz-Rubio, Manuel; Rey, Enrique

    2014-01-01

    AIM: To compare the need for infliximab dose intensification in two cohorts of patients with Crohn’s disease (CD) or ulcerative colitis (UC). METHODS: Single centre, uncontrolled, observational study. Consecutive patients with CD and UC who responded to infliximab induction doses were included. Data collected in a prospectively maintained database were retrospectively analysed. Differences in the rates of dose intensification per patient-month and the intensification-free survival time were compared. We also evaluated the interval between the first infliximab induction dose and the first infliximab escalated dose. The weight-adjusted infliximab administration costs were also calculated. RESULTS: Fifty nine patients with CD and 38 patients with UC were enrolled. The rate of intensification per patient-month was 3.9% for UC and 1.4% for CD (P = 0.005). The median time from baseline to intensification was significantly shorter in UC compared to CD [6.6 mo (IQR: 4.2-9.5 mo) vs 10.7 mo (IQR: 8.9-11.7 mo), P = 0.005]. In the survival analysis, the cumulative probability of avoiding infliximab dose intensification was significantly higher in CD (P = 0.002). In the multivariate analysis, disease (UC vs CD) was the only factor significantly associated with dose intensification. The infiximab administration costs during the first year were significantly higher for UC compared to CD (mean ± SD 234.9 ± 53.3 Euros/kg vs 212.3 ± 15.1 Euros/kg, P = 0.03). CONCLUSION: The rate of infliximab dose intensification per patient-month is significantly higher in UC patients. The infliximab administration costs are also significantly higher in patients with UC. PMID:25083091

  18. A budget impact model for biosimilar infliximab in Crohn's disease in Bulgaria, the Czech Republic, Hungary, Poland, Romania, and Slovakia.

    Science.gov (United States)

    Brodszky, Valentin; Rencz, Fanni; Péntek, Márta; Baji, Petra; Lakatos, Péter L; Gulácsi, László

    2016-01-01

    To estimate the budget impact of the introduction of biosimilar infliximab for the treatment of Crohn's disease (CD) in Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. A 3-year, prevalence-based budget impact analysis for biosimilar infliximab to treat CD was developed from third-party payers' perspective. The model included various scenarios depending on whether interchanging originator infliximab with biosimilar infliximab was allowed or not. Total cost savings achieved in biosimilar scenario 1 (interchanging not allowed) and BSc2 (interchanging allowed in 80% of the patients) were estimated to €8.0 million and €16.9 million in the six countries. Budget savings may cover the biosimilar infliximab therapy for 722-1530 additional CD patients. Introduction of biosimilar infliximab to treat CD may offset the inequity in access to biological therapy for CD between Central and Eastern European countries.

  19. Risk factors for surgical site infection and association with infliximab administration during surgery for Crohn's disease.

    Science.gov (United States)

    Uchino, Motoi; Ikeuchi, Hiroki; Matsuoka, Hiroki; Bando, Toshihiro; Ichiki, Kaoru; Nakajima, Kazuhiko; Tomita, Naohiro; Takesue, Yoshio

    2013-10-01

    Preoperative infliximab treatment may influence postoperative infectious complications in patients with Crohn's disease. The aim of this study was to identify predictors of surgical site infection after surgery for Crohn's disease and evaluate the effects of preoperative infliximab administration. We performed a prospective surveillance and review of surgical site infections. This study was conducted in the Surgical Department of Hyogo College of Medicine. A total of 405 consecutive patients with Crohn's disease who underwent abdominal surgery between January 2008 and December 2011 were included. Infection was diagnosed by the infection control team. The possible risk factors were analyzed by using logistic regression analyses to determine their predictive significance. Within the patient population, 20% of patients received infliximab, and 60% had penetrating disease. The median duration from the last infliximab infusion to surgery was 43 days (range, 4-80). The overall incidence of surgical site infection was 27%. The incidence of incisional surgical site infection was 18%, and the organ/space surgical site infection rate was 8%. In the multivariate analysis, proctectomy was the highest risk factor for all surgical site infection (OR, 3.4-11.8; p risk factor for surgical site infection. By contrast, there was a significantly reduced risk of incisional surgical site infection in patients with penetrating disease who received infliximab (OR, 0.1; p risk factor for surgical site infection in patients with Crohn's disease. The administration of preoperative infliximab was not a risk factor for surgical site infection.

  20. A systematic review on the efficacy and safety of Infliximab in patients with psoriasis

    Science.gov (United States)

    Wang, Jin; Zhan, Qingxia; Zhang, Litao

    2016-01-01

    ABSTRACT Objective: To assess the efficacy and safety of infliximab for the treatment of psoriasis in a meta-analysis framework. Methods: Data were extracted by searching the EMBASE (1974–2014), PubMed(1966–2014) and the Cochrane library2013.4th databases. Only randomized and placebo-controlled studies were selected in this study. Results: Statistically significant differences in efficacy were found for the infliximab (3 or 5 mg/kg) group compared with the control group which received placebo in the treatment of psoriasis vulgaris [OR 13.55, 95%CI (11.14,16.48)]or[OR85.45, 95%CI (39.13,186.58)]. There were also significant differences in efficacy between the infliximab (5 mg/kg) group and the placebo control group during treatment of psoriasis arthritis (PsA) [OR8.36, 95%CI (5.63, 12.40)]. A controlled trial used infliximab (5 mg/kg) in the treatment of palmoplantar psoriasis. This study showed that the effective rate of the infliximab group was 33.3% (4/12) when compared to the placebo control group, which was 8.3% (1/12). Conclusion: Infliximab is significantly associated with symptom relief, skin lesion improvement, and an increase in the quality of life of psoriasis patients. The most common drug-induced adverse events were pain, hepatic dysfunction, and infusion reaction. PMID:26528924

  1. Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty.

    Science.gov (United States)

    George, Michael D; Baker, Joshua F; Hsu, Jesse Yenchih; Wu, Qufei; Xie, Fenglong; Chen, Lang; Yun, Huifeng; Curtis, Jeffrey R

    2017-12-01

    The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty. A retrospective cohort study evaluated US Medicare patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received infliximab within 6 months of elective knee or hip arthroplasty from 2007 to 2013. Propensity-adjusted analyses examined whether infliximab stop timing (time between the most recent infusion and surgery) was associated with hospitalized infection within 30 days or prosthetic joint infection (PJI) within 1 year. Hospitalized infection within 30 days occurred after 270 of 4,288 surgeries (6.3%). Infliximab stop timing 10 mg/day was associated with increased risk of 30-day infection (OR 2.11 [95% CI 1.30-3.40]) and PJI (HR 2.70 [95% CI 1.30-5.60]). Other risk factors for infection included elderly age, comorbidities, revision surgery, and previous hospitalized infection. Administering infliximab within 4 weeks of elective knee or hip arthroplasty was not associated with a higher risk of short- or long-term serious infection compared to withholding infliximab for longer time periods. Glucocorticoid use, especially >10 mg/day, was associated with an increased infection risk. © 2017, American College of Rheumatology.

  2. Adalimumab administration after infliximab therapy is a successful treatment strategy for generalized pustular psoriasis.

    Science.gov (United States)

    Matsumoto, Ai; Komine, Mayumi; Karakawa, Masaru; Kishimoto, Megumi; Ohtsuki, Mamitaro

    2017-02-01

    We report a case of a 70-year-old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti-tumor necrosis factor (TNF)-α therapy to anti-interleukin-12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo-controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti-TNF-α antibodies that specifically block the interaction of TNF-α with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy. © 2016 Japanese Dermatological Association.

  3. Hodgkin's Lymphoma in Crohn's Disease Treated with Infliximab

    Directory of Open Access Journals (Sweden)

    Diana Carvalho

    2017-09-01

    Full Text Available Introduction: Lymphoproliferative disorders, particularly non-Hodgkin's and Hodgkin's lymphomas, are rare in patients with inflammatory bowel diseases. The use of thiopurines and infection by Epstein-Barr virus are well-known cofactors that can raise its prevalence. Other risk factors such as disease activity and biological treatment are the subject of discussion, without enough data in the literature to confirm a potential association. Methods: We report a case of Hodgkin's lymphoma in a patient who had been treated with azathioprine and was on long-term monotherapy with infliximab. Conclusions: We stress the importance of recognizing the possible occurrence of a lymphoproliferative disorder in association with anti-tumor necrosis factor-α therapy

  4. [Legionella pneumonia after infliximab in a patient with rheumatoid arthritis].

    Science.gov (United States)

    Giassi, Karina de Souza; Furlanetto, Vilson; Fialho, Sonia; Gomes Ribeiro, Giovana; Pereira, Ivânio Alves

    2014-01-01

    The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  5. Role of scintigraphy with {sup 99m}Tc-infliximab in predicting the response of intraarticular infliximab treatment in patients with refractory monoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Conti, F.; Ceccarelli, F.; Priori, R.; Iagnocco, A.; Valesini, G. [University of Rome, Rheumatology Unit, Faculty of Medicine and Dentistry, Rome (Italy); Malviya, G.; Signore, A. [University of Rome, Nuclear Medicine Unit, Faculty of Medicine and Psychology, Rome (Italy)

    2012-08-15

    The rationale for the present study was to evaluate the predictive role of {sup 99m}Tc-infliximab scintigraphy in therapy decision-making in patients with refractory monoarthritis and also candidates for intraarticular (IA) infliximab treatment. We studied 12 patients (5 with rheumatoid arthritis and 7 with spondyloarthropathy) with active monoarthritis (11 knees and 1 ankle) that had lasted for at least 3 months. Patients were evaluated clinically and ultrasonographically at baseline and 12 weeks after IA administration of infliximab. At the same time-points, {sup 99m}Tc-infliximab scintigraphy was performed: planar anterior and posterior images of arthritic joints were acquired at 6 and 20 h after injection and target-to-background (T/B) ratios were calculated. After treatment, a significant improvement in clinical and ultrasonographic parameters was recorded in six patients. Three patients had a partial response and three did not respond. Regarding scintigraphic evaluation, the T/B ratio analysis showed a significantly higher uptake in affected than in nonaffected joints before therapy (1.78 {+-} 0.46 vs. 1.29 {+-} 0.27, p = 0.006 at 6 h; 2.05 {+-} 0.50 vs. 1.41 {+-} 0.36 at 20 h, p = 0.002), and mean uptake at 20 h was also significantly higher than at 6 h (p = 0.0004). Scintigraphy showed a significant decrease in posttherapy T/B ratios of the affected joints (p = 0.0001 at 6 h and p = 0.0001 at 20 h), indicating a reduction in TNF into the affected joints. Most importantly, responders showed a significantly higher percentage increase in pretherapy uptake from 6 h to 20 h in the affected joints than nonresponders (p = 0.00001). The results of the present investigation suggest that {sup 99m}Tc-infliximab scintigraphy could be a useful tool to predict the clinical response to IA infliximab treatment in patients with refractory monoarthritis. (orig.)

  6. Real life Dosages and Costs of TNFα inhibitor therapy for RA patients in Denmark

    DEFF Research Database (Denmark)

    Hostenkamp, Gisela; Sørensen, Jan; Hetland, Merete Lund

    2009-01-01

    about the true long run cost. Taking the actual medication practice into account is important for the evaluation of the costs and optimal sequencing of new and existing biological treatments. Objectives: To investigate the drug cost of TNF-inhibitors in the treatment of RA using real-life data from...... of treatment. Cost estimates based on short term observational data or on instruction leaflets from manufacturers may provide wrong cost assessments of TNF-alpha therapy. It is important to take the long term cost structure into account to arrive at unbiased treatment cost estimates.......Background: When estimating the cost of biological treatment many analyses rely on cross sectional data or standard consumption patterns indicated in the manufacturers' instruction leaflet. Unless such consumption patterns truly reflect routine clinical practice they may result in wrong assumptions...

  7. Infliximab versus Cyclosporine Treatment for Severe Corticosteroid-Refractory Ulcerative Colitis: A Korean, Retrospective, Single Center Study

    Science.gov (United States)

    Kim, Eun Hye; Kim, Duk Hwan; Park, Soo Jung; Hong, Sung Pil; Kim, Tae Il; Kim, Won Ho; Cheon, Jae Hee

    2015-01-01

    Background/Aims In patients with corticosteroid-refractory ulcerative colitis (UC), cyclosporine or infliximab may be added to the treatment regimen to induce remission. Here, we aimed to compare the efficacy of cyclosporine and infliximab. Methods Between January 1995 and May 2012, the medical records of 43 patients with corticosteroid-refractory UC who received either infliximab or cyclosporine as a rescue therapy at a tertiary care hospital in Korea were reviewed. Results Among the 43 patients, 10 underwent rescue therapy with cyclosporine and the remaining 33 patients received infliximab. A follow-up of 12 months was completed for all patients. The colectomy rate at 12 months was 30% and 3% in the cyclosporine and the infliximab groups, respectively (p=0.034). However, the Cox proportional hazard model indicated that the treatment of rescue therapy was not an independent associate factor for preventing colectomy (p=0.164). In the subgroup analysis, infliximab with azathioprine was superior to cyclosporine for preventing colectomy (hazard ratio of infliximab with azathioprine compared with cyclosporine only, 0.073; 95% confidence interval, 0.008 to 0.629). Conclusions No difference between infliximab and cyclosporine with respect to preventing colectomy was noted. However, infliximab with azathioprine may be more effective than cyclosporine alone for preventing colectomy. PMID:25473080

  8. Combination of infliximab with thiopurines significantly reduces white cell and neutrophil counts in inflammatory bowel disease patients.

    Science.gov (United States)

    Parihar, V; Maceneaney, O; Maguire, S; Garry, C; O'Sullivan, M; Kennedy, M; Safaya, K; Smyth, C; Farrell, R

    2017-05-01

    The effects of thiopurines on white cell count are well documented. We compared the effects of infliximab 5 mg/kg monotherapy and combination of infliximab with thiopurines on the total and differential white cell count (WBC). 13 IBD patients treated with infliximab monotherapy and 18 IBD patients treated with a combination of infliximab and thiopurines were included in the study. Using retrospective data, cell counts were examined prior to induction of infliximab, and at 6 weeks and 1 year post-induction. The patients on combination therapy had an absolute WBC at 52 weeks of 5.7 whereas that of patients on Infliximab monotherapy at the same time point was 8.3 with comparable neutrophil count of 3.4 and 5.4. The results showed a significant reduction in white cell count and neutrophils at 6 weeks which persisted at 52 weeks in both groups (p infliximab and thiopurine (p Infliximab monotherapy. There was no significant change in the lymphocyte count. Full blood counts should be closely monitored in all patients starting infliximab therapy, in particular patients receiving concomitant thiopurines.

  9. Mulighed for aendring af ordinationsmønster

    DEFF Research Database (Denmark)

    Reuther, Lene Ørskov; Christensen, Hanne Rolighed; Mikkelsen, Camilla

    2009-01-01

    In 2005 the Central Drug Committee in co-operation with the hospitals in the county of Copenhagen (H:S) focused on the increasing use of and expenditure derived from three tumour necrosis factor alpha (TNF-alpha) inhibitors. While the three inhibitors are estimated to be equivalent regarding effi...... efficacy and safety, eternacept and adalimumab are twice as expensive as infliximab. With a little effort, the Central Drug Committee succeeded in changing clinicians' prescription pattern in a cost-effective manner. Udgivelsesdato: 2009-Sep...

  10. Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study

    NARCIS (Netherlands)

    van der Maas, A.; van den Bemt, B.J.; Wolbink, G.; Hoogen, F.H.J. van den; van Riel, P.L.; Broeder, A. den

    2012-01-01

    ABSTRACT: BACKGROUND: To get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort study METHODS: In a longitudinal, observational cohort of

  11. Clinical Use of Infliximab Trough Levels and Antibodies to Infliximab in Pediatric Patients With Inflammatory Bowel Disease.

    Science.gov (United States)

    Merras-Salmio, Laura; Kolho, Kaija-Leena

    2017-02-01

    Optimizing infliximab (IFX) treatment in pediatric patients with inflammatory bowel disease (IBD) by using serum infliximab (S-IFX) trough levels and antibodies to IFX is recommended. There is need for studies assessing this strategy in clinical practice. We retrospectively identified all pediatric patients with IBD (n = 146, median age 14.8 years) treated with IFX at our tertiary referral center from 2003 to 2014. All were analyzed for IFX trough levels (S-IFX, n = 475), and IFX antibody (IFX-Ab, n = 219) titers were included. Both were analyzed using enzyme-linked immunosorbent assay. We correlated these parameters with concurrently analyzed fecal calprotectin levels and the treatment outcome. If IFX had no efficacy, or a loss of response occurred, 40 of 64 (63%) had trough levels <2.0 mg/L, with negative IFX-Ab in 37 of 59 (63%). If the S-IFX was very low (<0.2 mg/L), 4 of 36 still had negative IFX-Ab. Concurrent azathioprine therapy did not relate to IFX-Ab. Fecal calprotectin was significantly lower in patients with clinical remission or ongoing therapy compared with those with subsequent loss of efficacy: medians 95 μg/g (33-308) and 670 μg/g (264-1473), P < 0.0001. The S-IFX median was substantially higher in patients with either remission or ongoing therapy, compared with those with no or loss of efficacy: 3.7 mg/L (1.8-5.4) and 1.2 mg/L (0.03-4.4, P = 0.01), respectively. Measuring IFX trough levels and fecal calprotectin has a potential impact on the treatment strategies and should be included in clinical routine. Low IFX trough levels associate with increased antibodies to IFX in most, but not in all cases.

  12. Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn's disease.

    Science.gov (United States)

    Oh, Eun Hye; Ko, Dae-Hyun; Seo, Hyungil; Chang, Kiju; Kim, Gwang-Un; Song, Eun Mi; Seo, Myeongsook; Lee, Ho-Su; Hwang, Sung Wook; Yang, Dong-Hoon; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun; Park, Sang Hyoung

    2017-02-28

    To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn's disease (CD) patients in Asian countries. IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician's judgment of patients' clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively ( P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively ( P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively ( P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice.

  13. Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.

    Science.gov (United States)

    Lu, Cathy; Waugh, Alistair; Bailey, Robert J; Cherry, Raeleen; Dieleman, Levinus A; Gramlich, Leah; Matic, Kata; Millan, Mario; Kroeker, Karen I; Sadowski, Daniel; Teshima, Christopher W; Todoruk, Dennis; Wong, Clarence; Wong, Karen; Fedorak, Richard N

    2012-09-28

    To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission. Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group. Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while those still in remission

  14. Crohn’s disease genotypes of patients in remission vs relapses after infliximab discontinuation

    Science.gov (United States)

    Lu, Cathy; Waugh, Alistair; Bailey, Robert J; Cherry, Raeleen; Dieleman, Levinus A; Gramlich, Leah; Matic, Kata; Millan, Mario; Kroeker, Karen I; Sadowski, Daniel; Teshima, Christopher W; Todoruk, Dennis; Wong, Clarence; Wong, Karen; Fedorak, Richard N

    2012-01-01

    AIM: To investigate genetic differences between Crohn’s disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission. METHODS: Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group. RESULTS: Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while

  15. Stability of infliximab dosing in inflammatory bowel disease: results from a multicenter US chart review.

    Science.gov (United States)

    Waters, Heidi; Vanderpoel, Julie; McKenzie, Scott; Lunacsek, Orsolya; Franklin, Meg; Lennert, Barbara; Goff, John; Augustyn, Damian H

    2011-01-01

    Infliximab dosing for inflammatory bowel disease (IBD) is based on patient weight and treatment response. Understanding dosing patterns may provide insight into treatment response and predictability of treatment cost. The purpose of this medical record review was to assess dose and dose frequency of infliximab maintenance treatment in patients with IBD using patient chart data. A retrospective chart review was conducted at 14 community gastroenterology clinics (GI clinics). Patients were aged ≥18 years, diagnosed with Crohn's disease (CD) or ulcerative colitis (UC), and had a first infliximab administration (index date) between January 1, 2005 and September 30, 2007. At least 24 months of continuous data availability were required with dosing data collected for 12 months after initiation of infliximab therapy. Patients with biologic use and/or participation in an IBD clinical trial within 12 months before the index date were excluded. Charts from 182 CD patients and 86 UC patients were analyzed. About half of the patients were female. Over 90% of patients initiated treatment with infliximab 5 mg/kg. Among CD patients and UC patients, respectively, 79% and 61% continued receiving this dose for maintenance therapy at stable intervals. This retrospective descriptive study is limited by the type and quantity of information available in patient charts from 14 GI clinics during the first year of infliximab treatment. Further, non-anti-tumor necrosis factor medication data were intermittently collected in some charts and, therefore, did not allow for analysis. Weight-based dosing and, presumably, patient response enabled providers to find the effective infliximab dose for IBD patients. The maintenance dose and administration frequency remained stable during the initial year.

  16. Predictors of long-term drug survival for infliximab in psoriasis.

    Science.gov (United States)

    Magis, Q; Jullien, D; Gaudy-Marqueste, C; Baumstark, K; Viguier, M; Bachelez, H; Guibal, F; Delaporte, E; Karimova, E; Montaudié, H; Boye, T; Aubin, F; Beylot-Barry, M; Richard, M-A

    2017-01-01

    Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset (PASI score >12) (OR = 5.18, 95% CI: 1.60-16.77, P = 0.006), high levels of initial psoriasis clearance (PASI-90 reduction or equivalent) (OR = 18.50, 95% CI: 4.56-74.45, P = 0.0001) and combination with methotrexate (OR = 13.15, 95% CI: 1.46-118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials. © 2016 European Academy of Dermatology and Venereology.

  17. Long-term safety and efficacy of biosimilar infliximab among patients with inflammatory arthritis switched from reference product

    Directory of Open Access Journals (Sweden)

    Abdalla A

    2017-03-01

    Full Text Available Abuelmagd Abdalla, Niamh Byrne, Richard Conway, Thomas Walsh, Geraldine Mannion, Michael Hanly, Miriam O’Sullivan, Ann Maria Curran, John J Carey Department of Rheumatology, Galway University Hospitals, Galway, Ireland Purpose: To evaluate the efficacy and safety of the biosimilar infliximab in adult patients with inflammatory arthritis switched from reference product in our center. Patients and methods: In April 2014, patients attending our rheumatology service for infliximab infusions were switched from reference product to the biosimilar infliximab following consent and hospital approval. Results: Around 34 patients with inflammatory arthritis were switched from reference product to biosimilar infliximab in 2014: 50% female, mean age 55 years (standard deviation=12.9, mean disease duration 14.79 years (9.7, median duration on infliximab 57 months, and two-thirds on oral disease-modifying antirheumatic drugs. There was no difference in efficacy or safety in the first 6 months of therapy. By the end of 2015, the mean follow-up on biosimilar infliximab was 15.8 (standard deviation=6.3 months. Our results showed no significant difference in Health Assessment Questionnaire score, patient global assessment of disease activity, number of disease flares, or the medication dose between the originator and the biosimilar infliximab. However, reported pain and C-reactive protein values were significantly higher during the longer follow-up period (p=0.043, 0.001 respectively. There was no significant difference in the number of adverse events or infusion reactions during follow-up periods. Only five (14.7% patients discontinued the biosimilar infliximab. Conclusion: Our patients experienced similar efficacy and safety for managing their arthritis with the biosimilar infliximab as the reference product infliximab, but at a much lower cost. Keywords: biologic therapy, rheumatic diseases, biosimilar exchange, infliximab, adult

  18. Designing an orally available nontoxic p38 inhibitor with a fragment-based strategy.

    Science.gov (United States)

    Guarnieri, Frank

    2015-01-01

    The MAPK p38 became a focal point of inflammatory research when it was recognized that it played a key role in the production of the pro-inflammatory molecules TNF-alpha, IL-beta, and cyclooxygenase-2 (COX-2). The pharmaceutical industry devoted enormous efforts to creating p38 inhibitors, because blocking p38 had the potential of downregulating a group of pro-inflammatory mediators, and thus, one drug could have a cocktail effect. The market potential seemed to be clearly established (Bonafede et al., Clinicoecon Outcomes Res 6:381-388, 2014) with a multiplicity of TNF-alpha antibodies and a soluble receptor (Mewar and Wilson, Br J Pharmacol 162:785-791, 2011) already on the market, although the relationship between TNF-alpha production and p38 activation is a complicated two-way (Sabio and Davis, Semin Immunol 26:237-245, 2014) signal transduction process. With the discovery that activated p38 stabilizes (Mancini and Di Battista, Inflamm Res 60:1083-1092, 2011) COX-2 mRNA and upregulates expression of IL-beta (Bachstetter and Van Eldik, Aging Dis 1:199-211, 2010) probably in a similar manner, inhibiting p38 appeared to be a way of blocking TNF-alpha, COX-2, and IL-beta simultaneously. At Locus Pharmaceuticals we jumped on this opportunity, because we believed that our fragment-based drug discovery approach was ideally suited for making a potent small molecule p38 inhibitor that did not bind in the ATP site, but also had the solubility, lack of planarity, and low molecular weight required of a clinical candidate. Just to be clear, in our experience highly planar compounds often result in poor pharmacokinetics, because they tend to bind strongly to plasma proteins. At Locus we typically repeated assays by adding increasing amounts of plasma to check for potency degradation in the presence of blood. We found this to be a useful early indicator of pharmacokinetics and in vivo behavior. It became clear from our work and the work of others that binding to the ATP site

  19. Infliximab en pacientes con espondilitis anquilosante activa: experiencia en el Hospital Nacional Edgardo Rebagliati Martins

    Directory of Open Access Journals (Sweden)

    Manuel Montero

    2007-06-01

    Full Text Available Infliximab es un medicamento efectivo en el tratamiento de pacientes con espondilitis anquilosante (EA activa. Sin embargo, debido a su alto costo, su uso indiscriminado es prohibitivo. Objetivo: Evaluar si un régimen de inducción con infliximab es efectivo en pacientes con EA activa. Diseño: Sólo expuestos. Lugar: Servicio de Reumatología del Hospital Nacional Edgardo Rebagliati. Participantes: Pacientes con espondilitis anquilosante activa refractaria. Intervenciones: infliximab a las 0, 2 y 6 semanas. Un paciente recibió dosis de 3 mg/kg y los restantes 5 mg/kg de infliximab. Todos los pacientes continuaron recibiendo sulfasalazina. Principales medidas de resultados: Se determinó la proporción de pacientes que alcanzaron mejoría de acuerdo a los criterios ASAS 20, ASAS 40 y BASDAI 50, en la última evaluación (mediana de 55 semanas. Resultados: En la última evaluación, cinco pacientes (71,4% presentaban respuesta ASAS 20 sostenida. Cuatro (57% y tres (43% de los pacientes alcanzaron BASDAI 50 y ASAS 40, respectivamente. Tres pacientes (43% recayeron en un tiempo promedio de 26,6 semanas. No se observó efectos adversos serios. Conclusiones: La infusión de tres dosis de infliximab es efectiva para controlar la actividad de la enfermedad de los pacientes con EA refractaria a AINEs y en algunos pacientes controla la enfermedad por periodos prolongados de tiempo.

  20. QUALITY OF LIFE IN CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS TREATED WITH INFLIXIMAB

    Directory of Open Access Journals (Sweden)

    R.V. Denisova

    2008-01-01

    Full Text Available Juvenile rheumatoid arthritis (JRA is chronic disease, leading to early incapacitating injury in patients. Treatment of JRA with new expensive biological agents allows obtaining long term remission of disease and improving its prognosis. Estimation of quality of life is one of the main effectiveness criteria of treatment. A quality of life in children who were 2–4 years old treated with infliximab was estimated. 43 patients with different types of JRA were examined. A quality of life was estimated with the help of questionnaire PEDSQL generic core scale, PEDSQL rheumatology module. Index of functional disability was estimated by childhood health assessment questionnaire (CHAQ. Significant increase of quality of life rates and decrease of index of functional disability was registered in 6 weeks of therapy with infliximab. The rates of quality of life in patients with JRA treated with infliximab were significantly equal to that in healthy children in the same age in 6, 12 and 24 months of treatment. Thus, treatment with infliximab significantly increases quality of life in children in 2–4 years old with JRA and their families, decreases negative influence of disease on child's living, improves physical activity and emotional state of patients, and allows improving contact between patients and healthy children in the same age.Key words: children, juvenile rheumatoid arthritis, quality of life, infliximab.

  1. Infliximab after Boston Keratoprosthesis in Stevens-Johnson Syndrome: An Update.

    Science.gov (United States)

    Robert, Marie-Claude; Črnej, Alja; Shen, Lucy Q; Papaliodis, George N; Dana, Reza; Foster, C Stephen; Chodosh, James; Dohlman, Claes H

    2017-06-01

    To report our experience using intravenous infliximab for the treatment of tissue melt after Boston keratoprosthesis (B-KPro) types I and II in patients with autoimmune disease. Case series. We identified four patients who were treated with intravenous infliximab in the context of tissue melt after B-KPro. Stevens-Johnson syndrome-associated corneal blindness was the primary surgical indication for B-KPro implantation in all patients. Two patients received a B-KPro type I and two patients received a B-KPro type II. The patients received intravenous infliximab for skin retraction around B-KPro type II, melting of the carrier graft or leak. Treatment resulted in a dramatic decrease in inflammation and, in some cases, arrest of the melting process. Cost and patient adherence were limiting factors to pursuing infliximab therapy. In addition, one patient developed infusion reactions. Intravenous infliximab may be considered as globe- and sight-saving therapy for tissue melt after B-KPro.

  2. Effect of Systemic Infliximab Therapy in Patients with Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Elif Betül Türkoğlu

    2015-08-01

    Full Text Available Objectives: To investigate the effect of systemic infliximab therapy on tear function tests and the ocular surface in patients with Sjögren’s syndrome secondary to various autoimmune diseases. Materials and Methods: This prospective study included 22 eyes of 22 patients with Sjögren’s syndrome who began treatment with systemic infliximab. Tear film break-up time (TBUT, anesthetized Schirmer’s 1 test, fluorescein staining test, and Ocular Surface Disease Index (OSDI scores were recorded before treatment and in the 3rd and 6th months of treatment. Results: In the 3rd month of infliximab therapy, no significant changes were observed in Schirmer’s values, TBUT, fluorescein staining, or OSDI scores (p=0.260, p=0.357, p=0.190 and p=0.07, respectively. In the 6th month of infliximab therapy, no significant changes were observed in TBUT, fluorescein staining, Schirmer’s value or OSDI scores (p=0.510, p=0.320, p=0.220 and p=0.344, respectively. Conclusion: Infliximab therapy, which is commonly used in systemic autoimmune diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and ankylosing spondylitis, did not show a positive effect on ocular surface and tear function tests. (Turk J Ophthalmol 2015; 45: 138-141

  3. [Acute severe ulcerative colitis treated with accelerated infliximab induction. Case report].

    Science.gov (United States)

    Fluxá, Daniela; Flores, Lilian; Kronberg, Udo; Moreno, Mauricio; Figueroa, Carolina; Ibáñez, Patricio; Lubascher, Jaime; Simian, Daniela; Quera, Rodrigo

    2017-08-01

    Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

  4. Inpatient infliximab is ineffective at preventing colectomy for steroid refractory extensive colitis.

    Science.gov (United States)

    Andrew, Rachel E; Lauria, Alexis; Puleo, Frances J; Berg, Arthur; Stewart, David B

    2017-11-01

    Despite data suggesting safety and efficacy in ulcerative colitis patients treated with inpatient infliximab, prior studies did not focus on patients with extensive colitis, the group at highest risk for requiring surgery. This was a single center, retrospective study (2008-2015) of consecutive patients who required admission because of severe extensive ulcerative colitis defined by preoperative symptoms and computed tomography scans and postoperative histology. Patients admitted for high-dose steroids were compared with steroid refractory inpatients provided with one or two infusions of infliximab. The primary study outcome was colectomy rates; secondary outcomes included mean length of stay and 60-d complication rates. A total of 174 patients required admission with steroids for extensive ulcerative colitis. Of these, 19 (10%) also received infliximab. Among the subjects treated with infliximab, 15 (78%) required total colectomy during that admission versus 81 (52%) who received steroids alone (P = 0.03). Postoperative readmission rates, surgical-site infections, return to the operating room, and all-complication rates were similar between the cohorts (P > 0.05). For steroid refractory extensive ulcerative colitis, inpatient infliximab did not lower colectomy rates or increase postoperative complications compared with patients treated with steroids alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Incidence and management of infusion reactions to infliximab in 186 italian patient’s with rheumatoid arthritis: the Padua experience

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: We report the incidence and treatment of infusion reactions to infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor a, in a large cohort of patients with rheumatoid arthritis. Patients and methods: One hundred eighty six patients with rheumatoid arthritis treated with infliximab for a total of 216.6 patient years were retrospectively evaluated. Patients received 2160 infliximab infusions at the Division of Rheumatology at the University Hospital of Padua from May, 2000 to April, 2004. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. Results: The overall incidence of infusion reactions to infliximab was 0.8% (19 out of 2160 of infusions, affecting 10.2% of patients (19 out of 186. Mild, moderate, or severe acute reactions occurred in 0.1% (3 of 2160, 0.6% (13 of 2160, and 0.04% (1 of 2160 of infliximab infusions, respectively. Delayed infusion reactions occurred in 0.09% (2 of 2160 of infusions. Use of specific treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With a prophylaxis protocol, all patients who experienced an initial mild acute reaction were able to receive additional infusions. Conclusions: Using appropriate treatment protocols, infliximab infusion reactions were effectively treated and prevented in patients with mild acute reactions upon retreatment. In the case of moderate to severe infusion reactions, the risks and the benefits of the continuation of infliximab therapy need to be carefully considered.

  6. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease

    NARCIS (Netherlands)

    Rutgeerts, P.; D'Haens, G.; Targan, S.; Vasiliauskas, E.; Hanauer, S. B.; Present, D. H.; Mayer, L.; van Hogezand, R. A.; Braakman, T.; DeWoody, K. L.; Schaible, T. F.; van Deventer, S. J.

    1999-01-01

    Infliximab, an anti-tumor necrosis factor monoclonal antibody, rapidly reduces signs and symptoms of active Crohn's disease. The aim of this study was to determine whether repeated infusions of infliximab would effectively and safely maintain the remitting benefit. The efficacy, safety,

  7. Induction and Maintenance Infliximab Therapy for the Treatment of Moderat-to Severe Crohns Disease in Children

    DEFF Research Database (Denmark)

    Pærregaard, Anders; NN, NN

    2007-01-01

    BACKGROUND AND AIMS: The REACH study evaluated the safety and efficacy of infliximab in children with moderately to severely active Crohn's disease. METHODS: Patients (n = 112) with a Pediatric Crohn's Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6...

  8. Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

    Directory of Open Access Journals (Sweden)

    Franco Scaldaferri

    Full Text Available Infliximab is an effective treatment for inflammatory bowel disease (IBD. Studies differ regarding the influence of body mass index (BMI on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported.Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α and anti-drug antibodies(ATI, and determine if these factors can predict future response.We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed.We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%. Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion.This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

  9. A prospective randomized controlled trial comparing infliximab and etanercept in patients with moderate-to-severe chronic plaque-type psoriasis: the Psoriasis Infliximab vs. Etanercept Comparison Evaluation (PIECE) study.

    Science.gov (United States)

    de Vries, A C Q; Thio, H B; de Kort, W J A; Opmeer, B C; van der Stok, H M; de Jong, E M G J; Horvath, B; Busschbach, J J V; Nijsten, T E C; Spuls, Ph I

    2017-03-01

    There are currently no independent data available comparing infliximab and etanercept for the treatment of psoriasis. To compare these biologics without funding from pharmaceutical companies. Overall, 50 patients were randomized to etanercept (n = 23) 50 mg subcutaneously twice weekly or infliximab (n = 25) 5 mg kg -1 intravenously at week 0, 2, 6, 14 and 22. After 24 weeks, 19 patients stopped and 22 continued treatment and were followed up to week 48. The primary outcome was ≥ 75% improvement of Psoriasis Area and Severity Index (PASI 75) at week 24. The secondary outcomes included PASI 75 at week 6 (onset of action) and week 12, Investigator's Global Assessment (IGA), Patient Global Assessment, impact on quality of life (Skindex-17 and SF-36), Treatment Satisfaction Questionnaire of Medication, duration of remission, maintenance treatment and safety. At week 24, PASI 75 was achieved in 72% (infliximab) vs. 35% (etanercept) (P = 0·01). The onset of action was achieved in 52% (infliximab) and 4% (etanercept). At week 12, 76% (infliximab) and 22% (etanercept) achieved PASI 75 (P infliximab) and 30% (etanercept) (P = 0·01). Skindex-17 symptom score was significantly better for infliximab. Maintenance treatment achieved PASI 75 for 67% (n = 6) infliximab vs. 50% (n = 5) etanercept, at week 48 (P = 0·65). Mild adverse events were reported in 76% (infliximab) vs. 66% (etanercept). Infliximab showed a rapid and significant higher level of efficacy until week 24 compared with etanercept. Long-term data showed no significant differences between both groups at week 48. Safety parameters were comparable. © 2016 British Association of Dermatologists.

  10. Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

    Science.gov (United States)

    Scaldaferri, Franco; D'Ambrosio, Daria; Holleran, Grainne; Poscia, Andrea; Petito, Valentina; Lopetuso, Loris; Graziani, Cristina; Laterza, Lucrezia; Pistone, Maria Teresa; Pecere, Silvia; Currò, Diego; Gaetani, Eleonora; Armuzzi, Alessandro; Papa, Alfredo; Cammarota, Giovanni; Gasbarrini, Antonio

    2017-01-01

    Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

  11. Toxic hepatitis induced by infliximab in a patient with rheumatoid arthritis with no relapse after switching to etanercept

    DEFF Research Database (Denmark)

    Carlsen, K M; Riis, L; Madsen, O R

    2009-01-01

    We present a case of toxic hepatitis related to infliximab treatment in a 38-year-old woman with rheumatoid arthritis (RA). The patient had previously been treated with different disease-modifying drugs (DMARDs) alone or in combination but had never revealed signs of liver dysfunction. Due to high...... elevations of the transaminases up to five times the upper normal limit were noted and treatment with infliximab was terminated. Serological tests for viral and autoimmune hepatitis and for ANA and anti-dsDNA were all negative. Specific infliximab antibodies could not be detected. Ultrasound of the liver...... was normal. Liver biopsy showed late signs of acute toxic hepatitis without MTX-related fibrosis. This is one the first cases that convincingly demonstrates that infliximab treatment may cause toxic hepatitis. Moreover, the case suggests a lack of hepatic cross-toxicity between infliximab and etanercept...

  12. Profile of infliximab in the treatment of pediatric Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Kierus J

    2015-06-01

    Full Text Available Jaroslaw Kierkus,1 Edyta Szymanska,2 Grzegorz Oracz,1 Anna Wiernicka,1 Maciej Dadalski1 1Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, 2Department of Pediatrics, Nutrition and Metabolic Disorders, The Children’s Memorial Health Institute, Warsaw, Poland Abstract: In recent years, a novel biologic therapy with monoclonal antibodies against tumor necrosis factor-alpha has revolutionized the treatment of Crohn’s disease. Infliximab, the first biologic agent, has been demonstrated to considerably improve both clinical and endoscopic outcomes. In view of the growing popularity of infliximab in the management of Crohn’s disease, we review the profile of the agent in the treatment of this disease in a pediatric setting. Keywords: infliximab, Crohn’s disease, children, biologic therapy, anti-TNF-agents

  13. The use of infliximab in a patient with idiopathic granulomatous hepatitis

    Science.gov (United States)

    Kapoor, Sabrina Reenu; Snowden, Neil

    2009-01-01

    We report a therapeutic response to infliximab in a patient with idiopathic granulomatous hepatitis resistant to treatment with methotrexate and corticosteroids. A 41-year-old woman presented with a 12-month history of fever, night sweat, gross hepatomegaly and 13 kg weight loss. Infection and malignancy were carefully excluded and a liver biopsy showed changes consistent with idiopathic granulomatous hepatitis. The patient was treated with high dose steroids and methotrexate, but her clinical symptoms and biochemical and radiological signs did not settle. Introduction of infliximab led to rapid and sustained resolution of symptoms, hepatomegaly and liver function tests (LFTs) after 1 year of follow-up. To our knowledge this is the first successful use of infliximab in idiopathic granulomatous hepatitis. PMID:21686858

  14. Review and Clinical Perspectives for the Use of Infliximab in Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Remo Panaccione

    2008-01-01

    Full Text Available Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn’s disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC differs from that of Crohn’s disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members’ clinical experiences.

  15. Review and clinical perspectives for the use of infliximab in ulcerative colitis

    Science.gov (United States)

    Panaccione, Remo; Fedorak, Richard N; Aumais, Guy; Bernard, Edmond-Jean; Bernstein, Charles N; Bitton, Alain; Croitoru, Ken; Dieleman, Levinus A; Enns, Robert; Feagan, Brian G; Franchimont, Denis; Greenberg, Gordon R; Griffiths, Anne-Marie; Marshall, John K; Pare, Pierre; Patel, Sunil; Penner, Robert; Render, Craig; Seidman, Ernest; Steinhart, A Hillary

    2008-01-01

    Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn’s disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC) differs from that of Crohn’s disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members’ clinical experiences. PMID:18354755

  16. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis

    DEFF Research Database (Denmark)

    Denton, C P; Engelhart, M; Tvede, N

    2008-01-01

    /kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. RESULTS: There was no significant change in skin......AIM: The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). METHODS: A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg.......025). CONCLUSION: In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis....

  17. Complement activation in plasma before and after infliximab treatment in Crohn disease

    DEFF Research Database (Denmark)

    Zimmermann-Nielsen, E; Agnholt, J; Thorlacius-Ussing, O

    2003-01-01

    complicated by fistulizing ano-rectal disease was collected before and after three Infliximab infusions (5 mg kg(-1)). RESULTS: Before treatment, the C3-activation capacities (C3-AC) in plasma from patients with Crohn disease were comparable with values obtained from healthy controls. The classical C pathway......-mediated C3-AC, mannan-binding lectin C4-AC, leucocyte count, C-reactive protein concentration and Crohn Disease Activity Index decreased significantly 8 weeks after the first infusion of Infliximab (P ... in plasma from patients with Crohn disease; the decrease observed in the classical pathway-mediated C3-AC after treatment with Infliximab reflects a general down-regulation in immune activation....

  18. TREATMENT WITH INFLIXIMAB IN PATIENT WITH EARLY POLYARTICULAR JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    T.V. Sleptsova

    2010-01-01

    Full Text Available The article presents a case report of severe polyarticular juvenile rheumatoid arthritis (JRA resistant to treatment with corticosteroids and classic immunosuppressive agents. Authors describe successful treatment with genetically engineered biological agent — infliximab in patient with early arthritis (duration of disease in less than two years: at 1st week of treatment pain and morning stiffness were stopped, and exudative lesions of joint significantly decreased. Inactive phase of disease was reached in 6 weeks, and movements in 8 of 9 joints were restored. Oral prednisolone was stopped. This case report shows high effectiveness of infliximab in patient with early JRA. Therapeutic treatment of early stages of disease before development of irreversible osteocartilaginous destruction with blocker of tumor necrotizing factor is very perspective. Key words: children, early juvenile rheumatoid arthritis, treatment, infliximab.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(5:127-132

  19. The incidence and management of infusion reactions to infliximab: a large center experience.

    Science.gov (United States)

    Cheifetz, Adam; Smedley, Michelle; Martin, Sara; Reiter, Monica; Leone, Grace; Mayer, Lloyd; Plevy, Scott

    2003-06-01

    To assess the incidence and management of infusion reactions to infliximab, a chimeric monoclonal antibody that targets human tumor necrosis factor-alpha, in patients with Crohn's disease treated at a large infusion center. A total of 165 consecutive patients who received 479 infliximab infusions in the Division of Clinical Immunology Infusion Center at Mount Sinai Medical Center from July, 1998 to January, 2001 were evaluated. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. The overall incidence of infusion reactions to infliximab was 6.1% (29 of 479) of infusions, affecting 9.7% (16 of 165) of patients. Mild, moderate, or severe acute reactions occurred in 3.1% (15 of 479), 1.2% (six of 479), and 1.0% (five of 479) of infliximab infusions, respectively. Use of treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With the prophylaxis protocol, all patients who experienced an initial mild or moderate acute reaction were able to receive additional infusions. Four patients experienced a total of five severe acute reactions. Three patients were retreated: two patients had no further problems, whereas one patient had a second severe acute reaction that rapidly resolved with treatment. Suggesting that acute infusion reactions are not type I hypersensitivity reactions, in 11 patients who experienced 14 acute infusion reactions, serum tryptase levels were normal. Delayed infusion reactions occurred in 0.6% (three of 479) of infusions. Infliximab infusions were accompanied by acute reactions in approximately 5% of infusions. These reactions did not seem to be true IgE-mediated type I hypersensitivity events. Using appropriate treatment protocols, these reactions were effectively treated and prevented upon retreatment in nearly all patients. Delayed reactions were rare, occurring in <1% of infusions.

  20. Long-term response rates to infliximab therapy for Crohn's disease in an outpatient cohort.

    Science.gov (United States)

    Teshima, Christopher W; Thompson, Adrienne; Dhanoa, LeRose; Dieleman, Levinus A; Fedorak, Richard N

    2009-05-01

    Infliximab's efficacy in the induction and maintenance of remission in luminal Crohn's disease has been confirmed by randomized, controlled trials. Less clearly described are long-term outcomes in the clinical practice setting since the establishment of regularly scheduled, every eight-week maintenance infliximab infusions. Existing reports describing clinical practice outcomes are limited by short durations of follow-up or by the use of episodic dosing, or focus on safety data rather than clinical outcomes. To examine induction and maintenance responses to infliximab in an outpatient inflammatory bowel disease clinic. A retrospective chart review was performed. Clinical outcomes were infliximab induction and maintenance responses, defined as the ability to stop and remain off corticosteroids while not requiring additional therapy for active disease. One hundred thirty-three patients were identified with records sufficiently detailed to be analyzed. Of these, 117 patients (88%) demonstrated a clinical response to induction; 104 of 117 (89%) were on concomitant immunosuppressive therapy; 80 of 104 on azathioprine/6-mercaptopurine (77%); and 24 of 104 on methotrexate (23%). The mean duration of clinical response was 94 weeks (95% CI 78.8 to 109.2). The proportion of patients who maintained response at 30 weeks was 83.2%, at 54 weeks was 63.6% and at 108 weeks was 44.9%. Adverse events occurred for 15 of 117 patients (12.8%), consisting of nine infusion reactions, four serum sickness-like reactions, one rash and one infection. Patients treated with infliximab therapy for luminal Crohn's disease in our outpatient clinic achieved excellent induction and maintenance of response rates, confirming the real-life efficacy of maintenance infliximab established in clinical trials.

  1. Infliximab Dosing Strategies and Predicted Trough Exposure in Children with Crohn’s Disease

    Science.gov (United States)

    Frymoyer, Adam; Piester, Travis L; Park, KT

    2016-01-01

    Objectives Standard infliximab maintenance dosing of 5 mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn’s disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3 μg/ml. Methods A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10 mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy. Results Based on the index case of a 10 year old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (IQR) simulated infliximab trough concentration at week 14 was 1.3 (0.5–2.7) μg/ml, and 2.4 (1.0–4.8) μg/ml for albumin levels of 3 and 4 g/dl, respectively. Among 1000 simulated children in the model, trough concentration >3 μg/ml at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4 g/dl, respectively. Conclusions Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy. PMID:26890885

  2. Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations.

    Science.gov (United States)

    Sieczkowska, J; Jarzębicka, D; Banaszkiewicz, A; Plocek, A; Gawronska, A; Toporowska-Kowalska, E; Oracz, G; Meglicka, M; Kierkus, J

    2016-02-01

    The growing incidence of inflammatory bowel disease (IBD) in children necessitates the use of biological treatments. Recently, an infliximab biosimilar was authorized in the European Union, which may result in switching patients. We present our preliminary experiences with such switches. The prospective study included 32 paediatric patients diagnosed with Crohn's disease (CD) and 7 children with ulcerative colitis (UC) at 3 academic hospitals, who were switched from infliximab originator to its biosimilar (Remsima). Patient characteristics, disease severity, laboratory parameters and adverse events were recorded. Means, medians and ranges were calculated. Mean age at diagnosis of CD and UC was 11.1 (2.7-15.3) and 12.3 years (8.5-14.8), respectively. Mean number of infliximab originator infusions before switching to the biosimilar was 9.9 (median 8, range 4-29) and 5.1 (5, 1-12) for the CD and UC group, respectively. Evaluation efficacy of last biosimilar doses of all patients revealed rates of clinical remission of 88 and 57% for CD and UC patients, respectively. Last follow-up assessment of patients who continued with biosimilar therapy showed that 16/20 (80%) CD patients and all 4 UC individuals were in remission. One infusion reaction to infliximab biosimilar was observed in a CD patient, which led to treatment discontinuation. The incidence of sporadic mild adverse events prior to and after switching did not differ significantly and was consistent with the safety profile of the infliximab molecule. Switching from infliximab originator to its biosimilar seems to be a safe option in children with CD. After the switch the biosimilar was just as effective as the originator. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Nonclinical Evaluation of PF-06438179: A Potential Biosimilar to Remicade®(Infliximab).

    Science.gov (United States)

    Derzi, Mazin; Johnson, Theodore R; Shoieb, Ahmed M; Conlon, Hugh D; Sharpe, Penny; Saati, Andrew; Koob, Sarah; Bolt, Michael W; Lorello, Leslie G; McNally, Jim; Kirchhoff, Carol F; Smolarek, Teresa A; Leach, Michael W

    2016-11-01

    PF-06438179, a potential biosimilar to Remicade ® (infliximab, Janssen Biotech, Inc.), is a chimeric mouse-human monoclonal antibody targeting human tumor necrosis factor alpha (TNF). Analytical (small subset reported here) and nonclinical studies compared the structural, functional, and in vivo nonclinical similarity of PF-06438179 with Remicade sourced from the United States (infliximab-US) and/or European Union (infliximab-EU). The peptide map profiles were superimposable, and peptide masses were the same, indicating identical amino acid sequences. Data on post-translational modifications, biochemical properties, and biological function provided strong support for analytical similarity. Administration of a single intravenous (IV) dose (10 or 50 mg/kg) of PF-06438179 or infliximab-EU to male rats was well tolerated. There were no test article-related clinical signs or effects on body weight or food consumption. Systemic exposures [maximum drug concentration (C max ) and area under the concentration-time curve (AUC)] in rats administered PF-06438179 or infliximab-EU were similar, with mean exposure ratio of PF-06438179 relative to infliximab-EU ranging from 0.88 to 1.16. No rats developed anti-drug antibodies. A 2-week IV toxicity study was conducted with once-weekly administration of 10 or 50 mg/kg of PF-06438179 to male and female rats. PF-06438179-related hyperplasia of sinusoidal cells occurred in the liver in rats administered 50 mg/kg, but was not adverse based on its minimal to mild severity. The no-observed adverse-effect level for PF-06438179 was 50 mg/kg. At this dose, C max was 1360 µg/mL and AUC at 168 h was 115,000 µg h/mL on day 8. The analytical and nonclinical studies have supported advancement of PF-06438179 into global comparative clinical trials. Pfizer Inc.

  4. [Efficacy of infliximab in the treatment of korean patients with crohns disease].

    Science.gov (United States)

    Kim, Sai Hui; Yang, Suk; Kim, Kyung Jo; Kim, Eun Hee; Yoon, Soon Man; Ye, Byong Duk; Byeon, Jeong Sik; Myung, Seung Jae; Kim, Jin Ho

    2009-08-01

    Infliximab has been proven to be effective for refractory luminal and fistulizing Crohns disease (CD). We performed this study to demonstrate the efficacy of infliximab in Korean CD patients. Medical records of 40 CD patients who had been treated with infliximab were reviewed retrospectively. Among 40 patients, 11 (27.5%) patients were treated for refractory luminal disease, 14 (35%) for fistulizing disease, and 15 (37.5%) for both types. Clinical response rate was higher in 26 patients with refractory luminal disease (Complete response (CR), 73.1%; Partial response (PR), 23.1%) than in 29 patients with fistulizing disease (CR, 41.4%; PR, 31%) (p=0.024). The clinical response rate tended to be higher in 28 patients with external fistulas (CR, 46.4%; PR, 32.2%) than 4 patients with internal fistulas (PR, 25%; NR, 75%) (p=0.064). Among patients with external fistulas, the response rate of 8 patients with enterocutaneous fistulas (CR, 50%; PR, 12.5%) was not different from 20 patients with perianal fistulas (CR, 45%; PR, 40%). Among 20 patients with perianal fistulas, the response rate of 6 patients with perianal fistulas without a history of operation (CR, 83.3%; PR, 0%) was higher than 14 patients with perianal fistulas resistant to previous surgical treatment (CR, 28.6%; PR, 57.1%) (p=0.044). As for adverse reaction, 7 patients experienced mild infusion reaction, and 2 patients developed serious infection. Infliximab is more effective for refractory luminal disease than for fistulizing disease. In addition, clinical responses to infliximab are different according to subtypes of fistulas. These findings should be considered for the proper use of infliximab.

  5. Canadian Association of Gastroenterology Clinical Practice Guidelines: The Use of Infliximab in Crohn's Disease

    Directory of Open Access Journals (Sweden)

    Remo Panaccione

    2004-01-01

    Full Text Available These guidelines are presented as a follow-up to the original Canadian Association of Gastroenterology Clinical Practice Guidelines: The use of infliximab in Crohn's disease, published in the Canadian Journal of Gastroenterology (1. The original guidelines represented publications between 1998 and 2000. The current guidelines have been updated to reflect knowledge gained from two pivotal randomized clinical trails, with the use of infliximab in the maintenance of inflammatory Crohn's disease in remission (2 and in the maintenance of fistulous Crohn's disease in remission (3.

  6. Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection

    DEFF Research Database (Denmark)

    Julsgaard, Mette; Christensen, Lisbet Ambrosius; Gibson, Peter R.

    2016-01-01

    and in umbilical cords, and in infants for every 3 months until the drug was no longer detected.  Results  The time from last exposure to anti-TNF agent during pregnancy correlated inversely with the concentration of the drugs in the umbilical cord (adalimumab: r = -0.64, P =.0003; infliximab: r = -0.77, P ... the drugs until 12 months of age. There was an inverse correlation between the time from last exposure during pregnancy and drug concentration in the umbilical cord. Infliximab was cleared more slowly than adalimumab from the infants. The combination of an anti-TNF agent and thiopurine therapy during...

  7. Induction and Maintenance Infliximab Therapy for the Treatment of Crohn's Disease with Perianal Fistulas in Children: Retrospective, Multicenter Study.

    Science.gov (United States)

    Iwańczak, Barbara M; Ryżko, Józef; Jankowski, Piotr; Sładek, Małgorzata; Wasilewska, Agata; Szczepanik, Mariusz; Sienkiewicz, Edyta; Szaflarska-Popławska, Anna; Więcek, Sabina; Kwiecień, Jarosław; Korczowski, Bartosz; Maślana, Jolanta

    2016-01-01

    Infliximab is a biological drug used for the treatment of Crohn's disease in children. The aim of this retrospective study was the estimation of effectiveness and safety of infliximab in the treatment of Crohn's disease with perianal fistulas in children. Analysis comprised 50 children with Crohn's disease with perianal fistulas aged 9 to 18 years (16 girls and 34 boys) who failed to respond to conventional therapy. The children were divided into two groups: the first group contained 23 children with simple fistulas and the second - 27 children with complex fistulas. All children were treated with infliximab, administered in the dose of 5 mg per kilogram of the body mass. In the induction phase infliximab was administered at weeks 0, 2 and 6 and after clinical response in maintenance phase the drug was administered every 8 weeks; together for 12 months. In 76% of children after induction therapy with infliximab and in 71.87% after maintenance therapy the complete closure of fistula occurred. During the first year after the treatment a recurrence of a fistula was observed in 30.43% of the children. In two children anaphylactic shock was observed during injection of infliximab. The remaining children tolerated the drug well. The treatment with infliximab was effective in the majority of fistulazing Crohn's disease and caused the closure of perianal fistula which improved quality of life.

  8. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial

    Science.gov (United States)

    Cornillie, Freddy; Hanauer, Stephen B; Diamond, Robert H; Wang, Jianping; Tang, Kezhen L; Xu, Zhenhua; Rutgeerts, Paul; Vermeire, Séverine

    2014-01-01

    Background Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment. Objective To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline). Design ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs. Results After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 μg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab. Conclusions Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher

  9. Infections and treatment of patients with rheumatic diseasesTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Atzeni, F.; Bendtzen, K.; Bobbio-Pallavicini, F.

    2008-01-01

    , and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role....../inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night...

  10. Effect of infliximab dose increase in rheumatoid arthritis at different trough concentrations: a cohort study in clinical practice conditions

    Directory of Open Access Journals (Sweden)

    Chamaida ePlasencia

    2015-10-01

    Full Text Available BackgroundEvidence supporting treatment intensification in rheumatoid arthritis is limited and controversial. We explored outcomes of infliximab dose increases and accounted for pre-existing trough levels in patients with active rheumatoid arthritis (RA.MethodsThis study was a retrospective study of 42 RA patients who received increased infliximab following an insufficient response (DAS28 > 3.2. Serum concentrations of infliximab and antibodies to infliximab (ATI and DAS28 and EULAR clinical response parameters were recorded for one year. Analyses were performed in three patient groups that were defined by infliximab serum concentration prior to treatment enhancement: No detectable, Low (< 1.1 µg/mL or High (≥ 1.1 µg/mL drug levels. Results No circulating infliximab was detected in 20 patients (47.6 %, but 13 (30.9 % and 9 (21.4 % patients exhibited Low and High levels, respectively. ATI were only detected in patients with No detectable drug levels because the drug interferes with ELISA. DAS28 disease activity globally showed a modest improvement after dose escalation, but this improvement did not persist after 6 and 12 months. Infliximab serum levels increased significantly in the High group (p=0.016, but no increase was achieved in the Low and No detectable groups. The three study groups exhibited similar disease activity over time, and no improvement was observed in the non-responder EULAR rates. ConclusionsThese results suggest that the efficacy of an infliximab dose increase is limited, and the response is independent of the infliximab trough serum concentration that is achieved prior to escalation.

  11. Comparable Immune Function Inhibition by the Infliximab Biosimilar CT-P13: Implications for Treatment of Inflammatory Bowel Disease.

    Science.gov (United States)

    Lim, Ki Jung; Lee, So Jung; Kim, Sunghwan; Lee, Su Yeon; Lee, Min Seob; Park, Yoon A; Choi, Eun Jin; Lee, Eun Beom; Jun, Hwang Keun; Cho, Jong Moon; Lee, SooYoung; Kwon, Ki Sung; Lim, Byung Pil; Jeon, Myung-Shin; Shin, Eui Cheol; Choi, Yong Sung; Fudim, Ella; Picard, Orit; Yavzori, Miri; Ben-Horin, Shomron; Chang, Shin Jae

    2017-05-01

    CT-P13 is the first biosimilar monoclonal antibody to infliximab, and was recently approved in the European Union, Japan, Korea, and USA for all six indications of infliximab. However, studies directly assessing the biologic activity of CT-P13 versus inflximab in the context of inflammatory bowel disease [IBD] are still scanty. In the present study, we aimed to compare the biological activities of CT-P13 and infliximab with specific focus on intestinal cells so as to gain insight into the potential biosimilarity of these two agents for treatment of IBD. CT-P13 and infliximab were investigated and compared by in vitro experiments for their neutralisation ability of soluble tumour necrosis factor alpha [sTNFα] and membrane-bound tumour necrosis factor alpha [mTNFα], suppression of cytokine release by reverse signalling, induction of regulatory macrophages and wound healing, and antibody-dependent cell cytotoxicity [ADCC]. CT-P13 showed similar biological activities to infliximab as gauged by neutralisation of soluble TNFα, as well as blockade of apoptosis and suppression of pro-inflammatory cytokines in intestinal Caco-2 cells. Infliximab and CT-P13 equally induced apoptosis and outside-to-inside signals through transmembrane TNFα [tmTNFα]. Moreover, regulatory macrophage induction and ensuing wound healing were similarly exerted by CT-P13 and infliximab. However, neither CT-P13 nor infliximab exerted any significant ADCC of ex vivo-stimulated peripheral blood monocytes or lamina propria mononuclear cells from IBD patients. These findings indicate that CT-P13 and infliximab exert highly similar biological activities in intestinal cells, and further support a mechanistic comparability of these two drugs in the treatment of IBD. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  12. Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis.

    Science.gov (United States)

    Papamichael, Konstantinos; Van Stappen, Thomas; Vande Casteele, Niels; Gils, Ann; Billiet, Thomas; Tops, Sophie; Claes, Karolien; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Severine; Ferrante, Marc

    2016-04-01

    Mucosal healing is an independent predictor of sustained clinical remission in patients with ulcerative colitis (UC) treated with infliximab. We investigated whether infliximab concentrations during induction therapy are associated with short-term mucosal healing (STMH) in patients with UC. We performed a retrospective, single-center analysis of data collected from a tertiary referral center from 101 patients with UC who received scheduled induction therapy with infliximab at weeks 0, 2, and 6 and had an endoscopic evaluation at baseline and after induction therapy. STMH was defined as Mayo endoscopic sub-score ≤1, assessed at weeks 10-14, with baseline sub-score ≥2. Infliximab concentrations were evaluated in serum samples collected at weeks 0, 2, 6, and 14 of infliximab therapy by using an enzyme-linked immunosorbent assay we developed. Fifty-four patients (53.4%) achieved STMH. Patients with STMH had a higher median infliximab concentration at weeks 2, 6, and 14 than patients without STMH. A receiver operating characteristic (ROC) analysis identified infliximab concentration thresholds of 28.3 (area under the ROC curve [AUROC], 0.638), 15 (AUROC, 0.688), and 2.1 μg/mL (AUROC, 0.781) that associated with STMH at weeks 2, 6, and 14, respectively. Multiple logistic regression analysis identified infliximab concentration ≥15 at week 6 (P = .025; odds ratio, 4.6; 95% confidence interval, 1.2-17.1) and ≥2.1 μg/mL at week 14 (P = .004; odds ratio, 5.6; 95% confidence interval, 1.7-18) as independent factors associated with STMH. In an analysis of data from real-life clinical practice, we associated infliximab concentrations during the induction therapy with STMH in patients with UC. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Magnitude of Increased Infliximab Clearance Imposed by Anti-infliximab Antibodies in Crohn's Disease Is Determined by Their Concentration.

    Science.gov (United States)

    Edlund, Helena; Steenholdt, Casper; Ainsworth, Mark A; Goebgen, Eva; Brynskov, Jørn; Thomsen, Ole Ø; Huisinga, Wilhelm; Kloft, Charlotte

    2017-01-01

    Antibodies (Abs) against infliximab (IFX) increase IFX clearance and can result in treatment failure and acute hypersensitivity reactions. However, interpretation of their clinical value is complicated by individual differences in Ab responses and methods used for quantification. The increase in IFX clearance imposed by anti-IFX Abs has generally been evaluated using a binary classification, i.e., positive or negative. This analysis aimed to investigate if anti-IFX Ab concentrations provide a more adequate prediction of alterations in clearance. Data originated from a clinical trial on Crohn's disease patients with IFX treatment failure. The trial was not originally designed for pharmacokinetic analysis. Therefore, published pharmacokinetic models were utilized as priors to enable covariate investigation. The impact of anti-IFX Abs on clearance was assessed using different mathematical relationships and exploiting information from two different quantification assays, measuring semi-quantitative "total" or "unbound neutralizing" concentrations of anti-IFX Ab, respectively. Inclusion of anti-IFX Ab status/concentration improved the model's performance for all investigated relationships. The anti-IFX Ab concentrations were superior to the binary classifications, indicating that the magnitude of increase in IFX clearance imposed by anti-IFX Abs closely relates to their concentration. Furthermore, total anti-IFX Ab concentrations appeared superior to the unbound neutralizing fraction in identifying high clearance individuals. Simulations showed that even at low concentrations, anti-IFX Abs lead to sub-therapeutic IFX concentrations, supporting a need of treatment interventions in all anti-IFX Ab positive patients. The developed model can serve as a basis for further investigations to refine treatment recommendations for patients with anti-IFX Abs.

  14. Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Svenson, M; Bendtzen, K

    2011-01-01

    BACKGROUND: Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD). AIM: To investigate the role of anti-IFX antibodies (Ab) and other risk factors. METHODS: The study included all IBD patients treated with IFX at a Danish university...

  15. INFLIXIMAB EFFECT ON CLINICAL AND LABORATORY ACTIVITY PARAMETERS IN CASES OF VARIOUS JUVENILE ARTHRITIS VARIANTS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2008-01-01

    Full Text Available The study analyses efficiency and safety of using mono clone antibodies for tumor necrosis factor (infliximab for children with system (n = 21 and articular (n = 59 juvenile arthritis (JA. Infliksimab was injected intravenously (average dose of 6,8 ± 2,3 mg/kg/per injection by a standard scheme (0, 2, 6, and each 8 following weeks. Together with antibcytokine therapy children still received immunity depressants (cyclosporine, methotraksat, leflunomid, peroral glucocorticoids. Research results prove that infliximab has pronounced hormone like anti-inflammatory effect after first injection for both patients with early and delayed articular JA variants. It reserved articular syndrome, reduced laboratory activity parameters, reduced degree of invalidity, improved quality of patients' lives. At the same time after three first infusions 88% of patients with system JA the effect was neutralized, articular syndrome activity increased, laboratory activity parameters increased, systematic indicators recurred. On the contrary, patients with both early and delayed JA variant the medication quickly and efficiently reduced activity of articular syndrome, personal estimations of pain levels and disease activity. Index of life quality was significantly improved, much like the selfbservice ability. Medication effect was registered after the first injection and remained over the whole period of observation (up to two years in 61% cases of delayed and 93% of early articular ja variant. Thus, infliximab therapy is a reasonable, efficient and safe treatment of patients with both early and delyed articular JA.Key words: juvenile arthritis, infliximab, treatment.

  16. Certolizumab pegol in patients with moderate to severe Crohn's disease and secondary failure to infliximab

    NARCIS (Netherlands)

    Sandborn, William J.; Abreu, Maria T.; D'Haens, Geert; Colombel, Jean-Frédéric; Vermeire, Severine; Mitchev, Krassimir; Jamoul, Corinne; Fedorak, Richard N.; Spehlmann, Martina E.; Wolf, Douglas C.; Lee, Scott; Rutgeerts, Paul

    2010-01-01

    Patients with moderate to severe Crohn's disease who receive infliximab may experience secondary failure (loss of response and/or hypersensitivity). Data on the utility of switching to certolizumab pegol in these patients are limited. A total of 539 patients with active Crohn's disease and secondary

  17. Inadvertent yellow fever vaccination of a patient with Crohn's disease treated with infliximab and methotrexate

    DEFF Research Database (Denmark)

    Ekenberg, C.; Friis-Møller, N.; Ulstrup, Thomas

    2016-01-01

    We present a case of a 56-year-old woman with Crohn's disease, treated with methotrexate and infliximab, who inadvertently received yellow fever vaccination (YFV) prior to a journey to Tanzania. She was not previously vaccinated against YF. YFV contains live-attenuated virus, and is contraindicated...

  18. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection

    NARCIS (Netherlands)

    Regueiro, Miguel; Feagan, Brian G.; Zou, Bin; Johanns, Jewel; Blank, Marion A.; Chevrier, Marc; Plevy, Scott; Popp, John; Cornillie, Freddy J.; Lukas, Milan; Danese, Silvio; Gionchetti, Paolo; Hanauer, Stephen B.; Reinisch, Walter; Sandborn, William J.; Sorrentino, Dario; Rutgeerts, Paul; Debinski, H.; Florin, T.; Hetzel, D.; Lawrance, I.; Radford-Smith, G.; Sloss, A.; Sorrentino, D.; Gassner, S.; Haas, T.; Reicht, G.; Reinisch, W.; Strasser, M.; Vogelsang, H.; Bossuyt, P.; Dewit, O.; D'Haens, G.; Franchimont, D.; Louis, E.; Vermeire, S.; Bernstein, C. N.; Bourdages, R.; Chiba, N.; Dhalla, S. S.; Feagan, B. G.; Fedorak, R. N.; Lachance, J. R.; Panaccione, R.; Ropeleski, M.; Singh Salh, B.; Lukas, M.; Colombel, J.-F.; Allez, M.; Desreumaux, P.; Dupas, J. L.; Grimaud, J.-C.; Hebuterne, X.; Laharie, D.; Lerebours, E.; Peyrin-Biroulet, L.; Reimund, J.-M.; Viennot, S.; Zerbib, F.; Antoni, C.; Atreya, R.; Baumgart, D. C.; Berg, C.; Boecker, U.; Bramkamp, G.; Bünning, C.; Ehehalt, R.; Howaldt, S.; Kucharzik, T.; Lamprecht, H. G.; Mudter, J.; Preiss, J. C.; Schreiber, S.; Seidler, U.; Altorjay, I.; Banai, J.; Lakatos, P. L.; Varga, M.; Vincze, A.; Avni-Biron, I.; Fishman, S.; Fraser, G. M.; Goldin, E.; Rachmilewitz, D.; Annese, V.; Ardizzone, S.; Biancone, L.; Bossa, F.; Danese, S.; Fries, W.; Gionchetti, P.; Maconi, G.; Terrosu, G.; Usai, P.; Gearry, R. B.; Hill, J.; Rowbotham, D. S.; Schultz, M.; Stubbs, R. S.; Wallace, D.; Walmsley, R. S.; Wyeth, J.; Malecka-Panas, E.; Paradowski, L.; Regula, J.; Beales, I. P.; Campbell, S.; Hawthorne, A. B.; Parkes, M.; Travis, S. P.; Achkar, J. P.; Behm, B. W.; Bickston, S. J.; Brown, K. J.; Chiorean, M. V.; DeVilliers, W. J. S.; Elliott, D. E.; Grunkmeier, D.; Hamilton, J. W.; Hanauer, S. B.; Hanson, J. S.; Hardi, R.; Helper, D. J.; Herfarth, H.; Higgins, P. D. R.; Holderman, W. H.; Kottoor, R.; Kreines, M. D.; Leman, B. I.; Li, X.; Loftus, E. V.; Noar, M.; Oikonomou, I.; Onken, J.; Peterson, K. A.; Phillips, R. P.; Randall, C. W.; Ricci, M.; Ritter, T.; Rubin, D. T.; Safdi, M.; Sandborn, W. J.; Sauberman, L.; Scherl, E.; Schwarz, R. P.; Sedghi, S.; Shafran, I.; Sninsky, C. A.; Stein, I.; Swoger, J.; Vecchio, J.; Weinberg, D. I.; Wruble, L. D.; Yajnik, V.; Younes, Z.

    2016-01-01

    BACKGROUND & AIMS: Most patients with Crohn's disease (CD) eventually require an intestinal resection. However, CD frequently recurs after resection. We performed a randomized trial to compare the ability of infliximab vs placebo to prevent CD recurrence. METHODS: We evaluated the efficacy of

  19. Infliximab for the treatment of fistulas in patients with Crohn's disease

    NARCIS (Netherlands)

    Present, D. H.; Rutgeerts, P.; Targan, S.; Hanauer, S. B.; Mayer, L.; van Hogezand, R. A.; Podolsky, D. K.; Sands, B. E.; Braakman, T.; DeWoody, K. L.; Schaible, T. F.; van Deventer, S. J.

    1999-01-01

    Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor alpha, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind,

  20. Recommendations for the long-term treatment of psoriasis with infliximab: A dermatology expert group consensus

    DEFF Research Database (Denmark)

    Reich, K.; Griffiths, C.; Barker, J.

    2008-01-01

    Background/Aims: Infliximab has been approved for the treatment of chronic plaque psoriasis for only a few years. As physicians gain confidence in initiating and maintaining this therapy, guidance on the management of patients beyond several months or years is needed. To date, there is little or ...

  1. Length of hospital stay and associated hospital costs with infliximab versus cyclosporine in severe ulcerative colitis

    NARCIS (Netherlands)

    Löwenberg, Mark; Duijvis, Nicolette W.; Ponsioen, Cyriel; van den Brink, Gijs R.; Fockens, Paul; D'Haens, Geert R. A. M.

    2014-01-01

    Cyclosporine and infliximab (IFX) seem equally effective as rescue therapy in hospitalized patients with severe ulcerative colitis (UC), although associated hospital stay and costs may differ. The aim of this study was to compare the duration of hospital stay and associated costs from initiation of

  2. Clinical outcome of adalimumab therapy in patients with ulcerative colitis previously treated with infliximab

    DEFF Research Database (Denmark)

    Christensen, Katrine Risager; Steenholdt, Casper; Brynskov, Jørn

    2015-01-01

    clinical outcomes of ADL therapy in a clinical setting where infliximab (IFX) had been used as first choice of anti-TNF agent, and followed by ADL as second line agent. METHODS: Retrospective, observational single-center cohort study including all ulcerative colitis patients treated with ADL at a tertiary...

  3. Recommendations for the treatment of ulcerative colitis with infliximab: A gastroenterology expert group consensus

    NARCIS (Netherlands)

    Reinisch, Walter; van Assche, Gert; Befrits, Ragnar; Connell, William; D'Haens, Geert; Ghosh, Subrata; Michetti, Pierre; Ochsenkühn, Thomas; Panaccione, Remo; Schreiber, Stefan; Silverberg, Mark S.; Sorrentino, Dario; van der Woude, C. Janneke; Vermeire, Séverine; Panes, Julian

    2012-01-01

    Background and aims: Infliximab is currently the only biologic approved for treatment of adults with moderate to severe, active ulcerative colitis (UC) unresponsive to conventional therapies. It rapidly controls symptoms, induces and sustains steroid-free remission, stimulates mucosal healing, and

  4. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid arthritis in six Central and Eastern European countries.

    Science.gov (United States)

    Brodszky, Valentin; Baji, Petra; Balogh, Orsolya; Péntek, Márta

    2014-05-01

    The first biosimilar monoclonal antibody (infliximab, CT-P13) was registered by the European Medicines Agency in 2013 for the treatment of several inflammatory conditions including rheumatoid arthritis (RA). Biosimilar infliximab is first being marketed in the Central and Eastern European countries. This paper presents the estimated budget impact of the introduction of biosimilar infliximab in RA over a 3-year time period in six selected countries, namely Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. A prevalence-based model was constructed for budget impact analysis. Two scenarios were compared to the reference scenario (RSc) where no biosimilar infliximab is available: biosimilar scenario 1 (BSc1), where interchanging the originator infliximab with biosimilar infliximab is disallowed, and only patients who start new biological therapy are allowed to use biosimilar infliximab; as well as biosimilar scenario 2 (BSc2), where interchanging the originator infliximab with biosimilar infliximab is allowed, and 80% of patients treated with originator infliximab are interchanged to biosimilar infliximab. Compared to the RSc, the net savings are estimated to be €15.3 or €20.8 M in BSc1 and BSc2, respectively, over the 3 years. If budget savings were spent on reimbursement of additional biosimilar infliximab treatment, approximately 1,200 or 1,800 more patients could be treated in the six countries within 3 years in the two biosimilar scenarios, respectively. The actual saving is most sensitive to the assumption of the acquisition cost of the biosimilar drug and to the initial number of patients treated with biological therapy. The study focused on one indication (RA) and demonstrated that the introduction of biosimilar infliximab can lead to substantial budget savings in health care budgets. Further savings are expected for other indications where biosimilar medicines are implemented.

  5. Contrast-enhanced ultrasonography with SonoVue after infliximab therapy in Crohn's disease.

    Science.gov (United States)

    Guidi, L; De Franco, A; De Vitis, I; Armuzzi, A; Semeraro, S; Roberto, I; Papa, A; Bock, E; Gasbarrini, G; Fedeli, G

    2006-01-01

    The introduction of biological treatments like monoclonal anti TNF-a antibodies (infliximab), is changing the clinical history of Crohn's disease (CD). The effects of these therapies are monitored emplying clinical indexes of active disease, laboratory parameters, endoscopy and histology, and also with imaging techniques. A new ultrasound contrast agent, SonoVue (Bracco SpA, Milano, Italy), is opening new perspectives in the study of microvasculature of several organs. Aim of this study is to evaluate by SonoVue enhanced ultrasonography (US) the occurrence of modifications in bowel wall microvasculature of CD patients and to correlate them with parameters of disease activity and to follow up the findings during infliximab therapy. After performing a basal color-doppler ultrasonography, the study of the affected bowel loop is performed after i.v. injection of SonoVue and the enhancement is evaluated on a qualitative basis. We report on the preliminary results obtained in twenty patients, eight of which have been treated with three infusions of infliximab (induction cycle) and evaluated at baseline and after the treatment. While at baseline we describe a positive correlation of SonoVue enhancement of the affected bowel loop with CRP, alpha1-glycoprotein and white blood cell number, after infliximab treatment in 6/8 cases a definite improvement was detected. Ultrasonographic evaluation of the changes of bowel wall enhancement after i.v. SonoVue during infliximab therapy might represent an useful, not invasive and relatively low cost imaging modality for the clinical monitoring of activity of small bowel Crohn's disease.

  6. Documented tuberculin skin testing among infliximab users following a multi-modal risk communication interventions.

    Science.gov (United States)

    Shatin, Deborah; Rawson, Nigel S B; Curtis, Jeffrey R; Braun, M Miles; Martin, Carolyn K; Moreland, Larry W; Becker, Angela F; Patkar, Nivedita M; Allison, Jeroan J; Saag, Kenneth G

    2006-01-01

    Following its licensure, tuberculosis (TB) was reported as a potential adverse effect of infliximab. Subsequently, the product circular was changed to recommend tuberculin skin testing before patients received infliximab, which was reinforced by several risk communication efforts. The aim of this study was to evaluate patterns and predictors of documented tuberculin skin testing in patients before and after manufacturer, federal, and academic risk communications. Patients administered infliximab were identified from 11 health plans located throughout the United States, and claims data were examined to determine whether the patients had received a tuberculin skin test. Patients were divided into three cohorts depending on the timing of their first infliximab treatment in relation to the risk communication efforts. The overall tuberculin skin testing rate doubled from 15.4% in the first cohort to 30.9% in the last cohort, while the rate of pre-infliximab treatment testing increased from 0 to 27.7% (Chi-squared test for trend, p skin testing rates were significantly higher in women, those with a diagnosis of rheumatoid or psoriatic arthritis, and those with a rheumatologist as prescriber. After multivariable analysis, only rheumatologist remained significantly associated with tuberculin skin testing. Although the tuberculin skin testing rate was relatively low overall, tuberculin skin testing doubled over 30 months of ongoing risk communication efforts and under ascertainment likely occurred. We also found variation in the tuberculin skin testing rate associated with physician specialty. This study demonstrates a significant change in patient care following risk communication efforts. (c) 2005 John Wiley & Sons, Ltd.

  7. Efficiency of adalimumab, etanercept and infliximab in ankylosing spondylitis in clinical practice.

    Science.gov (United States)

    Escudero-Vilaplana, Vicente; Ramírez-Herráiz, Esther; Alañón-Plaza, Estefanía; Trovato-López, Nicolás; García-Vicuña, Rosario; Carreño-Pérez, Luis; Morell-Baladrón, Alberto; Sanjurjo-Sáez, María

    2015-10-01

    Information on the use of ankylosing spondylitis (AS) therapies in clinical practice is a key factor in decision making, as more efficient treatments may involve substantial savings while maintaining the clinical benefits for the patient. To assess the mean annual doses and associated costs of the three main anti-tumour necrosis factor agents used in Spanish daily clinical practice in ankylosing spondylitis patients and to correlate these costs with disease activity. This retrospective, observational study included adult ankylosing spondylitis patients over a 4-year period that had been treated for at least 6 months with adalimumab, etanercept or infliximab at two University Hospitals in Spain. Disease activity was estimated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores at the start of anti-tumour necrosis factor (anti-TNF) therapy and in the last visit or whenever the drug was switched. Mean costs were estimated for a 52-week horizon from the delivered doses registered by pharmacy records. Outcomes were the doses and costs of anti TNFs administered to each patient, and the BASDAI score. A total of 119 patients (137 cases) were included (28 cases treated with adalimumab, 48 cases with etanercept and 61 with infliximab). Mean doses of adalimumab and etanercept were 92.8 and 88.8% of the initially prescribed doses, respectively, while the mean dose of infliximab administered was 102%. There were no statistical differences among treatments in terms of clinical effectiveness. Associated mean patient-year costs were significantly higher in the infliximab group (€14,235), compared to the other treatments [adalimumab €11,934; etanercept €10,516; (P ankylosing spondylitis patients, doses and associated costs of biological therapies can be reduced while controlling disease activity. Mean doses used in our clinical practice vary from the recommended doses and are significantly lower for adalimumab and etanercept than for infliximab. These

  8. Infliximab to Treat Refractory Inflammation After Pelvic Pouch Surgery for Ulcerative Colitis.

    Science.gov (United States)

    Kelly, Orlaith B; Rosenberg, Morgan; Tyler, Andrea D; Stempak, Joanne M; Steinhart, A Hillary; Cohen, Zane; Greenberg, Gordon R; Silverberg, Mark S

    2016-04-01

    Inflammatory pouch complications refractory to first-line therapies remain problematic following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We evaluated infliximab efficacy and associations with therapeutic response. Data from individuals who underwent colectomy and IPAA for UC (2000-2014) were reviewed. Patients with chronic refractory pouchitis (CP) and Crohn's disease (CD)-like outcomes treated with infliximab were included. Pre-treatment parameters and response at median 8 (initial) and 48 weeks (sustained) were measured. Complete response was defined as symptomatic and endoscopic resolution with modified Pouchitis Disease Activity Index (mPDAI) 2. Serum was analysed for Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-OmpC, anti-CBir1 and perinuclear Anti-Neutrophil Cytoplasmic Antibodies (pANCA). One hundred and fifty-two patients with CP or a CD-like phenotype were identified. Forty-two were treated with infliximab (33% male; age 32.6±2.6 years, 28.5% CD-like). Post-induction response was achieved in 74% (48% complete) and sustained response in 62.6% (29.6% complete). Mean mPDAI and C-reactive protein declined from 8.5±0.3 to 2±3.4 (p infliximab use (p Infliximab can effectively treat inflammatory pouch complications. Pre-treatment mPDAI <10 and early endoscopy may identify responders. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Five-year experience with infliximab: Follow up of the product familiarisation program.

    Science.gov (United States)

    Nguyen, Rebecca; Braue, Anna; Baker, Chris; Foley, Peter

    2016-11-01

    This 5-year retrospective analysis is of 22 patients who participated in the product familiarisation program (PFP) at St Vincent's Hospital Melbourne, prior to the listing of infliximab on the Pharmaceutical Benefit Scheme. Criteria for inclusion were being an adult with chronic plaque psoriasis, having a psoriasis area and severity index (PASI) score of at least 15 with an inadequate response or intolerance to three of the following: phototherapy, acitretin, cyclosporin and methotrexate. Participants were infused with infliximab 5 mg/kg on the standard induction (weeks 0, 2 and 6) and maintenance (8-weekly) protocols. At each visit PASI and dermatology life quality index (DLQI) scores were recorded. Success was determined as the proportion of patients achieving at least a 75% improvement in the PASI score from baseline (PASI 75). At 60 months after commencement of therapy, 31% of patients remained on infliximab. Those who did retained PASI 75 with a DLQI of 0 or 1. Of those who ceased infliximab, nine did so due to loss of efficacy, three for personal reasons, two for serious adverse events and one was lost to follow up. Adverse events included non-melanoma skin cancers, infections and abnormal liver enzymes. Infliximab in the Australian context has proven to be a highly effective treatment of chronic plaque psoriasis, and patients who remained on the drug derived a high level of satisfaction, assessed both subjectively (DLQI) and objectively (PASI 75). The variable response indicates that psoriasis is a heterogeneous disease and investigation into potential patient selection for treatment in the future is warranted. © 2015 The Australasian College of Dermatologists.

  10. A pharmacokinetic approach to model-guided design of infliximab schedules in ulcerative colitis patients

    Directory of Open Access Journals (Sweden)

    Alejandro Pérez-Pitarch

    2015-03-01

    Full Text Available Background: Infliximab, an anti-tumour necrosis factor approved for treatment of Crohn's disease and ulcerative colitis, is administered at predefined interdose-intervals. On insufficient response or loss of response, treatment can be intensified. The lack or loss of response is likely related to complex pharmacokinetics of infliximab. Aims: To explore optimal dosing strategies of infliximab in treatment-naïve patients with ulcerative colitis through predictive Monte Carlo simulations based on a validated population PK model. Methods: A population of 2,000 treatment-naïve patients was generated by Montecarlo simulation. Six dosing strategies for maintenance therapy were simulated on this population. Strategies 1 and 2 consisted on 5 mg/kg and 6 mg/kg doses, respectively, and 8 weeks inter-dose interval. Strategies 3 and 4 used Individualized doses, adjusted to albumin level, sex and body weight, and a fix inter-dose interval of 8 weeks to achieve a target trough concentration of 5 mg/L or 6 mg/L, respectively. Strategies 5 and 6 used a fix dose of 5 mg/kg and individualized inter-dose intervals, adjusted to the same covariates, to achieve a target concentration, of 5 mg/L or 6 mg/L, respectively. Results: Strategies 2-6 reached trough levels statistically higher than strategy 1 (p < 0.05. Strategy 5 proved to be the best dosing strategy. It was associated with a higher proportion of responder patients than strategy 1 (62 % vs. 40 % without reaching higher peak concentrations. Conclusions: Optimization of maintenance treatment of colitis with infliximab by a pharmacokinetic approach could benefit infliximab-naive patients with ulcerative colitis.

  11. PHARMACOECONOMIC ASPECTS OF TREATMENT WITH THE INHIBITORS OF TUMOR NECROSIS FACTOR OF THE CHRONIC UVEITIS REFRACTORY TO THE BASIC THERAPY (INCLUDING AN ASSOCIATED WITH JUVENILE IDIOPATHIC ARTHRITIS

    Directory of Open Access Journals (Sweden)

    A.V. Rudakova

    2011-01-01

    Full Text Available Therapy of chronic uveitis refractory to the basic treatment, in juvenile idiopathic arthritis (JIA is a very complex problem in pediatrics. Substantial progress in this area resulted after the implementation in practice of inhibitors of tumor necrosis factor (TNF, as the most effective in such clinical situation drugs adalimumab and infliximab are considered (although infliximab was not officially approved in JIA. Objective. To estimate the cost effectiveness of TNF inhibitors — adalimumab, and infliximab in chronic uveitis, refractory to the basic therapy (including associated with juvenile rheumatoid arthritis. Methods. A modeling on the basis of a comparative prospective cohort clinical study was carried out. The analysis was performed by the method «cost–effectiveness» from a position of health and social accounting perspective. Results. It was shown that the frequency and time of remission did not differ when treatment with infliximab (5 mg/kg at 0–2–6 weeks and further once in 6–8 weeks and adalimumab (24 mg/m2 once in 2 weeks. Adalimumab provides a long-term maintenance of remission (no recurrence in 60% of patients within 40 months of observation, whereas 1 year after the treatment with infliximab the frequency of exacerbations was returned to that observed before therapy. The proportion of patients without relapse in the treatment with infliximab for 40 months was 18.8%. Similar results were obtained in a subset of patients with chronic uveitis associated with JIA (with follow-up of 20 months of in a group of infliximab number patients without relapse was 11.1%, with adalimumab therapy — 63.6%. In the general population of patients with refractory chronic uveitis the factor «cost–effectiveness» calculated for a patient with the maintenance of remission for 3 years with adalimumab therapy was in 2,1–2,8 times less than in the treatment with infliximab. In chronic uveitis associated with JIA, the coefficient of

  12. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Radstake, T R D J; Svenson, M; Eijsbouts, A M

    2008-01-01

    BACKGROUND: Tumour necrosis factor alpha (TNFalpha) neutralising antibody constructs are increasingly being used to treat rheumatoid arthritis (RA). OBJECTIVE: To determine potential differences in clinical responses, soluble drug levels and antibody formation between patients with RA receiving...... infliximab and adalimumab. METHODS: 69 patients with RA fulfilling the 1987 American College of Rheumatology criteria and about to start treatment with infliximab or adalimumab, were enrolled consecutively. All patients had active disease (28-joint count Disease Activity Score >3.2). Infliximab was given...... intravenously at 3 mg/kg at baseline and after 2, 6 and 14 weeks. Adalimumab was administered as 40 mg biweekly subcutaneously. Concomitant drug treatment was monitored and continued at constant dosage during the study. All serum samples were tested for infliximab/adalimumab levels and anti...

  13. Induction and Maintenance Infliximab Therapy for the Treatment of Moderat-to Severe Crohns Disease in Children

    DEFF Research Database (Denmark)

    Pærregaard, Anders; NN, NN

    2007-01-01

    BACKGROUND AND AIMS: The REACH study evaluated the safety and efficacy of infliximab in children with moderately to severely active Crohn's disease. METHODS: Patients (n = 112) with a Pediatric Crohn's Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6....... Patients responding to treatment at week 10 were randomized to infliximab 5 mg/kg every 8 or 12 weeks through week 46. A concurrent immunomodulator was required. Clinical response (decrease from baseline in the PCDAI score > or =15 points; total score ... points) were evaluated at weeks 10, 30, and 54. RESULTS: At week 10, 99 of 112 (88.4%) patients responded to infliximab (95% confidence interval: [82.5%, 94.3%]) and 66 of 112 (58.9%) patients achieved clinical remission (95% confidence interval: [49.8%, 68.0%]). At week 54, 33 of 52 (63.5%) and 29 of 52...

  14. The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production

    Science.gov (United States)

    Kanojia, Gaurav; Have, Rimko ten; Bakker, Arjen; Wagner, Koen; Frijlink, Henderik W.; Kersten, Gideon F. A.; Amorij, Jean-Pierre

    2016-01-01

    In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn’s disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab. PMID:27706175

  15. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children

    DEFF Research Database (Denmark)

    Hyams, Jeffrey; Crandall, Wallace; Kugathasan, Subra

    2006-01-01

    BACKGROUND AND AIMS: The REACH study evaluated the safety and efficacy of infliximab in children with moderately to severely active Crohn's disease. METHODS: Patients (n = 112) with a Pediatric Crohn's Disease Activity Index (PCDAI) score >30 received infliximab 5 mg/kg at weeks 0, 2, and 6. Pati......, remission rates, but not response rates, at week 54 were superior with every 8-week dosing compared with every 12-week dosing. Udgivelsesdato: 2007-Mar...

  16. Discontinuation of Infliximab in Patients With Ulcerative Colitis Is Associated With Increased Risk of Relapse: A Multinational Retrospective Cohort Study.

    Science.gov (United States)

    Fiorino, Gionata; Cortes, Pablo Navarro; Ellul, Pierre; Felice, Carla; Karatzas, Pantelis; Silva, Marco; Lakatos, Peter L; Bossa, Fabrizio; Ungar, Bella; Sebastian, Shaji; Furfaro, Federica; Karmiris, Konstantinos; Katsanos, Konstantinos H; Muscat, Martina; Christodoulou, Dimitrios K; Maconi, Giovanni; Kopylov, Uri; Magro, Fernando; Mantzaris, Gerassimos J; Armuzzi, Alessandro; Boscà-Watts, Marta Maia; Ben-Horin, Shomron; Bonovas, Stefanos; Danese, Silvio

    2016-10-01

    Infliximab is a safe and effective therapy for ulcerative colitis (UC). We conducted a multicenter retrospective cohort study that included 7 European countries and Israel to examine whether infliximab discontinuation can be considered for patients who achieve sustained remission. We performed a retrospective cohort study, collecting medical records from 13 tertiary care referral inflammatory bowel disease centers of all patients with UC treated with infliximab (n = 193). We compared the disease course of patients with at least 12 months of clinical remission who discontinued infliximab (n = 111) with that of patients who continued scheduled treatment (controls, n = 82). We examined the incidence rates of relapse, hospitalization and colectomy, the comparative effectiveness of different therapeutic strategies after discontinuation, and assessed the rates of response, remission, and adverse effects after infliximab re-initiation. Statistical analyses used time-to-event methods. In the entire cohort, 67 patients (34.7%) relapsed during the follow-up period. The incidence rate of relapse was significantly higher after discontinuation (23.3 per 100 person-years) compared with the control group (7.2 per 100 person-years) in univariable analysis (log-rank P infliximab discontinuation (incidence of relapse: 15.0 per 100 person-years for thiopurines, 27.4 per 100 person-years for thiopurines plus aminosalicylates, and 31.2 per 100 person-years for aminosalicylates alone; log-rank P = .032). Response was regained in 77.1% of patients and remission in 51.4% of patients who re-initiated infliximab. However, 17.1% had infusion reactions and 17.1% reported other adverse events. In a multinational retrospective cohort study of patients with UC in sustained clinical remission, we associated discontinuation of infliximab with an increased risk of relapse. Treatment re-initiation is effective and safe. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights

  17. Mean Platelet Volume in Crohn's Disease Patients Predicts Sustained Response to a 52-Week Infliximab Therapy: A Pilot Study.

    Science.gov (United States)

    Sobolewska, Aleksandra; Włodarczyk, Marcin; Stec-Michalska, Krystyna; Fichna, Jakub; Wiśniewska-Jarosińska, Maria

    2016-02-01

    The loss of response to infliximab in Crohn's disease (CD) patients is currently a major clinical problem. Recently, mean platelet volume (MPV) has been proposed as a new biomarker of CD activity. Here, we hypothesized that MPV may be used as cheap and efficient biomarker of subclinical inflammation during 52-week therapy in CD patients responding to infliximab induction treatment. The aim of study was to establish whether MPV at baseline and pre-infusion at week 14 are good predictors of sustained response after week 14 in CD patients undergoing 52-week infliximab therapy. A retrospective study of 30 adult CD patients who underwent a 52-week course of treatment with infliximab and achieved response at week 14 to induction treatment was performed. The association between MPV, baseline disease parameters and maintained clinical response or remission during infliximab therapy was assessed. Higher MPV at week 14 was observed in CD patients with sustained response to infliximab after week 14 than in patients with loss of response (p = 0.0019). In patients with loss of response to maintenance infliximab treatment, lower ΔMPV between baseline and week 14 was calculated (p = 0.0003). MPV > 10.3 fl at week 14 predicts sustained response with 67 % sensitivity and 80 % specificity. ΔMPV between baseline and week 14 >0.4 fl predicts sustained response with 87 % sensitivity and 93 % specificity. MPV at week 14 and ΔMPV between baseline and week 14 are good predictors of sustained response to infliximab maintenance treatment in CD patients.

  18. Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure

    Science.gov (United States)

    Ungar, Bella; Haj-Natour, Ola; Kopylov, Uri; Yavzori, Miri; Fudim, Ella; Picard, Orit; Loebstein, Ronen; Lahat, Adi; Maor, Yaakov; Avidan, Benjamin; Lang, Alon; Weiss, Batia; Chowers, Yehuda; Eliakim, Rami; Ben-Horin, Shomron

    2015-01-01

    Abstract Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity. To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes. One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17–0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13–0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15–0.65, P = 0.002; OR 0.42 95% CI 0.18−0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07−16.1, p = 0.04, OR 4.45 95% CI 1.2−16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14−0.96, p = 0.04). P = 0.04, respectively), whereas episodic

  19. Analysis of Th Cell-related Cytokine Production in Behçet Disease Patients with Uveitis Before and After Infliximab Treatment.

    Science.gov (United States)

    Takeuchi, Masaru; Karasawa, Yoko; Harimoto, Kohzou; Tanaka, Atsushi; Shibata, Masaki; Sato, Tomohito; Caspi, Rachel R; Ito, Masataka

    2017-02-01

    To examine antigen-stimulated cytokine production by Behçet disease patients (BD) before and after infliximab infusion. PBMCs were obtained before and after infliximab infusion in BD patients with or without recurrent uveitis during at least 1 year of infliximab therapy, and from healthy subjects. PBMCs were cultured with IRBP, and Th-related cytokines in cultures were measured. Levels of IL-4, IL-6, IL-10 IL-17A, IL-17F, IL-31, IFN-γ, and TNFα were higher in BD before infliximab infusion than in healthy subjects, and these levels were the highest in BD with recurrent uveitis. After infliximab infusion, these cytokine levels were reduced to a greater extent in BD without recurrent uveitis than in BD with recurrence. Th-related cytokines produced by IRBP-stimulated PBMCs were elevated in BD, and infliximab infusion suppressed these cytokines to a greater extent in BD without recurrent uveitis than in those with recurrence.

  20. Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially insured population in the United States.

    Science.gov (United States)

    Schabert, Vernon F; Watson, Crystal; Gandra, Shravanthi R; Goodman, Seth; Fox, Kathleen M; Harrison, David J

    2012-01-01

    To calculate annual cost per treated patient of tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab for common approved indications, based on actual TNF-inhibitor use in clinical practice. Adults with ≥1 claim for etanercept, adalimumab, or infliximab between January 2005 and March 2009 were identified from the IMS LifeLink™ Health Plan Claims Database. Patients new to therapy or continuing therapy (i.e., a prior claim for a TNF-inhibitor) were analyzed separately. Included patients had been enrolled from 180 days before the first TNF-inhibitor claim (index date) through 360 days after the index date and had a diagnosis during the pre-index period for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients with Crohn's disease, ulcerative colitis, or juvenile idiopathic arthritis were excluded. Annual costs were calculated using wholesale acquisition costs for the TNF-inhibitor and Medicare Physician Fee Schedule for drug administration. Costs from restarting or switching TNF-inhibitor therapy during the first year were included. A total of 27,704 patients (11,528 new, 16,176 continuing) had claims for etanercept, adalimumab, or infliximab, most commonly (65%) for treatment of rheumatoid arthritis. The most commonly used agent was etanercept (14,777 patients; 53%), followed by adalimumab (6862 patients; 25%) and infliximab (6065 patients; 22%). Annual cost per treated patient was etanercept $14,873, adalimumab $17,766, and infliximab $21,256 across all indications. Annual cost per treated patient by disease was (etanercept/adalimumab/infliximab): rheumatoid arthritis ($14,314/$17,700/$20,390), psoriasis ($17,182/$17,682/$23,935), psoriatic arthritis ($15,030/$18,483/$24,974), and ankylosing spondylitis ($14,254/$16,925/$23,056). New and continuing patients showed similar results, with etanercept having the lowest costs. This analysis is limited to three TNF-inhibitors and a US managed-care population

  1. Infliximab vs. adalimumab in Crohn's disease: results from 327 patients in an Australian and New Zealand observational cohort study.

    Science.gov (United States)

    Doecke, J D; Hartnell, F; Bampton, P; Bell, S; Mahy, G; Grover, Z; Lewindon, P; Jones, L V; Sewell, K; Krishnaprasad, K; Prosser, R; Marr, D; Fischer, J; R Thomas, G; Tehan, J V; Ding, N S; Cooke, S E; Moss, K; Sechi, A; De Cruz, P; Grafton, R; Connor, S J; Lawrance, I C; Gearry, R B; Andrews, J M; Radford-Smith, G L

    2017-02-01

    Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators. To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy. We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011. Demographic and clinical data were prospectively recorded to identify independent factors associated with induction and maintenance of response to infliximab or adalimumab, or to either anti-TNFα therapy. Three hundred and twenty-seven patients (183 infliximab, 144 adalimumab) successfully applied for treatment. Eighty-nine percent responded in all groups and median maintenance of response was similar for the two agents. Concomitant immunomodulator with infliximab, but not adalimumab, demonstrated a significantly longer response overall (P = 0.002), and significantly fewer disease and treatment-related complications (P = 0.017). Corticosteroids at baseline, and/or in the preceding 12 months, were associated with a 9-13 times greater risk of disease flare during maintenance treatment as compared to no corticosteroids (P infliximab and adalimumab to have similar response characteristics. However, infliximab requires concomitant immunomodulator to achieve optimal maintenance of response comparable to adalimumab monotherapy. The results of this study will assist clinicians in further optimising patient care in their day-to-day clinical practice. © 2016 John Wiley & Sons Ltd.

  2. Evaluation of the infliximab therapy of severe form of pediatric Crohn's disease in Poland: Retrospective, multicenter studies.

    Science.gov (United States)

    Iwańczak, Barbara M; Ryżko, Józef; Jankowski, Piotr; Sładek, Małgorzata; Wasilewska, Agata; Szczepanik, Mariusz; Sienkiewicz, Edyta; Szaflarska-Popławska, Anna; Więcek, Sabina; Czaja-Bulsa, Grażyna; Korczowski, Bartosz; Maślana, Jolanta; Iwańczak, Franciszek; Kacperska, Magdalena

    2017-01-01

    Registration of infliximab in Poland has increased chances to induce clinical remission and mucosal healing in the severe form of pediatric Crohn's disease. The aim of this retrospective study was to assess the results and safety of infliximab therapy in the severe form of pediatric Crohn's disease. The study included 153 children with severe form of non-fistulizing Crohn's disease treated with infliximab. The clinical activity of Crohn's disease was assessed according to PCDAI scale, endoscopic scoring was graded according to SES-CD, body mass was measured with body mass index (BMI). Infliximab was administered at the dose 5 mg/kg body mass in the 0.2 and 6th week, and then, after clinical response, every 8 for the period of 12 months. One hundred thirty-six children (88.89%) achieved clinical response after induction therapy and 75.21% of children after the maintenance therapy. 39.68% of children achieved remission as graded with endoscopic scoring SES-CD. There was a statistically significant increase in body weight following the treatment. Side effects such as anaphylaxis, rash, and the activation of EBV infection appeared in 9 children at the time of infliximab injection. In other children the drug was well tolerated. Induction and maintenance therapy with infliximab resulted in clinical remission of Crohn's disease in 75.21% of children, and in the intestinal mucosa healing in 39.68% of children.

  3. Infliximab exerts a dose-dependent effect on retinal safety in the albino rabbit.

    Science.gov (United States)

    Zayit-Soudry, Shiri; Vainer, Igor; Zemel, Esther; Mimouni, Michael; Rabena, Melvin; Pieramici, Dante J; Perlman, Ido; Loewenstein, Anat

    2017-12-01

    To assess the retinal toxicity of an intravitreal injection of infliximab, a monoclonal antibody to tumor necrosis factor α, in a rabbit model. Two groups of adult albino rabbits (n = 5) received intravitreal injections of infliximab (0.1 ml) in the study eye and balanced salt solution (BSS, 0.1 ml) in the control eye at baseline. Group 1 was administered with 1.5 mg/0.1 ml, and group 2 was injected with 7.5 mg/0.1 ml of infliximab solution. Electroretinography (ERG) was performed at baseline and at 1, 7, 30, and 45 days after the injection. Visual evoked potentials (VEPs) were recorded at 7 and 45 days after the injection. After the last electrophysiological assessment, the rabbits were euthanized and retinal histopathology and immunhistochemistry for glial fibrillary acidic protein (GFAP) were performed. ERG responses demonstrated no significant deficit in retinal function in eyes injected with infliximab. Mean dark-adapted a-wave and b-wave maximal amplitude and semi-saturation constant values at baseline and throughout the 45 days of follow-up after the injection indicated no remarkable difference in outer retinal function between the control and experimental eyes. VEP responses were similar at each time point (7 and 45 days). No difference was seen in retinal histopathology and immunocytochemistry sections in eyes receiving the 1.5 mg/0.1 ml dose compared to the control eyes. However, increased GFAP labeling in retinal Müller cells was detected in rabbit eyes treated with the 7.5 mg/0.1 ml dose. Intravitreal injection of 1.5 mg/0.1 ml infliximab dose has no toxic effect on the integrity (functional or structural) of the retina in rabbits. A higher dose of 7.5 mg/0.1 ml may be slightly toxic as suggested by positive Müller cell GFAP expression. Additional studies of retinal toxicity at higher doses and after multiple injections are needed to establish the retinal safety of intravitreal infliximab therapy in humans.

  4. A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability

    Directory of Open Access Journals (Sweden)

    Becciolini A

    2017-06-01

    Full Text Available Andrea Becciolini,1 Maria Gabriella Raimondo,2 Chiara Crotti,2 Elena Agape,2 Martina Biggioggero,2 Ennio Giulio Favalli1 1Department of Rheumatology, 2Department of Clinical Sciences and Health Community, University of Milan, Division of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP, and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs – PLANETRA and PLANETAS – performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and

  5. Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs.

    Science.gov (United States)

    Thorlund, Kristian; Druyts, Eric; Toor, Kabirraaj; Mills, Edward J

    2015-05-01

    To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.

  6. Infliximab no tratamento da sarcoidose - Experiência de um hospital central

    Directory of Open Access Journals (Sweden)

    M. Aguiar

    2011-03-01

    Full Text Available Resumo: Apesar de tratamento agressivo e atempado, a Sarcoidose pode ser, por vezes, uma doença progressiva e bastante debilitante. O papel do factor de necrose tumoral (TNF-α na génese dos granulomas é ambíguo. Por um lado a sua presença é necessária para a formação e manutenção da inflamação granulomatosa, sendo, portanto, o seu antagonista utilizado com sucesso no tratamento de doentes com sarcoidose; por outro lado e para outras situações, há referência do aparecimento dessa patologia em doentes submetidos a Infliximab.O Infliximab foi por nós utilizado no tratamento de doentes com sarcoidose que não apresentavam resposta à corticoterapia ou a outras terapêuticas convencionais ou que desenvolviam efeitos secundários inaceitáveis a essa terapêutica. A dose inicial foi de 5 mg/Kg de peso e as doses subsequentes foram administradas na 2.a semana, na 6.a semana e depois, durante o período de um ano de 8 em 8 semanas.Dez doentes com diagnóstico de sarcoidose por biopsia, iniciaram terapêutica com este fármaco. Destes cinco eram homens e cinco mulheres, com uma idade média de 47,1 anos, variando a idade entre 28 e 63 anos. Três doentes apresentavam sintomas graves do sistema nervoso central, dois, cirrose hepática, uma inflamação granulomatosa da glândula lacrimal já submetida a múltiplas cirurgias, uma com envolvimento pulmonar extenso (estádio III, uma, com lúpus pérnio desfigurante e dois, com nódulos cutâneos desfigurantes. Oito doentes apresentavam mais do que um local de doença. Todos os doentes completaram pelo menos sete ciclos de tratamento. Em quatro doentes a dose de corticóides ou de outra terapêutica imunosupressora foi suspensa, em três foi reduzida, e apenas em uma doente foi necessário juntar corticóides à terapêutica com Infliximab. Cinco doentes apresentaram uma melhoria

  7. Uso de infliximab en pacientes de un centro reumatológico Use of infliximab in patients of a rheumatologic center

    Directory of Open Access Journals (Sweden)

    Ingrid Strusberg

    2005-03-01

    Full Text Available El objetivo de este estudio fue obtener información postmarketing sobre el uso de infliximab en un centro reumatológico de atención ambulatoria. Se realizó un análisis retrospectivo y prospectivo de las historias clínicas de pacientes con diagnóstico de artritis reumatoidea ( n=37 , artritis psoriásica ( n=5 , enfermedad mixta del tejido conectivo ( n=1 y espondilitis anquilosante ( n=2 que recibieron infliximab (3 mg / kg desde agosto de 2000 a junio de 2003. El análisis descriptivo se realizó con porcentajes, media o mediana y desviación estándar o intervalo intercuartilo . La prueba de Wilcoxon se utilizó para el análisis apareado de dosis de antiinflamatorios no esteroideos y metotrexato , anterior y posterior a la administración de infliximab. Se consideraron significativos valores de p £ 0.05. Se incluyeron 45 pacientes a los que se les administraron un total de 207 infusiones. En 2 pacientes el infliximab se discontinuó debido a lumbalgia severa durante la infusión y en otros 2 por anafilaxia intrainfusional. Otras reacciones adversas ocurridas durante las infusiones fueron moderadas y respondieron adecuadamente al tratamiento estándar. Se presentó un caso de artritis séptica de rodilla por estafilococos. Un caso de artritis reumatoidea con insuficiencia renal compensada recibió infliximab en dosis de 1.9 mg / kg cada 30 días, sin cambios en la función renal. Al momento, ningún paciente ha desarrollado tuberculosis activa. Debido a la mejoría clínica, se redujo la dosis de corticoides en 14/39 (35.9% pacientes, de antiinflamatorios no esteroideos en 15/43 (34.8% y de metotrexato en 12/34 (35.3%. En esta serie de casos se muestra el perfil de seguridad de infliximab, la posibilidad de reducir la dosis de drogas concomitantes, así como algunos enfoques individuales sobre situaciones para las cuales no disponemos de guías basadas en la evidencia médica, y en las que los reumatólogos debemos tomar decisiones seg

  8. Defining the ultrasound longitudinal natural history of newly diagnosed pediatric small bowel Crohn disease treated with infliximab and infliximab-azathioprine combination therapy.

    Science.gov (United States)

    Dillman, Jonathan R; Dehkordy, Soudabeh Fazeli; Smith, Ethan A; DiPietro, Michael A; Sanchez, Ramon; DeMatos-Maillard, Vera; Adler, Jeremy; Zhang, Bin; Trout, Andrew T

    2017-07-01

    Little is known about changes in the imaging appearances of the bowel and mesentery over time in either pediatric or adult patients with newly diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha (anti-TNF-α) therapy. To define how bowel ultrasound findings change over time and correlate with laboratory inflammatory markers in children who have been newly diagnosed with pediatric small bowel Crohn disease and treated with infliximab. We included 28 pediatric patients treated with infliximab for newly diagnosed ileal Crohn disease who underwent bowel sonography prior to medical therapy and at approximately 2 weeks, 1 month, 3 months and 6 months after treatment initiation; these patients also had laboratory testing at baseline, 1 month and 6 months. We used linear mixed models to compare mean results between visits and evaluate whether ultrasound measurements changed over time. We used Spearman rank correlation to assess bivariate relationships. Mean subject age was 15.3±2.2 years; 11 subjects were girls (39%). We observed decreases in mean length of disease involvement (12.0±5.4 vs. 9.1±5.3 cm, P=0.02), maximum bowel wall thickness (5.6±1.8 vs. 4.7±1.7 mm, P=0.02), bowel wall color Doppler signal (1.7±0.9 vs. 1.2±0.8, P=0.002) and mesenteric color Doppler signal (1.1±0.9 vs. 0.6±0.6, P=0.005) at approximately 2 weeks following the initiation of infliximab compared to baseline. All laboratory inflammatory markers decreased at 1 month (P-valuesinfliximab, when adjusted for age, sex, azathioprine therapy, scanning radiologist and baseline short pediatric Crohn's disease activity index score. The ultrasound appearance of the bowel changes as early as 2 weeks after the initiation of infliximab therapy. There is strong correlation between bowel wall color Doppler signal and fecal calprotectin.

  9. Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.

    Science.gov (United States)

    Rüddel, J; Schleenvoigt, B T; Schüler, E; Schmidt, C; Pletz, M W; Stallmach, A

    2016-09-01

    We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis.

    Science.gov (United States)

    Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

    2015-05-21

    Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.

  11. A review of six methods for monitoring infliximab concentrations and antibodies to infliximab
.

    Science.gov (United States)

    Cao, Fang; Cao, Hailong; Cao, Xiaocang

    2017-07-01

    Anti-TNF-α therapy, such as infliximab (IFX), has profoundly changed treatment to induce and maintain remission for inflammatory bowel diseases patients who do not respond to conventional therapies. Unfortunately, IFX, as a chimeric protein, is potentially immunogenic, and antibodies to infliximab (ATI) may interfere with the pharmacodynamics and pharmacokinetics of the drug, thus resulting in a loss of response for a substantial proportion of patients. The clinical efficacy of IFX is correlated with the levels of IFX and ATI. Therefore, monitoring patients for the trough levels of IFX and the presence of ATI is very important. The procedures and characteristics of six assays for monitoring IFX and ATI are described in this review, and the comparisons between them are also discussed. To date, there has been no optimal assay for monitoring IFX and ATI. Therefore, many technical problems need to be solved to make therapeutic drug and immunogenicity monitoring a part of routine clinical management.
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  12. Biologic-free remission by orthopaedic surgery in non-responder to infliximab for rheumatoid arthritis.

    Science.gov (United States)

    Kanbe, Katsuaki; Chiba, Junji; Inoue, Yasuo; Taguchi, Masashi; Yabuki, Akiko

    2015-01-01

    The aim of this study was to investigate remission and biologic-free remission after orthopaedic surgery and related clinical factors in non-responder to infliximab for rheumatoid arthritis (RA). We analyzed 74 patients who were treated with 3 mg/kg infliximab and methotrexate and underwent orthopaedic surgery after non-responder to infliximab with disease activity score (DAS) 28 (CRP) of ≥3.2. The rates of remission and biologic-free remission at 52 weeks after orthopaedic surgery were investigated and the clinical factors related to remission and biologic-free remission were analyzed by logistic regression and receiver-operating characteristic analyses. The rates of total remission and biologic-free remission were 37/74 (50 %) and 9/74 (12.2 %), respectively. Regarding orthopaedic surgery, the rates of remission and biologic-free remission were 25/38 (65.8 %) and 7/38 (18.4 %) for synovectomy, 7/20 (35 %) and 0/20 (0 %) for arthroplasty, and 5/16 (31.3 %) and 2/16 12.5) for others including spine surgery and foot surgery. DAS28(CRP) at baseline was significantly related to both remission and biologic-free remission. Prednisolone was negatively associated with remission, and DAS28(CRP) was related to biologic-free remission by logistic regression analyses. DAS28(CRP) below 3.7 was cutoff point for acquiring biologic-free remission of non-responder to infliximab after orthopaedic surgery. Therefore orthopaedic surgery may be effective to obtain remission or biologic-free remission in RA patients treated with biologics.

  13. Episcleritis Related to Drug-Induced Lupus Erythematosus following Infliximab Therapy: A Case Report

    OpenAIRE

    Chatziralli, Irini P.; Kanonidou, Evgenia; Chatzirallis, Alexandros; Dimitriadis, Prodromos; Keryttopoulos, Petros

    2011-01-01

    Drug-induced lupus erythematosus is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. Herein, we describe a patient with distinct clinical manifestations of anti-TNF-associated DILE related to infliximab therapy. The patient exhibited clinical and laboratory findings of lupus-like illnesses as well as ocular disorders, such as episcleritis. The main message is that the symptoms of DILE should not be over...

  14. Visceral leishmaniasis with cutaneous symptoms in a patient treated with infliximab followed by fatal consequences.

    Science.gov (United States)

    Juzlova, Katerina; Votrubova, Jana; Kacerovska, Denisa; Lukas, Milan; Bortlik, Martin; Rohacova, Hana; Nohynkova, Eva; Vojackova, Nadezda; Fialova, Jorga; Hercogova, Jana

    2014-01-01

    Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44-year-old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse. © 2013 Wiley Periodicals, Inc.

  15. Efficacy of infliximab in refractory posterior uveitis in Behcet's disease patients

    OpenAIRE

    Ayman K. El Garf; Amira A. Shahin; Sherif A. Shawky; Mohammed A. Azim; Dina A. Effat; Sherry K. Abdelrahman

    2018-01-01

    Aim of the work: Ocular manifestations are the main cause of morbidity in Behcet's disease (BD). Infliximab (IFX), a chimeric monoclonal antibody directed against tumor necrosis factor-alpha, may be efficient in refractory uveitis due to BD. The aim of this study was to assess the efficacy and safety of IFX in the treatment of patients with BD-associated refractory posterior uveitis (PU). Patient and Methods: Twenty patients with refractory Behcet's PU received IFX therapy as intravenous infu...

  16. Absence of radiographic progression of hip arthritis during infliximab treatment for ankylosing spondylitis.

    Science.gov (United States)

    Konsta, M; Sfikakis, P P; Bournia, V K; Karras, D; Iliopoulos, A

    2013-08-01

    This study aims to examine the impact of long-term treatment with the anti-TNF antibody infliximab on radiographic progression of hip arthritis in ankylosing spondylitis. Anteroposterior X-rays of the pelvis obtained at baseline from consecutive patients with ankylosing spondylitis and bilateral hip arthritis were compared with X-rays obtained after 6 ± 2.5 years (mean ± SD) of continuous infliximab treatment. Analysis was performed by the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-h) scoring system (min 0, max 4). Hip joint space width was also assessed by the average of measurements at three distinct sites between the acetabulum and femoral head. In 23 patients with active disease (21 men, mean age and disease duration of 45 and 16 years, respectively), the BASRI-h score at baseline was 1 in 7, 2 in 16, 3 in 16, and 4 in 7 hips (including two arthroplasties). Individual BASRI-h scores at baseline (2.50 ± 0.86, mean ± SD) remained unchanged in all patients at end of follow-up. At baseline, the average width of the whole joint space (3.56 ± 0.70 mm, n = 44) was not associated with disease activity measurements but negatively correlated with BAS functional index (Spearman r = -0.5, P = 0.007). After 2-10 years of infliximab treatment, the average width of the whole joint space in these patients (3.59 ± 0.79 mm) was not reduced. These results suggest that radiographic progression of hip arthritis in ankylosing spondylitis may be arrested during infliximab treatment.

  17. Infliximab for the Treatment of Crohn'S Disease: Review and Indications for Clinical Use in Canada

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    Remo Panaccione

    2001-01-01

    Full Text Available Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. It may affect any portion of the gastrointestinal tract from the mouth to the anus. Symptoms typically include cramping abdominal pain, diarrhea (which may be bloody and nausea. As the severity of the illness worsens, patients may experience constant abdominal pain, vomiting, weight loss and fever. From the perspective of the patient, disease symptoms significantly impair quality of life, and interfere with their work environment and activities of daily living. Unfortunately, there is no cure for Crohn's disease. Patients experience a chronic, relapsing course characterized by recurrent flares of their disease. Conventional medical treatment of Crohn's disease includes the use of non-specific anti-inflammatory drugs (5-aminosalicylic acid agents, prednisone, budesonide, immunosuppressives (6-mercaptopurine, azathioprine, methotrexate and antibiotics. A variable onset of action, incomplete response rates and a significant risk of adverse effects characterize current therapies. Although surgery is frequently used to treat complications or medically refractory disease, postoperative recurrence is a common problem. Infliximab, a murine chimeric monoclonal antibody directed toward tumour necrosis factor-alpha, is a highly effective treatment of active Crohn's disease. In randomized, placebo-controlled clinical trials, 33% of patients treated with infliximab 5 mg/kg achieved remission (Crohn's Disease Activity Index score less than 150, compared with only 4% of those receiving placebo (P<0.001. Additionally, infliximab is the only drug therapy shown to be effective for the treatment of fistulizing Crohn's disease. In studies done to date, infliximab appears to be well tolerated and has a favourable side effect profile.

  18. Serious adverse events with infliximab: analysis of spontaneously reported adverse events.

    Science.gov (United States)

    Hansen, Richard A; Gartlehner, Gerald; Powell, Gregory E; Sandler, Robert S

    2007-06-01

    Serious adverse events such as bowel obstruction, heart failure, infection, lymphoma, and neuropathy have been reported with infliximab. The aims of this study were to explore adverse event signals with infliximab by using a long period of post-marketing experience, stratifying by indication. The relative reporting of infliximab adverse events to the U.S. Food and Drug Administration (FDA) was assessed with the public release version of the adverse event reporting system (AERS) database from 1968 to third quarter 2005. On the basis of a systematic review of adverse events, Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to predefined categories of adverse events, including death, heart failure, hepatitis, infection, infusion reaction, lymphoma, myelosuppression, neuropathy, and obstruction. Disproportionality analysis was used to calculate the empiric Bayes geometric mean (EBGM) and corresponding 90% confidence intervals (EB05, EB95) for adverse event categories. Infliximab was identified as the suspect medication in 18,220 reports in the FDA AERS database. We identified a signal for lymphoma (EB05 = 6.9), neuropathy (EB05 = 3.8), infection (EB05 = 2.9), and bowel obstruction (EB05 = 2.8). The signal for granulomatous infections was stronger than the signal for non-granulomatous infections (EB05 = 12.6 and 2.4, respectively). The signals for bowel obstruction and infusion reaction were specific to patients with IBD; this suggests potential confounding by indication, especially for bowel obstruction. In light of this additional evidence of risk of lymphoma, neuropathy, and granulomatous infections, clinicians should stress this risk in the shared decision-making process.

  19. Efficacy of Infliximab Biosimilar CT-P13 Induction Therapy on Mucosal Healing in Ulcerative Colitis.

    Science.gov (United States)

    Farkas, Klaudia; Rutka, Mariann; Golovics, Petra A; Végh, Zsuzsanna; Lovász, Barbara D; Nyári, Tibor; Gecse, Krisztina B; Kolar, Martin; Bortlik, Martin; Duricova, Dana; Machkova, Nadezda; Hruba, Veronika; Lukas, Martin; Mitrova, Katarina; Malickova, Karin; Bálint, Anita; Nagy, Ferenc; Bor, Renáta; Milassin, Ágnes; Szepes, Zoltán; Palatka, Károly; Lakatos, Péter L; Lukas, Milan; Molnár, Tamás

    2016-11-01

    CT-P13 is the first biosimilar to infliximab that has been approved for the same indications as its originator infliximab. No data are available on the effect of infliximab biosimilar on mucosal healing. The aim of this study was to evaluate the efficacy of CT-P13 induction therapy on mucosal healing in patients with ulcerative colitis [UC]. UC patients, who received CT-P13 therapy from its local introduction at three Hungarian and one Czech inflammatory bowel disease centres, were prospectively enrolled. Sigmoidoscopy was performed after the end of the induction therapy at week 14. Mucosal healing was defined as Mayo endoscopic subscore 0 or 1. Complete mucosal healing was defined as Mayo endoscopic subscore 0. Trough level of CT-P13 was measured at week 14. Sixty-three UC patients who underwent CT-P13 induction therapy were enrolled in the study. Indication for the therapy was acute, severe flare up and chronic, refractory activity in 24 and 39 patients, respectively. Cumulative clinical response and steroid-free remission at week 14 were achieved in 82.5% and 47.6% of the patients, respectively. Sigmoidoscopy revealed steroid-free mucosal healing in 47.6% of the patients, and complete mucosal healing was present in 27%. Mayo endoscopic subscore decreased significantly at week 14 compared to baseline. Trough levels of infliximab correlated with mucosal healing. This is, to our knowledge, the first study examining the efficacy of CT-P13 induction therapy on mucosal healing in UC. The results indicate that mucosal healing is achieved in two-thirds of UC patients by the end of the induction treatment with CT-P13. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Induction and maintenance infliximab therapy in children with moderate to severe ulcerative colitis: Retrospective, multicenter study.

    Science.gov (United States)

    Iwańczak, Barbara M; Kierkuś, Jarosław; Ryżko, Józef; Szczepanik, Mariusz; Więcek, Sabina; Czaja-Bulsa, Grażyna; Kacperska, Magdalena; Korczowski, Bartosz; Maślana, Jolanta; Iwańczak, Franciszek

    2017-01-01

    Pediatric ulcerative colitis (UC) is a severe disease characterised by the presence of extensive inflammatory lesions in the colon. The administration of intravenous corticosteroids is recommended in patients with acute relapse of the disease, whereas early treatment with cyclosporine, tacrolimus or infliximab is recommended if there is no improvement. The aim of this study was to retrospectively evaluate the efficacy and safety of infliximab therapy in the treatment of moderate-to-severe and severe relapse of pediatric UC. The analysis included 42 children aged 4-18 years (23 girls, 19 boys) treated in 7 pediatric gastroenterology departments in Poland during the past 4 years. The disease duration ranged from 2 to 100 months. The clinical activity of UC ranged from 35 to 85 points according to the PUCAI scale. Twenty-one children were diagnosed with pancolitis, 10 children with extensive UC, and the remaining with the left-sided UC. In the induction therapy infliximab was administered at doses of 5 mg/kg in the 0.2 and 6 weeks, and after the clinical response every 8 weeks to 12 months. Treatment results were assessed in 10 and 54 weeks. After the induction therapy the clinical response was achieved in 14 children (33.33%) and clinical remission in 11 children (26.19%). Two children required surgical treatment, and the remaining 2 suffered from anaphylactic shock. After the maintenance therapy clinical remission was maintained in 12 children (57.14%), whereas 3 children required surgery (colectomy). Infliximab therapy in children with moderate-to-severe UC induces remission and, in some children, proves to be effective in preventing early colectomy.

  1. A Severe Case of Ipilimumab-Induced Ileocolitis Refractory to Glucocorticosteroids and Infliximab

    Directory of Open Access Journals (Sweden)

    Behdod Poushanchi

    2018-01-01

    Full Text Available Ipilimumab is a monoclonal antibody that works as an immunotherapeutic agent through selective targeting of T cells to strengthen the response to metastatic melanoma. It is well known that this pharmaceutical agent can cause the adverse effect of colitis. We report a rare presentation of ileocolitis refractory to both glucocorticosteroids and infliximab with a resultant pneumatosis and perforation requiring subtotal colectomy and end ileostomy.

  2. Crohn's Disease Associated with Sweet's Syndrome and Sjögren's Syndrome Treated with Infliximab

    Directory of Open Access Journals (Sweden)

    Erina N. Foster

    2005-01-01

    Full Text Available The association of Crohn's disease (CD and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions.

  3. Identification of acute phase reactants and cytokines useful for monitoring infliximab therapy in ankylosing spondylitis.

    Science.gov (United States)

    Romero-Sánchez, Consuelo; Robinson, William H; Tomooka, Beren H; Londoño, John; Valle-Oñate, Rafael; Huang, Feng; Deng, Xiaohu; Zhang, Liyun; Yang, Chunhua; Yu, David Tak Yan

    2008-11-01

    Although most ankylosing spondylitis patients show an apparent clinical response to infliximab therapy, there is considerable individual variation. Because current clinical assessment relies heavily on subjective patient self-evaluation, biomarkers of high sensitivity and specificity are much needed. Here, we assessed potential biomarkers in 47 ankylosing spondylitis patients who received three standard pulses of infliximab. Before each infusion and at week 10, the following were measured: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count, serum levels of metalloproteinase-3 (MMP-3), and 22 different cytokines. We discovered that, 2 weeks after the first infusion, the combination of ESR, CRP, and platelet count distinguished responders from non-responders with 81.3% sensitivity and 72.7% specificity. The distinguishing power was much less when each acute phase reactant was used alone. Among the 22 cytokines, serum IL-1alpha was able to distinguish responders from non-responders at week 6, with sensitivity of 84.9% and specificity of 53.8%. Serum IL-1alpha was probably generated from the joint compartments, as synovial fluid levels were much higher than corresponding serum levels. Although infliximab infusions led to rapid and significant suppression of serum MMP-3 levels, serum MMP-3 levels did not distinguish responders from non-responders. Besides identifying potential biomarkers, our results also demonstrate the usefulness of using sensitivity and specificity to assess usefulness of potential biomarkers.

  4. EFFECTIVENESS AND SAFETY OF INFLIXIMAB IN PATIENTS WITH EARLY AND LATE JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Е.I. Alexeeva

    2010-01-01

    Full Text Available The article presents results of a study of effectiveness and safety of infliximab — monoclonal antibodies to the tumor necrotizing factor (TNF in treatment of 100 patients11 months — 17 years old with early and late articular types of juvenile rheumatoid arthritis. The duration of treatment was 3 months — 2 years. Infliximap was delivered intravenously by scheme: infusion on 0, 2nd, 6th weeks and then every 8th week. The single dose of infliximab in patients with early rheumatoid arthritis was 6.7 (5.5; 9.0 mg/kg, with late type — 6.0 (5.0; 7.0 mg/kg of body weight. 102 weeks of treatment with anti-TNF-agent provided development of clinical remission, decrease and normalization of laboratory tests of disease’s activity, total restoration of joint’s function, increase of quality of life (on 97% in patients with early type, and 72% 0 in ones with late type. The drug was abolished in 39 (39% of patients, 23% — due to the development of secondary inefficiency, and 11% — due to the development of unfavorable effects.Key words: children, early and late rheumatoid arthritis, treatment, infliximab.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(3:30-42

  5. The effect of infliximab on depressive symptoms in patients with ankylosing spondylitis.

    Science.gov (United States)

    Ersözlü-Bozkırlı, E D; Keşkek, S O; Bozkırlı, E; Yücel, A E

    2015-01-01

    Ankylosing spondylitis is a chronic inflammatory disease which physically, psychologically, and socially affects the patient's life. Previous studies have reported a correlation between ankylosing spondylitis and depression. In this study we investigated the effect of infliximab on depression in ankylosing spondylitis patients. A total of 29 patients with ankylosing spondylitis were enrolled in this prospective study. Infliximab was administered intravenously at a dose of 5 mg/kg at baseline, weeks 2 and 6. The measurements of morning stiffness, modified Schober's test, chest expansion, erythrocyte sedimentation rate, C-reactive protein, Bath ankylosing spondylitis disease activity index, Bath ankylosing spondylitis functional index and Beck depression inventory scores were compared with baseline and 12th week. The modified Schober's test and chest expansion increased, the morning stiffness duration, erythrocyte sedimentation rate and C-reactive protein levels decreased after infliximab treatment (p ankylosing spondylitis disease activity index, Bath ankylosing spondylitis functional index and Beck depression invantory scores of patients after 12 weeks (p ankylosing spondylitis..

  6. Short-Term Response to Infliximab in Rheumatoid Pattern Polyarthropathy Complicating Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    ilke Coskun Benlidayi

    2015-12-01

    Full Text Available Ulcerative colitis (UC is a progressive inflammatory disease (IBD of the bowel which can be accompanied by extra-intestinal findings such as peripheral and axial arthropathies. Patients with UC sometimes display rheumatoid pattern polyarthropathy which is challenging to differ from rheumatoid arthritis. We describe a case with rheumatoid pattern polyarthropathy complicating UC and her favourable response to infliximab therapy. A 25-year-old female with a diagnosis of UC was admitted due to swelling and pain in multiple joints. Laboratory tests revealed elevated acute phase reactants. Since the patient was refractory to the combination therapy comprising methotrexate, sulphasalazine and steroid, she was started on an infliximab regimen. She experienced an improvement both in terms of pain scores and biochemical findings. The patient was asymptomatic with reduced acute phase reactants following a 6-month-course of anti-tumor necrosis factor (anti-TNF therapy. Infliximab serves as an effective treatment option for the management of rheumatoid pattern peripheral polyarthritis associated with UC. [Cukurova Med J 2015; 40(4.000: 818-821

  7. Infliximab-induced skin manifestations in patients with inflammatory bowel disease.

    Science.gov (United States)

    Hellström, Alec Eligius; Färkkilä, Martti; Kolho, Kaija-Leena

    2016-01-01

    The use of infliximab in rheumatoid and inflammatory bowel diseases (IBD) has been associated with a variety of adverse skin reactions, including paradoxical psoriatic lesions. The prevalence and possible predictors for these lesions were under observation in our cross-sectional prospective study. Nurses screened the skin of 118 adult patients with IBD during infliximab infusions between 4 September 2013 and 30 September 2014 based on the structured questionnaire. Data on skin manifestations, concomitant medications, extraintestinal manifestations and inflammatory markers were collected for analysis. Non-infectious skin manifestations were observed in 27 (22.9%) patients during the study period, of which eight (29.6%) were new-onset, eight (29.6%) were exacerbations of existing lesions and 11 (40.7%) were baseline lesions that did not worsen during the study. Scaling eczema was the most commonly described skin manifestation (n = 8; 29.6%), followed by exacerbated atopic eczema (n = 5; 18.5%) and plausible infliximab-induced psoriasiform lesions (n = 5; 18.5%). The strongest associating factor for skin manifestations was Crohn's disease, in nearly 80% of afflicted patients. Anti-TNF-α therapy is frequently associated with newly onset skin reactions, most commonly in patients with Crohn's disease. Non-infectious skin manifestations can be treated topically and do not require cessation of anti-TNF-α therapy.

  8. Efficacy and safety of infliximab in psoriatic patients over the age of 65.

    Science.gov (United States)

    Chiricozzi, Andrea; Pavlidis, Athanasios; Dattola, Annunziata; Bianchi, Luca; Chimenti, Maria Sole; Fida, Monika; Saraceno, Rosita

    2016-11-01

    Clinical data on the long-term safety and efficacy of infliximab on psoriatic patients who are older than 65 years are limited. The aim is to report the long-term efficacy, safety and tolerance of infliximab in geriatric patients. This was a retrospective study conducted at the Department of Dermatology of the University of Rome Tor Vergata. Clinical data were reported at week 12, 52, 104, 208. 151 charts were evaluated. A total of 27 patients were included. Range of the age was between 65 and 85 years; mean age was 73 years ±5.4; female to male ratio was 1:2; mean age of onset of psoriasis was 43 years±17. The average of treatment duration was 39 months ±27 (range 1-100). Fourteen patients suffered from plaque type psoriasis and 13 from psoriatic arthritis. At the baseline the mean PASI score was 15.6 ± 10.2. At week 12, 52, 104, and 208 the mean PASI was 2, 2.3, 1.9 and 1.8 respectively. A reduction in the mean PASI was maintained in the long-term treatment in 12 patients (p infliximab is effective and safe in patients over 65 years old and that IV therapy is also associated with a high compliance.

  9. Effect of infliximab top-down therapy on weight gain in pediatric Crohns disease.

    Science.gov (United States)

    Kim, Mi Jin; Lee, Woo Yong; Choi, Kyong Eun; Choe, Yon Ho

    2012-12-01

    This retrospective-medical-record review was conducted to evaluate effect of infliximab therapy, particularly with a top-down strategy, on the nutritional parameters of children with Crohns disease (CD). 42 patients who were diagnosed with Crohns disease at the Pediatric Gastroenterology center of a tertiary care teaching hospital and achieved remission at two months and one year after beginning of treatment were divided into four subgroups according to the treatment regimen; azathioprine group (n = 11), steroid group (n = 11), infliximab top-down group (n = 11) and step-up group (n = 9). Weight, height, and serum albumin were measured at diagnosis, and then at two months and one year after the initiation of treatment. At 2 months, the Z score increment for weight was highest in the steroid group, followed by the top-down, step-up, and azathioprine groups. At one year, the Z score increment was highest in top-down group, followed by steroid, azathioprine, and step-up group. There were no significant differences between the four groups in Z score increment for height and serum albumin during the study period. The top-down infliximab treatment resulted in superior outcome for weight gain, compared to the step-up therapy and other treatment regimens.

  10. Efficacy and safety of dose escalation of infliximab therapy in Japanese patients with psoriasis: Results of the SPREAD study.

    Science.gov (United States)

    Torii, Hideshi; Nakano, Masayuki; Yano, Toshiro; Kondo, Kazuoki; Nakagawa, Hidemi

    2017-05-01

    Although infliximab is approved for psoriasis, its efficacy is reduced over time in some patients. The aim of this phase III trial is to evaluate efficacy and safety of infliximab dose escalation in Japanese psoriasis patients with loss of efficacy to standard-dose therapy. Patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis or psoriatic erythroderma who showed loss of efficacy to standard-dose therapy received infliximab dose escalation (10 mg/kg every 8 weeks) from weeks 0 to 32. Loss of efficacy was defined as not maintaining 50% reduction in the Psoriasis Area and Severity Index (PASI 50) after achieving PASI 75. Efficacy and safety were evaluated up to week 40. Fifty-one patients received dose escalation and 43 completed the study. PASI 75 and median improvement rate of PASI score at week 40 were 44% and 70.0%, respectively, showing efficacy in skin symptoms. Efficacies in quality of life, nail psoriasis and joint pain were also obtained. Median serum infliximab level increased from less than 0.1 to 1.1 μg/mL from weeks 0 to 40, showing positive correlation between efficacy and serum infliximab level at week 40. Favorable efficacy was observed in patients with detectable serum infliximab levels (≥0.1 μg/mL) at baseline. Incidences of adverse events, serious adverse events, serious infections and serious infusion reactions were 92%, 10%, 4% and 0%, respectively. No marked difference was observed in both efficacy and safety among psoriasis types. No new safety concerns were observed. Infliximab dose escalation was effective and well-tolerated in psoriasis patients with loss of efficacy to standard-dose therapy, suggesting that dose escalation may be a useful therapeutic option for these patients. © 2016 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  11. Accelerated Infliximab Infusion: Safety, Factors Predicting Adverse Events, Patients' Satisfaction and Cost Analysis. A Cohort Study in IBD Patients.

    Science.gov (United States)

    Mazzuoli, S; Tricarico, D; Demma, F; Furneri, G; Guglielmi, F W

    2016-01-01

    Standard Infliximab infusion consists of a 2-hour intravenous administration. Recently, Infliximab shortened infusion has been included in the Infliximab label as possible maintenance regimen for patients tolerating Infliximab induction therapy. To verify if accelerated 1-hour Infliximab infusions are as safe as standard administrations, in patients with Inflammatory Bowel Disease. Seventy-four patients treated between September 2008 and November 2014 were evaluated. Patients were eligible for 1-hour infusion if they had no history of infusion reactions during the previous 2-hour infusions. Twenty-three patients received 2-hour infusions, 16 patients received 1-hour infusions, 35 patients received 2-hour infusions followed by 1-hour infusions. A total of 1,123 Infliximab infusions were administered. The proportion of patients experiencing infusion reaction was: 4% over the 1-hour infusions and 9% over the 2-hour (P = 0.318). Adverse reaction/infusion rate was 0.55% over the 1-hour infusions and 0.66% over the 2-hour (P = 0.835). In the logistic model, accelerated infusion was the only statistically significant predictor of infusion reaction risk reduction (-90%; P = 0.024). Mean satisfaction was 8/10 (±0.84) with 1-hour regimen and 6/10 (±0.56) with 2-hour infusions (P = 0.000). The mean total cost was reduced by 47% with the 1-hour regimen (133.54€ and 250.86€ for 1-hour and 2-hour infusions, respectively). Accelerated Infliximab infusion does not increase the acute infusion reaction incidence. In patients with inflammatory bowel disease, the 1-hour regimen should be preferred to 2-hour protocol also due to positive effects on indirect costs and patient's satisfaction.

  12. Transcriptional Signatures Related to Glucose and Lipid Metabolism Predict Treatment Response to the Tumor Necrosis Factor Antagonist Infliximab in Patients with Treatment-Resistant Depression

    Science.gov (United States)

    Mehta, Divya; Raison, Charles L.; Woolwine, Bobbi J.; Haroon, Ebrahim; Binder, Elisabeth B.; Miller, Andrew H.; Felger, Jennifer C.

    2013-01-01

    The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6hr, 24hr, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2 fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6hr and 24hr after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation. PMID:23624296

  13. Tratamento com infliximabe da doença de Behçet ativa Therapy with infliximab in active Behçet's disease

    Directory of Open Access Journals (Sweden)

    Alexandre Wagner Silva de Souza

    2005-04-01

    Full Text Available Os autores descrevem o caso de uma paciente de 41 anos de idade com diagnóstico de doença de Behçet, diagnosticada em abril de 2000. A paciente apresentava envolvimento mucocutâneo, articular e neurológico persistentes, apesar do tratamento com colchicina, corticosteróides e metotrexato, durante os três anos que se seguiram ao diagnóstico. Em abril de 2003, a paciente mantinha-se com a doença ativa, necessitando de altas doses de corticosteróides e de metotrexato. Optou-se, então, pela administração do infliximab, 3mg/kg por via endovenosa. Uma semana depois, havia ocorrido regressão completa das manifestações da doença de Behçet nesta paciente.The authors describe the case of a 41 years old woman with the diagnosis of Behçet's syndrome since April 2000, when she presented mucocutaneous, articular and ocular manifestations. The disease remained active despite of the treatment with colchicine, corticosteroid and methotrexate, during the three years following diagnosis. In April 2003, the patient still needed high doses of corticosteroid and methotrexate. Nevertheless, the disease remained active. Treatment with infliximab was then started with intravenous 3 mg/Kg and, one week later, all the manifestations of this patient were in complete remission.

  14. Retreatment and maintenance therapy with infliximab in fistulizing Crohn' disease Retratamiento y tratamiento de mantenimiento con infliximab en la enfermedad de Crohn fistulizante

    Directory of Open Access Journals (Sweden)

    L. Rodrigo

    2004-08-01

    Full Text Available Objectives: infliximab has clearly demonstrated its efficacy in the short-term treatment of fistulizing Crohn' disease. We present here the results of retreatment and long-term maintenance therapy. Patients and methods: eighty one consecutive patients with active fistulizing Crohn' disease, in whom previous treatments had failed, were treated with infliximab. All patients received as the initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6. Those patients who failed to respond after the initial cycle (group 1, n= 25, or those who relapsed after having responded (group 2, n=13, received retreatment with three similar doses (weeks 0,2, and 6. Those who responded to retreatment were included in a long-term maintenance programme (n=44, with repeated doses (5 mg/kg i.v. infusions every eight weeks for 1-2 years. Results: in the initial treatment 56% of the patients responded partially; this response being complete in 44%. In the retreatment, 28% of group 1 (non-responders presented a complete response, compared to 77% in group 2 (relapsers (pObjetivos: el infliximab ha demostrado su eficacia en el tratamiento a corto plazo de la enfermedad de Crohn (EC fistulosa. En este trabajo presentamos los resultados del retratamiento y del tratamiento de mantenimiento a largo plazo. Pacientes y métodos: se trataron con infliximab un total de 81 pacientes consecutivos con EC fistulosa activa, en los cuales, habían fallado tratamientos previos. Todos los pacientes recibieron como tratamiento inicial infusiones a dosis de 5 mg/kg i.v. en las semanas 0, 2 y 6. Aquellos pacientes que no respondieron después del ciclo inicial (grupo 1, n=25, o los que recayeron después de haber respondido (grupo 2, n=13, recibieron retratamiento con 3 dosis similares (semanas 0, 2 y 6. Aquellos que respondieron a la terapia de retratamiento fueron incluidos en un programa de mantenimiento a largo plazo (n=44, con dosis repetidas (infusiones con 5 mg/kg i.v. cada 8

  15. Efficacy and safety of TNF-α inhibitors for active ankylosing spondylitis patients: Multiple treatment comparisons in a network meta-analysis

    Science.gov (United States)

    Liu, Wei; Wu, Yuan-Hao; Zhang, Lei; Liu, Xiao-Ya; Bin Xue; Bin Liu; Wang, Yi; Ji, Yang

    2016-09-01

    Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with impact on axial skeleton, peripheral joints and enthuses, and it may result in severe disabilities of those parts. Tumor necrosis factor-α (TNF-α) inhibitors are considered as an effective treatment for patients with active AS. In this study, we conducted a network meta-analysis to compare the clinical outcomes of active AS patients treated with TNF-α inhibitors. Randomized controlled trials (RCTs) evaluating the efficacy and safety of TNF-α inhibitors were retrieved in literature search and selected for meta-analysis. Changes in ASAS20 response, ASAS40 response and BASDAI 50% response were regarded as efficacy outcomes; serious adverse events (SAE) and all cause withdrawals were regarded as safety outcomes. Both traditional pairwise meta-analysis and network meta-analysis were performed. The results showed that adalimumab and infliximab had better clinical outcomes. Infliximab consistently appeared to be the most effective TNF-α inhibitors with a high risk of adverse events for patients with active AS; meanwhile, adalimumab ranked highest with respect to adverse effects with efficacy secondary to infliximab. As a result, we were unable to conclude the optimal TNF-α inhibitor and this issue should be solved by future researchers.

  16. Inhibitors of cysteine cathepsin and calpain do not prevent ultraviolet-B-induced apoptosis in human keratinocytes and HeLa cells

    DEFF Research Database (Denmark)

    Bang, Bo; Baadsgaard, Ole; Skov, Lone

    2004-01-01

    been demonstrated to play a role in the execution of programmed cell death induced by other stimuli, e.g. TNF-alpha. The purpose of the present study was therefore to investigate whether inhibitors of cysteine cathepsins and calpains could prevent UVB-induced apoptosis in HeLa cells and keratinocytes....... This was done by investigating the effect of the irreversible cysteine protease inhibitor zFA-fmk, the cathepsin B inhibitor CA-074-Me and the calpain inhibitor ALLN on the viability of UVB-irradiated human keratinocytes and HeLa cells. At concentrations of 10 microM and above zVAD-fmk conferred partial dose......-dependent protection against UVB-induced apoptosis in HeLa cells and keratinocytes. Moreover, caspase-3 activity was completely blocked at zVAD-fmk concentrations of 1 microM in HeLa cells. This indicates that caspase-independent mechanisms could be involved in UVB-induced apoptosis. However, the protease inhibitors z...

  17. INVESTIGATION OF A ROLE OF THE IMMUNOGENICITY OF INFLIXIMAB IN THE THERAPY OF ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    O. A. Rumyantseva

    2016-01-01

    Full Text Available At present, there are a number of unsolved problems associated with unawareness of the causes and ways to prevent the inefficacy of tumor necrosis factor-α  inhibitors.Objective: to study the causes of secondary inefficacy of infliximab (INF, by analyzing its concentrations and antidrug antibody levels in the serum of ankylosing spondylitis (AS patients receiving long INF,  as well as a possibility to overcome its secondary inefficacy through plasmapheresis.Subjects and methods. 54 patients with active AS (BASDAI > 4 underwent regular long-term  (1-to-10-year treatment with INF 5 mg/kg according to the standard scheme. During the therapy blood samples were taken before a regular INF infusion to quantify the levels of antibodies to the drug and its concentration. According to the efficiency of the drug, two groups were formed: 1 27 (50% patients with INF inefficacy (an exacerbation occurred 2–4 weeks after infusion; 2 27 patients with drug efficacy. The levels of anti-double stranded DNA antibodies and antinuclear factor were estimated in 27 patients to investigate a relationship between the immunogenicity of INF and the presence of autoantibodies in its secondary inefficacy. A plasmapheresis session was carried out in 5 patients before a regular IFN infusion.Results and discussion. Anti-INF antibodies were found in 28 (52% patients, these being more common  in the patients with drug inefficacy than in the others (67 and 37%, respectively; p < 0.05. In the patients with INF inefficacy, anti-INF antibody levels were significantly higher than in those with preserved drug effect (18.33 and 4.67 U/ml, respectively; р < 0.05. Moreover, the serum concentration of INF was not significantly different in these groups (1.6 and 2.96 μg/ml. There was an inverse correlation  between INF concentrations and anti-INF antibodies (r = -0.7; p < 0.05. The level of autoantibodies  did not correlate with that of anti-INF antibodies. Following

  18. The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure

    DEFF Research Database (Denmark)

    Krintel, Sophine B; Grunert, Veit Peter; Hetland, Merete L

    2013-01-01

    To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure.......To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure....

  19. Individualized Therapy Is a Long-Term Cost-Effective Method Compared to Dose Intensification in Crohn's Disease Patients Failing Infliximab

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Brynskov, Jørn; Thomsen, Ole Ø

    2015-01-01

    or by infliximab intensification. However, the sum of healthcare costs related to Crohn's disease was substantially lower (31 %) for patients randomized to algorithm-based interventions than infliximab intensification in the intention-to-treat population: $11,940 versus $17,236; p = 0.005. For per...

  20. Use of TNF-inhibitors and ustekinumab for psoriasis during pregnancy

    DEFF Research Database (Denmark)

    Lund, Tamara; Thomsen, Simon Francis

    2017-01-01

    From 2002 to 2016 a total of seven women with severe refractory psoriasis were exposed to the TNF-inhibitors infliximab and adalimumab or to the IL12/23 inhibitor ustekinumab during one or more pregnancies. Maternal, fetal or teratogenic toxicity were not detected during pregnancy and puerperium....... All pregnancies were uneventful and resulted in delivery of 10 healthy children in total, one of the women is due February 2017. Postpartum, five of the women were lactating, but none of the women or newborns developed adverse reactions. Data on safety of treatment during breastfeeding are sparse...

  1. Serial intralesional injections of infliximab in small bowel Crohn’s strictures are feasible and might lower inflammation

    DEFF Research Database (Denmark)

    Hendel, Jakob; Karstensen, John Gásdal; Vilmann, Peter

    2014-01-01

    BACKGROUND: Crohn's disease can cause strictures throughout the gastrointestinal tract. Endoscopic balloon dilatation is a well-established treatment, but recurrence is seen in up to three out of four cases. Infliximab is playing an increasingly important role in the modern systemic treatment...... of severe Crohn's disease. Combining the anti-inflammatory effects of infliximab with the proven effect of endoscopic balloon dilatation could possibly improve outcome. In small studies, intralesional injections in perianal fistulas have been effective and endoscopic injection therapy in colonic strictures...... is feasible. OBJECTIVE: We wanted to assess whether serial intralesional injection of infliximab in small bowel strictures is feasible and reduces local inflammation. METHODS: We included six patients with Crohn's disease and inflammatory small bowel strictures. They were treated with endoscopic serial...

  2. Comparison of Infliximab and Adalimumab in Biologic-Naive Patients With Ulcerative Colitis: A Nationwide Danish Cohort Study

    DEFF Research Database (Denmark)

    Singh, Siddharth; Nyboe Andersen, Nynne; Andersson, Mikael

    2017-01-01

    BACKGROUND & AIMS: We compared the effectiveness and safety of infliximab and adalimumab in biologic-naïve patients with ulcerative colitis (UC), in a nationwide register-based propensity score-matched study of patients in Denmark. METHODS: We collected data from 1719 adults with UC, 15-75 years...... old, in Denmark who were treated with either infliximab or adalimumab as their first biologic agent. We compared rates of all-cause hospitalization, UC-related hospitalization, major abdominal surgery, and serious infections after a variable 2:1 propensity score matching, accounting for baseline...... clinical characteristics, disease severity, healthcare use, and use of UC-related medications. RESULTS: Compared to patients treated with infliximab, patients treated with adalimumab had a higher risk for all-cause hospitalization (hazard ratio [HR], 1.84; 95% CI, 1.18-2.85), with a trend towards higher...

  3. Secondary Loss of Response to Infliximab in Pediatric Crohn Disease: Does It Matter How and When We Start?

    Science.gov (United States)

    Bolia, Rishi; Rosenbaum, Jeremy; Schildkraut, Vered; Hardikar, Winita; Oliver, Mark; Cameron, Donald; Alex, George

    2018-04-01

    A significant proportion of children with Crohn disease develop a secondary loss of response (LOR) to infliximab. Our aim was to study the impact of initial treatment strategies on secondary LOR. We reviewed the medical records of children with Crohn disease who received scheduled maintenance infliximab therapy for at least 12 months. We compared children who developed LOR with those who did not; with regards to their clinical and laboratory parameters, disease phenotype, and treatment strategy before developing LOR. A total of 73 children (median age at diagnosis 11 (2-16) years, 41 boys) who had received a median duration of 33 (13-110) months of infliximab therapy were included in the final analysis. LOR was seen in 25(34.2%). Demographic variables, disease phenotype (age, disease location, and behavior), inflammatory parameters, and pediatric Crohn disease activity index at induction with infliximab we