WorldWideScience

Sample records for disease-modifying antirheumatic drug

  1. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    NARCIS (Netherlands)

    Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

  2. Disease-modifying antirheumatic drugs in pregnancy - Current status and implications for the future

    NARCIS (Netherlands)

    Vroom, Fokaline; de Walle, Hermien E. K.; van de Laar, Mart A. J. F.; Brouwers, Jacobus R. B. J.; de Jong-van den Berg, Lolkje T. W.

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD

  3. Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Gabay, Cem; Riek, Myriam; Hetland, Merete Lund;

    2016-01-01

    OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. METHODS: Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were...... of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2...

  4. Chinese herbs as immunomodulators and potential disease-modifying antirheumatic drugs in autoimmune disorders.

    Science.gov (United States)

    Ho, Ling-Jun; Lai, Jenn-Haung

    2004-04-01

    Autoimmune diseases are a group of illnesses with multiple organ involvement. The prototype of this group of disorders is rheumatoid arthritis (RA) that aside from systemic organ involvement mainly presents with progressive destruction of many joints. Both activation and defective apoptosis of immune effector cells like T and B lymphocytes and macrophages play critical roles in the pathogenesis of autoimmune disorders. Current therapy for autoimmune diseases recommends a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Because of limited success in prevention of RA joint destruction for currently available DMARDs, the development of more effective and less toxic DMARDs has been one of the major goals for pharmaceutical companies. The introduction of leflunomide and anti-tumor necrosis factor alpha therapies to the market recently serves as examples. In this context, the experience from ancient Chinese medicine gives an alternative consideration looking for potential DMARDs. Two commonly prescribed Chinese antirheumatic herbs are Tripterygium wilfordii hook f (TWHf) and tetrandrine (Tet) that preserve both anti-inflammatory and immunosuppressive effects. Importantly, the TWHf- or Tet-mediated immunomodulatory mechanisms are evidently different from the known DMARDs. The synergistic effects have also been demonstrated between these two Chinese antirheumatic herbs and DMARDs like FK506, cyclosporin and possibly chloroquine. Another potential Chinese herb for this consideration is Ginkgo biloba. This review summarizes evidence-based in vivo and in vitro studies on Chinese herbs as immunomodulators and potential DMARDs.

  5. Cost Effectiveness Analysis of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. A Systematic Review Literature

    Directory of Open Access Journals (Sweden)

    Maurizio Benucci

    2011-01-01

    Full Text Available The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs are the standard treatment of rheumatoid arthritis (RA and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate. The European League Against Rheumatism (EULAR recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.

  6. The efficacy of leflunomide monotherapy in rheumatoid arthritis : towards the goals of disease modifying antirheumatic drug therapy

    NARCIS (Netherlands)

    Smolen, J.S.; Emery, P.; Kalden, J.R.; Riel, P.L.C.M. van; Dougados, M.; Strand, C.V.; Breedveld, F.C.

    2004-01-01

    This expert review of results from the leflunomide phase II and III clinical trials database demonstrates that leflunomide meets all 3 goals desired of disease modifying antirheumatic drug (DMARD) therapy: reducing the signs and symptoms of the disease; inhibiting structural damage; and improving ph

  7. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update

    NARCIS (Netherlands)

    Smolen, J.S.; Landewe, R.; Breedveld, F.C.; Buch, M.; Burmester, G.; Dougados, M.; Emery, P.; Gaujoux-Viala, C.; Gossec, L.; Nam, J.; Ramiro, S.; Winthrop, K.; Wit, M. de; Aletaha, D.; Betteridge, N.; Bijlsma, J.W.J.; Boers, M.; Buttgereit, F.; Combe, B.; Cutolo, M.; Damjanov, N.; Hazes, J.M.; Kouloumas, M.; Kvien, T.K.; Mariette, X.; Pavelka, K.; Riel, P.L.C.M. van; Rubbert-Roth, A.; Scholte-Voshaar, M.; Scott, D.L.; Sokka-Isler, T.; Wong, J.B.; Heijde, D. van der

    2014-01-01

    In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an int

  8. Patients' considerations in the decision-making process of initiating disease-modifying anti-rheumatic drugs

    NARCIS (Netherlands)

    Nota, Ingrid; Drossaert, Constance H.C.; Taal, Erik; Laar, van de Mart A.F.J.

    2015-01-01

    Objectives To explore what considerations patients have when deciding about disease-modifying anti-rheumatic drugs (DMARDs) and what information patients need to participate in the decision-making process. Methods In-depth face-to-face interviews were conducted with 32 inflammatory arthritis patien

  9. Ten years of publicly funded biological disease-modifying antirheumatic drugs in Australia.

    Science.gov (United States)

    Hopkins, Ashley M; Proudman, Susanna M; Vitry, Agnes I; Sorich, Michael J; Cleland, Leslie G; Wiese, Michael D

    2016-02-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA) treatment were among the first high-cost medicines to be subsidised in Australia. High-cost medicines pose several challenges to the Australian National Medicines Policy, which aims to provide timely access to effective medicines at a cost individuals and the community can afford. Thus, novel restriction criteria were developed to encourage cost-effective use of bDMARDs. Government expenditure on bDMARD subsidies for RA treatment grew to about $383 million in 2014. Evidence that initiation and continuation criteria for bDMARDs meet usually applied cost-benefit criteria is lacking. The combined expenditure on tocilizumab, certolizumab pegol and golimumab (added to the Australian Government's Pharmaceutical Benefits Scheme in 2010) was $93 million in 2014, which is 210% over the initial estimate. Present and future challenges with regard to bDMARDs for RA and other high-cost drugs include improved expenditure predictions, monitoring of cost-effectiveness in relation to actual use and strategic development, regulation and use of biosimilars. Ten years of documentation on clinical and laboratory findings indicating eligibility to initiate and continue on bDMARDs remains un-used. These data represent an untapped opportunity to promote quality of use of bDMARDs and biosimilars and to improve cost predictions for high-cost drugs.

  10. Treatment adherence to disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Xia Y

    2016-05-01

    Full Text Available Yunfei Xia,1,* Rulan Yin,1,2,* Ting Fu,1,2 Lijuan Zhang,1,2 Qiuxiang Zhang,1,2 Genkai Guo,1 Liren Li,2 Zhifeng Gu11Department of Rheumatology, Affiliated Hospital of Nantong University, 2School of Nursing, Nantong University, Nantong, People’s Republic of China *These authors contributed equally to this work Objective: Nonadherence in rheumatoid arthritis (RA patients using disease-modifying antirheumatic drugs (DMARDs may lead to joint damage and function loss. The aim of this cross-sectional study was to explore Chinese RA patients’ adherence rates and investigate potential risk factors for nonadherence.Methods: A total of 122 RA patients were recruited from the Affiliated Hospital of Nantong University from January 2014 to April 2015. Patients were asked to complete a set of standardized self-report questionnaires (Compliance Questionnaire on Rheumatology, Health Assessment Questionnaire, Short Form-36 questionnaire, 28-joint Disease Activity Score, Hospital Anxiety and Depression Scale, and Visual Analog Scale. Independent samples t-tests, chi-square analyses, and logistic regression modeling were used to analyze these data.Results: Based on Compliance Questionnaire on Rheumatology, 38% of the patients adhered to DMARDs. Adherence was associated with education, income, depression, and the total number of DMARDs. Other demographic and clinical characteristics were not associated with adherence. Logistic regression models identified income, depression, and the total number of DMARDs as predictors of medication nonadherence.Conclusion: In this study, 62% of patients with RA were not adherent to their DMARD prescription. Education, income, depression, and the total number of DMARDs were associated with medication adherence, and income, depression, and the total number of DMARDs were independent predictors of medication adherence in patients with RA. These findings could help medical personnel develop helpful interventions to improve

  11. Systematic review of disease-modifying antirheumatic drugs for juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Kemper Alex R

    2012-03-01

    Full Text Available Abstract Background Treatment of juvenile idiopathic arthritis (JIA with disease-modifying antirheumatic drugs (DMARDs may improve outcomes compared to conventional therapy (e.g., non-steroidal anti-inflammatory drugs, intra-articular corticosteroids. The purpose of this systematic review was to evaluate the comparative effectiveness and safety of DMARDs versus conventional therapy and versus other DMARDs. Results A systematic evidence review of 156 reports identified in MEDLINE®, EMBASE®, and by hand searches. There is some evidence that methotrexate is superior to conventional therapy. Among children who have responded to a biologic DMARD, randomized discontinuation trials suggest that continued treatment decreases the risk of having a flare. However, these studies evaluated DMARDs with different mechanisms of action (abatacept, adalimumab, anakinra, etanercept, intravenous immunoglobulin, tocilizumab and used varying comparators and follow-up periods. Rates of serious adverse events are similar between DMARDs and placebo in published trials. This review identified 11 incident cases of cancer among several thousand children treated with one or more DMARD. Conclusions Few data are available to evaluate the comparative effectiveness of either specific DMARDs or general classes of DMARDs. However, based on the overall number, quality, and consistency of studies, there is moderate strength of evidence to support that DMARDs improve JIA-associated symptoms. Limited data suggest that short-term risk of cancer is low.

  12. Effectiveness of conventional disease-modifying antirheumatic drugs in psoriatic arthritis: A systematic review.

    Science.gov (United States)

    Maese, Jesús; Díaz Del Campo, Petra; Seoane-Mato, Daniel; Guerra, Mercedes; Cañete, Juan D

    2017-01-13

    Due to the clinical heterogeneity of psoriatic arthritis (PsA), recommendations have been developed by international groups to guide therapeutic decisions of the rheumatologist. The objective of the current systematic review (RS) was to evaluate the evidence of efficacy of disease-modifying antirheumatic drugs (DMARDs) in PsA. Literature search in Medline, EMBASE, Cochrane Library, from 2008 to 2014. We included RS, randomized clinical trials and observational studies, in patients with PsA and an evaluation of efficiency of conventional DMARDs (methotrexate, sulfasalazine, leflunomide), according to the following outcomes: peripheral and axial symptoms; peripheral radiological damage; enthesitis according to power Doppler ultrasound or magnetic resonance imaging (enthesitis count before and after therapy); dactylitis; uveitis. Title and abstract were used to retrieve 1,662 documents for this review (Medline, n=433; EMBASE n=1,132; Cochrane, n=97), and 48 studies were selected for detailed reading; finally, 8 studies were included. Since the studies included are not robust, and there are arguments to support the effectiveness of methotrexate, the evidence observed with the treatment of DMARDs in PsA is not conclusive. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  13. Patient access to reimbursed biological disease-modifying antirheumatic drugs in the European region

    Science.gov (United States)

    Kaló, Zoltán; Vokó, Zoltán; Östör, Andrew; Clifton-Brown, Emma; Vasilescu, Radu; Battersby, Alysia; Gibson, Edward

    2017-01-01

    ABSTRACT Background & Objectives: Biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) are not always accessible to all patients in accordance with international guidelines, partly owing to their high direct costs against a background of restricted healthcare budgets. This study compares the size of RA patient populations with access to reimbursed bDMARDs across 37 European countries, Russia, and Turkey, according to their treatment eligibility defined by European League Against Rheumatism (EULAR) recommendations and national reimbursement criteria. Methods: The size of the RA patient population eligible for bDMARD treatment was estimated in a population model using published RA epidemiological data and clinical criteria defined by 2013 EULAR recommendations along with national reimbursement criteria defined in a survey of the 39 countries in November 2015. Results: According to EULAR recommendations, 32% of the total RA population in the European region is eligible for bDMARD treatment. However, only an average 59% of this EULAR-eligible population remains eligible after applying national reimbursement criteria (from 86% in ‘high access’ to 13% in ‘low-access’ countries). Conclusion: Access to reimbursed bDMARDs remains unequal in the European region. As biosimilars of bDMARDs are introduced, changes in reimbursement criteria may increase access to bDMARDs and reduce this inequality. PMID:28740623

  14. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis

    Science.gov (United States)

    Emery, Paul; Sebba, Anthony; Huizinga, Tom W J

    2013-01-01

    Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX. PMID:23918035

  15. Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

    Science.gov (United States)

    Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

    2011-09-15

    Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied.

  16. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Genovese, Mark C; Yang, Fang; Østergaard, Mikkel;

    2016-01-01

    OBJECTIVE: To assess early effects on joint structures of VX-509 in combination with stable disease-modifying antirheumatic drug (DMARD) therapy using MRI in adults with rheumatoid arthritis (RA). METHODS: This phase II, placebo-controlled, double-blind, dose-ranging study randomised patients...... synovitis scores were significantly different from placebo for all VX-509 doses (pTreatment was generally well tolerated. CONCLUSIONS: VX-509 plus a DMARD reduced the signs and symptoms of RA in patients with an inadequate response to a DMARD...... alone. MRI responses were detected at week 12. Treatment was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01754935; results....

  17. Effects of synthetic and biological disease modifying antirheumatic drugs on lipid and lipoprotein parameters in patients with rheumatoid arthritis.

    Science.gov (United States)

    Naerr, Gerhard W; Rein, Philipp; Saely, Christoph H; Drexel, Heinz

    2016-06-01

    Dyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data. The aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters. Recent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio. Anti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis

    DEFF Research Database (Denmark)

    Lie, Elisabeth; Kristensen, Lars Erik; Forsblad-d'Elia, Helena

    2015-01-01

    OBJECTIVE: To assess the effect of comedication with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) on retention to tumour necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA). METHODS: Data...

  19. Similar effects of disease-modifying antirheumatic drugs, glucocorticoids, and biologic agents on radiographic progression in rheumatoid arthritis: meta-analysis of 70 randomized placebo-controlled or drug-controlled studies, including 112 comparisons

    DEFF Research Database (Denmark)

    Graudal, Niels; Jürgens, Gesche

    2010-01-01

    To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents.......To define the differences in effects on joint destruction in rheumatoid arthritis (RA) patients between therapy with single and combination disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, and biologic agents....

  20. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    Science.gov (United States)

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  1. Assessing the effectiveness of synthetic and biologic disease-modifying antirheumatic drugs in psoriatic arthritis – a systematic review

    Directory of Open Access Journals (Sweden)

    Kingsley GH

    2015-05-01

    positive benefit. For biologics, TNF inhibitors already licensed for use were effective and similar benefits were seen with newer agents including ustekinumab, secukinumab, brodalumab, and abatacept, although the latter did not impact on skin problems. Important limitations of the systematic review included, first, the fact that for many agents there were little data and, second, much of the recent data for newer biologics were only available in abstract form. Conclusion: Conventional disease-modifying agents, with the possible exception of leflunomide, do not show clear evidence of disease-modifying effects in psoriatic arthritis, though a newer synthetic disease-modifying agents, apremilast, appears more effective. Biologic agents appear more beneficial, although more evidence is required for newer agents. This review suggests that it may be necessary to review existing national and international management guidelines for psoriatic arthritis. Keywords: psoriatic arthritis, disease-modifying antirheumatic drugs, biologics

  2. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

    Science.gov (United States)

    Smolen, Josef S; Landewé, Robert; Breedveld, Ferdinand C; Dougados, Maxime; Emery, Paul; Gaujoux-Viala, Cecile; Gorter, Simone; Knevel, Rachel; Nam, Jackie; Schoels, Monika; Aletaha, Daniel; Buch, Maya; Gossec, Laure; Huizinga, Tom; Bijlsma, Johannes W J W; Burmester, Gerd; Combe, Bernard; Cutolo, Maurizio; Gabay, Cem; Gomez-Reino, Juan; Kouloumas, Marios; Kvien, Tore K; Martin-Mola, Emilio; McInnes, Iain; Pavelka, Karel; van Riel, Piet; Scholte, Marieke; Scott, David L; Sokka, Tuulikki; Valesini, Guido; van Vollenhoven, Ronald; Winthrop, Kevin L; Wong, John; Zink, Angela; van der Heijde, Désirée

    2010-01-01

    Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion. PMID:20444750

  3. Non-adherence to disease-modifying antirheumatic drugs is associated with higher disease activity in early arthritis patients in the first year of the disease

    OpenAIRE

    2015-01-01

    INTRODUCTION: Non-adherence to disease-modifying antirheumatic drugs (DMARDs) hampers the targets of rheumatoid arthritis (RA) treatment, obtaining low disease activity and decreasing radiological progression. This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis. METHODS: Adult patients from an ongoing cohort study on treatment adherence were selected if they fulfilled ...

  4. Drogas Modificadoras de la Artritis Reumatoide (DMAR Disease Modifying Antirheumatic Drugs (DMARD

    Directory of Open Access Journals (Sweden)

    José Francisco Díaz-Coto

    2011-02-01

    Full Text Available El nuevo paradigma terapéutico de la artritis reumatoide establece que todo paciente con actividad de la enfermedad debe recibir alguna droga modificadora de la artritis reumatoide. Estas drogas reciben este nombre ya que han demostrado en estudios clínicos controlados modificar el curso natural de la enfermedad.The new paradigm for the treatments of rheumatoid arthritis stablish that all patients suffering disease this should receive some drugs which modifys rheumatoid arthritis. These drugs are so named because according to the controlled clinical studies they have shown the ability of modifying the natural course of the diseases.

  5. [Acupuncture Therapy versus Disease-modifying Antirheumatic Drugs for the Treatment of Ankylosing Spondylitis--a Meta-analysis].

    Science.gov (United States)

    Lv, Zheng-tao; Zhou, Xiang; Chen, An-min

    2015-01-01

    We conducted a meta-analysis evaluating the efficacy and safety of acupuncture compared to disease-modifying antirheumatic drugs in patients with ankylosing spondylitis. Four databases including Pubmed, EMBASE, Cochrane library, and ISI Web of Science were searched in December 2014, taking also the reference section into account. Randomized controlled trials that aimed to assess the efficacy of acupuncture therapy were identified. The inclusion criteria for the outcome measurements were the clinical effect, ESR, occipital wall test, chest expansion, CRP and finger ground distance. Finally, six studies met these inclusion criteria. Two reviewers screened each article independently and were blinded to the findings of each other. We analyzed data from 6 RCTs involving 541 participants. Acupuncture therapy could further improve the clinical effect (OR = 3.01; 95% CI, 1.48-6.13; P = 0.002) and reduce ESR level (SMD = -0.77; 95% CI, -1.46 to -0.08; P = 0.03) compared to DMARDs; a combination of acupuncture and DMARDs could further improve clinical effect (OR = 3.20, 95% CI, 1.36-7.54; P = 0.008), occipital-wall distance (SMD = -0.84; 95% CI, -1.37 to -0.31; P = 0.002), chest expansion (SMD = 0.38; 95% CI, 0.16-0.60; P = 0.0009), and finger-ground distance (SMD = -0.48; 95% CI, -0.87 to -0.09; P = 0.02) as compared to DMARDs treatment alone. Our findings support that acupuncture therapy could be an option to relieve symptoms associated with AS. These results should be interpreted cautiously due to the generally poor methodological qualities of the included trials. © 2015 S. Karger GmbH, Freiburg.

  6. Can traditional disease-modifying anti-rheumatic drugs be withdrawn or tapered in psoriatic arthritis?

    Science.gov (United States)

    Lubrano, Ennio; Soriano, Enrique; FitzGerald, Oliver

    2013-01-01

    Psoriatic arthritis (PsA) is a complex, multisystem disease with musculoskeletal and skin manifestations frequently associated with features of the metabolic syndrome. For many years, treatment strategies were largely borrowed from the rheumatoid arthritis literature, with clinical trials of traditional DMARDs in PsA often inadequate and using limited outcome measures. Nonetheless, DMARDs - in particular, methotrexate - remain the treatment of first choice for most rheumatologists treating this disease, especially for those with prominent polyarticular involvement. While there is no agreed definition of remission in PsA, a number of longitudinal studies suggests that remission can be achieved in approximately 25% of patients treated with traditional DMARDs, with drug-free remission possible in disease remission is achieved.

  7. Biologic Disease-Modifying Antirheumatic Drugs in a National, Privately Insured Population: Utilization, Expenditures, and Price Trends.

    Science.gov (United States)

    Atzinger, Christopher B; Guo, Jeff J

    2017-02-01

    Spending on biologic drugs is a significant driver of drug expenditures for payers in private health plans. Biologic disease-modifying antirheumatic drugs (DMARDs) are some of the most effective and costly treatments in a physician's arsenal. Understanding the total annual expenditure, the average cost per prescription, and the impact of cost-sharing is important for drug benefit managers. To assess drug utilization, expenditures, out-of-pocket (OOP) cost, and price trends of biologic DMARDs in patients with rheumatoid arthritis (RA) in a large managed care organization. We conducted a retrospective database analysis of pharmacy claims data from January 2004 to December 2013 using the Optum Clinformatics Data Mart database, which covers 13.3 million lives. Pharmacy claims for 40,373 patients with RA were identified during the study period. In all, 9 biologic DMARDs approved for the treatment of RA, including infliximab, etanercept, adalimumab, certoizumab, golimumab, tocilizumab, anakinra, abatacept, and rituximab, and 1 nonbiologic oral, small molecule-targeted synthetic drug, tofacitinib, were included in this study. Descriptive statistics were used to analyze the total annual number of prescriptions, the total annual expenditures, the average annual cost per drug (a proxy of drug price), and the average OOP cost (copay plus deductible and coinsurance). All measurements were also stratified by study drugs and by insurance type. Of the 40,373 patients with RA included in the study, approximately 76% were female (mean age, 55 years at diagnosis). Approximately 77% of the patients were white, and almost 48% lived in the South or Midwest region of the United States. Approximately 62% of patients had a point of service insurance plan. Expenditures on biologic DMARDs increased from $166 million in 2004 to $243 million in 2013, and the number of prescriptions and refills increased from 59,960 in 2004 to 105,295 in 2013. Prescriptions for biologic DMARDs increased more

  8. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update

    Science.gov (United States)

    Smolen, Josef S; Landewé, Robert; Breedveld, Ferdinand C; Buch, Maya; Burmester, Gerd; Dougados, Maxime; Emery, Paul; Gaujoux-Viala, Cécile; Gossec, Laure; Nam, Jackie; Ramiro, Sofia; Winthrop, Kevin; de Wit, Maarten; Aletaha, Daniel; Betteridge, Neil; Bijlsma, Johannes W J; Boers, Maarten; Buttgereit, Frank; Combe, Bernard; Cutolo, Maurizio; Damjanov, Nemanja; Hazes, Johanna M W; Kouloumas, Marios; Kvien, Tore K; Mariette, Xavier; Pavelka, Karel; van Riel, Piet L C M; Rubbert-Roth, Andrea; Scholte-Voshaar, Marieke; Scott, David L; Sokka-Isler, Tuulikki; Wong, John B; van der Heijde, Désirée

    2014-01-01

    In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least

  9. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.

    Science.gov (United States)

    Smolen, Josef S; Landewé, Robert; Bijlsma, Johannes; Burmester, Gerd; Chatzidionysiou, Katerina; Dougados, Maxime; Nam, Jackie; Ramiro, Sofia; Voshaar, Marieke; van Vollenhoven, Ronald; Aletaha, Daniel; Aringer, Martin; Boers, Maarten; Buckley, Chris D; Buttgereit, Frank; Bykerk, Vivian; Cardiel, Mario; Combe, Bernard; Cutolo, Maurizio; van Eijk-Hustings, Yvonne; Emery, Paul; Finckh, Axel; Gabay, Cem; Gomez-Reino, Juan; Gossec, Laure; Gottenberg, Jacques-Eric; Hazes, Johanna M W; Huizinga, Tom; Jani, Meghna; Karateev, Dmitry; Kouloumas, Marios; Kvien, Tore; Li, Zhanguo; Mariette, Xavier; McInnes, Iain; Mysler, Eduardo; Nash, Peter; Pavelka, Karel; Poór, Gyula; Richez, Christophe; van Riel, Piet; Rubbert-Roth, Andrea; Saag, Kenneth; da Silva, Jose; Stamm, Tanja; Takeuchi, Tsutomu; Westhovens, René; de Wit, Maarten; van der Heijde, Désirée

    2017-06-01

    Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national

  10. Pharmacological treatment of spondyloarthritis: exploring the effectiveness of nonsteroidal anti-inflammatory drugs, traditional disease-modifying antirheumatic drugs and biological therapies

    Science.gov (United States)

    Caso, Francesco; Costa, Luisa; Del Puente, Antonio; Di Minno, Matteo Nicola Dario; Lupoli, Gelsy; Scarpa, Raffaele; Peluso, Rosario

    2015-01-01

    Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. The therapy target of spondyloarthritis relies mainly in improving patients’ quality of life, controlling articular inflammation, preventing the structural joints damage and preserving the functional abilities, autonomy and social participation of patients. Among these, traditional disease-modifying antirheumatic drugs have been demonstrated to be effective in the management of peripheral arthritis; moreover, in the last decade, biological therapies have improved the approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α inhibitors are currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs has failed. The aim of this review is to summarize the current experience and evidence about the pharmacological approach in spondyloarthritis patients. PMID:26568809

  11. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

    Science.gov (United States)

    Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique

    2014-12-01

    This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.

  12. A case of essential thrombocythemia and ankylosing spondylitis treated with a combination of anagrelide, disease-modifying antirheumatic drugs, and etanercept

    Directory of Open Access Journals (Sweden)

    Zeremski Vanja

    2016-01-01

    Full Text Available Introduction. A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory rheumatic disease affecting the spine and sometimes peripheral joints in which reactive mild to moderate thrombocytosis is a common finding. There have been no previously reported cases of essential thrombocythemia associated with ankylosing spondylitis. Case Outline. We report a case of a 32-year-old man with human leukocyte antigen B27-positive ankylosing spondylitis and Janus kinase 2-positive essential thrombocythemia who was treated first with a combination of anagrelide and disease-modifying antirheumatic drugs and, after liver toxicity, with a combination of anagrelide and etanercept (TNF-α antagonist. Both diseases were gradually brought under control. Conclusion. Our case of ankylosing spondylitis and essential thrombocythemia suggests that concomitant etanercept and anagrelide therapy is safe, as well as effective.

  13. Disease-modifying Antirheumatic Drugs (DMARD) and Combination Therapy of Conventional DMARD in Patients with Spondyloarthritis and Psoriatic Arthritis with Axial Involvement.

    Science.gov (United States)

    Simone, Davide; Nowik, Marcin; Gremese, Elisa; Ferraccioli, Gianfranco F

    2015-11-01

    Treatment with nonsteroidal antiinflammatory drugs (NSAID) is the recommended first-line therapy in patients with axial spondyloarthritis (axSpA); and for those patients who have persistently active disease, the introduction of tumor necrosis factor-α (TNF-α) inhibitors is indicated. Conventional nonbiological disease-modifying antirheumatic drugs (DMARD), although effective and used in clinical practice for peripheral arthritis, are not recommended. Few studies have been conducted with the aim of evaluating the effect of conventional DMARD, either alone or in combination, in axSpA. As for psoriatic arthritis (PsA), DMARD are widely used, but few trials are available about their effects on axial involvement, which is not often assessed as a primary outcome in clinical trials. In rheumatoid arthritis, combination therapy of 2 or more conventional DMARD appears to confer better response than methotrexate monotherapy, and may even be a viable alternative to TNF-α inhibitors. In peripheral PsA, combination therapy can be used after treatment failure with 1 DMARD, but few studies have been conducted. However, available evidence for the combination of conventional DMARD indicates a lack of any significant benefit on axial symptoms; thus this treatment approach does not represent an effective alternative to anti-TNF-α therapy.

  14. A scoping review of the use of non-biologic disease modifying anti-rheumatic drugs in the management of large vessel vasculitis.

    Science.gov (United States)

    Misra, Durga Prasanna; Sharma, Aman; Kadhiravan, Tamilarasu; Negi, Vir Singh

    2017-02-01

    Takayasu's arteritis (TA) and Giant cell arteritis (GCA) comprise the large vessel vasculitides (LVV). Patients with LVV are treated with disease-modifying anti-rheumatic drugs (DMARDs), both conventional (cDMARDs) and biologic (bDMARDs). We undertook a scoping review to assess the effectiveness of cDMARDs in TA and GCA. We could identify 11 studies in TA and 18 studies in GCA. There were only 3 randomized controlled trials on methotrexate, one on hydroxychloroquine and two on cyclosporine in GCA, the others being case series (including all studies on TA). Most of these studies had small patient numbers (median 15 in TA and 27 in GCA). Outcome measures reported in different studies were heterogenous. Overall, methotrexate, leflunomide, azathioprine, mycophenolate mofetil and cyclophosphamide were effective in TA (low quality of evidence). Methotrexate (high quality of evidence), hydroxychloroquine and cyclosporine (moderate quality of evidence) appeared to be ineffective in GCA. Azathioprine (moderate quality of evidence), leflunomide, mycophenolate mofetil, cyclophosphamide and dapsone (low quality of evidence) were effective in GCA. There exists a paucity of high quality evidence to guide use of cDMARDs in TA and GCA. There is an unmet need to conduct large multi-centric randomized placebo-controlled trials to accurately assess the utility on cDMARDs in LVV.

  15. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    Directory of Open Access Journals (Sweden)

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs versus DMARDs alone for ankylosing spondylitis (AS with reduced pulmonary function vital capacity (FVC%. Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT, Borg scale after 6MWT, and St. George’s Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P=0.04. Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5% in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55% in the DMARDs group (P=0.04. Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%.

  16. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    Science.gov (United States)

    Rocha-Muñoz, Alberto Daniel; Brambila-Tapia, Aniel Jessica Leticia; Zavala-Cerna, María Guadalupe; Vásquez-Jiménez, José Clemente; De la Cerda-Trujillo, Liliana Faviola; Vázquez-Del Mercado, Mónica; Rodriguez-Jimenez, Norma Alejandra; Díaz-Rizo, Valeria; Díaz-González, Viviana; Cardona-Muñoz, Ernesto German; Dávalos-Rodríguez, Ingrid Patricia; Salazar-Paramo, Mario; Gamez-Nava, Jorge Ivan; Nava-Zavala, Arnulfo Hernan; Gonzalez-Lopez, Laura

    2015-01-01

    Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%. PMID:26078986

  17. Etanercept in the treatment of disease-modifying anti-rheumatic drug (DMARD)-refractory polyarticular course juvenile idiopathic arthritis: experience from Japanese clinical trials.

    Science.gov (United States)

    Mori, Masaaki; Takei, Syuji; Imagawa, Tomoyuki; Imanaka, Hiroyuki; Nerome, Yasuhito; Kurosawa, Rumiko; Kawano, Yoshifumi; Yokota, Shumpei; Sugiyama, Noriko; Yuasa, Hirotoshi; Fletcher, Tracey; Wajdula, Joseph S

    2011-12-01

    Efficacy, safety, and pharmacokinetics results from 4 studies-3 open-label (OL) and 1 randomized double-blind (DB)-have provided data for approval of etanercept for treatment of disease-modifying anti-rheumatic drug (DMARD)-refractory juvenile idiopathic arthritis (JIA) in Japan. Results from the 3 shorter-term (2 OL and 1 DB) studies are reported here. Subjects (4-17 years) enrolled in the OL studies had active JIA, i.e. ≥5 swollen joints and ≥3 joints with limitation of motion and pain or tenderness. Subjects enrolled in the primary OL study received etanercept 0.4 mg/kg subcutaneously twice weekly; in the lower-dose OL study subjects received etanercept 0.2 mg/kg. Subjects in the primary OL study who completed ≥48 weeks could continue into a 12-week DB dose-down extension study in which subjects received etanercept 0.4 or 0.2 mg/kg twice weekly. The primary endpoint in all 3 studies, i.e. 30% improvement in the American College of Rheumatology criteria for JIA (ACR Pedi 30) at 12 weeks, was achieved by ≥80% of subjects by week 2 and sustained to week 12. Common adverse events reported were injection site reactions, nasopharyngitis, and gastroenteritis. These results provide further evidence that etanercept is effective therapy for DMARD-refractory polyarticular JIA patients.

  18. Vaccinations in adults with chronic inflammatory joint disease: Immunization schedule and recommendations for patients taking synthetic or biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Morel, Jacques; Czitrom, Séverine Guillaume; Mallick, Auriane; Sellam, Jérémie; Sibilia, Jean

    2016-03-01

    The risk of infection associated with autoimmune diseases is further increased by the use of biotherapies. Recommendations to minimize this risk include administering the full complement of vaccines on the standard immunization schedule, as well as the pneumococcal and influenza vaccines. Adults with chronic inflammatory joint disease (IJD) may receive a 13-valent pneumococcal conjugate vaccine, as well as a live attenuated vaccine against recurrent herpes zoster, recently licensed by European regulatory authorities. Live attenuated vaccines can be given only after an interval without immunosuppressant and/or glucocorticoid therapy. The effectiveness of vaccines, as assessed based on titers of protective antibodies, varies across vaccine types and disease-modifying antirheumatic drugs (DMARDs). Thus, methotrexate and rituximab are usually associated with decreased vaccine responses. The risks associated with vaccines are often considerably exaggerated by the media, which serve lobbies opposed to immunizations and make some patients reluctant to accept immunizations. Increasing immunization coverage may diminish the risk of treatment-related infections. A physician visit dedicated specifically to detecting comorbidities in patients with chronic IJD may result in improved immunization coverage. In this review, we discuss immunizations for adults with chronic IJD based on the treatments used, as well as immunization coverage. Many questions remain unanswered and warrant investigation by studies coordinated by the French networks IREIVAC (Innovative clinical research network in vaccinology) and IMIDIATE (Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research).

  19. Biological targets in the treatment of rheumatoid arthritis: a comprehensive review of current and in-development biological disease modifying anti-rheumatic drugs

    Directory of Open Access Journals (Sweden)

    Manil Kukar

    2009-09-01

    Full Text Available Manil Kukar1, Olga Petryna1, Petros Efthimiou21Rheumatology Division, Lincoln Medical and Mental Health Center, New York, NY, USA; 2Lincoln Medical and Mental Health Center, Weill Cornell Medical College, New York, NY, USAAbstract: Enhanced understanding of the rheumatoid arthritis (RA pathophysiology and the role of cytokines has enabled the development of innovative biological agents in the last 10 years that target specific parts of the immune response. Failure to achieve adequate response with traditional disease modifying anti-rheumatic drugs (DMARDs and increasing evidence of ongoing radiographic deterioration of the affected joints despite seemingly clinical response were essential stimuli for the development of biologics. The current and upcoming biological agents are primarily aimed at neutralizing circulating and cell-bound pro-inflammatory cytokines, interfering in the interaction of antigen-presenting and T-lymphocytes, eliminating circulating B-lymphocytes or by interfering with the intracellular signaling mechanisms of immuno-competent cells that lead to inflammation. These agents have improved the currently available treatments due to greater efficacy, fast action and greater tolerability. However, use of these agents has also been associated with significant, although rare, adverse events and considerable cost. Therefore, these agents should be used with caution by experienced clinicians. The present work aims to provide a global and updated review of the current and in-development biological DMARDs for the treatment of RA.Keywords: biological agents, rheumatoid arthritis, immunomodulators, treatment, cytokines

  20. Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

    Science.gov (United States)

    Finckh, Axel; Bansback, Nick; Marra, Carlo A; Anis, Aslam H; Michaud, Kaleb; Lubin, Stanley; White, Marc; Sizto, Sonia; Liang, Matthew H

    2009-11-03

    Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Decision analytic model with probabilistic sensitivity analyses. Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. U.S. adults with very early RA (symptom duration provider and societal. 3 management strategies were compared: a symptomatic or "pyramid" strategy with initial nonsteroidal anti-inflammatory drugs, patient education, pain management, and low-dose glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs) at 1 year for nonresponders; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate. Cost per quality-adjusted life-year (QALY) gained. By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater. The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for patients for whom several biologics

  1. Aggressive combination therapy with intra-articular glucocorticoid injections and conventional disease-modifying anti-rheumatic drugs in early rheumatoid arthritis: second-year clinical and radiographic results from the CIMESTRA study

    DEFF Research Database (Denmark)

    Hetland, M.L.; Stengaard-Pedersen, K.; Junker, P.;

    2008-01-01

    OBJECTIVE: To investigate whether clinical and radiographic disease control can be achieved and maintained in patients with early, active rheumatoid arthritis (RA) during the second year of aggressive treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and intra-articular c......OBJECTIVE: To investigate whether clinical and radiographic disease control can be achieved and maintained in patients with early, active rheumatoid arthritis (RA) during the second year of aggressive treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and intra......% in monotherapy), but hypertension was not more prevalent. CONCLUSION: Continuous methotrexate and intra-articular corticosteroid treatment resulted in excellent clinical response and disease control at 2 years, and the radiographic erosive progression was minimal. Addition of ciclosporine during the first 76...

  2. Phase III, multicenter, open-label, long-term study of the safety of abatacept in Japanese patients with rheumatoid arthritis and an inadequate response to conventional or biologic disease-modifying antirheumatic drugs

    OpenAIRE

    Takeuchi, Tsutomu; Matsubara, Tsukasa; Urata, Yukitomo; Suematsu, Eiichi; Ohta, Shuji; Honjo, Shigeru; Abe, Tohru; Yamamoto, Ami; Miyasaka, Nobuyuki; ,

    2014-01-01

    Objectives To examine the long-term safety of intravenous (IV) abatacept treatment in Japanese patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) or other conventional or biologic disease-modifying antirheumatic drugs. Methods This Phase III, open-label, long-term study (NCT00484289) comprised Japanese patients with RA who had completed abatacept Phase I or Phase II studies, and new patients intolerant to MTX. Patients from Phase I and Phase II studies re...

  3. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis.

    Science.gov (United States)

    Nam, Jackie L; Takase-Minegishi, Kaoru; Ramiro, Sofia; Chatzidionysiou, Katerina; Smolen, Josef S; van der Heijde, Désirée; Bijlsma, Johannes W; Burmester, Gerd R; Dougados, Maxime; Scholte-Voshaar, Marieke; van Vollenhoven, Ronald; Landewé, Robert

    2017-06-01

    To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations. MEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained. The RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or 'spacing' was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B). This systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Tetsuo Kobayashi

    Full Text Available To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD in patients with rheumatoid arthritis (RA.In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs related to RA were also determined.After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP (P = 0.04 for both and anti-cyclic citrullinated peptide (CCP IgG levels (P = 0.03 and P = 0.04 than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both and the anti-CCP IgG levels (P = 0.02 for both from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006, after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs.The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA.

  5. Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis.

    Science.gov (United States)

    Kobayashi, Tetsuo; Ito, Satoshi; Kobayashi, Daisuke; Shimada, Atsushi; Narita, Ichiei; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

    2016-01-01

    To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA). In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined. After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs. The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA.

  6. Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs in rheumatoid arthritis: results of the GO-MORE study in Spain.

    Science.gov (United States)

    Alonso, Alberto; González, Carlos M; Ballina, Javier; García Vivar, María L; Gómez-Reino, Juan J; Marenco, Jose Luis; Fernández-Nebro, Antonio; Ordás, Carmen; Cea-Calvo, Luis; Arteaga, María J; Sanmartí, Raimon

    2015-01-01

    To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs). The patients received subcutaneous golimumab 50mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment. A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR>5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%). The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  7. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William;

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  8. Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms.

    Science.gov (United States)

    Ajeganova, S; van Steenbergen, H W; van Nies, J A B; Burgers, L E; Huizinga, T W J; van der Helm-van Mil, A H M

    2016-05-01

    Disease-modifying antirheumatic drug (DMARD)-free sustained remission, the sustained absence of synovitis after cessation of DMARD therapy, is a relevant long-term outcome of rheumatoid arthritis (RA) if (1) its occurrence is promoted by treatment and (2) this status reflects resolution of symptoms and disability. This study investigated both items. 1007 patients with RA diagnosed between 1993 and 2011, included in the Leiden Early Arthritis Clinic, were studied on achieving DMARD-free sustained remission. Patients included in 1993-1995 were initially treated with non-steroidal anti-inflammatory drugs, in 1996-1998 mild DMARDs were started early, from 1999 onwards methotrexate was initiated promptly and from 2005 onwards disease activity score (DAS)-steered treatment was common. Remission rates were compared using Kaplan-Meier curves and Cox proportional regression. In total, 155 patients achieved DMARD-free sustained remission. Specific treatment strategies were significantly associated with achieving remission (p<0.001). Cox regression adjusted for anticitrullinated protein antibody/rheumatoid factor, swollen joint count, erythrocyte sedimentation rate, C-reactive protein revealed HRs for DMARD-free sustained remission of 1.13 (95% CI 0.48 to 2.64) in patients diagnosed in 1996-1998, 2.39 (1.07 to 5.32) in patients treated with early methotrexate (inclusion 1999-2004) and 3.72 (1.60 to 8.62) in those treated early with methotrexate and DAS-steered therapy (inclusion 2005-2011). At the time of remission, the Health Assessment Questionnaire was at the level of the general population (median 0.13, IQR 0-0.63). Also, patient-rated visual analogue scale (VAS) morning stiffness, fatigue, pain and disease activity were low (median (IQR) mm, 14 (2-27), 10 (0-47), 6 (0-20), 7 (0-20), respectively). More intensive treatment strategies increased the chance for DMARD-free sustained remission, indicating that RA chronicity can be influenced. Patients with RA achieving DMARD

  9. Intensification to triple therapy non-biologic disease-modifying antirheumatic drugs for rheumatoid arthritis in the United States from 2009 to 2014

    Science.gov (United States)

    Sparks, Jeffrey A.; Krumme, Alexis A.; Shrank, William H.; Matlin, Olga S.; Brill, Gregory; Pezalla, Edmund J.; Choudhry, Niteesh K.; Solomon, Daniel H.

    2016-01-01

    Objective Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (bDMARD) have similar efficacy in rheumatoid arthritis (RA). We investigated intensification to triple therapy after initial non-biologic (nbDMARD) prescription among patients with RA. Methods We used US insurance claims data to evaluate triple therapy use from 2009–2014. Patients with a visit for RA and initial nbDMARD prescription were included. Frequencies and rates to intensification to triple therapy or bDMARD were calculated. We evaluated whether sociodemographic, temporal, geographic, clinical, and healthcare utilization factors were associated with triple therapy intensification using Cox regression. Among those who intensified therapy, we investigated factors associated with triple therapy use by logistic regression. Results There were 24,576 patients initially with mean age of 50.3 (SD 12.3) years, and 78% were female. During the study period, 2,739 (11.1%) intensified treatment to bDMARD compared to 181 (0.7%) who intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients who intensified to triple therapy were more likely to use glucocorticoids (HR 1.91, 95%CI 1.41–2.60) compared to no glucocorticoids and more likely to use nonsteroidal anti-inflammatory drugs (NSAID, HR 1.48, 95%CI 1.10–1.99) compared to no NSAID use within 180 days of initial nbDMARD prescription. Among those who intensified treatment to triple therapy or bDMARD, significant associations for triple therapy use included older age, US region (highest odds for triple therapy use in the West, lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nbDMARD prescription. Conclusion Despite reports published during the study period suggesting equivalent efficacy of triple therapy and b

  10. Brief Report: Intensification to Triple Therapy After Treatment With Nonbiologic Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis in the United States From 2009 to 2014.

    Science.gov (United States)

    Sparks, Jeffrey A; Krumme, Alexis A; Shrank, William H; Matlin, Olga S; Brill, Gregory; Pezalla, Edmund J; Choudhry, Niteesh K; Solomon, Daniel H

    2016-07-01

    Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (DMARDs) have similar efficacy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate intensification to triple therapy after initial nonbiologic prescription among patients with RA. The use of triple therapy among patients with RA in 2009-2014 was evaluated using US insurance claims data. Patients with a health care visit for RA and an initial nonbiologic DMARD prescription were included. Frequencies of intensification to triple therapy or a biologic DMARD and rates of intensification per 6-month time period were calculated. Using Cox regression, we evaluated whether sociodemographic, temporal, geographic, clinical, and health care utilization factors were associated with intensification to triple therapy. Among those patients whose therapy was intensified, we investigated factors associated with triple therapy use by logistic regression. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for intensification to triple therapy in relation to various clinical and demographic factors were calculated. There were 24,576 patients with a mean ± SD age of 50.3 ± 12.3 years, and 78% were female. During the study period, treatment was intensified to biologic DMARDs in 2,739 patients (11.1%) compared to 181 patients (0.7%) whose treatment was intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients whose treatment was intensified to triple therapy were more likely to receive glucocorticoids (HR 1.91 [95% CI 1.41-2.60]) compared to patients who did not use glucocorticoids and were more likely to use nonsteroidal antiinflammatory drugs (NSAIDs) (HR 1.48, 95% CI 1.10-1.99 versus no NSAID use). Among those patients whose treatment was intensified to triple therapy or biologic DMARDs, factors significantly associated with triple

  11. Development of a web-based patient decision aid for initiating disease modifying anti-rheumatic drugs using user-centred design methods.

    Science.gov (United States)

    Nota, Ingrid; Drossaert, Constance H C; Melissant, Heleen C; Taal, Erik; Vonkeman, Harald E; Haagsma, Cees J; van de Laar, Mart A F J

    2017-04-26

    A main element of patient-centred care, Patient Decision Aids (PtDAs) facilitate shared decision-making (SDM). A recent update of the International Patient Decision Aids Standards (IPDAS) emphasised patient involvement during PtDA development, but omitted a methodology for doing so. This article reports on the value of user-centred design (UCD) methods for the development of a PtDA that aims to support inflammatory arthritis patients in their choice between disease modifying anti-rheumatic drugs (DMARDs). The IPDAS development process model in combination with UCD methods were applied. The process was overseen by an eight-member multidisciplinary steering group. Patients and health professionals were iteratively consulted. Qualitative in-depth interviews combined with rapid prototyping were conducted with patients to assess their needs for specific functionality, content and design of the PtDA. Group meetings with health professionals were organized to assess patients' needs and to determine how the PtDA should be integrated into patient pathways. The current literature was reviewed to determine the clinical evidence to include in the PtDA. To evaluate usability among patients, they were observed using the PtDA while thinking aloud and then interviewed. The combination of patient interviews with rapid prototyping revealed that patients wanted to compare multiple DMARDs both for their clinical aspects and implications for daily life. Health professionals mainly wanted to refer patients to a reliable, easily adjustable source of information about DMARDs. A web-based PtDA was constructed consisting of four parts: 1) general information about SDM, inflammatory arthritis and DMARDs; 2) an application to compare particular DMARDs; 3) value clarification exercises; and 4) a printed summary of patients' notes, preferences, worries and questions that they could bring to discuss with their rheumatologist. The study demonstrated that UCD methods can be of great value for the

  12. Cost-effectiveness of treatment strategies using combination disease-modifying anti-rheumatic drugs and glucocorticoids in early rheumatoid arthritis.

    Science.gov (United States)

    Wailoo, Allan; Hernández Alava, Mónica; Scott, Ian C; Ibrahim, Fowzia; Scott, David L

    2014-10-01

    The aim of this study was to estimate the cost-effectiveness of combination DMARDs with short-term glucocorticoids in early active RA using data from the 2-year Combination of Anti-Rheumatic Drugs in Early RA (CARDERA) trial. CARDERA enrolled 467 patients with active RA of Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Studies on disease-modifying antirheumatic drugs. II. Synthesis and activity of the metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quino line-3-carboxylate (TAK-603).

    Science.gov (United States)

    Baba, A; Makino, H; Ohta, Y; Sohda, T

    1998-07-01

    The metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl)quinoline -3-carboxylate (1, TAK-603), which is under clinical evaluation as a new type of disease-modifying antirheumatic drug (DMARD), were prepared to confirm their structures and to study their pharmacological properties. Of the metabolites identified, the 4-(4-hydroxy-3-methoxyphenyl) derivative (2c, M-I) was found to have an anti-inflammatory effect in an adjuvant arthritic rat model, although its potency in this model was slightly lower than that of the parent compound.

  14. Golimumab for the treatment of rheumatoid arthritis after the failure of previous disease-modifying antirheumatic drugs: a NICE single technology appraisal.

    Science.gov (United States)

    Tosh, Jonathan; Archer, Rachel; Davis, Sarah; Stevenson, Matt; Stevens, John W

    2013-08-01

    As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of golimumab (Simponi(®); Merck Sharp & Dohme, USA) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) after the failure of previous disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at The University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article provides details of the manufacturer's initial submission, the ERG's clarification questions and the ERG report submitted to NICE. The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer's submission to NICE. The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA: GO-FORWARD and Kay et al. (DMARD-experienced population) and GO-AFTER (tumour necrosis factor [TNF]-α inhibitor-experienced population). The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. The trials for golimumab, as well as comparator treatments, were synthesized using mixed-treatment comparison methods for the DMARD-experienced population and an indirect comparison using the Bucher method for the TNF-α inhibitor-experienced population. The trials used were appropriate, although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible. The manufacturer provided a DMARD-experienced population model and a TNF-α inhibitor-experienced population model. The models allowed sequences of

  15. Severe adverse drug reactions to biological disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis in clinical practice.

    Science.gov (United States)

    Leon, Leticia; Gomez, Alejandro; Vadillo, Cristina; Pato, Esperanza; Rodriguez-Rodriguez, Luis; Jover, Juan Angel; Abasolo, Lydia

    2017-06-06

    Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients. A 14-year retrospective longitudinal study was performed. RA patients followed in an out-patient clinic starting bDMARDs after the age of 65 were included. discontinuation due to a severe ADR related to bDMARDs (etanercept, infliximab, adalimumab, rituximab, golimumab, certolizumab, abatacept and tocilizumab). Covariables: sociodemographic, clinical and therapy. Incidence rates of discontinuation were estimated using survival techniques and comparison between bDMARDs discontinuation rates and other associated factors were run by Cox regression models. We analysed 286 courses of bDMARDs therapy in 146 elderly patients (604 patient-years). 78% were women, with a mean age at diagnosis of 66.5±7 years, and a median time to the start of the first bDMARDs of 6±4 years. The incidence of discontinuation due to severe ADR estimated was 10.2% patient-years, with a median survival of around 7 years. The most frequent cause was infections. Etanercept had the lowest risk of severe ADR compared to other bDMARDs. Our study reflects the 'real world' experience in elderly RA patients on bDMARDs, with non-selected patients for a 14-year follow-up.

  16. The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers.

    Science.gov (United States)

    Kearsley-Fleet, Lianne; Závada, Jakub; Hetland, Merete Lund; Nordström, Dan C; Aaltonen, Kalle J; Listing, Joachim; Zink, Angela; Gati, Tamas; Rojkovich, Bernadette; Iannone, Florenzo; Gremese, Elisa; van Riel, Piet L C M; van de Laar, Martinus A F J; Lie, Elisabeth; Kvien, Tore K; Canhão, Helena; Fonseca, João E; Rotar, Žiga; Loza, Estibaliz; Carmona, Loreto; Askling, Johan; Johansson, Kari; Finckh, Axel; Dixon, William G; Hyrich, Kimme L

    2015-06-01

    Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan.

    Science.gov (United States)

    Takeuchi, Tsutomu; Ishida, Kota; Shiraki, Katsuhisa; Yoshiyasu, Takashi

    2017-06-26

    Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

  18. Efficacy and safety of an anti-CD20 monoclonal antibody (Reditux™) for the treatment of patients with moderate to severe rheumatoid arthritis following the failure of conventional synthetic disease-modifying anti-rheumatic drugs.

    Science.gov (United States)

    Bhati, Manjeet; Bandyopadhyay, Syamasis

    2016-08-01

    Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy's Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6 months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1 g Reditux™, at least 15 days apart, with continued stable doses of methotrexate. Efficacy and safety after 24 weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46 years; 67.5 % females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24 weeks (p treatment. The treatment was well tolerated by patients without any clinically relevant serious adverse events over 24 weeks. Though limited by number of patients and retrospective in nature, this analysis serves as a real-world evidence of efficacy and safety of Dr. Reddy's rituximab (Reditux™) in the treatment of csDMARD-failed patients with RA over a 6-month period.

  19. Tocilizumab in patients with active rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs or tumor necrosis factor inhibitors: subanalysis of Spanish results of an open-label study close to clinical practice.

    Science.gov (United States)

    Álvaro-Gracia, José M; Fernández-Nebro, Antonio; García-López, Alicia; Guzmán, Manuel; Blanco, Francisco J; Navarro, Francisco J; Bustabad, Sagrario; Armendáriz, Yolanda; Román-Ivorra, José A

    2014-01-01

    To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70

    Directory of Open Access Journals (Sweden)

    Orme ME

    2012-12-01

    Full Text Available Michelle E Orme,1 Katherine S MacGilchrist,2 Stephen Mitchell,2 Dean Spurden,3 Alex Bird31Icera Consulting, Swindon, Wiltshire, UK; 2Systematic Review Department, Abacus International, Bicester, Oxfordshire, UK; 3Pfizer UK Limited, Tadworth, Surrey, UKBackground: Biologic disease-modifying antirheumatic drugs (bDMARDs extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate.Methods: Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists. Phase II or III randomized controlled trials reporting American College of Rheumatology (ACR criteria scores of 20, 50, and 70 between 12 and 30 weeks' follow-up and enrolling adult patients meeting ACR classification criteria for rheumatoid arthritis previously treated with and with an inadequate response to conventional DMARDs were eligible. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using fixed and random-effects, logit-link models fitted to the binomial ACR 20/50/70 trial data.Results: The systematic review identified 10,625 citations, and after a review of 2450 full-text papers, there were 29 and 14 eligible studies for the combination and monotherapy meta-analyses, respectively. In the combination analysis, all licensed bDMARD combinations had significantly higher odds of ACR 20/50/70 compared to DMARDs alone, except for the rituximab comparison, which did not reach significance for the ACR 70 outcome (based on the 95% credible interval. The etanercept combination was

  1. Presence of power Doppler synovitis in rheumatoid arthritis patients with synthetic and/or biological disease-modifying anti-rheumatic drug-induced clinical remission: experience from a Chinese cohort.

    Science.gov (United States)

    Geng, Yan; Han, Jingjing; Deng, Xuerong; Zhang, Zhuoli

    2014-08-01

    The aim of this study was to evaluate the ultrasonographic synovitis in rheumatoid arthritis (RA) patients who reached clinical remission. Two hundred and two RA patients were enrolled into this study. One hundred and eleven RA patients achieved clinical remission with the treatment of synthetic and/or biologic disease-modifying anti-rheumatic drugs (DMARDs). Subclinical synovitis was assessed by power Doppler ultrasonography (PDUS). PD synovitis was semi-quantitatively recorded. Twenty-two joint regions were imaged: bilateral wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints. PD remission was defined as a total PD score of 0. The subclinical synovitis in the RA patients who achieved clinical remission was evaluated. The correlations between PD total scores and clinical/laboratory parameters were analyzed. Among the 111 RA patients who achieved clinical remission, 110 (99.1 %), 67 (60.4 %), 55 (49.5 %), 50 (45.0 %), and 54 (48.6 %) patients, respectively, satisfied DAS28 (CRP), DAS28 (ESR), CDAI, SDAI, and 2010 ACR/EULAR remission criteria. However, only 54 (48.6 %) patients achieved PD remission. Subclinical synovitis was detectable in 57 (51.8 %), 30 (44.8 %), 22 (40.0 %), 19 (38.0 %), and 18 (33.3 %) patients accordingly. On the contrary, 11 (26.8 %) out of 41 patients who fulfilled all five clinical remission criteria had evidence of subclinical synovitis. In those 91 patients who did not achieved clinical remission, total PD score was correlated with swollen joint counts (SJC), tender joint counts (TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complex disease activity indexes (P peptide. Among those 57 patients with subclinical synovitis after reaching clinical remission, no correlation was found between PD total score and SJC, TJC, ESR, CRP, and complex disease activity indexes. Presence of subclinical synovitis is common in patients achieving clinical remission. The stricter clinical

  2. Association between use of disease-modifying antirheumatic drugs and diabetes in patients with ankylosing spondylitis, rheumatoid arthritis, or psoriasis/psoriatic arthritis: a nationwide, population-based cohort study of 84,989 patients

    Directory of Open Access Journals (Sweden)

    Chen HH

    2017-05-01

    Full Text Available Hsin-Hua Chen,1–7 Der-Yuan Chen,1–6 Chi-Chen Lin,1,2 Yi-Ming Chen,1–4 Kuo-Lung Lai,3,4 Ching-Heng Lin1 1Department of Medical Research, Taichung Veterans General Hospital, 2Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, 3School of Medicine, National Yang-Ming University, Taipei, 4Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 5School of Medicine, Chung-Shan Medical University, 6Department of Medical Education, Taichung Veterans General Hospital, Taichung, 7Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan Purpose: The aim of this study is to investigate the association between the use of disease-modifying antirheumatic drugs (DMARDs and diabetes mellitus (DM in patients with ankylosing spondylitis (AS, rheumatoid arthritis (RA, or psoriasis/psoriatic arthritis (PS/PSA.Patients and methods: This retrospective cohort study used a nationwide, population-based administrative database to enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti-tumor necrosis factor (anti-TNF drugs or nonbiologic DMARDs. Multivariable analysis was used to estimate the effect of different therapies on the risk of DM.Results: The incidence rates of DM per 1,000 person-years were 8.3 for users of anti-TNF drugs, 13.3 for users of cyclosporine (CSA, 8.4 for users of hydroxychloroquine (HCQ, and 8.1 for users of other nonbiologic DMARDs. Compared with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios (aHRs for DM were significantly lower for those who used anti-TNF drugs with HCQ (aHR: 0.49, 95% confidence interval [CI]: 0.36–0.66 and those who used HCQ alone (aHR: 0.70, 95% CI: 0.63–0.78, but not for those who used anti-TNFs without HCQ (aHR: 1.23, 95% CI: 0.94–1.60 or CSA (aHR: 1.14, 95% CI: 0.77–1

  3. Use of tofacitinib in real clinical practice to treat patients with rheumatoid arthritis resistant to synthetic and biological disease-modifying antirheumatic drugs: Results of a multicenter observational study

    Directory of Open Access Journals (Sweden)

    D. E. Karateev

    2016-01-01

    Full Text Available Tofacitinib (TOFA, a member of a new class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs, is a promising medication for the treatment of rheumatoid arthritis (RA and other immunoinflammatory diseases. The paper describes the Russian experi-ence with TOFA used to treat severe RA.Patients and methods. 101 RA patients (18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months who were positive for rheumatoid factor (89.1% and anti-cyclic citrullinated peptide antibodies (74.7% and resistant to therapy with synthetic DMARDs (sDMARDs (80.2% and biological agents (19.8% were given TOFA at a dose of 5 mg twice daily, which could be doubled if necessary. TOFA was used alone (n=9 or in combination with methotrexate (MT (n=75 or other sDMARDs (n=17. The achievement of low disease activity (LDA and clinical remission at 3 and 6 months of treatment by DAS28-ESR SDAI, and CDAI scores, and the indices of safety and tolerability were assessed.Results. A total of 93 (92.1% of the 101 patients completed a 24-week period of the investigation. 8 (7.9% patients prematurely discontinued TOFA after an average of 2.75±0.71 months. At the end of the study, the patients achieved the primary endpoint (LDA including remission in terms of DAS28-ESR ≤3.2 (34.7%, SDAI ≤11 (47.5%, and CDAI ≤10 (48.5% and the secondary endpoints (clinical remission in terms of DAS28-ESR ≤2.6 (17.8%, SDAI ≤3.3 (8.9%, and CDAI ≤2.8 (6.9%. When TOFA was combined with MT, the discontinuation rate for the former was significantly lower (2.7% than when TOFA was used in combination with other sDMARDs (29.4% or alone (11.1%; p<0.01. At 3 and 6 months of follow-up, LDA was achieved more frequently when TOFA was combined with MT than when other treatment regimens were used. Fatal outcomes and serious adverse events (AEs, as AEs previously undescribed in the literature, were not seen during a follow-up within

  4. Real-life experience of using conventional disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Retrospective analysis of the efficacy of methotrexate, sulfasalazine, and leflunomide in PsA in comparison to spondyloarthritides other than PsA and literature review of the use of conventional DMARDs in PsA

    Science.gov (United States)

    Roussou, Euthalia; Bouraoui, Aicha

    2017-01-01

    Objective With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). Material and Methods A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. Results A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Conclusion Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts. PMID:28293446

  5. CARDIOVASCULAR RISK IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS BEFORE DISEASE-MODIFYING ANTIRHEUMATIC THERAPY (PRELIMINARY DATA OF THE REMARCА STUDY

    Directory of Open Access Journals (Sweden)

    Yu. N. Gorbunova

    2014-01-01

    Full Text Available Objective: to estimate the level of cardiovascular risk in patients with early rheumatoid arthritis (RA before therapy with disease-modifying antirheumatic drugs (DMARDs.Subjects and methods: Seventy-three patients with early RA who had not previously taken DMARDs or glucocorticoids were examined. Disease activity was assessed by the DAS28, SDAI, and CDAI. All the patients were examined by a cardiologist. The investigators assessed traditional risk factors (RF, by determining the overall coronary risk according tothe modified SCORE scale, the degree of a risk for cardiovascular events (CVE, carried out 24-hour ECG and blood pressure monitoring, echocardiography (EchoCG, and carotid duplex scanning, identified coronary artery calcification by multislice spiral computed tomography, and, if indicated, performed stress EchoCG and coronary angiography.Results. The diagnosis of coronary heart disease was established in 13 patients. NYHA functional class I or II chronic heart failure (HF was diagnosed in 8 patients, systolic HF in 2, HF with preserved left ventricular ejection fraction in 6 cases. There was left ventricular hypertrophy in 22 (30.1% patients, carotid atherosclerotic plaques in 26 (35.6%, coronary artery calcification in 30 (41.1%, hypertension in 38 (52.1%, abdominal obesity in 34 (46.6%, dyslipidemia in 40 (54.8%, hypercholesterolemia in 37 (50.7%, hypoalphalipoproteinemia in 21 (28.8%, hypertriglyceridemia in 12 (16.4%, low physical activity in 30 (41.1%, and smoking in 13 (17.8%. Thirty-three of 53 women weremenopausal. Fasting hyperglycemia was found in 11 (15.1% patients; type 2 diabetes mellitus in 4 (5.5%. Thirty-one (42.5% patients had at least three RFs. In accordance with the current classification of the degree of cardiovascular risk, very high, high, moderate, and low risks for CVE were observed in 58, 8, 8, and 26% of the RA patients, respectively.Conclusion. Most rheumatoid factor- and anticyclic citrullinated

  6. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

    Science.gov (United States)

    Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

    2017-09-01

    To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

  7. Kinase inhibitors: a new class of antirheumatic drugs

    Directory of Open Access Journals (Sweden)

    Kyttaris VC

    2012-09-01

    Full Text Available Vasileios C KyttarisDivision of Rheumatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USAAbstract: The outlook for patients with rheumatoid arthritis has improved significantly over the last three decades with the use of disease-modifying antirheumatic drugs. However, despite the use of methotrexate, cytokine inhibitors, and molecules targeting T and B cells, a percentage of patients do not respond or lose their response over time. The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. In the past decade, small molecules targeting several kinases, such as p38 MAPK, Syk, and JAK have been developed. Several p38 MAPK inhibitors proved ineffective in treating rheumatoid arthritis. The Syk inhibitor, fostamatinib, proved superior to placebo in Phase II trials and is currently under Phase III investigation. Tofacitinib, a JAK1/3 inhibitor, was shown to be efficacious in two Phase III trials, while VX-509, a JAK3 inhibitor, showed promising results in a Phase II trial. Fostamatinib and tofacitinib were associated with increased rates of infection, elevation of liver enzymes, and neutropenia. Moreover, fostamatinib caused elevations of blood pressure and diarrhea, while tofacitinib was associated with an increase in creatinine and elevation of lipid levels.Keywords: rheumatoid arthritis, kinase inhibitors, mitogen-activated phosphokinase p38, spleen tyrosine kinase, Janus kinases

  8. [Comorbid autoimmune pathology in patients treated with disease modifying drugs].

    Science.gov (United States)

    Goncharova, Z A; Sizyakina, L P; Belovolova, R A; Megeryan, V A

    2016-01-01

    Because of intensive growth of the prevalence of multiple sclerosis (MS) and other autoimmune diseases (AID) during the last years, the comorbidity of MS and AID is not a rarity. In this literature review, the development of comorbid AID in patients with MS is considered to be the probable complication of disease modifying therapy with drugs of different groups. The authors present the own data on the prevalence of comorbid autoimmune pathology in patients with MS treated with disease modifying drugs.

  9. A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs

    Directory of Open Access Journals (Sweden)

    G. Pasero

    2011-09-01

    Full Text Available The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and infl ammation, but without any infl uence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs. This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and lefl unomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive (“therapeutic pyramid” or of more aggressive treatment, through the simultaneous use of two or more DMARDs (“combination therapy”.

  10. Consensus development on eligibility of government subsidisation of biologic disease modifying anti-rheumatic agents for treatment of ankylosing spondylitis: The Singapore experience.

    Science.gov (United States)

    Cheung, Peter P; Lahiri, Manjari; Teng, Gim-Gee; Lui, Nai-Lee; Chia, Faith L; Koh, Dow-Rhoon; Koh, Wei-Howe; Ng, Swee-Cheng; Suresh, Ernest; Leong, Khai-Pang; Lim, Anita Y N; Thumboo, Julian; Lau, Tang-Ching; Leong, Keng-Hong

    2015-07-14

    The beneficial effects of biologic disease-modifying anti-rheumatic drugs (bDMARDs), such as tumour necrosis factor inhibitors (anti-TNF) in active ankylosing spondylitis (AS) are well established. The significant costs on patients in the absence of financial subsidization can limit their use. The objective was to describe a consensus development process on recommendations for government-assisted funding of biologic therapy for AS patients in Singapore. Evidence synthesis followed by a modified RAND/UCLA Appropriateness Method (RAM) was used. Eleven rheumatologists rated indications for therapies for different proposed clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate 10 practice recommendations. It was agreed that a bDMARD (anti-TNF) is indicated if a patient has active AS with a Bath Ankylosing Spondylitis Activity Index (BASDAI) ≥ 4 and spinal pain of ≥ 4 cm on visual analogue scale (VAS) on two occasions at least 12 weeks apart, despite being on a minimum of two sequential non-steroidal anti-inflammatory drugs at maximal tolerated dose for at least 4 weeks, in addition to adherence to an appropriate physiotherapy program for at least 3 months. To qualify for continued biologic therapy, a patient must have documentation of response every 3 months and at least 50% improvement in BASDAI and reduction of spinal pain VAS ≥ 2 cm. A validated and feasible consensus process can enable pragmatic standardized recommendations to be developed for bDMARD subsidization for AS patients in a local Asian context. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  11. Safety of anti-rheumatic drugs for rheumatoid arthritis in pregnancy and lactation.

    Science.gov (United States)

    Ngian, Gene-Siew; Briggs, Andrew M; Ackerman, Ilana N; Van Doornum, Sharon

    2016-09-01

    Women with rheumatoid arthritis (RA) are often of childbearing age and therefore questions regarding reproductive health and the use of medications, including disease-modifying anti-rheumatic drugs (DMARDs) may arise during the clinical consultation. Each patient requires individual assessment in order to effectively manage the disease while minimizing any treatment-associated risks to the fetus. Although good-quality controlled trials are lacking, there is an increasing volume of evidence surrounding the use of immunosuppressive therapies in pregnancy and lactation. This review summarizes the currently available information which can be of benefit to clinicians guiding patients and their families through the risks and benefits of continuing RA therapy during pregnancy and lactation. Further studies and ongoing surveillance of drug safety in pregnancy are required to resolve the uncertainties that remain regarding synthetic and biologic DMARDs.

  12. Immunomodulation of rheumatologic disorders with non-biologic disease modifying antirheumtic drugs.

    Science.gov (United States)

    Walker, Ulrich A

    2016-04-01

    Although biological agents have revolutionized the immunomodulation of many rheumatic disorders, conventional disease modifying antirheumatic drugs (DMARDs) remain important glucocorticosteroid sparing agents and combination partners. In rheumatoid arthritis, low-dose glucocorticosteroids can be regarded as a DMARD due to preventive effects on joint erosions. Therapy with methothrexate and possibly also other DMARDs may alter the natural evolution of rheumatoid arthritis severity over time and therapy should be instituted as early as possible. Leflunomide is an equipotent alternative to methotrexate in rheumatoid arthritis, if methotrexate cannot be tolerated. Hydroxychloroquine inhibits toll-like receptor signaling and exerts antithrombotic and antihyperlipidemic effects, all thought to be beneficial in systemic lupus erythematosus. Hydroxychloroquine improves organ involvement in lupus, prevents lupus flares, and reduces mortality. It should be given to every lupus patient without contraindications.

  13. New antirheumatic drugs: any real added value? A critical overview of regulatory criteria for their marketing approval.

    Science.gov (United States)

    Bertele', Vittorio; Assisi, Alessandro; Di Muzio, Valeria; Renzo, Danila; Garattini, Silvio

    2007-09-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disorder causing chronic polyarticular synovial inflammation and progressive joint damage. New anti-rheumatic drugs, such as leflunomide, infliximab, etanercept, adalimumab and anakinra, have recently become available. The aim of this paper is to summarize and critically evaluate the type of studies and clinical endpoints accepted by the European Medicines Agency (EMEA) to approve these new drugs. Information regarding the approval of antirheumatic drugs was obtained from European Public Assessment Reports (EPARs) and published pivotal studies. Leflunomide is the only non-biological disease-modifying anti-rheumatic drug (DMARD) to receive recent approval for RA treatment, but strong evidence of its superiority over conventional therapies is lacking. Anakinra in combination with methotrexate received approval as a DMARD for RA on the basis of two pivotal trials in which American College of Rheumatology response criteria (ACR 20 response) were used as the sole primary endpoint. For easier demonstration of efficacy, studies leading to first approval of etanercept, infliximab and adalimumab were carried out on non-responders to DMARDs. Once on the market, these drugs gained an extension of the indication to methotrexate-naïve patients. Studies that provided the basis for approval were not adequately designed, given the lack of an active control and the choice of ACR response as the only clinical endpoint. Consequently, only a weak proof of efficacy emerged for the treatment of signs and symptoms of RA, and these drugs failed to show real benefit in slowing radiographic progression. Serious infections, changes in blood cell counts, severe skin and hepatic infections were the main adverse events that emerged from the clinical studies. Therefore, the unconvincing benefit of the new antirheumatic drugs can scarcely outweigh the risk associated with their use. Moreover, the monthly costs in Italy of the new biological

  14. Pharmacological influence of antirheumatic drugs on proteoglycans from interleukin-1 treated articular cartilage.

    Science.gov (United States)

    Steinmeyer, J; Daufeldt, S

    1997-06-01

    The purpose of this study was to examine whether drugs used in the treatment of arthritic disorders possess any inhibitory potential on the proteoglycanolytic activities of matrix metalloproteinases (MMPs), and to determine whether drugs which inhibit these enzymes also modulate the biosynthesis and release of proteoglycans (PGs) from interleukin-1-(IL-1) treated articular cartilage explants. The cartilage-bone marrow extract and the glycosaminoglycan-peptide complex (DAK-16) dose-dependently inhibited MMP proteoglycanases in vitro when tested at concentrations ranging from 0.5 to 55 mg/mL, displaying an IC50 value of 31.78 mg/mL and 10.64 mg/mL (1.9 x 10[-4] M) respectively. (R,S)-N-[2-[2-(hydroxyamino)-2-oxoethyl]-4-methyl-1-oxopentyl++ +]-L-leucyl-L-phenylalaninamide (U-24522) proved to be a potent inhibitor of MMP proteoglycanases (IC50 value 1.8 x 10[-9] M). None of the other tested drugs, such as possible chondroprotective drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), disease modifying antirheumatic drugs (DMARDs), glucocorticoids and angiotensin-converting enzyme inhibitors tested at a concentration of 10(-4) M displayed any significant inhibition. Only U-24522, tested at a concentration ranging from 10(-4) to 10(-6) M, significantly inhibited the IL-1-induced augmentation of PG loss from cartilage explants into the nutrient media, whereas DAK-16 and the cartilage-bone marrow extract were ineffective. DAK-16 and the cartilage-bone marrow extract did not modulate the IL-1-mediated reduced biosynthesis and aggregability of PGs by the cartilage explants. The addition of 10(-5) M U-24522, however, partially maintained the aggregability of PGs ex vivo. In our experiments, both possible chondroprotective drugs as well as U-24522 demonstrated no cytotoxic effects on chondrocytes.

  15. Quantitative gait analysis as a method to assess mechanical hyperalgesia modulated by disease-modifying antirheumatoid drugs in the adjuvant-induced arthritic rat

    Science.gov (United States)

    Simjee, Shabana Usman; Jawed, Huma; Quadri, Javeria; Saeed, Sheikh Arshad

    2007-01-01

    In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease-modifying effects in the adjuvant-induced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease-modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.1). In earlier experiments, chloroquine and methotrexate failed to suppress carageenan-induced edema, suggesting that the mode of antiarthritic action may be different from those of nonsteroidal anti-inflammatory agents. Since these disease-modifying antirheumatic drugs are reported to have an immunomodulatory role, especially the gold salt, which influences the monocyte–macrophage system, it is suggested that the observed antiarthritic effects of disease-modifying antirheumatic drugs may be partly attributed to their immunomodulatory activity. PMID:17848187

  16. Short time administration of antirheumatic drugs - Methotrexate as a strong inhibitor of osteoblast's proliferation in vitro

    Directory of Open Access Journals (Sweden)

    Annussek Tobias

    2012-09-01

    Full Text Available Abstract Introduction Due to increasing use of disease modifying antirheumatic drugs (DMARDs as first line therapy in rheumatic diseases, dental and maxillofacial practitioner should be aware of drug related adverse events. Especially effects on bone-metabolism and its cells are discussed controversially. Therefore we investigate the in vitro effect of short time administration of low dose methotrexate (MTX on osteoblasts as essential part of bone remodelling cells. Methods Primary bovine osteoblasts (OBs were incubated with various concentrations of MTX, related to tissue concentrations, over a period of fourteen days by using a previously established standard protocol. The effect on cell proliferation as well as mitochondrial activity was assessed by using 3-(4, 5-dimethylthiazol-2-yl 2, 5-diphenyltetrazolium bromide (MTT assay, imaging and counting of living cells. Additionally, immunostaining of extracellular matrix proteins was used to survey osteogenic differentiation. Results All methods indicate a strong inhibition of osteoblast`s proliferation by short time administration of low dose MTX within therapeutically relevant concentrations of 1 to 1000nM, without affecting cell differentiation of middle-stage differentiated OBs in general. More over a significant decrease of cell numbers and mitochondrial activity was found at these MTX concentrations. The most sensitive method seems to be the MTT-assay. MTX-concentration of 0,01nM and concentrations below had no inhibitory effects anymore. Conclusion Even low dose methotrexate acts as a potent inhibitor of osteoblast’s proliferation and mitochondrial metabolism in vitro, without affecting main differentiation of pre-differentiated osteoblasts. These results suggest possible negative effects of DMARDs concerning bone healing and for example osseointegration of dental implants. Especially the specifics of the jaw bone with its high vascularisation and physiological high tissue metabolism

  17. Management of Rheumatoid Arthritis Patients with Interstitial Lung Disease: Safety of Biological Antirheumatic Drugs and Assessment of Pulmonary Fibrosis.

    Science.gov (United States)

    Mori, Shunsuke

    2015-01-01

    Interstitial lung disease (ILD) is one of the major causes of morbidity and mortality of patients with rheumatoid arthritis (RA). Accompanying the increased number of reports on the development or exacerbation of ILD in RA patients following therapy with biological disease-modifying antirheumatic drugs (DMARDs), RA-associated ILD (RA-ILD) has aroused renewed interest. Although such cases have been reported mainly in association with the use of tumor necrosis factor inhibitors, the use of other biological DMARDs has also become a matter of concern. Nevertheless, it is difficult to establish a causative relationship between the use of biological DMARDs and either the development or exacerbation of ILD. Such pulmonary complications may occur in the natural course of RA regardless of the use of biological DMARDs. Since rheumatologists currently aim to achieve remission in RA patients, the administration of biological DMARDs is increasing, even for those with RA-ILD. However, there are no reliable, evidence-based guidelines for deciding whether biological DMARDs can be safely introduced and continued in RA-ILD patients. A standardized staging system for pulmonary conditions of RA-ILD patients is needed when making therapeutic decisions at baseline and monitoring during biological DMARD therapy. Based on the available information regarding the safety of biological DMARDs and the predictive factors for a worse prognosis, this review discusses candidate parameters for risk evaluation of ILD in RA patients who are scheduled to receive biological antirheumatic therapy.

  18. The effect of newer anti-rheumatic drugs on osteogenic cell proliferation: an in-vitro study

    Directory of Open Access Journals (Sweden)

    Laing Patrick

    2009-05-01

    Full Text Available Abstract Background Disease modifying anti-rheumatic drugs (DMARDs may interfere with bone healing. Previous studies give conflicting advice regarding discontinuation of these drugs in the peri-operative setting. No consensus exists in current practice especially with the newer DMARDs such as Leflunomide, Etanercept, and Infliximab. The aim of this study was to assess the in-vitro effect of these drugs alone and in relevant clinical combinations on Osteoblast activity. Methods Osteoblasts were cultured from femoral heads obtained from five young otherwise healthy patients undergoing total hip replacement. The cells were cultured using techniques that have been previously described. A full factorial design was used to set up the experiment on samples obtained from the five donors. Normal therapeutic concentrations of the various DMARDs were added alone and in combination to the media. The cell proliferation was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multilevel regression analysis was used to estimate which drugs or combination of drugs significantly affected cell proliferation. Results Infliximab and Leflunomide had an overall significant inhibitory effect (p Conclusion Our study indicates that in-vitro osteoblast proliferation can be inhibited by the presence of certain DMARDs. Combinations of drugs had an influence and could negate the action of a drug on osteoblast proliferation. The response to drugs may be donor-dependent.

  19. Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs

    DEFF Research Database (Denmark)

    Olsen, N; Halberg, P; Halskov, O;

    1988-01-01

    In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed...

  20. Disease-modifying anti-rheumatic drugs til behandling af ankyloserende spondylitis

    DEFF Research Database (Denmark)

    Madsen, Ole Rintek; Egsmose, Charlotte

    2009-01-01

    Ankylosing spondylitis (AS) is an inflammatory disorder affecting the axial skeleton, peripheral joints, entheses and extra-articular sites. Patients with early disease, a higher level of erythrocyte sedimentation rate and/or peripheral arthritis might benefit from sulfasalazine. Otherwise...

  1. Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis.

    Science.gov (United States)

    Di Munno, O; Delle Sedie, A; Rossini, M; Adami, S

    2005-01-01

    This article reviews the effects of DMARDs (including biologic agents) on bone metabolism in rheumatoid arthritis (RA). At present there is no evidence that methotrexate, at least at dosages ranging from 5 to 20 mg/week, negatively affects bone mass as measured by DXA (BMD) as documented in both cross-sectional and longitudinal studies. Most studies of cyclosporine (CyA) use reporting a reduction in erosions and joint damage with no adverse effects on bone, did not measure BMD; CyA treatment is associated with a dose-dependent increase of bone turnover as well as a decrease in both animal and human studies; however, its use in RA setting at a dose < or =5 mg/Kg/ day has so far not been associated with clinical relevant adverse effects on bone metabolism. Anti-TNF-alpha agents, infliximab reduced markers of bone turnover in two longitudinal studies. Data on BMD are not available in RA; nevertheless, an increase in BMD has been documented in spondyloarthropathies with infliximab and etanercept. No clinical data concerning BMD are available on leflunomide as well as on the newer biologic agents (adalimumab, rituximab, anakinra).

  2. Effet of tocilizumab, tumor necrosis factor α inhibitors and disease-modifying anti-rheumatic drugs treating systemic-onset juvenile idiopathic arthritis%托珠单抗和肿瘤坏死因子α抑制剂及改善病情抗风湿药物治疗全身型幼年特发性关节炎的临床效果

    Institute of Scientific and Technical Information of China (English)

    梁芳芳; 彭程; 罗书立; 李永柏; 杨军

    2016-01-01

    Objective To analyze clinical effect of tocilizumab,tumor necrosis factor α (TNF-α)inhibitors and disease-modifying anti-rheumatic drugs (DMARDs) on systemic-onset juvenile idiopathic arthritis (SoJIA).Methods Totally 30 children with SoJIA from December 2013 to December 2015 in Shenzhen Children's Hospital were randomly divided into tocilizumab group(10 cases),TNF-o inhibitors group(10 cases)and DMARDs group(10 cases).The tocilizumab group was treated with tocilizumab and methotrexate;the TNF-α inhibitors group was treated with TNF-α inhibitors and methotrexate;the DMARDs group was treated with DMARDs and glucocorticoid or non-steroidal anti-inflammatory drugs.After 3 and 6 months of treatment,joint pain index,joint swelling index,recurrent fever time and erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),serum ferritin(SF),American College of Rheumatology(ACR) 30 improvement rate and ACR 50 improvement rate were analyzed.Adverse reactions were observed.Results After 3 and 6 months of treatment,joint pain indexes,joint swelling indexes,recurrent fever times and levels of ESR,CRP,SF were all significantly lower than those before treatment in 3 groups [DMARD group:(2.19 ± 0.22),(1.39 ± 0.42) scores vs (2.45 ± 0.21)scores;(2.5±0.5),(2.0±0.3)scores vs (3.5±0.3)scores;(2.67±0.21),(2.06±0.33)months vs (3.78 ± 1.65)months;(61 ± 15),(45 ± 12) mm/1 h vs (84 ± 17) mm/1 h;(69 ± 10),(44 ± 14)mg/L vs (85 ±17)mg/L;(866 ±265),(639 ±96)mg/L vs (2 522 ± 1 686) mg/L;TNF-α inhibitor group:(1.83 ±0.35),(1.02 ± 0.17) scores vs (2.34 ± 0.26) scores;(2.0 ± 0.5),(1.5 ± 0.3) scores vs (3.3 ± 0.3) scores;(1.53±0.36),(1.62±0.24)months vs (3.66 ±1.52)months;(44±12),(34±9)mm/1 h vs (82±19)mm/1 h;(54±15),(30 ± 11) mg/L vs (87 ± 19) mg/L;(574 ± 164),(464 ± 81)mg/L vs (2 496 ±1 826) mg/L;Tocilizumab group:(1.65 ± 0.34),(0.74 ± 0.20) scores vs (2.23 ± 0.25) scores;(1.6 ± 0.4),(0.8 ± 0.5) scores vs (3.4 ± 0.4) scores;(1.63 ± 0.27),(0.80

  3. Antirheumatic drugs and reproduction in women and men with chronic arthritis.

    Science.gov (United States)

    Bazzani, Chiara; Andreoli, Laura; Agosti, Michele; Nalli, Cecilia; Tincani, Angela

    2015-01-01

    The impact of rheumatic disease on fertility and reproduction can be remarkable. Many disease-related factors can influence patients' sexual functioning, perturb fertility and limit family planning. Antirheumatic pharmacological treatment can also have a crucial role in this field. Proper counselling, preferably provided by a multidisciplinary team of rheumatologists, obstetricians, gynaecologists and neonatologists, is recommended for patients taking antirheumatic drugs, not only at the beginning, but also during the course of treatment. Paternal exposure to antirheumatic drugs was not found to be specifically associated with congenital malformation and adverse pregnancy outcome, therefore discontinuation of these drugs while planning for conception should be weighed against the risk of disease flare. Drugs in Food and Drug Administration (FDA) category 'X' should be withdrawn in a timely manner in women who desire a pregnancy. Meanwhile, disease control can be achieved with anti-tumour necrosis factor (TNF)-α agents, which are not teratogenic drugs. If maternal disease control is permissive, they can be stopped as soon as the pregnancy test turns positive and be resumed during pregnancy in case of a flare.

  4. [Disease-modifying drugs in pediatric patients with multiple sclerosis].

    Science.gov (United States)

    Bykova, O V; Nankina, I A; Drozdova, I M; Kvasova, O V; Batysheva, T T; Boiko, A N

    2016-01-01

    The vast majority of therapies are being evaluated and introduced for the treatment of adult multiple sclerosis (MS). A role of these drugs in the management of pediatric MS has yet to be defined both in Russia and in the whole world. Despite the fact that today the study of new drugs in the pediatric population have included in routine practices of the big pharmaceutical agencies, such as FDA and EMA, recommendations for the treatment of pediatric patients with MS are based not so much on a long period of systematic clinical research, but on professional consensus of international expert associations, in particular, the International pediatric multiple sclerosis study group (IPMSSG). The clinical trials include the small number of patients which is not comparable to those conducted in adults. Therefore, there is a need for study designs for assessment of efficacy and safety of the drugs for MS treatment in children and adolescents. The authors present the IPMSSG concept on the treatment of pediatric MS taking into account peculiarities of the Russian legislation and experience of national experts.

  5. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

    OpenAIRE

    Spessotto,Caroline Vieira; Cavalli,Hanaie; Eboni,Audred Cristina Biondo; Machado,Rafael Berlezi; Mousquer,Analara Munardi; Palazzo,Lara Both; Finkelsztejn, Alessandro; Goncalves, Marcus Vinicius Magno; Sato,Henry Koiti; Siquineli,Fabio; Fragoso,Yara Dadalti

    2016-01-01

    ABSTRACT Objective The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Un...

  6. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

    OpenAIRE

    Caroline Vieira Spessotto; Hanaie Cavalli; Audred Cristina Biondo Eboni; Rafael Berlezi Machado; Analara Munardi Mousquer; Lara Both Palazzo; Alessandro Finkelsztejn; Marcus Vinicius Magno Goncalves; Henry Koiti Sato; Fabio Siquineli; Yara Dadalti Fragoso

    2016-01-01

    ABSTRACT Objective The treatment of multiple sclerosis (MS) with disease-modifying-drugs (DMDs) is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in...

  7. The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?

    DEFF Research Database (Denmark)

    Qvist, Per; Bay-Jensen, Anne-Christine; Christiansen, Claus;

    2008-01-01

    Till date, the pharmaceutical industry has failed to bring effective and safe disease modifying osteoarthritic drugs (DMOADs) to the millions of patients suffering from this serious and deliberating disease. We provide a review of recent data reported on the investigation of DMOADs in clinical...... trials, including compounds inhibiting matrix-metalloproteinases (MMPs), bisphosphonates, cytokine blockers, calcitonin, inhibitors of inducible nitric oxide synthase (iNOS), doxycycline, glucosamine, and diacereine. We discuss the challenges associated with the drug development process in general...

  8. A short history of anti-rheumatic therapy. I. An introduction on traditional and drug treatments

    Directory of Open Access Journals (Sweden)

    G. Pasero

    2011-06-01

    Full Text Available The origins of anti-rheumatic therapy are very old and mainly related to the use of traditional, sometimes extravagant, treatments, as a part of folk medicine. Spa therapy has long been used for the treatment of rheumatic diseases, as well as, in later times, physical treatments, including electrotherapy. Drug treatment has developed beginning from substances of vegetable origin, such as willow and colchicum extracts. Then it has been spread out through the chemical synthesis of compounds with specific action and therefore more effective, owing to the great development of pharmaceutical industry.

  9. [The trend of developing new disease-modifying drugs in Alzheimer's disease].

    Science.gov (United States)

    Arai, Hiroyuki; Furukawa, Katsutoshi; Tomita, Naoki; Ishiki, Aiko; Okamura, Nobuyuki; Kudo, Yukitsuka

    2016-03-01

    Development of symptomatic treatment of Alzheimer s disease by cholinesterase inhibitors like donepezil was successful. However, it is a disappointment that development of disease-modifying drugs such as anti-amyloid drug based on amyloid-cascade theory has been interrupted or unsuccessful. Therefore, we have to be more cautious regarding inclusion criteria for clinical trials of new drugs. We agree that potentially curative drugs should be started before symptoms begin as a preemptive therapy or prevention trial. The concept of personalized medicine also is important when ApoE4-related amyloid reducing therapy is considered. Unfortunately, Japanese-ADNI has suffered a setback since 2014. However, Ministry of Health, Labour and Welfare gave a final remark that there was nothing wrong in the data managing process in the J-ADNI data center. We should pay more attention to worldwide challenges of speeding up new drug development.

  10. Phosphocitrate Is Potentially a Disease-Modifying Drug for Noncrystal-Associated Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Yubo Sun

    2013-01-01

    Full Text Available Phosphocitrate (PC, a calcification inhibitor, inhibits the development of crystal-associated osteoarthritis (OA in Hartley guinea pigs. However, the molecular mechanisms underlying its disease-modifying effect remain elusive. This study sought to test the hypothesis that PC has calcium crystal-independent biological activities which are, at least in part, responsible for its disease-modifying activity. We found that PC inhibited the proliferation of OA fibroblast-like synoviocytes in the absence of calcium crystals. Consistent with its effect on cell proliferation, PC downregulated the expression of numerous genes classified in cell proliferation. PC also downregulated the expression of many genes classified in angiogenesis and inflammatory response including prostaglandin-endoperoxide synthase 2, interleukin-1 receptor, type I, and chemokine (C-C motif ligand 2. In contrast, PC upregulated the expression of many genes classified in musculoskeletal tissue development, including aggrecan, type I collagen, and insulin-like growth factor binding protein 5. These findings suggest that PC is not only a promising disease-modifying drug for crystal-associated OA but also for noncrystal-associated OA.

  11. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Caroline Vieira Spessotto

    2016-08-01

    Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

  12. Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment of rheumatoid arthritis. 2015 ACORDAR project.

    Science.gov (United States)

    Muñoz-Fernández, Santiago; Bustabad Reyes, María Sagrario; Calvo Alén, Jaime; Castaño Sánchez, Manuel; Chamizo Carmona, Eugenio; Corominas, Héctor; Fernández-Llanio Comella, Nagore; Hidalgo Calleja, María Cristina; Pérez Venegas, José Javier; Rodríguez Heredia, José Manuel; Romero Yuste, Susana María; Ruiz-Esquide Torino, Virginia

    2017-01-03

    To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  13. Radiographic outcome in Hispanic early rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Contreras-Yanez, Irazu, E-mail: uzari02@hotmail.com.mx [Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Seccion XVI, C.P. 14000, Tlalpan, Mexico, D.F. (Mexico); Rull-Gabayet, Marina, E-mail: rull.marina@gmail.com [Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Seccion XVI, C.P. 14000, Tlalpan, Mexico, D.F. (Mexico); Vazquez-LaMadrid, Jorge, E-mail: docjvlradiologo@yahoo.com [Department of Radiology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Seccion XVI, C.P. 14000, Tlalpan, Mexico, D.F. (Mexico); Pascual-Ramos, Virginia, E-mail: virtichu@gmail.com.mx [Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15, Seccion XVI, C.P. 14000, Tlalpan, Mexico, D.F. (Mexico)

    2011-08-15

    Objectives: To determine rates of incident erosive disease in early rheumatoid arthritis patients, to identify baseline predictors and to evaluate erosion's impact on patient-reported outcomes. Methods: 82 patients with {<=}12 months of disease duration, {>=}3 years of follow-up and conventional treatment were included. Consecutive evaluations assessed swollen and tender joint counts, treatment and comorbidity, acute reactant-phase determinations and patient-reported outcomes. Digitized radiographs of the hands and feet were obtained at baseline and yearly thereafter. RA was defined as erosive when at least one unequivocal cortical bone defect was detected. Descriptive statistics and Cox regression analysis were performed. Results: At baseline, 71 of the patients were Female Sign , population median (range) age was of 38.7 (16-78.2) years, 58 patients had antibodies and all the patients had active disease and substantial disability. Follow-up cohort was of 299.3 person-years. At last follow-up (49 {+-} 13.8 months), 28 patients developed erosions. Erosion's location was the feet, in 12 patients. Incident rates of erosive disease at one, two, three and four years were of 8.1, 12.8, 13.8 and 5.6 per 100 person-years, respectively. Higher C-reactive protein (HR: 1.20, 95%CI: 1.04-1.4, p = 0.01) and positive antibodies (HR: 5.09, 95%CI: 1.08-23.86, p = 0.04) were baseline predictors of incident erosive disease. Erosions had minor impact on patient-reported outcomes. Conclusion: Rheumatoid arthritis patients with antibodies and higher C reactive protein at baseline are at risk for incident erosions which appear most frequently at the feet. Up to 1/3 patients conventionally treated develop incident erosions, which minimally impact function.

  14. ANALYSIS OF DISEASE MODIFYING DRUGS ADMINISTRATION FREGUENCY AND CAUSES OF THEIR WITHDRAWAL IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E V Pavlova

    2000-01-01

    Full Text Available Aim of studdy: To assess the frequency of practical application of different basic drugs in rheumatoid arthritis (RA. Material and methods: Tlxe study was conducted basing of questionner of pts and analysis of ycases by randomized sampling among 103 consequent pts (M:F= 13:90 with reliable RA (ARA, 1987 in rheumatologic department of Clinical Hospital Nol in Ekaterinburg. 74% of pts under study demonstrated systemic manifestations: anemia (in 47 pts, lymphadenopathy (in 34, rheumatoid nodules (in 15, Sjogren s syndrome (in 4, nephropathy (in 4, vascular disturbances including Raynaud s phenomenon, capillarites (by 1 pt. Results: In the course of disease basic therapy was prescribed to 88 out of103 (85.4% pts and one and the same patient could take different basic drugs. Aminochinoline drugs prevailed, after them more frequent were immunodepressants and gold preparations. More rarely pts had sulfasalazin, cuprenil and wobenzym. In general, in 133 out of 184 cases of prescribing basic drugs they were canceled. The reason for cancellation were: prevalently absence of the drug in the pharmaceutical stores (in 48 cases averagely in 8 months of taking the drug; then they insufficient efficacy (44 cases averagely in 1.3 year. In 18 cases pts themselves stopped treatment averagely in 3.5 months of drug taking. Conclusion: In the majority of cases of basic drugs cancellation in RA the cause is their absence in sail especially on free of charge prescription. Cases ofself-cancellation of the drug demonstrate the need of explaining to pts the necessity> of long-term taking disease-modifying drugs.

  15. Randomized, placebo controlled trial of withdrawal of slow-acting antirheumatic drugs and of observer bias in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Gøtzsche, P C; Hansen, M; Stoltenberg, M;

    1996-01-01

    Patients with rheumatoid arthritis, in stable treatment with methotrexate, penicillamine, or sulfasalazine, were randomized in a double-blind fashion either to continuation of their usual treatment or to placebo. 112 patients were included; 52 patients who refused participation had no more severe...... between the observers' evaluations of the joints. The effect of slow-acting antirheumatic drugs was unequivocal and no observer bias occurred....

  16. Adherence to Disease Modifying Drugs among Patients with Multiple Sclerosis in Germany: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Kerstin Hansen

    Full Text Available Long-term therapies such as disease modifying therapy for Multiple Sclerosis (MS demand high levels of medication adherence in order to reach acceptable outcomes. The objective of this study was to describe adherence to four disease modifying drugs (DMDs among statutorily insured patients within two years following treatment initiation. These drugs were interferon beta-1a i.m. (Avonex, interferon beta-1a s.c. (Rebif, interferon beta-1b s.c. (Betaferon and glatiramer acetate s.c. (Copaxone.This retrospective cohort study used pharmacy claims data from the data warehouse of the German Institute for Drug Use Evaluation (DAPI from 2001 through 2009. New or renewed DMD prescriptions in the years 2002 to 2006 were identified and adherence was estimated during 730 days of follow-up by analyzing the medication possession ratio (MPR as proxy for compliance and persistence defined as number of days from initiation of DMD therapy until discontinuation or interruption.A total of 52,516 medication profiles or therapy cycles (11,891 Avonex, 14,060 Betaferon, 12,353 Copaxone and 14,212 Rebif from 50,057 patients were included into the analysis. Among the 4 cohorts, no clinically relevant differences were found in available covariates. The Medication Possession Ratio (MPR measured overall compliance, which was 39.9% with a threshold MPR≥0.8. There were small differences in the proportion of therapy cycles during which a patient was compliant for the following medications: Avonex (42.8%, Betaferon (40.6%, Rebif (39.2%, and Copaxone (37%. Overall persistence was 32.3% at the end of the 24 months observation period, i.e. during only one third of all included therapy cycles patients did not discontinue or interrupt DMD therapy. There were also small differences in the proportion of therapy cycles during which a patient was persistent as follows: Avonex (34.2%, Betaferon (33.4%, Rebif (31.7% and Copaxone (29.8%.Two years after initiating MS-modifying therapy, only

  17. Huperzine A: is it an effective disease-modifying drug for Alzheimer’s disease?

    Directory of Open Access Journals (Sweden)

    Zhong Ming eQian

    2014-08-01

    Full Text Available Alzheimer's disease (AD is a progressive neurodegenerative disorder for which there is no cure. Huperzine A (HupA is a natural inhibitor of acetylcholinesterase (AChE derived from the Chinese folk medicine Huperzia serrata (Qian Ceng Ta. It is a licensed anti-AD drug in China and is available as a nutraceutical in the US. A growing body of evidence has demonstrated that HupA has multifaceted pharmacological effects. In addition to the symptomatic, cognitive-enhancing effect via inhibition of AChE, a number of recent studies have reported that this drug has non-cholinergic effects on AD. Most important among these is the protective effect of HupA on neurons against amyloid beta-induced oxidative injury and mitochondrial dysfunction as well as via the up-regulation of nerve growth factor and antagonizing N-methyl-D-aspartate receptors. The most recent discovery that HupA may reduce brain iron accumulation lends further support to the argument that HupA could serve as a potential disease-modifying agent for AD and also other neurodegenerative disorders by significantly slowing down the course of neuronal death.

  18. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation.

    Science.gov (United States)

    Götestam Skorpen, Carina; Hoeltzenbein, Maria; Tincani, Angela; Fischer-Betz, Rebecca; Elefant, Elisabeth; Chambers, Christina; da Silva, Josè; Nelson-Piercy, Catherine; Cetin, Irene; Costedoat-Chalumeau, Nathalie; Dolhain, Radboud; Förger, Frauke; Khamashta, Munther; Ruiz-Irastorza, Guillermo; Zink, Angela; Vencovsky, Jiri; Cutolo, Maurizio; Caeyers, Nele; Zumbühl, Claudia; Østensen, Monika

    2016-05-01

    A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?

    Science.gov (United States)

    Losina, Elena; Daigle, Meghan E.; Reichmann, William M.; Suter, Lisa G.; Hunter, David J.; Solomon, Daniel H.; Walensky, Rochelle P.; Jordan, Joanne M.; Burbine, Sara A.; Paltiel, A. David; Katz, Jeffrey N.

    2013-01-01

    Objective Disease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment. Design We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20–100%), pain relief (10–100%), major toxicity (0.1–2%), and cost ($1,000–$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization. Results Base case DMOADs added 4.00 quality-adjusted life years (QALYs) and $230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15%. Cost-effectiveness was most sensitive to likelihoods of suspended progression and pain relief. DMOADs costing $3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20% and 70%. At a cost of $5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%. Conclusions Cost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteria. PMID:23380251

  20. The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis

    OpenAIRE

    Pierre Branger; Jean-Jacques Parienti; Maria Pia Sormani; Gilles Defer

    2016-01-01

    Background The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS. Materials and Methods We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase...

  1. Discoidin Domain Receptor 2 as a Potential Therapeutic Target for Development of Disease-Modifying Osteoarthritis Drugs.

    Science.gov (United States)

    Manning, Lauren B; Li, Yefu; Chickmagalur, Nithya S; Li, Xiaolong; Xu, Lin

    2016-11-01

    Osteoarthritis (OA) is the most common form of arthritis disorders, but the identification of therapeutic targets to effectively prevent OA has been increasingly difficult. The goal of this investigation is to provide experimental evidence that discoidin domain receptor 2 (DDR2) may be an ideal target for the development of disease-modifying OA drugs. Ddr2 was conditionally deleted from articular cartilage of adult mouse knee joints. Aggrecan-CreERT2;floxed Ddr2 mice, which were generated by crossing Aggrecan-CreERT2 mice with floxed Ddr2 mice, then received tamoxifen injections at the age of 8 weeks. The mice were then subjected to destabilization of the medial meniscus (DMM) surgery. At 8 and 16 weeks after DMM, mice were euthanized for the collection of knee joints. In a separate experiment, Aggrecan-CreERT2;floxed Ddr2 mice were subjected to DMM at the age of 10 weeks. The mice then received tamoxifen injections at 8 weeks after DMM. The mice were euthanized for the collection of knee joints at 16 weeks after DMM. The progressive process of articular cartilage degeneration was significantly delayed in the knee joints of Ddr2-deficient mice in comparison to their control littermates. Articular cartilage damage in the knee joints of the mice was associated with increased expression profiles of both Ddr2 and matrix metalloproteinase 13. These findings suggest that DDR2 may be an ideal target for the development of disease-modifying OA drugs.

  2. The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers

    NARCIS (Netherlands)

    Kearsley-Fleet, Lianne; Zavada, Jakub; Lund Hetland, Merete; Nordstrom, Dan C.; Aaltonen, Kalle J.; Listing, Joachim; Zink, Angela; Gati, Tamas; Rojkovich, Bernadette; Iannone, Florenzo; Gremese, Elisa; van Riel, Piet L.C.M.; van de Laar, Mart A F J; Lie, Elisabeth; Kvien, Tore K.; Canhao, Helena; Fonseca, Joao E.; Rotar, Ziga; Loza, Estibaliz; Carmona, Loretto; Askling, Johan; Johansson, Kari; Finckh, Axel; Dixon, William G.; Hyrich, Kimme L.

    2015-01-01

    Objective. Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and

  3. Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs.

    Science.gov (United States)

    Roivainen, Anne; Hautaniemi, Sannamari; Möttönen, Timo; Nuutila, Pirjo; Oikonen, Vesa; Parkkola, Riitta; Pricop, Luminita; Ress, Rudyard; Seneca, Nicholas; Seppänen, Marko; Yli-Kerttula, Timo

    2013-02-01

    This study evaluated the potential of functional imaging to monitor disease activity and response to treatment with disease-modifying antirheumatic drugs (DMARD) in DMARD-naive patients with early rheumatoid arthritis (RA). The study involved 17 patients with active RA in whom combination therapy was initiated with methotrexate, sulfasalazine, hydroxychloroquine, and low-dose oral prednisolone. Clinical disease activity was assessed at screening, at baseline and after 2, 4, 8 and 12 weeks of therapy. (18)F-FDG PET/CT of all joints was performed at baseline and after 2 and 4 weeks of therapy. (18)F-FDG maximum standardized uptake values showed a reduction of 22 ± 13 % in 76 % of patients from baseline to week 2 and a reduction of 29 ± 13 % in 81 % of patients from baseline to week 4. The percentage decrease in (18)F-FDG uptake from baseline to week 2 correlated with clinical outcome, as measured by the disease activity score (DAS-28) at week 12. In addition, changes in C-reactive protein levels and erythrocyte sedimentation rate were positively associated with changes shown by PET. (18)F-FDG PET/CT findings after 2 and 4 weeks of triple combination oral DMARD therapy correlated with treatment efficacy and clinical outcome in patients with early RA. (18)F-FDG PET/CT may help predict the therapeutic response to novel drug treatments.

  4. A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The chemical advances of the 20th century led to the synthesis of non steroidal anti-inflammatory drugs (NSAIDs, beginning from phenylbutazone and indomethacin and continuing with other new drugs, including ibuprofen, diclofenac, naproxen, piroxicam and, more recently, the highly selective COX-2 inhibitors (coxibs. This progress derived from the discovery of the mechanism of action of these drugs: the inhibition of synthesis of prostaglandins due to the cycloxigenase enzyme system, according to the experimental contributions of John R. Vane.

  5. Fingolimod: A Disease-Modifier Drug in a Mouse Model of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Potenza, Rosa Luisa; De Simone, Roberta; Armida, Monica; Mazziotti, Valentina; Pèzzola, Antonella; Popoli, Patrizia; Minghetti, Luisa

    2016-10-01

    Fingolimod phosphate (FTY720), the first approved oral therapy for multiple sclerosis, primarily acts as an immunomodulator. Its concomitant effects in the central nervous system, however, indicate a potentially broader spectrum of activity in neurodegenerative diseases. In the present study, we investigated the possible effects of fingolimod in a mouse model of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by a strong neuroinflammatory component. Fingolimod (0.1 and 1 mg/kg i.p.) was administered to mSOD1(G93A) mice, a well-characterized mouse model of ALS, starting from the onset of motor symptoms to the end stage of the disease. The drug was able to improve the neurological phenotype (p < 0.05) and to extend the survival (p < 0.01) of ALS mice. The beneficial effect of fingolimod administration was associated with a significant modulation of neuroinflammatory and protective genes (CD11b, Foxp3, iNOS, Il1β, Il10, Arg1, and Bdnf) in motor cortex and spinal cord of animals. Our data show, for the first time, that fingolimod is protective in ALS mice and that its beneficial effects are accompanied by a modulation of microglial activation and innate immunity. Considering that the treatment was started in already symptomatic mice, our data strongly support fingolimod as a potential new therapeutic approach to ALS.

  6. Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis : A Nominal Group Technique and Best-Worst Scaling

    NARCIS (Netherlands)

    Kremer, Ingrid E. H.; Evers, Silvia M. A. A.; Jongen, Peter J.; van der Weijden, Trudy; van de Kolk, Ilona; Hiligsmann, Mickael

    2016-01-01

    Objectives Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifyin

  7. Medication possession ratio: implications of using fixed and variable observation periods in assessing adherence with disease-modifying drugs in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kozma CM

    2013-06-01

    Full Text Available Chris M Kozma,1 Michael Dickson,2 Amy L Phillips,3 Dennis M Meletiche31CK Consulting Associates, LLC St Helena Island, SC, 2University of South Carolina College of Pharmacy, Columbia, SC, 3EMD Serono Inc, Rockland, MA, USABackground: The purpose of this study was to compare two methods of adherence calculation using administrative data for patients with multiple sclerosis (MS who are prescribed disease-modifying drugs.Methods: Pharmacy-billed disease-modifying drug prescription claims were selected from the 2007–2008 LifeLink™ Health Plan Claims Database. The index date was the first disease-modifying drug prescription claim. Two cohorts were created: all patients with a disease-modifying drug claim in 2007 and a subset with continuous eligibility for 12 months post-index. Adherence was calculated across all disease-modifying drugs for 12 months post-index. Medication possession ratios (MPRs with variable (start to end of therapy and fixed (365 days duration denominators were calculated. Variable MPR was calculated by summing days supply from the first to the last prescription (inclusive divided by time between the last prescription date plus days supply and the first prescription date. Variable MPR was evaluated for all patients and the continuously eligible cohort. Fixed MPR used the same numerator but divided by 365 days of follow-up and evaluated only for the continuously eligible cohort.Results: There were 3405 patients with MS and a disease-modifying drug claim in 2007 and 2145 in the continuously eligible cohort. Means for variable MPR ranged from 87.5% ± 16.6% for the continuously eligible cohort to 90.5% ± 16.0% for the 2007 cohort. The comparable value for fixed MPR was 78.0% ± 28.2% for the continuously eligible cohort. Fixed MPR gave a consistently lower rate of adherence than variable MPR at an 80% adherence threshold.Conclusion: Different adherence measures can yield different outcomes, especially when using different

  8. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients

    DEFF Research Database (Denmark)

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny

    2012-01-01

    OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide.METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab.RESULTS: 1195 patients...... were treated with rituximab plus methotrexate, 177 with rituximab plus leflunomide and 505 with rituximab alone. Significantly more patients achieved a European League Against Rheumatism good response at 6 months when treated with rituximab plus leflunomide (29.1%) compared with rituximab plus...... methotrexate (21.1%) and rituximab alone (19.3%; p=0.02 and p=0.01, respectively). Similar results were observed at 12 months. Adverse events occurred in 10.2%, 13.2% and 13.9% of patients on rituximab plus leflunomide, rituximab plus methotrexate and rituximab alone, respectively.CONCLUSIONS: Leflunomide...

  9. Non-biologic disease-modifying antirheumatic drugs (DMARDs) improve pain in inflammatory arthritis (IA): a systematic literature review of randomized controlled trials.

    Science.gov (United States)

    Steiman, Amanda J; Pope, Janet E; Thiessen-Philbrook, Heather; Li, Lihua; Barnabe, Cheryl; Kalache, Fares; Kung, Tabitha; Bessette, Louis; Flanagan, Cathy; Haraoui, Boulos; Hochman, Jacqueline; Leclercq, Sharon; Mosher, Dianne; Thorne, Carter; Bykerk, Vivian

    2013-05-01

    Evidence supports early use of non-biologic DMARDs to prevent irreversible damage in inflammatory arthritides, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and possibly ankylosing spondylitis (AS). However, there is a paucity of data exploring their effects on pain as a primary outcome in these conditions. This systematic literature review investigated the effect of non-biologic DMARDs on pain levels in IA and examined whether disease duration impacted efficacy. We searched Medline, Embase, Cochrane Central, and Cochrane Database of Systematic Reviews, abstracts from the 2008 to 2010 American College of Rheumatology annual congresses, and citation lists of retrieved publications. Only randomized, double-blind controlled trials were analyzed. Quality was assessed with the Risk of Bias tool. Descriptive statistics were used in meta-analysis. 9,860 articles were identified, with 33 eligible for inclusion: 8 in AS, 6 in PsA, 9 in early RA (ERA), and 10 in established RA. In ERA and established RA, all studies of DMARDs (monotherapy and combination therapies) consistently revealed statistically significant reductions in pain except three oral gold studies. In AS, sulfasalazine studies showed significant pain reduction, whereas use of other DMARDs did not. In PsA, 5 of 6 studies reported VAS-pain improvement. From the studies included, we were unable to assess the influence of disease duration on pain outcomes in these rheumatic conditions. DMARDs improve pain in early and established RA. Sulfasalazine may improve pain in AS and PsA. Further study is needed to assess the relationship between disease duration and DMARD efficacy in reducing pain in these conditions.

  10. Prediction of remission and low disease activity in disease-modifying anti-rheumatic drug-refractory patients with rheumatoid arthritis treated with golimumab

    Science.gov (United States)

    Kutzbach, Abraham Garcia; Amital, Howard; Pavelka, Karel; Lazaro, María Alicia; Moots, Robert J.; Wollenhaupt, Jürgen; Zerbini, Cristiano A. F.; Louw, Ingrid; Combe, Bernard; Beaulieu, Andre; Schulze-Koops, Hendrik; Dasgupta, Bhaskar; Fu, Bo; Huyck, Susan; Weng, Haoling H.; Govoni, Marinella; Durez, Patrick

    2016-01-01

    Objective. To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. Methods. We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ⩾3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR <2.6) at month 6 and LDA (DAS28-ESR ⩽3.2) at month 1. Results. In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648–0.809 (R2 = 0.0397–0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. Conclusion. A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy. PMID:27114562

  11. Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to methotrexate or other traditional disease-modifying anti-rheumatic drugs

    DEFF Research Database (Denmark)

    Singh, Jasvinder A; Hossain, Alomgir; Tanjong Ghogomu, Elizabeth

    2016-01-01

    +MTX/DMARD (Peto OR [can be interpreted as RR due to low event rate] 1.12 (95% CI 0.99 to 1.27); absolute risk 1% (0% to 2%), As well, the NMA estimate for TNF biologic+MTX/DMARD (Peto OR 1.20 (95% Crl 1.01 to 1.43)) showed moderate quality evidence of an increase in the risk of serious adverse events. The other...... quality (downgraded for serious imprecision), results were inconclusive for cancer (Peto OR 1.07 (95% CI 0.68 to 1.68) for all biologic+MTX/DMARD combinations. The NMA estimates of TNF biologic+MTX/DMARD (Peto OR 1.21 (95% Crl 0.63 to 2.38) and non-TNF biologic+MTX/DMARD (Peto OR 0.99 (95% Crl 0.58 to 1...

  12. 门诊抗风湿药的使用及处方分析%Review of antirheumatic drugs in outpatient prescription in Luoyang Orthopedic Hospital

    Institute of Scientific and Technical Information of China (English)

    秦娜

    2009-01-01

    目的 了解本院门诊抗风湿药物的使用情况,为临床合理、有效应用抗风湿药提供参考.方法 采用WHO推荐的限定日剂量(DDD)、药物利用指数(DUI)等方法,对本院2007年11月处方6872张中的抗风湿药物处方1236张进行分析.结果 抗风湿药物以二联和三联及以上用药为主,其中二联378张(30.58%).三联及以上752张(60.84%).使用频率最高的药物种类是非甾体抗炎药(52.41%).使用频率居前三位的药物是奈丁美酮、氨基葡萄糖、柳氮磺吡啶,大部分药物的DUI值≤1,只有双氯芬酸钾、白芍总苷略大于1.结论 本院抗风湿药物使用情况摹本趋于合理,以非甾体类抗炎药、氨基葡萄糖和改变病情抗风湿药为主,部分不合理用药情况应引起临床医师关注.%Objective To analyze the usage of antirheumatic drugs in outpatient prescription in our hospital and provide references for rational use of antirheumatic drugs in the clinic. Methods The age and disease of the patients were analyzed, and the frequency of usage and the rationality of antirheumatic drugs in November 2007 were analyzed according to the DDDs order and DUI. Results Of the total prescription reviewed, combination of two,three and more drugs were up to 91.42%. The use of nabumetone, Glucosamine sulfate and sulfasalazine were most frequently used. The DUIs of most drugs were less than 1 except Diclofenac kalium and total glucosides of paeony.Conclusion Overall, the usage of the antirheumatic drugs is reasonable at Luoyang Orthopedic hospital.

  13. Gold Finger: Metal Jewellery as a Disease Modifying Antirheumatic Therapy!

    Directory of Open Access Journals (Sweden)

    T. Hlaing

    2009-01-01

    Full Text Available Polyarticular psoriatic arthritis is a chronic, progressive and disabling auto-immune disease often affecting the small joints of the hands in a symmetrical fashion. The disease can progress rapidly causing joint swelling and damaging cartilage and bone around the joints resulting in severe deformities. We report a very unusual case of a 49-year-old woman who presented with polyarticular psoriatic arthritis affecting all proximal interphalangeal (PIP joints of both hands except the left ring finger PIP joint. On clinical examination there was no evidence of arthritis in the left ring finger PIP joint. We confirmed the paucity of joint damage in the PIP joint of the left ring finger using more modern imaging modalities such as musculoskeletal ultrasound and MRI scan of the small joints of the hands. All other PIP joints in both hands demonstrated advanced degrees of joint damage secondary to chronic psoriatic inflammatory arthritis. We postulated that wearing a gold wedding ring has helped protecting the PIP joint of the left ring finger from the damaging effect of inflammatory arthritis. The possible mechanisms by which metal jewellery (gold ring confer protection to adjacent joints was discussed.

  14. Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon beta treatment.

    Science.gov (United States)

    Trojano, M; Pellegrini, F; Paolicelli, D; Fuiani, A; Zimatore, G B; Tortorella, C; Simone, I L; Patti, F; Ghezzi, A; Portaccio, E; Rossi, P; Pozzilli, C; Salemi, G; Lugaresi, A; Bergamaschi, R; Millefiorini, E; Clerico, M; Lus, G; Vianello, M; Avolio, C; Cavalla, P; Iaffaldano, P; Direnzo, V; D'Onghia, M; Lepore, V; Livrea, P; Comi, G; Amato, M P

    2009-11-15

    There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs. To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFNbeta) treatment response in a cohort of relapsing (RR) MS patients. A cohort of 2570 IFNbeta-treated RRMS was prospectively followed for up to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by 1 point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique. The multivariate Cox Regression analyses showed that male patients had a significant (p=0.0097) lower risk for 1st relapse and a trend (p=0.0897) for a higher risk to reach 1 point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR=0.86; 95% CI=0.76-0.98; p=0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for 1 point EDSS progression (HR=1.33; 95% CI: 1.00-1.76; panalysis seem to suggest that male patients do not respond to IFNbeta treatment in the same way of females.

  15. The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Pierre Branger

    Full Text Available The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL or second-line (SL disease-modifying drugs (DMDs and brain volume changes over time in RRMS.We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed.Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57--0.15; P = 0.02. Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046 but not between FLDMDs (-0.33%/y and placebo (P = 0.11 or between FLDMDs and SLDMDs (P = 0.49. Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001 and FLDMDs (-0.46%/y, P<0.005, but no difference was detected between FLDMDs and placebo (P = 0.12.SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS.

  16. O uso de drogas anti-reumáticas na gravidez Use of anti-rheumatic drugs during pregnancy

    Directory of Open Access Journals (Sweden)

    Roger A. Levy

    2005-06-01

    sendo estudada na prevenção do bloqueio cardíaco total da síndrome do lúpus neonatal. O uso de prednisona e prednisolona é limitado a menor dose eficaz, não atinge a circulação fetal, mas pode induzir os efeitos colaterais maternos já conhecidos. Azatioprina e ciclosporina são utilizadas, quando indicadas formalmente, sem aparente risco fetal. Metotrexato e leflunomide devem ser evitados a qualquer custo e o tratamento interrompido três meses antes da tentativa de concepção. Todas as decisões terapêuticas em pacientes grávidas devem ser individualizadas e os riscos e benefícios considerados.The prescription of anti-rheumatic drugs in fertile patients should take into account the current knowledge about their effects on conception, pregnancy and lactation. Judicious advice and pregnancy planning is ideal when possible. With the incorporation of new substances and the constant appearance of recent data in the literature this subject has to be continuously updated. The FDA risk factor rating is sometimes contradictory to our practice, in part because results from animal studies may not be directly applicable to humans. Biologic response modifiers seem to be safely used during pregnancy, since they are large molecules that are not capable of crossing the placenta. Non-steroidal anti-inflammatory drugs including specific COX-2 inhibitors may impair implantation of the ovum but can be used once pregnancy is under way, they should be avoided after 32 weeks, when there is a relationship with fetal complications. COX-2 inhibitors must be avoided due to its risk of renal mal-formation. Low-dose aspirin can be used safely during pregnancy. Low molecular weight heparins are preferred, since the unfractionated heparins have an increased risk of inducing thrombocytopenia and bleeding. Hydroxychloroquine is used and in fact recommended in lupus pregnancy with patients' benefits and no fetal risk. Warfarin is teratogenic if given between the 6th and 9th gestational

  17. [Side-effects of the treatment with disease modifying drugs in patients with multiple sclerosis: an analysis of register data in the Yaroslavl region].

    Science.gov (United States)

    Spirin, N N; Kasatkin, D S; Stepanov, I O; Shipova, E G; Baranova, N S

    2012-01-01

    Authors have followed up 230 patients with multiple sclerosis treated with disease modifying drugs (DMD) using the data of the Multiple sclerosis register of the Yaroslavl oblast during 2009-2011. Original drugs and their generics registered in Russia are used. Patients received interferon-beta 1a for intramuscular introduction (avonex - 3.0%), interferon-beta 1a for hypodermic injection (rebif - 19.2%, genfakson - 8.5%), interferon-beta 1b (betaferon - 16.5%, extavia - 18.2%, ronbetal - 18.0%), glatimer acetate (copaxone - 16.7%). Adverse effects were recorded and subjective tolerability of the drug by the patient was assessed. Statistically significant differences in the safety profile between some bioanalogues and original DMD were identified. This finding suggests that effects of different DMD should be studied in depth in clinical and post marketing trials.

  18. Management of Psoriatic Arthritis: Traditional Disease-Modifying Rheumatic Agents and Targeted Small Molecules.

    Science.gov (United States)

    Soriano, Enrique R

    2015-11-01

    Traditional disease-modifying antirheumatic drugs (DMARD) remain the first-line treatment of psoriatic arthritis (PsA), despite lack of randomized controlled trials, and with evidence based on observational studies. Anti-tumor necrosis factor agents remain a top choice for biologic treatment, complemented with new biologics with different targets (IL12-23 and IL17). Unmet needs have been identified for patients who do not respond to treatment. Among targeted small molecules Apremilast is approved for the treatment of PsA and Tofactitinib is under investigation. The drugs discussed herein have the potential to address unmet needs; however, additional research is required to identify more effective therapies for PsA.

  19. Identification of patients at risk of non-adherence to oral antirheumatic drugs in rheumatoid arthritis using the Compliance Questionnaire in Rheumatology: an ARCO sub-study.

    Science.gov (United States)

    Marras, Carlos; Monteagudo, Indalecio; Salvador, Georgina; de Toro, Francisco J; Escudero, Alejandro; Alegre-Sancho, Juan J; Raya, Enrique; Ortiz, Ana; Carmona, Loreto; Mestre, Yvonne; Cea-Calvo, Luis; Calvo-Alén, Jaime

    2017-07-01

    The ARCO study (Study on Adherence of Rheumatoid Arthritis patients to SubCutaneous and Oral Drugs), a multicenter, non-interventional retrospective study, was primarily designed to assess the percentage of patients [aged ≥18 years with an established rheumatoid arthritis (RA) diagnosis] with non-adherence to prescribed subcutaneous biologicals. This paper reports data for the secondary objective from a subset of patients, namely to evaluate non-adherence to prescribed oral antirheumatic drugs in RA patients in Spain using the validated Compliance Questionnaire Rheumatology (CQR). Patients also completed the Morisky-Green Medication Adherence Questionnaire, Beliefs about Medicines Questionnaire, and a questionnaire (developed and validated in Spain) on patient satisfaction with RA treatment and preferences. A total of 271 patients (76.7% females; mean age 55.6 years) were being treated with oral drugs for RA, of which 234 completed the CQR questionnaire. Non-adherence was reported in 49/234 (20.9%) patients. The proportion of non-adherence in younger patients (aged ≤48 years; 37.5%) was double that recorded in patients aged >48 years (p = 0.006). Patients with a perception of lower efficacy also had a higher risk of non-adherence (p = 0.012). Multivariable analysis showed that younger age and male gender were independently associated with risk of non-adherence. There was only slight agreement between the CQR and Morisky-Green assessment tools (kappa coefficient = 0.186), possibly reflecting the fact that both questionnaires measure slightly different aspects of medication adherence. In conclusion, one out of five RA patients was identified as at risk for non-adherence with the CQR, and this was more frequent in younger patients and in males.

  20. An evaluation of adherence in patients with multiple sclerosis newly initiating treatment with a self-injectable or an oral disease-modifying drug

    Directory of Open Access Journals (Sweden)

    Munsell M

    2016-12-01

    Full Text Available Michael Munsell,1 Molly Frean,1 Joseph Menzin,1 Amy L Phillips2 1Boston Health Economics, Inc., Waltham, MA, USA; 2Health Economics & Outcomes Research, EMD Serono Inc., Rockland, MA, USA Objective: As the multiple sclerosis (MS disease-modifying drug (DMD treatment options have expanded to include oral therapies, it is important to understand whether route of administration is associated with DMD adherence. The objective of this study was to compare adherence to DMDs in patients with MS newly initiating treatment with a self-injectable versus an oral DMD. Methods: This retrospective database study used IMS Health Real World Data Adjudicated Claims – US data between July 1, 2010 and June 30, 2014. Adherence was measured by medication possession ratio (MPR, calculated as the total number of treated days divided by the total number of days from the first treated day until the end of 12-month follow-up. A binary measure representing adherence (MPR ≥0.8 versus nonadherence (MPR <0.8 to therapy was used. Logistic regression evaluated the likelihood of adherence to index DMD type (self-injectable vs oral. Covariates included patient baseline characteristics (ie, age, sex, comorbidities and index DMD type. Results: The analysis included 7,207 self-injectable and 1,175 oral DMD-treated patients with MS. In unadjusted analyses, the proportion of patients adherent to therapy (MPR ≥0.8 did not differ significantly between the self-injectable (54.1% and the oral DMD cohorts (53.0%; P=0.5075. After controlling for covariates, index DMD type was not a significant predictor of adherence (odds ratio [OR] 1.062; 95% confidence interval [CI]: 0.937–1.202; P=0.3473. Higher likelihood of adherence was associated with male sex (OR 1.20; 95% CI: 1.085–1.335; P=0.0005 and age groups older than 18–34 years (ORs 1.220–1.331; P<0.01. Depression was associated with a lower likelihood of adherence (OR 0.618; 95% CI: 0.511–0.747; P<0.0001. Conclusion: Male

  1. Disease-Modifying Drugs Reduce Cortical Lesion Accumulation and Atrophy Progression in Relapsing-Remitting Multiple Sclerosis: Results from a 48-Month Extension Study

    Directory of Open Access Journals (Sweden)

    Francesca Rinaldi

    2015-01-01

    Full Text Available Cortical lesions (CLs and atrophy are pivotal in multiple sclerosis (MS pathology. This study determined the effect of disease modifying drugs (DMDs on CL development and cortical atrophy progression in patients with relapsing-remitting MS (RRMS over 48 months. Patients (n=165 were randomized to sc IFN β-1a 44 μg, im IFN β-1a 30 μg, or glatiramer acetate 20 mg. The reference population comprised 50 DMD-untreated patients with RRMS. After 24 months, 43 of the untreated patients switched to DMDs. The four groups of patients were followed up for an additional 24 months. At 48 months the mean standard deviation number of new CLs was significantly lower in patients treated with sc IFN β-1a (1.4 ± 1.0, range 0–5 compared with im IFN β-1a (2.3 ± 1.3, range 0–6, P=0.004 and glatiramer acetate (2.2 ± 1.5, range 0–7, P=0.03. Significant reductions in CL accumulation and new white matter and gadolinium-enhancing lesions were also observed in the 43 patients who switched to DMDs after 24 months, compared with the 24 months of no treatment. Concluding, this study confirms that DMDs significantly reduce CL development and cortical atrophy progression compared with no treatment.

  2. 慢作用抗风湿药对类风湿关节炎患者血脂的影响%Effect of slow-acting antirheumatic drugs on lipid profile in patients with rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    徐华; 陈颖娟

    2009-01-01

    目的 探讨类风湿关节炎患者抗风湿治疗对血脂及疾病活动相关指标的影响. 方法 选择在我院治疗的符合1987年美国风湿病学会诊断标准的类风湿关节炎患者82例,联合应用慢作用药甲氨蝶呤、柳氮磺胺吡啶、硫酸羟氯喹治疗,以健康体检者79例作为对照.分别测定健康对照组、类风湿关节炎组治疗前及治疗后12个月的疾病活动分数(DAS28)、血沉、C-反应蛋白、血脂.结果类风湿关节炎患者血胆崮醇、低密度脂蛋白胆固醇、三酰甘油治疗前较对照组高(均P<0.01);高密度脂蛋白治疗前较对照组低(P<0.01);治疗12个月后,类风湿关节炎患者疾病活动分数、血沉、C-反应蛋白与治疗前比较明显降低[(6.7±0.6)与(2.1±0.9)、(62±18)mm/h与(13±9)mm/h、(2.2±0.3)mg/L与(0.3±0.2)mg/L,均P<0.01];血高密度脂蛋白与治疗前比较明显增高,分别为(1.0±0.1)mmol/L与(1.5±0.3)mmol/L(P<0.01). 结论 病情活动的类风湿关节炎患者血脂水平异常,控制炎症过程的药物,使疾病活动分数、血沉或C-反应蛋白下降的同时,导致血清高密度脂蛋白的水平升高,可能使类风湿关节炎患者动脉粥样硬化及心血管事件的风险降低.%Objective To investigate the effect of slow-acting antirheumatic drugs on lipid profile and disease activity index in patients with rheumatoid arthritis (RA). Methods Eighty-two patients with RA who met the American College of Rheumatology (ACR) criteria were treated with disease-modifying antirheumatic drugs including methopterin (MTX), salazosulfapyridine (SASP) and hydroxychloroquine sulfate, while seventy-nine healthy volunteers were used for control. All persons were followed up for 12 months. The observations included 28 joint indices score (DAS-28), lipid profile, c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results Compared with the control group before treatment, RA patients exhibited higher serum levels

  3. 2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

    Science.gov (United States)

    Goodman, Susan M; Springer, Bryan; Guyatt, Gordon; Abdel, Matthew P; Dasa, Vinod; George, Michael; Gewurz-Singer, Ora; Giles, Jon T; Johnson, Beverly; Lee, Steve; Mandl, Lisa A; Mont, Michael A; Sculco, Peter; Sporer, Scott; Stryker, Louis; Turgunbaev, Marat; Brause, Barry; Chen, Antonia F; Gililland, Jeremy; Goodman, Mark; Hurley-Rosenblatt, Arlene; Kirou, Kyriakos; Losina, Elena; MacKenzie, Ronald; Michaud, Kaleb; Mikuls, Ted; Russell, Linda; Sah, Alexander; Miller, Amy S; Singh, Jasvinder A; Yates, Adolph

    2017-08-01

    This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence-based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi-step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease-modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional

  4. Searching for disease modifiers-PKC activation and HDAC inhibition - a dual drug approach to Alzheimer's disease that decreases Abeta production while blocking oxidative stress.

    Science.gov (United States)

    Kozikowski, Alan P; Chen, Yihua; Subhasish, Tapadar; Lewin, Nancy E; Blumberg, Peter M; Zhong, Zhenyu; D'Annibale, Melissa A; Wang, Weng-Long; Shen, Yong; Langley, Brett

    2009-07-01

    amyloid processing while showing neuroprotection. These findings may offer a new approach to therapies that exhibit disease-modifying effects, as opposed to symptomatic relief, in the treatment of AD.

  5. Disease-modifying agents in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Coyle P

    2009-01-01

    Full Text Available Since 1993, six disease-modifying therapies for multiple sclerosis (MS have been proven to be of benefit in rigorous phase III clinical trials. Other agents are also available and are used to treat MS, but definitive data on their efficacy is lacking. Currently, disease-modifying therapy is used for relapsing forms of MS. This includes clinically isolated syndrome/first-attack high-risk patients, relapsing patients, secondary progressive patients who are still experiencing relapses, and progressive relapsing patients. The choice of agent depends upon drug factors (including affordability, availability, convenience, efficacy, and side effects, disease factors (including clinical and neuroimaging prognostic indicators, and patient factors (including comorbidities, lifestyle, and personal preference. This review will discuss the disease-modifying agents used currently in MS, as well as available alternative agents.

  6. An evaluation of adherence in patients with multiple sclerosis newly initiating treatment with a self-injectable or an oral disease-modifying drug

    Science.gov (United States)

    Munsell, Michael; Frean, Molly; Menzin, Joseph; Phillips, Amy L

    2017-01-01

    Objective As the multiple sclerosis (MS) disease-modifying drug (DMD) treatment options have expanded to include oral therapies, it is important to understand whether route of administration is associated with DMD adherence. The objective of this study was to compare adherence to DMDs in patients with MS newly initiating treatment with a self-injectable versus an oral DMD. Methods This retrospective database study used IMS Health Real World Data Adjudicated Claims – US data between July 1, 2010 and June 30, 2014. Adherence was measured by medication possession ratio (MPR), calculated as the total number of treated days divided by the total number of days from the first treated day until the end of 12-month follow-up. A binary measure representing adherence (MPR ≥0.8) versus nonadherence (MPR <0.8) to therapy was used. Logistic regression evaluated the likelihood of adherence to index DMD type (self-injectable vs oral). Covariates included patient baseline characteristics (ie, age, sex, comorbidities) and index DMD type. Results The analysis included 7,207 self-injectable and 1,175 oral DMD-treated patients with MS. In unadjusted analyses, the proportion of patients adherent to therapy (MPR ≥0.8) did not differ significantly between the self-injectable (54.1%) and the oral DMD cohorts (53.0%; P=0.5075). After controlling for covariates, index DMD type was not a significant predictor of adherence (odds ratio [OR] 1.062; 95% confidence interval [CI]: 0.937–1.202; P=0.3473). Higher likelihood of adherence was associated with male sex (OR 1.20; 95% CI: 1.085–1.335; P=0.0005) and age groups older than 18–34 years (ORs 1.220–1.331; P<0.01). Depression was associated with a lower likelihood of adherence (OR 0.618; 95% CI: 0.511–0.747; P<0.0001). Conclusion Male sex and age older than 18–34 years were significantly associated with a higher likelihood of adherence, while depression was associated with a lower likelihood of adherence. Index DMD type

  7. [Hematotoxic lesions caused by non-steroidal antirheumatic agents].

    Science.gov (United States)

    Stobbe, H; Hüge, W

    1980-12-01

    Among the lesions of haematopoiesis conditioned by medicaments the lesions by non-steroidal antirheumatic drugs occupy the first place. They get their significance by the fact that they are not so infrequently irreparable and thus show an unfavourable prognosis. On principle in pathogenetic respect lesions by immunologic reactions which vastly do not depend on the dosage, are to be demarcated from the toxically conditioned side-effects which depend on dosage. Conditioned by drugs aplastic syndromes of the bone marrow are not in every case strongly depending on dosage. For this is to be assumed an individual, particular sensitivity of the haematopoietic stem cells (stem cell defect). Of the anti-rheumatic drugs used for the basic therapy chloroquine derivations, gold, D-penicillamine, immunosuppressives and levamisol may effect disturbances of the haematopoiesis, for which facts are examples are given. This concerns also the symptomatically acting antirheumatic drugs. An overestimation of rare side-effects of drugs should not block the application of certain medicaments, however, they should be given only in such a high dosage as it is necessary. In combinations of antirheumatic drugs every individual drug is considered as causative factor. Interactions are particularly be taken into consideration. Control programmes, particularly with certain laboratory parameters, give the early recognition of side-effects and render possible to avoid severe effects.

  8. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients: results of a 1-year follow-up study from the CERERRA collaboration.

    NARCIS (Netherlands)

    Chatzidionysiou, K.; Lie, E.; Nasonov, E.; Lukina, G.; Hetland, M.L.; Tarp, U.; Riel, P.L.C.M. van; Nordstrom, D.C.; Gomez-Reino, J.; Pavelka, K.; Tomsic, M.; Kvien, T.K.; Vollenhoven, R.F. van; Gabay, C.

    2012-01-01

    OBJECTIVES: To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide. METHODS: 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab. RESULTS: 1195 patient

  9. Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide in rituximab-treated rheumatoid arthritis patients : results of a 1-year follow-up study from the CERERRA collaboration

    NARCIS (Netherlands)

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny; Lukina, Galina; Hetland, Merete Lund; Tarp, Ulrik; van Riel, Piet L. C. M.; Nordstrom, Dan C.; Gomez-Reino, Juan; Pavelka, Karel; Tomsic, Matija; Kvien, Tore K.; van Vollenhoven, Ronald F.; Gabay, Cem

    2012-01-01

    Objectives To compare the effectiveness and safety of rituximab alone or in combination with either methotrexate or leflunomide. Methods 10 European registries submitted anonymised datasets with baseline, 3, 6, 9 and 12-month clinical data from patients who started rituximab. Results 1195 patients w

  10. Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who are steroid- and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls

    DEFF Research Database (Denmark)

    Laurberg, Trine Bay; Frystyk, Jan; Ellingsen, Torkell;

    2009-01-01

    OBJECTIVE: Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1) that pla......OBJECTIVE: Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1...

  11. 改变病情抗风湿药治疗银屑病关节炎的回顾性临床研究%Treatment of psoriatic arthritis with disease modifying antirheumatic drugs:a retrospective clinical study

    Institute of Scientific and Technical Information of China (English)

    张改连; 黄烽

    2008-01-01

    目的 分析改变病情抗风湿药(DMARDs)治疗银屑病关节炎(PsA)的用药状况、疗效及安全性.方法 对114例住院PsA患者使用DMARDs的情况进行总结,并分析其中66例随访资料完整者的疗效和安全性.结果 109例(95.6%)使用DMARDs,61例(53.5%)使用非甾体抗炎药(NSAIDs)、33例(28.9%)使用糖皮质激素,7例(6.1%)使用植物药,3例(2.6%)使用生物制剂.94例(82.5%)患者使用甲氨蝶呤(MTX),其次为柳氮磺吡啶(SSZ)64例(56.1%)、来氟米特(LEF)Z7例(23.7%);治疗方案包括联合用药82例(75.2%),单一用药27例(24.8%).随访的66例患者中,对皮肤和关节同时有效者24例(36.4%),其中13例复发.常用治疗方案中,MTX联合LEF和,或SSZ的疗效显著优于LEF,不良反应没有增加.结论 DMARDs是治疗PsA的最常用药,其中MTX使用最多,治疗方案以联合用药为主,但总体疗效并不高.PsA的治疗应选择MTX、LEF和/或SSZ的联合方案.

  12. A comparative study of renal dysfunction in patients with inflammatory arthropathies: strong association with cardiovascular diseases and not with anti-rheumatic therapies, inflammatory markers or duration of arthritis.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    AIMS: The aim of this study was to investigate the prevalence of chronic kidney disease (CKD) among comparable patients with rheumatoid arthritis (RA) and seronegative inflammatory arthritis, and to explore any predictive factors for renal impairment. METHODS: Consecutive patients with peripheral joint disease (oligo and polyarthritis) were recruited from our inflammatory arthritis clinics. We divided patients in two groups: RA group and seronegative inflammatory arthritis group. The cohort consisted of 183 patients (RA = 107, seronegative arthritis = 76 [psoriatic arthritis = 69, undifferentiated oligoarthritis = 7]). Estimated glomerular filtration rate (eGFR) was calculated using the established Modification of Diet in Renal Disease equation. Demographic details, disease-specific characteristics, anti-rheumatic drugs and the presence of cardiovascular diseases were recorded. RESULTS: In total, 17.48% (n = 32) of the cohort had CKD. There was no statistically significant variation between the two groups as regards baseline demographics, disease characteristics, use of anti-rheumatic drugs and the presence of individual cardiovascular diseases. We found that eGFR and the presence of CKD were similar among these groups. Among patients with CKD, 72% had undiagnosed CKD. No association of statistical significance was noted between CKD and the use of corticosteroids, disease-modifying antirheumatic drugs and anti-tumor necrosis factor agents. The association of cardiovascular diseases with CKD remained significant after adjusting for confounders (age, gender, duration of arthritis, high C-reactive protein, use of anti-rheumatic drugs). CONCLUSIONS: Patients with inflammatory arthritis are more prone to have CKD. This could have serious implications, as the majority of rheumatology patients use non-steroidal anti-inflammatory drugs and different immunosuppressives, such as methotrexate. No association of kidney dysfunction was noted with inflammatory disease

  13. Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Goldberg, Lawrence D D; Edwards, Natalie C; Fincher, Contessa; Doan, Quan V; Al-Sabbagh, Ahmad; Meletiche, Dennis M

    2009-09-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered

  14. Adalimumab-induced lichenoid drug eruption.

    Science.gov (United States)

    El Habr, Constantin; Meguerian, Zarouwi; Sammour, Rita

    2014-01-01

    Tumor necrosis factor (TNF)-α inhibitors are being widely and increasingly used for the management of a spectrum of rheumatologic diseases that are refractory to conventional disease modifying anti-rheumatic drugs. Various cutaneous side effects have been reported after treatment with TNF-α inhibitors. We present a case report of a 26-year-old male patient who developed a lichenoid drug eruption few months after the initiation of adalimumab for the management of Crohn's disease. We also highlight the clinical and histopathologic differences between lichenoid drug eruptions and idiopathic lichen planus.

  15. Non-healing tongue ulcer in a rheumatoid arthritis patient medicated with leflunomide. An adverse drug event?

    OpenAIRE

    Eleni-Marina KALOGIROU; Katsoulas, Nikolaos; Tosios, Konstantinos I.; Lazaris, Andreas C; Alexandra SKLAVOUNOU

    2017-01-01

    Leflunomide is a member of the disease modifying anti-rheumatic drugs group used as a treatment modality in active rheumatoid and psoriatic arthritis. “Oral ulcers” are reported in 3-5% of leflunomide medicated rheumatoid arthritis patients with adverse events, but they are not described in detail in the literature. We present a case of an ulcer in the tongue of a rheumatoid arthritis patient managed with leflunomide and contemplate on its pathogenesis. Key words:Leflunomide, oral ulcer, DHOD...

  16. Non-healing tongue ulcer in a rheumatoid arthritis patient medicated with leflunomide. An adverse drug event?

    Science.gov (United States)

    Kalogirou, Eleni-Marina; Katsoulas, Nikolaos; Tosios, Konstantinos I; Lazaris, Andreas C; Sklavounou, Alexandra

    2017-02-01

    Leflunomide is a member of the disease modifying anti-rheumatic drugs group used as a treatment modality in active rheumatoid and psoriatic arthritis. "Oral ulcers" are reported in 3-5% of leflunomide medicated rheumatoid arthritis patients with adverse events, but they are not described in detail in the literature. We present a case of an ulcer in the tongue of a rheumatoid arthritis patient managed with leflunomide and contemplate on its pathogenesis. Key words:Leflunomide, oral ulcer, DHODH.

  17. The cross-reactivity of binding antibodies with different interferon beta formulations used as disease-modifying drugs in multiple sclerosis patients.

    Science.gov (United States)

    Wencel-Warot, Agnieszka; Michalak, Slawomir; Warot, Marcin; Kalinowska-Lyszczarz, Alicja; Kazmierski, Radoslaw

    2016-11-01

    Interferon beta (IFNb) preparations are commonly used as first-line therapy in relapsing-remitting multiple sclerosis (RRMS). They are, however, characterized by limited efficacy, partly due to the formation of anti-IFNb antibodies in patients.In this pilot study, we assessed with the ELISA method the presence of the binding antibodies (BAbs) against interferon beta after 2 years of therapy with subcutaneous interferon beta 1a (Rebif) in 49 RRMS patients. Antibody levels were established again within 1 year after treatment withdrawal. We used 3 interferons that are commercially available for MS therapy, namely Avonex (Biogen Idec Limited), Rebif (Merck Serono), and Betaferon (Bayer Pharma AG), as antigens.BAbs reacting with Rebif were found in 24.4% to 55% of patients, depending on the units of their expression. The levels of anti-Rebif antibodies remained high in 8 patients and in 4 patients they dropped significantly. Strong correlations were obtained in all assays (anti-Rebif-anti-Avonex, anti-Rebif-anti-Betaferon, and anti-Betaferon-anti-Avonex) and the existence of cross-reactivity in the formation of antibodies against all the tested formulations of interferon beta was confirmed. The levels of BAbs remain significant in the clinical context, and their assessment is the first choice screening; however, methods of BAbs evaluation can be crucial for further decisions. More studies are needed to confirm our results; specifically it would be of interest to evaluate methods of neutralizing antibodies identification, as we only assessed the binding antibodies. Nevertheless, our results support the concept that in interferon nonresponders, that are positive for binding antibodies, switching the therapy to alternative disease-modifying agent (for example glatiramer acetate, fingolimod, or natalizumab) is justified, whereas the switch to another interferon formulation will probably be of no benefit.

  18. Changes in first-line injectable disease-modifying therapy for multiple sclerosis: predictors of non-adherence, switching, discontinuation, and interruption of drugs.

    Science.gov (United States)

    Degli Esposti, Luca; Piccinni, Carlo; Sangiorgi, Diego; Perrone, Valentina; Aledda, Lucia; Marrosu, Maria Giovanna; Lombardo, Fabio

    2017-01-11

    This study was aimed to describe changes of Disease-Modifying Treatments (DMT) in an Italian cohort of patients with multiple sclerosis (MS) and to identify predictors of therapeutic modifications. Patients with MS and treated with the first-line injectable DMT (interferons-IFNs or glatiramer) between 1/7/2009 and 31/10/2012 were selected from administrative databases of the MS Center of Cagliari (Sardinia, Italy). Socio-demographic, therapeutic, and clinical information was collected in the 6 months preceding the index date. All patients were followed for 36 months to evaluate therapeutic changes in terms of non-adherence, switch, temporary discontinuation, and permanent interruption. Predictors of changes were estimated by multivariable regression models. Data on 1698 patients were collected: glatiramer was prescribed in 27% of cases, IFNβ-1b in 22%, IFNβ-1a-im in 20%, IFNβ-1a-sc-44mcg in 19%, and IFNβ-1a-sc-22mcg in 12%. Non-adherence was observed in 25% of cases, therapeutic switch in 30%, discontinuation in 37%, and permanent interruption in 28%. The risk of non-adherence was higher for IFNβ-1b, compared with IFNβ-1a-im (adjOR = 1.73). Therapeutic switch occurred especially in patients recently diagnosed (each year from diagnosis causes a decrease of this risk adjHR = 0.97); the risk of discontinuation was higher with EDSS = 4-6 and 7-9 (adjHR = 1.52 and 4.42, respectively). The risk of permanent interruption increased with the augmentation of disability (adjHR = 1.67 and 5.43 for EDSS 4-6 and 7-9). This study mirrored a detailed framework of DMT prescription and identified factors related to changes in the MS therapy. These findings could support healthcare providers in the evaluation and maximization of benefits associated with a long-term DMT.

  19. Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy.

    Science.gov (United States)

    Löscher, Wolfgang

    2002-06-01

    chronic models should be used relatively early in drug development to minimize false positives. Interestingly, the pharmacology of elicited kindled seizures in fully kindled rats and spontaneous recurrent seizures in post-status models is remarkably similar. However, when these models are used for studying the antiepileptogenic effects of drugs, marked differences between models exist, indicating that the processes underlying epileptogenesis differ among models, even among different post-status models of TLE. A problem for clinical validation of TLE models is the lack of an AED, which effectively prevents epilepsy in humans. Thus, at present, it is not possible to judge which chronic model is best suited for developing new strategies in the search for antiepileptogenic and disease-modifying drugs, but rather a battery of models should be used to avoid false negative or positive predictions.

  20. Disease modifying therapies for relapsing multiple sclerosis.

    Science.gov (United States)

    Wingerchuk, Dean M; Weinshenker, Brian G

    2016-08-22

    Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.

  1. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    Science.gov (United States)

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA.

  2. SHOULD DISEASE-MODIFYING THERAPY BE STOPPED IN PATIENTS WITH RHEUMATOID ARTHRITIS BEFORE ENDOPROSTHETIC JOINT REPLACEMENT?

    Directory of Open Access Journals (Sweden)

    N. A. Savenkova

    2011-01-01

    Full Text Available Objective: to analyze disease activity, functional state, quality of life (QL, and the frequency of infectious complications in methotrexate (MT – or leflunomide (LF-treated patients with rheumatoid arthritis (RA who had undergone endoprosthetic replacement of the large joints of the lower limbs. Subjects and methods. One hundred and fourteen patients with RA who had undergone endoprosthetic replacement of the knee and hip joints were divided into 3 groups: 1 36 patients who continuously received MT or LF in the perioperative period; 2 42 patients who dis- continued MT or LF 2 and 4 weeks, respectively, prior to surgery; 3 36 patients who took no disease-modifying anti-rheumatic drugs (DMARDs within 12 months before surgery. Disease activity was estimated by the DAS28 index. QL was determined using the EQ-5D questionnaire and functional capacity was estimated by the HAQ index. Results and discussion. In all the groups, there was a preponderance of patients with moderate RA activity (more than 60%. In Groups 1 and 2, the mean dose of MT was about 10 mg weekly and that of LF was 20 mg daily. The use duration of glucocorticoids (GC and their doses were comparable in all the groups. Twelve months after surgery, DAS28 significantly reduced from 4.22±1.08 to 3.58±1.07 months in Group 1 (p = 0.01; in Group 2, the decrease was insignificant: from 4.17±1.17 to 3.80±1.15 (p > 005; in Group 3, RA activity remained as before. All the groups achieved 50% functional improvement; better results were obtained in the group of patients who continued to use DMARDs in the perioperative period (∆HAQ=-0.67. The difference in the Eq-5D index corresponded to a moderate QL improvement: ∆EQ-5D = 0.28, 0.29, and 0.31 in Groups 1, 2, and 3, respectively (p < 0.05. There were no significant group differences. Deep infection in the endoprosthetic replacement area was detected in 2.8, 2.4, and 8.3% of cases, respectively (p > 005. Conclusion. Continuous use of MT

  3. Acute fulminant drug induced necrotizing pancreatitis in a patient with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Pablo Miramontes

    2015-03-01

    Full Text Available Drug-induced acute necrotizing pancreatitis is a rare adverse event, although it has been reported in association with different drugs, including non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and analgesic agents commonly used in rheumatology. In different reviews of the pancreotoxicity of drugs, infliximab and etanercept are mentioned among all medications implicated in drug-induced pancreatitis, but clinical cases of acute pancreatitis complicating treatment with these anti-TNF-α agents have been exceptionally reported. We describe a patient with ankylosing spondylitis treated with etanercept, who developed an acute fulminant necrotizing pancreatitis that resulted in death. Doctors should pay close attention to patients taking biologic drugs in which a complaint of abdominal pain lasting for several days with no apparent cause may require a prompt referral for medical consultation.

  4. A short history of anti-rheumatic therapy. II. Aspirin

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrün worked, recorded acetyl-salicylic acid under the name “Aspirin”. In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases.

  5. Interactions among Low Dose of Methotrexate and Drugs Used in the Treatment of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Marinella Patanè

    2013-01-01

    Full Text Available Methotrexate (MTX is a nonbiological disease-modifying antirheumatic drug that has shown both a good control of clinical disease and a good safety. Usually drug-drug interactions (DDIs represent the most limiting factor during the clinical management of any disease, in particular when several drugs are coadministered to treat the same disease. In this paper, we report the interactions among MTX and the other drugs commonly used in the management of rheumatoid arthritis. Using Medline, PubMed, Embase, Cochrane libraries, and Reference lists, we searched for the articles published until June 30, 2012, and we reported the most common DDIs between MTX and antirheumatic drugs. In particular, clinically relevant DDIs have been described during the treatment with MTX and NSAIDs, for example, diclofenac, indomethacin, or COX-2 inhibitors, and between MTX and prednisone or immunosuppressant drugs (e.g., leflunomide and cyclosporine. Finally, an increase in the risk of infections has been recorded during the combination treatment with MTX plus antitumor necrosis factor-α agents. In conclusion, during the treatment with MTX, DDIs play an important role in both the development of ADRs and therapeutic failure.

  6. Drugs used in incident systemic lupus erythematosus - results from the Finnish nationwide register 2000-2007.

    Science.gov (United States)

    Elfving, P; Puolakka, K; Kautiainen, H; Virta, L J; Pohjolainen, T; Kaipiainen-Seppänen, O

    2016-05-01

    The objectives of the study were to examine the initial, first-year anti-rheumatic outpatient therapy in patients with incident SLE, as well as the concomitant use of drugs for certain comorbidities, compared to the use in the general population. The Finnish nationwide register data on special reimbursements for medication costs was screened to identify the inception cohort of 566 adult SLE patients (87% females, mean age 46.5 ± 15.9 years) over the years 2000-2007. The patients were linked to the national Drug Purchase Register. Of those, 90% had purchased at least once some disease-modifying anti-rheumatic drugs (DMARDs) during the first year. Hydroxychloroquine was the most common (76%), followed by azathioprine (15%) and methotrexate (13%). With the exception of increase in mycophenolate mofetil, the proportions remained stable over the whole study period 2000-2007. Drugs for cardiovascular diseases, dyslipidemia, diabetes mellitus, hypothyroidism and obstructive pulmonary disease were more frequently purchased than in the sex- and age-adjusted population, with rate ratios ranging from 1.6 to 7.8. Over the years 2000-2007, almost all the patients with incident SLE in Finland started with a DMARD. Higher percentages of SLE patients were on medication for several common chronic diseases than in the population as a whole.

  7. Established and novel disease-modifying treatments in multiple sclerosis.

    Science.gov (United States)

    Cross, A H; Naismith, R T

    2014-04-01

    Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease-modifying therapies introduced in the 1990s, the beta-interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long-term postmarketing efficacy and safety data in a general MS population. Because of this lack of long-term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit-to-risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e

  8. Functional Components from Nature-Derived Drugs for the Treatment of Rheumatoid Arthritis.

    Science.gov (United States)

    Ma, Qin; Jiang, Jian-Guo

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic systemic disorder characterized by persistent synovitis and systemic inflammation. Currently, the widely used drugs for the treatment of RA are disease-modifying antirheumatic drugs, biological agents and glucocorticoids. But their clinical use has been limited because of their adverse effects with a high frequency and high cost of treatment. It is essential to find novel candidate agents. Traditional Chinese medicine (TCM) has been used for RA treatment for a long period of time. In recent years, significant amounts of studies have shown that some TCMs and their active ingredients have obvious therapeutic effects on RA. In this review, the compounds in TCMs that have an effect in clinic or animal experiments of RA are critically reviewed and summarized. Moreover, the relationship between chemical structures of the compound and their activities is analyzed. The relevant researches are described from the aspects of source, methods, result, and related mechanism analysis. The existing studies show that most effective compounds in TCM for RA treatment belong to alkaloids, flavonoids, terpenoids, phenols and quinines. It is hoped that the data summarized in this review will be beneficial to the screening of new nature-derived antirheumatic drugs.

  9. Bioinformatics Analysis for the Antirheumatic Effects of Huang-Lian-Jie-Du-Tang from a Network Perspective

    Directory of Open Access Journals (Sweden)

    Haiyang Fang

    2013-01-01

    Full Text Available Huang-Lian-Jie-Du-Tang (HLJDT is a classic TCM formula to clear “heat” and “poison” that exhibits antirheumatic activity. Here we investigated the therapeutic mechanisms of HLJDT at protein network level using bioinformatics approach. It was found that HLJDT shares 5 target proteins with 3 types of anti-RA drugs, and several pathways in immune system and bone formation are significantly regulated by HLJDT’s components, suggesting the therapeutic effect of HLJDT on RA. By defining an antirheumatic effect score to quantitatively measure the therapeutic effect, we found that the score of each HLJDT’s component is very low, while the whole HLJDT achieves a much higher effect score, suggesting a synergistic effect of HLJDT achieved by its multiple components acting on multiple targets. At last, topological analysis on the RA-associated PPI network was conducted to illustrate key roles of HLJDT’s target proteins on this network. Integrating our findings with TCM theory suggests that HLJDT targets on hub nodes and main pathway in the Hot ZENG network, and thus it could be applied as adjuvant treatment for Hot-ZENG-related RA. This study may facilitate our understanding of antirheumatic effect of HLJDT and it may suggest new approach for the study of TCM pharmacology.

  10. Lung involvement and drug-induced lung disease in patients with rheumatoid arthritis.

    Science.gov (United States)

    Atzeni, Fabiola; Boiardi, Luigi; Sallì, Salvatore; Benucci, Maurizio; Sarzi-Puttini, Piercarlo

    2013-07-01

    Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. Usual interstitial pneumonia and nonspecific interstitial pneumonia seem to be the most frequent patterns in RA patients with ILD, although the proportion of patients with usual interstitial pneumonia is higher than among patients with other systemic rheumatic autoimmune diseases. RA patients with ILD most frequently present with chronic symptoms of cough and dyspnea when climbing stairs or walking uphill. A physical examination may reveal inhalatory crackles and a pulmonary function test demonstrates restrictive physiology, often with reduced diffusing capacity. High-resolution computed tomography is generally sufficient to confirm a diagnosis of ILD, although a minority of cases may require a surgical lung biopsy. Conventional disease-modifying antirheumatic drugs such as methotrexate (MTX) or leflunomide (LEF) and biological agents such as TNF-blocking agents or rituximab may trigger or aggravate ILD in RA patients, and infections may contribute to increased mortality in such patients. LEF should not be used in patients with a history of MTX pneumonitis. The prevalence of interstitial pneumonia among RA patients treated with anti-TNF agents ranges from 0.5 to 3%; however, as the evidence that anti-TNF increases or decreases the risk of ILD is controversial, it is not clear whether this indicates more severe RA requiring biological therapy or the effect of exposure to potentially toxic drugs such as MTX or LEF. The development of treatment-related ILD is a paradoxical adverse event, and patients should be warned about this rare but serious complication of biological or disease-modifying antirheumatic drug therapy.

  11. Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

    NARCIS (Netherlands)

    Visser, Leo H.; Heerings, Marco A.; Jongen, Peter J.; van der Hiele, Karin

    2016-01-01

    Background: The adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study inve

  12. A Case of SAPHO Syndrome with Endodontic Implications and Treatment with Biologic Drugs.

    Science.gov (United States)

    Cotti, Elisabetta; Careddu, Roberto; Schirru, Elia; Marongiu, Silvia; Barca, Maria Pina; Manconi, Paolo Emilio; Mercuro, Giuseppe

    2015-09-01

    SAPHO syndrome (SS) is an autoinflammatory disease characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis. Among the sites affected by the osteoarticular manifestations of SS are the anterior chest wall and the mandible. The etiology of SS is still unknown; theories advocate a genetic predisposition and an infectious cause in association with disorders of the immune system. We report a case of SS in which there was the involvement of the mandible with a lesion of endodontic origin. A 44-year-old white woman diagnosed with SS at the university hospital was referred to the Department of Conservative Dentistry and Endodontics for a consultation. She reported spontaneous pain localized to the periapical area of tooth #19 with a history of multiple restorative and endodontic treatments. It was diagnosed as a previously treated tooth with symptomatic apical periodontitis (AP) at the time of the endodontic evaluation. A second retreatment was then performed in 1 appointment under local anesthesia. During retreatment, a separated instrument and a ledge were found in the mesiobuccal canal, and attempts to bypass it were not successful; the canal was then obturated to the reachable length. Within the same month, the patient was also administered an anti-tumor necrosis factor alpha biologic medication in association with a disease-modifying antirheumatic drugs for the treatment of SS. Within 3 months, the overall therapy had led to a marked improvement of the systemic and mandibular symptoms, and a periapical radiograph showed almost complete healing of the lesion. Medical examinations have shown a total remission of signs and symptoms starting 6 months after the initiation of treatment. After 5 years, the disease is under control, and tooth #19 is symptom free and shows absence of AP. The endodontists need to be aware of the existence of SS and the possible effects of the use of disease-modifying antirheumatic drugs and biologic medications on the

  13. New oral disease-modifying therapies for multiple sclerosis

    OpenAIRE

    2009-01-01

    Several promising, oral disease-modifying therapies for multiple sclerosis are currently being evaluated in clinical trials. The arrival of effective oral agents for multiple sclerosis will be a major advance in the global effort to alter the natural history of this chronic disease.

  14. The risk/benefit profile of biologic drugs in real-world rheumatology practice. From ANTARES to MonitorNet

    Directory of Open Access Journals (Sweden)

    C.M. Montecucco

    2011-09-01

    Full Text Available Le principali artriti croniche ad eziopatogenesi immunoflogistica, nelle quali trovano applicazione i farmaci “biologici” (v. oltre sono la reumatoide e le sieronegative: artrite psoriasica, spondilite anchilosante, artriti reattive ed artriti “enteropatiche” (1-7. L’artrite reumatoide (AR è una malattia cronica progressiva delle articolazioni associata a significativa morbilità, deformità e riduzione della qualità di vita. La prevalenza nella popolazione, a livello mondiale, è compresa tra 0,3 ed 1%. Pur interessando in modo elettivo le articolazioni, l’AR è una malattia sistemica che può condurre a severa disabilità ed a complicanze talora fatali. La terapia farmacologica tradizionale si basa su varie combinazioni di farmaci definiti sintomatici, come gli anti-infiammatori non-steroidei (FANS, gli analgesici ed i corticosteroidi e quelli “di fondo” chiamati correntemente DMARDs (disease modifying anti-rheumatic drugs...

  15. Poorer functionality is related to better quality of life response following the use of biological drugs: 6-month outcomes in a prospective cohort from the Public Health System (Sistema Único de Saúde), Minas Gerais, Brazil.

    Science.gov (United States)

    de Oliveira Junior, Haliton Alves; dos Santos, Jéssica Barreto; Acurcio, Francisco Assis; Almeida, Alessandra Maciel; Kakehasi, Adriana Maria; Alvares, Juliana; de Carvalho, Luis Fernando Duarte; Cherchiglia, Mariangela Leal

    2015-06-01

    We aim to analyze factors associated with the quality of life (QOL) response of individuals with rheumatic diseases treated by the Public Health System (Sistema Único de Saúde) with biological disease-modifying antirheumatic drugs (bDMARDs). Data from 428 patients using bDMARDs were collected using a standardized form at baseline and 6 months after the onset of treatment. The average reduction of the scores on EuroQol-five dimension was 0.11 ± 0.18 6 months after the onset of treatment with bDMARDs, denoting significant improvement of the participants' QOL. All the investigated types of disease exhibited significant improvement at the 6-month assessment, without any difference among them (p = 0.965). The participants with baseline poorest functionality and best QOL exhibited the best QOL outcomes after 6 months of treatment. Our study showed that the use of biological drugs induced considerable improvement in the participants' QOL.

  16. short history of anti-rheumatic therapy. IV. Corticosteroids

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available In 1948 a corticosteroid compound was administered for the first time to a patient affected by rheumatoid arthritis by Philip Showalter Hench, a rheumatologist at the Mayo Clinic in Rochester, Minnesota (USA. He was investigating since 1929 the role of adrenal gland-derived substances in rheumatoid arthritis. For the discovery of cortisone and its applications in anti-rheumatic therapy, Hench, along with Edward Calvin Kendall and Tadeusz Reichstein, won the 1950 Nobel Prize for Medicine. In this review we summarize the main stages that led to the identification of the so-called compound E, which was used by Hench. We also consider the subsequent development of steroid therapy in rheumatic diseases, through the introduction of new molecules with less mineralocorticoid effects, such as prednisone, and more recently, deflazacort.

  17. Disease-modifying therapies in relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Fabricio González-Andrade

    2010-07-01

    Full Text Available Fabricio González-Andrade1, José Luis Alcaraz-Alvarez21Department of Medicine, Metropolitan Hospital, Quito, Ecuador; 2School of Medicine, University of Mayab, Merida, MexicoClinical question: What is the best current disease-modifying therapy for relapsing–remitting multiple sclerosis?Results: The evidence shows that the most effective disease-modifying therapy for delaying short- to medium-term disability progression, prevention of relapses, reducing the area and activity of lesions on magnetic resonance imaging, with the least side effects, is high-dose, high-frequency subcutaneous interferon-β1a 44 μg three times per week.Implementation: The pitfalls in treatment of MS can be avoided by remembering the following points: • The most effective therapy to prevent or delay the appearance of permanent neurological disability with the fewest side effects should be chosen, and treatment should not be delayed.• Adherence to treatment should be monitored closely, and needs comprehensive patient information and education to establish long-term adherence, which is a critical determinant of long-term outcome.• The correct approach to the disease includes disease management, symptom management, and patient management. A combination of tools is necessary to ease the various symptoms, which fall into three broad categories, i.e. rehabilitation, pharmacological, and procedural.• It is important to understand that no treatment modality should be used alone, unless it is in itself sufficient to remedy the particular symptom/problem.Keywords: relapsing–remitting multiple sclerosis, interferon, disease-modifying therapy, relapse prevention

  18. Drug: D01809 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 9.gif Antirheumatic [DS:H00630] Therapeutic category: 4420 ATC code: M01CC02 map07050 Antirheumatics - DMARDs and biological agents... Therapeutic category of drugs in Japan [BR:br08301] 4 Agents affecting cellular function 44 Allergic agents... 442 Stimulation therapy agents 4420 Stimulation therapy agents... Penicillamine and similar agents M01CC02 Bucillamine D01809 Bucillamine (JP16/IN

  19. The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis.

    Science.gov (United States)

    Kretzschmar, Benedikt; Pellkofer, Hannah; Weber, Martin S

    2016-04-01

    Three oral disease-modifying drugs-fingolimod, teriflunomide, and dimethyl fumarate (DMF)-are available for treatment of relapsing forms of multiple sclerosis (MS). All three agents were approved in the last decade, primarily on the basis of a moderate to substantial reduction in the occurrence of MS relapses and central nervous system lesion formation detected by MRI. In the trials leading to approval, the first oral disease-modifying drug, fingolimod, reduced the annualized relapse rate (ARR) from 0.40 in placebo-treated patients to 0.18 (FREEDOMS) and from 0.33 in patients treated with interferon β1a intramuscularly to 0.16 (TRANSFORMS). Teriflunomide, approved on the basis of the two placebo-controlled trials TEMSO and TOWER, demonstrated a reduction in the ARR from 0.54 to 0.37 and from 0.50 to 0.32 respectively. The latest oral MS medication, approved in 2014, is DMF, which had been used in a different formulation for treatment of psoriasis for decades. In the 2-year DEFINE study, the proportion of patients with a relapse was reduced to 27 %, compared with 46 % in placebo arm, whereas in the CONFIRM trial, the ARR was reduced from 0.40 (placebo) to 0.22 in the DMF-treated group of patients. In this review, we will elucidate the mechanisms of action of these three medications and compare their efficacy, safety, and tolerability as a practical guideline for their use. We will further discuss effects other than relapse reduction these small molecules may exert, including potential activities within the central nervous system, and briefly summarize emerging data on new oral MS drugs in clinical development.

  20. Kynurenic acid content in anti-rheumatic herbs.

    Science.gov (United States)

    Zgrajka, Wojciech; Turska, Monika; Rajtar, Grażyna; Majdan, Maria; Parada-Turska, Jolanta

    2013-01-01

    The use of herbal medicines is common among people living in rural areas and increasingly popular in urbanized countries. Kynurenic acid (KYNA) is a metabolite of kynurenine possessing anti-inflammatory, anti-oxidative and pain reliving properties. Previous data indicated that the content of KYNA in the synovial fluid of patients with rheumatoid arthritis is lower than in patients with osteoarthritis. Rheumatoid arthritis is a chronic, systemic inflammatory disorder affecting about 1% of the world's population. The aim of the presented study was to investigate the content of KYNA in 11 herbal preparations used in rheumatic diseases. The following herbs were studied: bean pericarp, birch leaf, dandelion root, elder flower, horsetail herb, nettle leaf, peppermint leaf and willow bark. An anti-rheumatic mixture of the herbs Reumatefix and Reumaflos tea were also investigated. The herbs were prepared according to producers' directions. In addition, the herbal supplement Devil's Claw containing root of Harpagophytum was used. KYNA content was measured using the high-performance liquid chromatography method, and KYNA was detected fluorometrically. KYNA was found in all studied herbal preparations. The highest content of KYNA was found in peppermint, nettle, birch leaf and the horsetail herb. The lowest content of KYNA was found in willow bark, dandelion root and in the extract from the root of Harpagophytum. These findings indicate that the use of herbal preparations containing a high level of KYNA can be considered as a supplementary measure in rheumatoid arthritis therapy, as well as in rheumatic diseases prevention.

  1. Amyloid heart disease: genetics translated into disease-modifying therapy.

    Science.gov (United States)

    Sperry, Brett W; Tang, W H Wilson

    2017-06-01

    Given increased awareness and improved non-invasive diagnostic tools, cardiac amyloidosis has become an increasingly recognised aetiology of increased ventricular wall thickness and heart failure with preserved ejection fraction. Once considered a rare disease with no treatment options, translational research has harnessed novel pathways and led the way to promising treatment options. Gene variants that contribute to amyloid heart disease provide unique opportunities to explore potential disease-modifying therapeutic strategies. Amyloidosis has become the model disease through which gene therapy using small interfering RNAs and antisense oligonucleotides has evolved. © 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.

  2. EFFECT OF «TREAT-TO-TARGET» ANTIRHEUMATIC THERAPY ON DIASTOLIC DYSFUNCTION OF THE LEFT AND RIGHT VENTRICLES IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING 18 MONTHS OF OBSERVATION

    Directory of Open Access Journals (Sweden)

    I. G. Kirillova

    2015-01-01

    Full Text Available Aim. To study the effect of «treat-to-target» antirheumatic therapy on diastolic dysfunction of the left (DDLV and right (DDLV ventricles in patients with early rheumatoid arthritis (RA during 18 months of observation.Material and methods. The study included patients with early RA (n=66; 71% women; age - 56 [46; 61] years with moderate/high activity (DAS28 5.3 [5.0; 6.2], seropositive on rheumatoid factor (77% and/or cyclic citrullinated peptide antibodies (100%, disease modifying anti-rheumatic drugs (DMARD and glucocorticoids naive. Treatment with methotrexate (MTX with the escalation of the dose up to 25-30 mg/week subcutaneously was initiated in all the patients. After 3 months in 47 (71% patients biologics were added to MTX due to its inefficiency. In 18 months remission of RA was achieved in 44% of the patients. 51 (77% patients had a cardioprotective therapy. The target blood pressure (BP level was achieved in 38 (58% patients. Evaluation of traditional cardiovascular risk factors, 24-hour BP monitoring and echocardiography were performed in all patients initially and in 18 months of MTX/MTX + biologics use.Results. After 18 months DDLV incidence decreased by 7% (from 49% to 42%; p>0.05 and DDRV incidence decreased by 5% (from 24% to 17%; p>0.05. A more significant decrease in DDLV incidence [from 23 (62% to 18 (49%] and of DDRV incidence (from 12 (32% to 6 (16%] (р=0.05, was found in MTX + biologics group than in MTX only group [DDLV incidence remained unchanged - 7 (28%, and DDRV incidence increased from 3(12% to 4 (16%; p>0.05]. The normalization of left ventricle (LV diastolic function in early RA patients depended primarily on the efficacy of antihypertensive treatment, and of right ventricle (RV diastolic function - on the achievement of target BP level and RA remission. Reduced erythrocyte sedimentation rate (ESR and C-reactive protein (CRP plasma levels were associated with the improved LV diastolic function [E/A LV and

  3. EFFECT OF «TREAT-TO-TARGET» ANTIRHEUMATIC THERAPY ON DIASTOLIC DYSFUNCTION OF THE LEFT AND RIGHT VENTRICLES IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING 18 MONTHS OF OBSERVATION

    Directory of Open Access Journals (Sweden)

    I. G. Kirillova

    2015-09-01

    Full Text Available Aim. To study the effect of «treat-to-target» antirheumatic therapy on diastolic dysfunction of the left (DDLV and right (DDLV ventricles in patients with early rheumatoid arthritis (RA during 18 months of observation.Material and methods. The study included patients with early RA (n=66; 71% women; age - 56 [46; 61] years with moderate/high activity (DAS28 5.3 [5.0; 6.2], seropositive on rheumatoid factor (77% and/or cyclic citrullinated peptide antibodies (100%, disease modifying anti-rheumatic drugs (DMARD and glucocorticoids naive. Treatment with methotrexate (MTX with the escalation of the dose up to 25-30 mg/week subcutaneously was initiated in all the patients. After 3 months in 47 (71% patients biologics were added to MTX due to its inefficiency. In 18 months remission of RA was achieved in 44% of the patients. 51 (77% patients had a cardioprotective therapy. The target blood pressure (BP level was achieved in 38 (58% patients. Evaluation of traditional cardiovascular risk factors, 24-hour BP monitoring and echocardiography were performed in all patients initially and in 18 months of MTX/MTX + biologics use.Results. After 18 months DDLV incidence decreased by 7% (from 49% to 42%; p>0.05 and DDRV incidence decreased by 5% (from 24% to 17%; p>0.05. A more significant decrease in DDLV incidence [from 23 (62% to 18 (49%] and of DDRV incidence (from 12 (32% to 6 (16%] (р=0.05, was found in MTX + biologics group than in MTX only group [DDLV incidence remained unchanged - 7 (28%, and DDRV incidence increased from 3(12% to 4 (16%; p>0.05]. The normalization of left ventricle (LV diastolic function in early RA patients depended primarily on the efficacy of antihypertensive treatment, and of right ventricle (RV diastolic function - on the achievement of target BP level and RA remission. Reduced erythrocyte sedimentation rate (ESR and C-reactive protein (CRP plasma levels were associated with the improved LV diastolic function [E/A LV and

  4. Disease-modifying therapies in Chinese children with multiple sclerosis.

    Science.gov (United States)

    Yang, Fen; Huang, D Hui; Yang, Yang; Wu, Wei Ping

    2014-01-01

    Limited data are available about the use of disease-modifying therapies (DMTs) in children with multiple sclerosis (MS). This study aimed to present our experience using DMTs in Chinese children with MS and provide additional evidence to consider treating these patients with cyclophosphamide. A retrospective chart review was conducted and data were obtained from 25 children with MS. Only three (12%) of these patients received and responded well to first-line interferon β-1b therapy, while 10 (40%) chose cyclophosphamide and 12 (48%) refused to use DMTs. For the 10 patients being treated with cyclophosphamide, the median annualized relapse rate decreased from 3.0 to 1.0, and the median score on the Expanded Disability Status Scale decreased from 3.5 to 2.0. After 12 months of treatment, no gadolinium-enhancing lesions were reported in seven of the 10 patients. The use of DMTs plays an important role in the treatment of children with MS. If first-line therapies fail, cyclophosphamide may be a good option.

  5. Drug: D00969 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00969 Drug Meloxicam (JAN/USAN/INN); Mobic (TN) C14H13N3O4S2 351.0347 351.4007 D00...nd analgesics, anti-inflammatory agents 1149 Others D00969 Meloxicam (JAN/USAN/IN...MMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS M01AC Oxicams M01AC06 Meloxicam... D00969 Meloxicam (JAN/USAN/INN) USP drug classification [BR...:br08302] Analgesics Nonsteroidal Anti-inflammatory Drugs Meloxicam D00969 Meloxicam (JAN/USAN/INN) Anti-inf

  6. The biological and clinical activity of anti-malarial drugs in autoimmune disorders.

    Science.gov (United States)

    Taherian, Elham; Rao, Anshul; Malemud, Charles J; Askari, Ali D

    2013-01-01

    Chloroquine and hydroxychloroquine are 4-aminoquinoline compounds commonly employed as anti-malarial drugs. Chloroquine and its synthetic analogue, hydroxychloroquine also belong to the disease-modifying anti-rheumatic drug class because these drugs are immunosuppressive. The immunosuppressive activity of chloroquine and hydroxychloroquine is likely to account for their capacity to reduce T-cell and B-cell hyperactivity as well as pro-inflammatory cytokine gene expression. This review evaluated experimental and clinical trials results as well as clinical response data relative to the use of chloroquine and/or hydroxychloroquine as first-line medical therapies in systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome, the anti-phospholipid syndrome and in the treatment of sarcoidosis. A primary outcomes measure in these clinical trials was the extent to which chloroquine and/or hydroxychloroquine reduced disease progression or exacerbations and/or the use and dosage of corticosteroids. The relative efficacy of chloroquine and hydroxychloroquine in modifying the clinical course of these autoimmune disorders is balanced against evidence that these drugs induce adverse effects which may reduce their use and effectiveness in the therapy of autoimmune disorders.

  7. Chromosome substitution strain assessment of a Huntington's disease modifier locus.

    Science.gov (United States)

    Ramos, Eliana Marisa; Kovalenko, Marina; Guide, Jolene R; St Claire, Jason; Gillis, Tammy; Mysore, Jayalakshmi S; Sequeiros, Jorge; Wheeler, Vanessa C; Alonso, Isabel; MacDonald, Marcy E

    2015-04-01

    Huntington's disease (HD) is a dominant neurodegenerative disorder that is due to expansion of an unstable HTT CAG repeat for which genome-wide genetic scans are now revealing chromosome regions that contain disease-modifying genes. We have explored a novel human-mouse cross-species functional prioritisation approach, by evaluating the HD modifier 6q23-24 linkage interval. This unbiased strategy employs C57BL/6J (B6J) Hdh(Q111) knock-in mice, replicates of the HD mutation, and the C57BL/6J-chr10(A/J)/NaJ chromosome substitution strain (CSS10), in which only chromosome 10 (chr10), in synteny with the human 6q23-24 region, is derived from the A/J (AJ) strain. Crosses were performed to assess the possibility of dominantly acting chr10 AJ-B6J variants of strong effect that may modulate CAG-dependent Hdh(Q111/+) phenotypes. Testing of F1 progeny confirmed that a single AJ chromosome had a significant effect on the rate of body weight gain and in Hdh(Q111) mice the AJ chromosome was associated subtle alterations in somatic CAG instability in the liver and the formation of intra-nuclear inclusions, as well as DARPP-32 levels, in the striatum. These findings in relatively small cohorts are suggestive of dominant chr10 AJ-B6 variants that may modify effects of the CAG expansion, and encourage a larger study with CSS10 and sub-strains. This cross-species approach may therefore be suited to functional in vivo prioritisation of genomic regions harbouring genes that can modify the early effects of the HD mutation.

  8. Are current disease-modifying therapeutics in multiple sclerosis justified on the basis of studies in experimental autoimmune encephalomyelitis?

    Science.gov (United States)

    Farooqi, Nasr; Gran, Bruno; Constantinescu, Cris S

    2010-11-01

    The precise aetio-pathology of multiple sclerosis remains elusive. However, important recent advances have been made and several therapies have been licensed for clinical use. Many of these were developed, validated or tested in the animal model, experimental autoimmune encephalomyelitis (EAE). This systematic review aims to assess whether the current disease modifying treatments and those that are the closest to the clinic are justified on the basis of the results of EAE studies. We discuss some aspects of the utility and caveats of EAE as a model for multiple sclerosis drug development.

  9. The Neuroprotective Disease-Modifying Potential of Psychotropics in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Edward C. Lauterbach

    2012-01-01

    Full Text Available Neuroprotective treatments in Parkinson's disease (PD have remained elusive. Psychotropics are commonly prescribed in PD without regard to their pathobiological effects. The authors investigated the effects of psychotropics on pathobiological proteins, proteasomal activity, mitochondrial functions, apoptosis, neuroinflammation, trophic factors, stem cells, and neurogenesis. Only findings replicated in at least 2 studies were considered for these actions. Additionally, PD-related gene transcription, animal model, and human neuroprotective clinical trial data were reviewed. Results indicate that, from a PD pathobiology perspective, the safest drugs (i.e., drugs least likely to promote cellular neurodegenerative mechanisms balanced against their likelihood of promoting neuroprotective mechanisms include pramipexole, valproate, lithium, desipramine, escitalopram, and dextromethorphan. Fluoxetine favorably affects transcription of multiple genes (e.g., MAPT, GBA, CCDC62, HIP1R, although it and desipramine reduced MPTP mouse survival. Haloperidol is best avoided. The most promising neuroprotective investigative priorities will involve disease-modifying trials of the safest agents alone or in combination to capture salutary effects on H3 histone deacetylase, gene transcription, glycogen synthase kinase-3, α-synuclein, reactive oxygen species (ROS, reactive nitrogen species (RNS, apoptosis, inflammation, and trophic factors including GDNF and BDNF.

  10. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?

    LENUS (Irish Health Repository)

    Lonergan, Roisin

    2012-02-01

    Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development

  11. Drug: D05493 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nflammatory drugs (NSAIDs) CAS: 71002-09-0 PubChem: 47207162 LigandBox: D05493 NIKK...D05493 Drug Pirazolac (USAN/INN) C17H12ClFN2O2 330.0571 330.7408 D05493.gif Antirheumatic nonsteroidal antii

  12. Disease-modifying therapies and infectious risks in multiple sclerosis.

    Science.gov (United States)

    Winkelmann, Alexander; Loebermann, Micha; Reisinger, Emil C; Hartung, Hans-Peter; Zettl, Uwe K

    2016-04-01

    Immunomodulatory and immunosuppressive treatments for multiple sclerosis (MS) are associated with an increased risk of infection, which makes treatment of this condition challenging in daily clinical practice. Use of the expanding range of available drugs to treat MS requires extensive knowledge of treatment-associated infections, risk-minimizing strategies and approaches to monitoring and treatment of such adverse events. An interdisciplinary approach to evaluate the infectious events associated with available MS treatments has become increasingly relevant. In addition, individual stratification of treatment-related infectious risks is necessary when choosing therapies for patients with MS, as well as during and after therapy. Determination of the individual risk of infection following serial administration of different immunotherapies is also crucial. Here, we review the modes of action of the available MS drugs, and relate this information to the current knowledge of drug-specific infectious risks and risk-minimizing strategies.

  13. Risk of serious infection in biological treatment of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Singh, Jasvinder A; Cameron, Chris; Noorbaloochi, Shahrzad

    2015-01-01

    BACKGROUND: Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMAR...

  14. Short story of antirheumatic therapy.VIII. The immunodepressants

    Directory of Open Access Journals (Sweden)

    P. Marson

    2012-03-01

    Full Text Available The use of immunosuppressive drugs in rheumatology is fairly recent, starting just after the Second World War with the introduction of the first alkylating agents in oncohematology. When it became clear that some rheumatic diseases, particularly rheumatoid arthritis and systemic lupus erythematosus, showed an immune-mediated pathogenesis, including proliferation of immunocompetent cells, an application was soon found for immunosuppressive drugs in their treatment. This review outlines the historical milestones that led to the current use of drugs belonging to the major groups of immunosuppressants, i.e. alkylating agents (cyclophosphamide, folic acid (methotrexate and purine (azathioprine antagonists. We will also talk about the history of cyclosporin A, the first “selective” immunosuppressive agent, and that of some immunoactive drugs used more recently in rheumatology, such as mycophenolate mofetil, dapson and thalidomide.

  15. Disease-modifying treatments for progressive multiple sclerosis.

    Science.gov (United States)

    Comi, Giancarlo

    2013-10-01

    The last 20 years have seen major progress in the treatment of relapsing-remitting multiple sclerosis (RRMS) using a variety of drugs targeting immune dysfunction. In contrast, all clinical trials of such agents in primary progressive multiple sclerosis (PPMS) have failed and there is limited evidence of their efficacy in secondary progressive disease. Evolving concepts of the complex interplay between inflammatory and neurodegenerative processes across the course of multiple sclerosis (MS) may explain this discrepancy. This paper will provide an up-to-date overview of the rationale and results of the published clinical trials that have sought to alter the trajectory of both primary and secondary MS, considering studies involving drugs with a primary immune target and also those aiming for neuroprotection. Future areas of study will be discussed, building on these results combined with the experience of treating RRMS and new concepts emerging from laboratory science and animal models.

  16. Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease.

    Science.gov (United States)

    Smolen, Josef S; Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves

    2016-07-01

    The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for the treatment of RA' released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.

  17. Drug: D06909 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for dampness Antirheumatic drugs D0690...D06909 Crude, Drug Aralia rhizome (JP16); Dokkatsu Essential oil, Triterpenoid [CPD...data rhizome Therapeutic category of drugs in Japan [BR:br08301] 5 Crude drugs an...d Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D06909 Aralia rhizome (JP16)...9 Araliae cardatae rhizoma; Dokkatsu Crude drugs [BR:br08305] Dicot plants: asterids Araliaceae (ginseng family) D06909 Aralia rhizome PubChem: 51091251 ...

  18. Drug: D09079 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09079 Formula, Drug Dokkatsukakkonto Pueraria root [DR:D06693], Ephedra herb [DR:D...e in Japan [BR:br08304] Formulas Formulas for dampness Antirheumatic formulas D09079 Dokkatsukakkonto PubChem: 96025760 ... ...za [DR:D04365], Araliae cardatae rhizoma [DR:D06909], Rehmannia root [DR:D06736] Traditional Chinese Medicin

  19. Drug: D06951 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06951 Formula, Drug Keishakuchimoto Cinnamon bark [DR:D06712], Anemarrhena rhizome...tional Chinese medicines 5200 Traditional Chinese medicines D06951 Keishakuchimoto Traditional Chinese Medic...ine in Japan [BR:br08304] Formulas Formulas for dampness Antirheumatic formulas D06951 Keishakuchimoto PubChem: 51091293 ...

  20. Drug: D00080 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00080 Drug Chondroitin sulfate A (JAN) (C14H21NO14S)n D00080.gif Same as: C00634 A...ntirheumatic agents, non-steroids M01AX25 Chondroitin sulfate D00080 Chondroitin sulfate A (JAN) CAS: 24967-

  1. Drug: D08330 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 23 D08330.gif Antidote, chelating ATC code: M01CC01 map07050 Antirheumatics - DMARDs and biological agents A...D08330 Drug Penicillamine hydrochloride; Pemine (TN) C5H11NO2S. HCl 185.0277 185.67

  2. Drug: D06694 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available root Major component: Anemonin [CPD:C16913] Therapeutic category of drugs in Japan [BR:br08301] 5 Crude drugs... and Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs... D06694 Clematis root (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for dampness Antirheumatic drugs...4 *Clematis root; Irei-sen Crude drugs [BR:br08305] Dicot plants: others Ranunculaceae (buttercup family) D06694 Clematis root PubChem: 47208345 ...

  3. Use of an electronic drug monitoring system for ambulatory patients with chronic disease: how does it impact on nurses' time spent documenting clinical care?

    Science.gov (United States)

    Hordern, Antonia; Callen, Joanne; Gibson, Kathryn; Robertson, Louise; Li, Ling; Hains, Isla M; Westbrook, Johanna I

    2012-01-01

    Medication monitoring of ambulatory rheumatology patients on Disease Modifying Anti-Rheumatic Drugs (DMARDS) is time consuming and complex, with possibilities for error. Electronic systems have the potential to improve the process. The aim of this study was to evaluate the impact of an electronic Drug Monitoring System (eDMS) on the time nurses' spent on clinical documentation associated with monitoring. The study was conducted with all nurses (n=4) in the Rheumatology Department of a large metropolitan Australian teaching hospital. The eDMS was designed as a module of the Hospital Clinical Information System (HCIS) to assist clinicians in monitoring rheumatology patients on DMARDS. Timing data were collected using a modified time and motion work measurement technique using software on a handheld computer. Data included the time nurses spent on documentation regarding medication monitoring before and after the implementation of the eDMS. Results showed that following implementation of the eDMS nurses spent significantly less time documenting medication monitoring information (13.6% to 7.2%, PeDMS. Consequently, there was a significant decrease in the time nurses spent using the HCIS (13.01% to 2.8%, peDMS made the process of drug monitoring quicker and simpler for nurses and thus permitted them to increase their time spent in direct patient care.

  4. Price analysis of multiple sclerosis disease-modifying therapies marketed in the United States.

    Science.gov (United States)

    Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

    2016-11-01

    This study assessed trends in the average wholesale price (AWP) at the market entry of disease-modifying therapies (DMTs) approved by Food and Drug Administration (FDA) in the period 1987-2014. DMT regulatory information was derived from the FDA website. The AWPs per unit at market entry data were derived from the Red Book (Truven Health Analytics Inc.). The AWP history for each DMT was collected from its date of approval to 31 December 2014. The FDA approved label defined daily dose (DDD) for adult patients was obtained from FDA approved labels. The AWP per DDD and the AWP/DDD per year of therapy were computed. Descriptive statistics, Wilcoxon tests, t-test, and multiple linear regression were performed. The statistical significance level was set at 0.05. The FDA approved 12 multiple sclerosis (MS) DMTs, including five new drug applications (NDAs) and seven biologic license applications (BLAs) as of 31 December 2014. The FDA granted orphan designation to five DMTs. There was one DMT approved by the FDA in the 1980s, three in the 1990s, three in 2000s, and five in the period 2010-2014. The market entry inflation-adjusted AWP per DDD was $10.23 for the first DMT (mitoxantrone hydrochloride) that was approved in the 1980s. The median market entry inflation-adjusted AWP per DDD was $12.41 (interquartile range [IQR] = 4.51) for DMTs approved in the 1990s, $71.26 (IQR = 58.35) in the 2000s, and $172.56 (IQR = 84.97) in the period 2010-2014. The median AWP per DDD was statistically significantly different (p = 0.011) for orphan (median = $41.82, IQR = 56.077) compared to non-orphan drugs (median = $171.32, IQR = 199.29). Year of market entry was positively associated with DMT prices at US market entry (p = 0.01). The AWP per DDD for DMTs at market entry increased substantially over time. The increase in DMTs prices exceeded the general consumer price index.

  5. A short history of anti-rheumatic therapy - V. Analgesics

    Directory of Open Access Journals (Sweden)

    P. Marson

    2011-06-01

    Full Text Available The pharmacological treatment of pain has very ancient origins, when plant-derived products were used, including mandrake extracts and opium, a dried latex obtained from Papaver somniferum. In the XVI and XVII centuries opium came into the preparation of two compounds widely used for pain relief: laudanum and Dover’s powder. The analgesic properties of extracts of willow bark were then recognized and later, in the second half of the XIX century, experimental studies on chemically synthesized analgesics were planned, thus promoting the marketing of some derivatives of para-amino-phenol and pyrazole, the predecessors of paracetamol and metamizol. In the XX century, nonsteroidal anti-inflammatory drugs were synthesized, such as phenylbutazone, which was initially considered primarily a pain medication. The introduction on the market of centrally acting analgesics, such as tramadol, sometimes used in the treatment of rheumatic pain. is quite recent.

  6. Rational Design of Antirheumatic Prodrugs Specific for Sites of Inflammation

    Science.gov (United States)

    Onuoha, Shimobi C.; Ferrari, Mathieu; Sblattero, Daniele

    2015-01-01

    Objective Biologic drugs, such as the anti–tumor necrosis factor (anti‐TNF) antibody adalimumab, have represented a breakthrough in the treatment of rheumatoid arthritis. Yet, concerns remain over their lack of efficacy in a sizable proportion of patients and their potential for systemic side effects such as infection. Improved biologic prodrugs specifically targeted to the site of inflammation have the potential to alleviate current concerns surrounding biologic anticytokine therapies. The purpose of this study was to design, construct, and evaluate in vitro and ex vivo the targeting and antiinflammatory capacity of activatable bispecific antibodies. Methods Activatable dual variable domain (aDVD) antibodies were designed and constructed to target intercellular adhesion molecule 1 (ICAM‐1), which is up‐regulated at sites of inflammation, and anti‐TNF antibodies (adalimumab and infliximab). These bispecific molecules included an external arm that targets ICAM‐1 and an internal arm that comprises the therapeutic domain of an anti‐TNF antibody. Both arms were linked to matrix metalloproteinase (MMP)–cleavable linkers. The constructs were tested for their ability to bind and neutralize both in vitro and ex vivo targets. Results Intact aDVD constructs demonstrated significantly reduced binding and anti‐TNF activity in the prodrug formulation as compared to the parent antibodies. Human synovial fluid and physiologic concentrations of MMP enzyme were capable of cleaving the external domain of the antibody, revealing a fully active molecule. Activated antibodies retained the same binding and anti‐TNF inhibitory capacities as the parent molecules. Conclusion The design of a biologic prodrug with enhanced specificity for sites of inflammation (synovium) and reduced specificity for off‐target TNF is described. This construct has the potential to form a platform technology that is capable of enhancing the therapeutic index of drugs for the treatment of

  7. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies.

    Science.gov (United States)

    Melzer, N; Meuth, S G

    2014-03-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future.

  8. Psoriatic arthritis: treatment strategies using anti-inflammatory drugs and classical DMARDs

    Directory of Open Access Journals (Sweden)

    E. Lubrano

    2012-06-01

    Full Text Available Psoriatic Arthritis (PsA is a chronic inflammatory disease typically characterized by arthritis and psoriasis variably associated with other extra-articular manifestations. PsA has been considered a milder and less disabling disease compared with rheumatoid arthritis (RA, even if some studies showed that PsA had joint erosions and damage. In addition, about 20-40% of PsA patients have axial skeleton involvement that may lead to functional limitation and deformity. The treatment of PsA ranged from initial treatment with non-steroidal anti-inflammatory drugs (NSAIDs to one or more disease-modifying anti-rheumatic agents (DMARDs for the suppression of inflammation in patients with recalcitrant peripheral joint disease. In clinical practice, the most widely used DMARDs are methotrexate (level of evidence B, sulfasalazine (level of evidence A, leflunomide (level of evidence A, and ciclosporin (level of evidence B. However, the efficacy of these agents in inhibiting joint erosions has not been assessed in controlled studies. Finally, the effectiveness of DMARDs in treating enthesitis and dactylitis is controversial. The present paper revised the evidence-based results on treatment with “conventional” therapy for PsA. The revision was based on all the subsets of the diseases, namely the various manifestations of the articular involvement (peripheral, axial, enthesitis, dactylitis as well as the skin and nail involvement.

  9. A commentary on TREAT: The trial of early aggressive drug therapy in juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Baildam Eileen

    2012-06-01

    Full Text Available Abstract Polyarticular juvenile idiopathic arthritis (JIA is a category of JIA where multiple joints are affected by chronic inflammation, and where serious and lasting damage to joints is the expected natural history in untreated disease. There is evidence of response to disease-modifying antirheumatic and biologic drugs, but little evidence of permanent remission from any of the existing therapeutic trials. The TREAT trial by Wallace et al., recently published in Arthritis and Rheumatism, used a collaborative multicenter approach to studying early aggressive treatment of polyarticular JIA in an attempt to achieve full clinical inactive disease after 6 months of treatment. The study's main finding that the earlier in the disease course that treatment is started, the better the chance of disease control, has provided evidence that there is a 'window of opportunity' for treating JIA as there is in adult rheumatoid arthritis (RA. The study provides both a platform and an impetus for concentrating future treatment trials on early rather than established disease and investigating a standard of starting treatment within 10 to 12 weeks.

  10. Interstitial lung disease in patients with rheumatoid arthritis: spontaneous and drug induced.

    Science.gov (United States)

    Hallowell, Robert W; Horton, Maureen R

    2014-03-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by the destruction of articular joint structures. RA is a systemic condition that often affects multiple organs, including the heart, lungs, and kidneys. Pulmonary complications of RA are relatively common and include pleural effusion, rheumatoid nodules, bronchiectasis, obliterative bronchiolitis, and opportunistic infections. Interstitial lung disease (ILD) is a common occurrence in patients with RA, and can range in severity from an asymptomatic incidental finding to a rapidly progressing life-threatening event. Usual interstitial pneumonia and non-specific interstitial pneumonia are the two most common patterns, though others have been reported. Various disease-modifying anti-rheumatic drugs-in particular, methotrexate and the tumor necrosis factor-alpha inhibitors-have been associated with RA-ILD in numerous case reports and case series, though it is often difficult to distinguish association from causality. Treatment for RA-ILD typically involves the use of high-dose corticosteroids, often in conjunction with alternative immunosuppressant agents such as azathioprine or mycophenolate mofetil, and outcomes vary widely depending on the initial pattern of lung disease. Additional research into the mechanisms driving RA-ILD is needed to guide future therapy.

  11. Leflunomide for the treatment of rheumatoid arthritis in clinical practice - Incidence and severity of hepatotoxicity

    NARCIS (Netherlands)

    van Roon, EN; Jansen, TLTA; Houtman, NM; Spoelstra, P; Brouwers, JRBJ

    2004-01-01

    Objective: Leflunomide is a novel disease modifying antirheumatic drug (DMARD). Because of reports on possible hepatotoxicity and adaptations in the recommendations for monitoring liver function during leflunomide treatment, we conducted a study to evaluate the incidence and severity of hepatotoxici

  12. Optimizing the expediency of TNFi in rheumatoid arthritis: offering a TNFi holiday in patients having reached low-disease activity in the maintenance phase

    NARCIS (Netherlands)

    Ingen, I.L. van; Lamers-Karnebeek, F.; Jansen, T.L.Th.A.

    2014-01-01

    Introduction: The treatment of rheumatoid arthritis (RA) has been revolutionized since the introduction of biological disease-modifying antirheumatic drugs such as tumour necrosis factor alpha inhibitors (TNFi), and clinical remission has become a realistic target in the treatment strategy.

  13. Management of disease-modifying treatments in neurological autoimmune diseases of the central nervous system

    Science.gov (United States)

    Salmen, A; Gold, R; Chan, A

    2014-01-01

    The therapeutic armamentarium for autoimmune diseases of the central nervous system, specifically multiple sclerosis and neuromyelitis optica, is steadily increasing, with a large spectrum of immunomodulatory and immunosuppressive agents targeting different mechanisms of the immune system. However, increasingly efficacious treatment options also entail higher potential for severe adverse drug reactions. Especially in cases failing first-line treatment, thorough evaluation of the risk–benefit profile of treatment alternatives is necessary. This argues for the need of algorithms to identify patients more likely to benefit from a specific treatment. Moreover, paradigms to stratify the risk for severe adverse drug reactions need to be established. In addition to clinical/paraclinical measures, biomarkers may aid in individualized risk–benefit assessment. A recent example is the routine testing for anti-John Cunningham virus antibodies in natalizumab-treated multiple sclerosis patients to assess the risk for the development of progressive multi-focal leucoencephalopathy. Refined algorithms for individualized risk assessment may also facilitate early initiation of induction treatment schemes in patient groups with high disease activity rather than classical escalation concepts. In this review, we will discuss approaches for individiualized risk–benefit assessment both for newly introduced agents as well as medications with established side-effect profiles. In addition to clinical parameters, we will also focus on biomarkers that may assist in patient selection. Other Articles published in this series Paraneoplastic neurological syndromes. Clinical and Experimental Immunology 2014, 175: 336–48. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies. Clinical and Experimental Immunology 2014, 175: 359–72. Monoclonal antibodies in treatment of multiple

  14. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth?

    DEFF Research Database (Denmark)

    Putrik, Polina; Ramiro, Sofia; Kvien, Tore K;

    2014-01-01

    To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare.......To explore criteria regulating treatment with reimbursed biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) across Europe and to relate criteria to indicators of national socioeconomic welfare....

  15. Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheumatoid arthritis patients in clinical practice

    DEFF Research Database (Denmark)

    Ornbjerg, Lykke Midtbøll; Østergaard, Mikkel; Bøyesen, Pernille;

    2013-01-01

    To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice.......To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice....

  16. Indirect treatment comparison of abatacept with methotrexate versus other biologic agents for active rheumatoid arthritis despite methotrexate therapy in the United kingdom

    DEFF Research Database (Denmark)

    Guyot, Patricia; Taylor, Peter C; Christensen, Robin;

    2012-01-01

    To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom.......To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom....

  17. MRI quantification of rheumatoid arthritis: current knowledge and future perspectives

    DEFF Research Database (Denmark)

    Boesen, Mikael; Østergaard, Mikkel; Cimmino, Marco A

    2009-01-01

    The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method for detect......The international consensus on treatment of rheumatoid arthritis (RA) involves early initiation of disease modifying anti-rheumatic drugs (DMARDs) for which a reliable identification of early disease is mandatory. Conventional radiography of the joints is considered the standard method...

  18. When to Initiate Disease-Modifying Drugs for Relapsing Remitting Multiple Sclerosis in Adults?

    Directory of Open Access Journals (Sweden)

    Mona Alkhawajah

    2011-01-01

    Full Text Available For patients with Relapsing Remitting Multiple Scierosis Beta Interfaerons and Glatiramer Acetate were the first to be licensed for treatment. This review deals with one major question: when to initiate therapy? Through exploring the unique characteristics of the disease and treatement we suggest an approach that should be helpful in the process of decision-making.

  19. Nanoparticle system for the local delivery of disease modifying osteoarthritic drugs

    NARCIS (Netherlands)

    Periyasamy, P.C.; Wennink, J.W.H.; Wang, R.; Karperien, M.; Dijkstra, P.J.; Post, J.N.

    2013-01-01

    Purpose: The purpose of this study is to develop the nanoparticles that i) can be injected intra-articularly ii) target to cartilage due to an opposite charge difference with the extracellular cartilaginous matrix and iii) due to their small size can penetrate into the cartilage. In this way retenti

  20. Finasteride inhibits the disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesis.

    Science.gov (United States)

    Samba Reddy, Doodipala; Ramanathan, G

    2012-09-01

    Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively susceptible to recurrent, unprovoked seizures due to precipitating risk factors. Progesterone has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. Progesterone markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of the limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy.

  1. A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    Full Text Available One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparing the treatment difference at the end of the delayed-start period with that at the end of the placebo-controlled period. We conducted simulations to identify the optimal noninferiority testing procedure to ensure the method was robust across scenarios and assumptions, and to evaluate the appropriate modeling approach for analyzing the delayed-start period. We then applied this methodology to Phase 3 solanezumab clinical trial data for mild Alzheimer's disease patients. Simulation results showed a testing procedure using a proportional noninferiority margin was robust for detecting disease-modifying effects; conditions of high and moderate discontinuations; and with various missing data mechanisms. Using all data from all randomized patients in a single model over both the placebo-controlled and delayed-start study periods demonstrated good statistical performance. In analysis of solanezumab data using this methodology, the noninferiority criterion was met, indicating the treatment difference at the end of the placebo-controlled studies was preserved at the end of the delayed-start period within a pre-defined margin. The proposed noninferiority method for delayed-start analysis controls Type I error rate well and addresses many challenges posed by previous approaches. Delayed-start studies employing the proposed analysis approach could be used to provide evidence of a disease-modifying effect. This method has been communicated with FDA and has been

  2. Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA.

    Science.gov (United States)

    Smolen, Josef S; Boers, Maarten; Abadie, Eric C; Breedveld, Ferdinand C; Emery, Paul; Bardin, Thomas; Goel, Niti; Ethgen, Dominique J; Avouac, Bernard P; Dere, Willard H; Durez, Patrick; Matucci-Cerinic, Marco; Flamion, Bruno; Laslop, Andrea; Lekkerkerker, Frits J; Miossec, Pierre; Mitlak, Bruce H; Ormarsdóttir, Sif; Paolozzi, Laurence; Rao, Ravi; Reiter, Susan; Tsouderos, Yannis; Reginster, Jean-Yves

    2011-02-01

    Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.

  3. EFFECT OF THERAPY WITH ANTI-TNF α DRUGS AND DMARD ON DISEASE ACTIVITY AND HEALTH RELATED QUALITY OF LIFE AMONG WOMEN WITH RHEUMATOID ARTHRITIS.

    Science.gov (United States)

    Kopciuch, Dorota; Paczkowska, Anna; Leszczynsk, Piotr; Michalak, Michal; Nowakowskai, Elzbieta

    2016-01-01

    The aim of this pilot study was to evaluate the response to 16 and 52 weeks of treatment with adalimumab and etanercept and its effect on disease activity and quality of life in patients with rheumatoid arthritis (RA). Patients were selected from 2155 medical cards of patients of Connective Tissue Health Centre (Poznań, Poland) who were refractory to conventional treatment with disease modifying anti-rheumatic drugs. To assess the disease activity, Disease Activity Score (DAS28) was used and the measurement of quality of life was evaluated with the Polish version of the WHOQoL-Bref questionnaire. To assess the disability, we have used Health Assessment Questionnaire Disability Index (HAQ-DI) and to assess the patients' pain caused by RA, Visual Analogue Scale (VAS) was used. The results of the study show a significant decrease in inflammatory activity of the disease and, consequently, an improvement in quality of life after anti-TNF α treatment. Results obtained with TNF-blockers after 52 weeks of treatment in RA objectively show the efficacy of these drugs and also the patients' perception of the effect on their quality of life. Study results also indicate changes in disability caused by RA and patients' pain due to disease between 16 and 52 weeks of treatment.

  4. [Animal experiment studies on the effect of intra-articular injections of antiphlogistic-antirheumatic agents on articular cartilage in vivo].

    Science.gov (United States)

    Kalbhen, D A; Schauer, M; Wentsche, B

    1978-01-01

    Animal experiments have shown that weekly intraarticular injections of various antiphlogistic/antirheumatic drugs into the knee joint induce progressive degenerative alterations in joint cartilage. The observed degenerations and destructions are most similar to the pathophysiology of osteoarthrosis in humans. By X-ray and macroscopic techniques the degenerative processes can be studied qualitatively and quantitatively. A decrease of joint space is a sensitive and early indicator of osteoarthrosis and showed that 10 weeks after intraarticular application of Ibuprofen, Phenylbutazone, Oxyphenbutazone, Flufenamic acid, Niflumic acid, Na-salicylate, Clofezone, Bumadizone and Dexamethasone the degenerative alterations in the injected knee joints were more severe than by applications of Chloroquine,D-penicillamine, Salicylamide and Indometacin. The degenerative effect on articular cartilage by the investigated drugs can be explained by their inhibitory potency on anabolic metabolism of connective tissue. The results of our animal experiments lead to the conclusion, that antiinflammatory drugs may also in man induce or accelerate degenerative joint diseases especially after long term treatment with high doses of these drugs.

  5. Drug: D01305 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 1 ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS M01AX Other antiinflamma...tory and antirheumatic agents, non-steroids M01AX18 Fepr

  6. Thyroid Autoimmunity and Function after Treatment with Biological Antirheumatic Agents in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Bliddal, Sofie; Dinsen, Stina; Feldt-Rasmussen, Ulla

    2017-01-01

    With the increased pro-inflammatory response in both rheumatoid arthritis and thyroid autoimmune diseases, treatment with biological antirheumatic agents (BAAs) of the former may affect the course of the latter. In hepatitis C and cancer patients, treatment with biological agents substantially...... increases the risk of developing thyroid autoimmunity. As the use of BAAs in the treatment of rheumatoid arthritis is increasing, this review aimed to investigate if such use affected thyroid status in rheumatoid arthritis patients. We conducted a systematic literature search and included six studies...... status: a reduction of thyroid peroxidase and thyroglobulin antibody concentrations, and a reduction of thyrotropin levels in hypothyroid patients. Despite the small number of studies, they presented compliant data. The BAAs used in rheumatoid arthritis thus did not seem to negatively affect thyroid...

  7. Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

    Directory of Open Access Journals (Sweden)

    Hasegawa Yoshinori

    2009-09-01

    Full Text Available Abstract Background To determine whether oral administration of geranylgeranylacetone (GGA, a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP 70, protects against drug-induced lung injury/fibrosis in vivo. Methods We used a bleomycin (BLM-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2 in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry. Results We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the de novo induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice. Conclusion GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.

  8. Clinical and biological phenotypes of frontotemporal dementia: Perspectives for disease modifying therapies.

    Science.gov (United States)

    Gazzina, S; Manes, M A; Padovani, A; Borroni, B

    2017-06-01

    Frontotemporal Dementia (FTD) is a progressive neurodegenerative condition which encompasses a group of clinically, neuropathologically and genetically heterogeneous disorders characterized by selective involvement of the frontal and temporal lobes. FTD is characterized by changes in behaviour and personality, frontal executive deficits and language dysfunction. Different phenotypes have been defined on the basis of presenting clinical symptoms, behavioural variants of FTD (bvFTD) and primary progressive aphasia (PPA), which includes nonfluent/agrammatic variant PPA (avPPA) and semantic variant PPA (svPPA). These presentations can overlap with atypical parkinsonian disorders (i.e., corticobasal syndrome, progressive supranuclear palsy) and amyotrophic lateral sclerosis. Each syndrome can be associated with one or more neuropathological hallmark, and in some cases it may be due to autosomal inherited disorder caused by mutations in a number of genes. Currently, there is no specific treatment available to prevent disease progression. FTD treatment is based on symptomatic management, and most therapies lack quality evidence from randomized, placebo-controlled clinical trials. Recent advances in the understanding of FTD pathophysiology and genetics have led to the development of potentially disease-modifying therapies. In this review, we discussed current knowledge and recommendations with regards to symptomatic and disease-modifying therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. SQ grass sublingual allergy immunotherapy tablet for disease-modifying treatment of grass pollen allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Dahl, Ronald; Roberts, Graham; de Blic, Jacques

    2016-01-01

    BACKGROUND: Allergy immunotherapy is a treatment option for allergic rhinoconjunctivitis (ARC). It is unique compared with pharmacotherapy in that it modifies the immunologic pathways that elicit an allergic response. The SQ Timothy grass sublingual immunotherapy (SLIT) tablet is approved in North...... America and throughout Europe for the treatment of adults and children (≥5 years old) with grass pollen-induced ARC. OBJECTIVE: The clinical evidence for the use of SQ grass SLIT-tablet as a disease-modifying treatment for grass pollen ARC is discussed in this review. METHODS: The review included...... the suitability of SQ grass SLIT-tablet for patients with clinically relevant symptoms to multiple Pooideae grass species, single-season efficacy, safety, adherence, coseasonal initiation, and cost-effectiveness. The data from the long-term SQ grass SLIT-tablet clinical trial that evaluated a clinical effect 2...

  10. Fostering adherence to injectable disease-modifying therapies in multiple sclerosis.

    Science.gov (United States)

    Lugaresi, Alessandra; Rottoli, Maria Rosa; Patti, Francesco

    2014-09-01

    Multiple sclerosis requires long-term management, often with disease-modifying therapies. Poor medication adherence, especially to injectables, can increase relapse and hospitalisation rates and consume healthcare resources. We discuss adherence definitions and terminology and its prevalence in multiple sclerosis (MS). Typical causes of poor adherence in patients with MS include: insufficient efficacy or tolerability, concurrent disorders, and consequences of MS (e.g., forgetfulness, depression, fatigue and poor motor skills). Ways to improve adherence rates are reviewed, focusing on interdisciplinary healthcare teams, good communication between healthcare workers and patients (and their families), ongoing support and digital tools to promote adherence. We consider open communication and continuing education to be key, and that MS nurses have a pivotal role in ensuring patients' adherence to MS medicines.

  11. Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents

    Directory of Open Access Journals (Sweden)

    Alessandro Finkelsztejn

    2012-10-01

    Full Text Available OBJECTIVE: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. METHODS: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. RESULTS: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. CONCLUSIONS: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

  12. The Disease-Modifying Effects of Hyaluronan in the Osteoarthritic Disease State

    Directory of Open Access Journals (Sweden)

    Mathew A Nicholls

    2017-08-01

    Full Text Available Hyaluronic acid (HA has been a treatment modality for patients with knee osteoarthritis (OA for many years now. Since HA was first introduced for the treatment of painful knee OA, much has been elucidated regarding both the etiology of this disease and the mechanisms by which HA may mitigate joint pain and tissue destruction. The objectives of this article are to (1 describe the etiology and pathophysiology of OA including both what is known about the genetics and biochemistry, (2 describe the role of HA on disease progression, (3 detail the antinociceptive and anti-inflammatory actions of HA in OA, and (4 present evidence of disease-modifying effects of HA in the preservation and restoration of the extracellular matrix. These data support that HA is not only just a simple device used for viscosupplementation but also a biologically active molecule that can affect the physiology of articular cartilage.

  13. Established patterns of animal study design undermine translation of disease-modifying therapies for Parkinson’s disease

    Science.gov (United States)

    Zeiss, Caroline J.; Allore, Heather G.; Beck, Amanda P.

    2017-01-01

    Translation of disease-modifying therapies in neurodegenerative disease has been disappointing. Parkinson’s disease (PD) was used to compare patterns of preclinical study design for symptomatic and potentially disease-modifying interventions. We examined the relationship of model, intervention type and timing, outcomes and outcome measures in 543 animal and human studies (1973–2015) across a contemporary cohort of animal and human interventional studies (n = 445), animal studies for approved interventions (n = 28), animal and human studies for those that failed to translate (n = 70). Detailed study design data were collected for 216 studies in non-human primate (NHP) and rodent toxin-induced models. Species-specific patterns of study design prevailed regardless of whether interventions were symptomatic or potentially disease-modifying. In humans and NHPs, interventions were typically given to both sexes well after the PD phenotype was established, and clinical outcome measures were collected at single (symptomatic) or multiple (disease-modifying) time-points. In rodents, interventions often preceded induction of the model, acute toxic protocols were common, usually given to young males, clinical outcome measures were used less commonly, and outcomes were less commonly assessed at multiple time points. These patterns were more prevalent in mice than rats. In contrast, study design factors such as randomization and blinding did not differ appreciably across symptomatic and disease-modifying intervention categories. The translational gap for potentially disease-modifying interventions in PD in part results from study designs, particularly in mice, that fail to model the progressive nature and relatively late intervention characteristic of PD, or that anchor mechanistic and neuropathologic data to longitudinal clinical outcomes. Even if measures to improve reproducibility are broadly adopted, perpetuation of these norms will continue to impede effective translation

  14. Development of Glatopa® (Glatiramer Acetate): The First FDA-Approved Generic Disease-Modifying Therapy for Relapsing Forms of Multiple Sclerosis.

    Science.gov (United States)

    Bell, Christine; Anderson, James; Ganguly, Tanmoy; Prescott, James; Capila, Ishan; Lansing, Jonathan C; Sachleben, Richard; Iyer, Mani; Fier, Ian; Roach, James; Storey, Kristina; Miller, Paul; Hall, Steven; Kantor, Daniel; Greenberg, Benjamin M; Nair, Kavita; Glajch, Joseph

    2017-01-01

    The multiple sclerosis (MS) treatment landscape in the United States has changed dramatically over the past decade. While many disease-modifying therapies (DMTs) have been approved by the US Food and Drug Administration (FDA) for the treatment of relapsing forms of MS, DMT costs continue to rise. The availability of generics and biosimilars in the MS-treatment landscape is unlikely to have a major impact on clinical benefit. However, their availability will provide alternative treatment options and potentially lower costs through competition, thus increasing the affordability of and access to these drugs. In April 2015, the first generic version of the complex drug glatiramer acetate (Glatopa® 20 mg/mL) injection was approved in the United States as a fully substitutable generic for all approved indications of the 20 mg/mL branded glatiramer acetate (Copaxone®) dosage form. Despite glatiramer acetate's complex nature-being a chemically synthesized (ie, nonbiologic) mixture of peptides-the approval occurred without conducting any clinical trials. Rather, extensive structural and functional characterization was performed to demonstrate therapeutic equivalence to the innovator drug. The approval of Glatopa signifies an important milestone in the US MS-treatment landscape, with the hope that the introduction of generic DMTs and eventually biosimilar DMTs will lead to future improvements in the affordability and access of these much-needed treatments for MS.

  15. Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

    Science.gov (United States)

    Lyberg, Torstein; Bottazzi, Barbara; Meroni, Pier Luigi; Leone, Roberto; Hjeltnes, Gunnbjorg

    2017-01-01

    Background Pentraxin 3 is proposed to be a marker of inflammation and cardiovascular risk, but its role in inflammatory rheumatic diseases (IRDs) is still uncertain. Therefore, we wanted to examine if anti-rheumatic treatment reduced serum PTX3 (s-PTX3) levels in IRDs, and if s-PTX3 levels were related to other markers of inflammation and to endothelial function (EF). Methods We examined s-PTX3, EF and established inflammatory biomarkers in 114 IRD patients from the PSARA study before and after 6 weeks and 6 months of treatment with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNF) therapy with or without MTX co-medication. Results s-PTX3 levels in all IRD diagnoses were above the upper limit of the reference range. In contrast to established inflammatory markers, in particular CRP and ESR, s-PTX3 levels did not change significantly after 6 weeks and 6 months of anti-rheumatic therapy. There was no difference in change in s-PTX3 levels from baseline to 6 weeks and 6 months between MTX monotherapy and anti-TNF regimens. CRP, ESR and EF were not related to changes in s-PTX3 neither in crude nor adjusted analyses. Conclusion IRD patients have increased s-PTX3 levels, which, in contrast to other inflammatory markers, do not seem to improve within 6 months of therapy with MTX and/or anti-TNF. Thus, s-PTX3 might reflect a persisting immune process, even a causal factor of inflammation, not inhibited by the standard anti-rheumatic treatment. Furthermore, even though s-PTX3 is thought to be a strong predictor of cardiovascular prognosis, it was not related to EF. PMID:28225768

  16. Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

    Science.gov (United States)

    Deyab, Gia; Hokstad, Ingrid; Whist, Jon Elling; Småstuen, Milada Cvancarova; Agewall, Stefan; Lyberg, Torstein; Bottazzi, Barbara; Meroni, Pier Luigi; Leone, Roberto; Hjeltnes, Gunnbjorg; Hollan, Ivana

    2017-01-01

    Pentraxin 3 is proposed to be a marker of inflammation and cardiovascular risk, but its role in inflammatory rheumatic diseases (IRDs) is still uncertain. Therefore, we wanted to examine if anti-rheumatic treatment reduced serum PTX3 (s-PTX3) levels in IRDs, and if s-PTX3 levels were related to other markers of inflammation and to endothelial function (EF). We examined s-PTX3, EF and established inflammatory biomarkers in 114 IRD patients from the PSARA study before and after 6 weeks and 6 months of treatment with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNF) therapy with or without MTX co-medication. s-PTX3 levels in all IRD diagnoses were above the upper limit of the reference range. In contrast to established inflammatory markers, in particular CRP and ESR, s-PTX3 levels did not change significantly after 6 weeks and 6 months of anti-rheumatic therapy. There was no difference in change in s-PTX3 levels from baseline to 6 weeks and 6 months between MTX monotherapy and anti-TNF regimens. CRP, ESR and EF were not related to changes in s-PTX3 neither in crude nor adjusted analyses. IRD patients have increased s-PTX3 levels, which, in contrast to other inflammatory markers, do not seem to improve within 6 months of therapy with MTX and/or anti-TNF. Thus, s-PTX3 might reflect a persisting immune process, even a causal factor of inflammation, not inhibited by the standard anti-rheumatic treatment. Furthermore, even though s-PTX3 is thought to be a strong predictor of cardiovascular prognosis, it was not related to EF.

  17. Adherence to disease-modifying therapies and attitudes regarding disease in patients with multiple sclerosis.

    Science.gov (United States)

    Ožura, Ana; Kovač, Lea; Sega, Saša

    2013-12-01

    Although currently there is no cure for MS the course of the disease can be influenced by disease modifying therapy (DMT). For therapy to be sufficiently efficient, it is crucial that patients take their medication regularly as prescribed. Adherence describes the extent to which a patient acts in accordance with the prescribed timing, dosing, and frequency of medication administration. To date, there are no known data about adherence rates among patients with MS in Slovenia. We wanted to assess adherence in patients with MS, who are treated with first line DMTs and discover reasons for non-adherence. A number of 451 patients were invited to participate. They received two questionnaires via post mail. The adherence rate and putative reasons for non-adherence were assessed by the use of standardized self-report Multiple Sclerosis Treatment Experience Questionnaire (MSTEQ). Patients' attitudes regarding disease, therapy and relationship with their physician were assessed by another questionnaire. The analysis of results included 299 patients. Among the patients 18.5% missed at least one medication dose in the past 28 days. Patients taking Avonex were significantly more adherent then patients on other DMTs (p=0.005). Our study showed a higher then expected adherence among Slovenian patients with MS (81.5%). Our research did not confirm the influence of side effects or patients' attitudes regarding illness and therapy on adherence. However we found unexpectedly high percentage (71.8%) of patients belief that psychological factors are involved in MS aetiology.

  18. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    Science.gov (United States)

    Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo

    2011-11-01

    Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials.

  19. Disease-modifying effect of intravenous immunoglobulin in an experimental model of epilepsy

    Science.gov (United States)

    Chen, Min; Arumugam, Thiruma V.; Leanage, Gayeshika; Tieng, Quang M.; Yadav, Ashwin; Ullmann, Jeremy F. P.; She, David T.; Truong, Vy; Ruitenberg, Marc J.; Reutens, David C.

    2017-01-01

    Novel therapies that prevent or modify the development of epilepsy following an initiating brain insult could significantly reduce the burden of this disease. In light of evidence that immune mechanisms play an important role in generating and maintaining the epileptic condition, we evaluated the effect of a well-established immunomodulatory treatment, intravenous immunoglobulin (IVIg), on the development of epilepsy in an experimental model of epileptogenesis. In separate experiments, IVIg was administered either before (pre-treatment) or after (post-treatment) the onset of pilocarpine status epilepticus (SE). Our results show that both pre- and post-treatment with IVIg attenuated acute inflammation in the SE model. Specifically, IVIg reduced local activation of glial cells, complement system activation, and blood-brain barrier damage (BBB), which are all thought to play important roles in the development of epilepsy. Importantly, post-treatment with IVIg was also found to reduce the frequency and duration of subsequent spontaneous recurrent seizures as detected by chronic video-electroencephalographic (video-EEG) recordings. This finding supports a novel application for IVIg, specifically its repurposing as a disease-modifying therapy in epilepsy. PMID:28074934

  20. Aluminum in the diet and Alzheimer's disease: from current epidemiology to possible disease-modifying treatment.

    Science.gov (United States)

    Frisardi, Vincenza; Solfrizzi, Vincenzo; Capurso, Cristiano; Kehoe, Patrick G; Imbimbo, Bruno P; Santamato, Andrea; Dellegrazie, Flora; Seripa, Davide; Pilotto, Alberto; Capurso, Antonio; Panza, Francesco

    2010-01-01

    In recent years, interest in the potential role of metals in the pathogenesis of Alzheimer's disease (AD) has grown considerably. In particular, aluminum (Al) neurotoxicity was suggested after its discovery in the senile plaques and neurofibrillary tangles that represent the principal neuropathological hallmarks of AD. Al is omnipresent in everyday life and can enter the human body from several sources, most notably from drinking water and food consumption. The evidence supporting association from ingestion of Al from drinking water is somewhat stronger than for its ingestion from food. However, other elements present in drinking water, such as fluoride, copper, zinc, or iron could also have an effect on cognitive impairment or modify any Al neurotoxicity. Some epidemiological studies, but not all, suggested that silica could be protective against Al damage, because it reduces oral absorption of Al and/or enhances Al excretion. Some epidemiological investigations suggested an association between chronic exposure to Al and risk of AD, although this relationship falls short of all the criteria generally attributed to causation. Future studies need to be more rigorous to truly test the validity of previous findings and in doing so attempt to identify dose-response relationships between Al and AD risk which may provide new routes to disease-modifying treatment of AD or possibly some lifestyle modification, to supplement existing symptomatic approaches.

  1. Involvement of NFκB in the antirheumatic potential of Chenopodium album L., aerial parts extracts.

    Science.gov (United States)

    Arora, Sumit K; Itankar, Prakash R; Verma, Prashant R; Bharne, Ashish P; Kokare, Dadasaheb M

    2014-08-08

    Chenopodium album L. (C. album) is commonly known as Bathua in Hindi (Family: Chenopodiaceae). Traditionally, the plant is used as a laxative, diuretic, sedative and the infusion of the plant is used for the treatment of rheumatism. However, no scientific validation is available on the antirheumatic potential of the plant. In the present investigation, role of NF kappa B (NFκB) in the antiarthritic potential of extracts of aerial parts of Chenopodium album was explored and evaluated. The defatted aerial parts of Chenopodium album were successively extracted with ethylacetate, acetone, methanol and 50% methanol to study their antioxidant capacity followed by antiarthritic potential using Complete Freund׳s adjuvant (CFA) induced arthritis model in rats. The polyphenol, flavonoid and flavanone contents of different extracts were quantified and correlated with their antioxidant capacity, antiarthritic activity and NFκB inhibition potential. The experimental data indicated that the acetone extract of Chenopodium album (ACCA) has shown significant reduction in rat paw edema (80.13%) at dose level of 200 mg/kg per oral in 21 days of this study. On 22nd day, hematological and biochemical parameters were estimated and it was observed that the altered hematological parameters (Hb, RBC, WBC and ESR), biochemical parameters (Serum creatinine, total proteins and acute phase proteins) and loss in body weight in the arthritic rats were significantly brought back to near normal level by the ACCA extract. ACCA extract significantly decreased the NFκB expression in paraventricular nucleus of hypothalamus and this effect is comparable with standard indomethacine in CFA treated rats. The polyphenolic and flavonoid content of different extracts were in the range of 14.56±0.21-42.00±0.2 mg (gallic acid equivalent/g extract) and 2.20±0.003-7.33±0.5 mg (rutin equivalent/g extract) respectively. The antiarthritic activity possessed by ACCA extract can be correlated directly to its

  2. Pharmacology of sinomenine, an anti-rheumatic alkaloid from Sinomenium acutum

    Directory of Open Access Journals (Sweden)

    Yamasaki,Hidemasa

    1976-02-01

    -receptors probably on fibroblasts (for granulation tissue growth and on T-cells (for adjuvant arthritis, since these effects were clearly inhibited by the H2-antagonist burimamide but not by the H1-antagonist mepyramine. The anti-rheumatic effect on Sinomenium acutum are probably genuine and can probably be attributed to the histamine-releasing properties of sinomenine.

  3. Drug retention rates and treatment discontinuation among anti-TNF-α agents in psoriatic arthritis and ankylosing spondylitis in clinical practice.

    Science.gov (United States)

    Fabbroni, Marta; Cantarini, Luca; Caso, Francesco; Costa, Luisa; Pagano, Veronica Anna; Frediani, Bruno; Manganelli, Stefania; Galeazzi, Mauro

    2014-01-01

    The study aim was to determine treatment persistence rates and to identify causes of discontinuation in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients in clinical practice. Patients treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) were retrospectively included. Treatment persistence rates were analyzed by means of a stepwise logistic regression. Differences between therapy duration were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease considering completed courses of therapy versus courses that were discontinued. 268 patients received a total of 353 anti-TNF treatment courses (97 ADA, 180 ETA, and 76 INF). Comparison among therapies showed significant difference regarding the treatment persistence rates due to the contrast between ETA and INF (P = 0.0062). We observed that 84.7% of patients were still responding after 6 months of follow-up. Comparison among diseases showed that there were significant differences between PsA and AS (P = 0.0073) and PsA and PsA with predominant axial involvement (P = 0.0467) in terms of duration of the therapy, while there were no significant differences with regard to the persistence rate. In this cohort, anti-TNF-α therapy was associated with high drug persistence rates. As in rheumatoid arthritis, switching to another anti-TNF-α agent can be an effective option when, during the treatment of AS or PsA, therapy is suspended because of inefficacy or an adverse event. Combination therapy with DMARDs was associated with a better persistence rate.

  4. From bariatric to metabolic surgery: Looking for a "disease modifier" surgery for type 2 diabetes.

    Science.gov (United States)

    Cordera, Renzo; Adami, Gian Franco

    2016-01-25

    In this review the recent evolution of the comprehension of clinical and metabolic consequences of bariatric surgery is depicted. At the beginning bariatric surgery aim was a significant and durable weight loss. Later on, it became evident that bariatric surgery was associated with metabolic changes, activated by unknown pathways, partially or totally independent of weight loss. Paradigm of this "metabolic" surgery is its effects on type 2 diabetes mellitus (T2DM). In morbid obese subjects it was observed a dramatic metabolic response leading to decrease blood glucose, till diabetes remission, before the achievement of clinically significant weight loss, opening the avenue to search for putative anti-diabetic "intestinal" factors. Both proximal duodenal (still unknown) and distal (GLP1) signals have been suggested as hormonal effectors of surgery on blood glucose decrease. Despite these findings T2DM remission was never considered a primary indication for bariatric surgery but only a secondary one. Recently T2DM remission in obese subjects with body mass index (BMI) greater than 35 has become a primary aim for surgery. This change supports the idea that "metabolic surgery" definition could more appropriate than bariatric, allowing to explore the possibility that metabolic surgery could represent a "disease modifier" for T2DM. Therefore, several patients have undergone surgery with a primary aim of a definitive cure of T2DM and today this surgery can be proposed as an alternative therapy. How much surgery can be considered truly metabolic is still unknown. To be truly "metabolic" it should be demonstrated that surgery could cause T2DM remission not only in subjects with BMI > 35 but also with BMI < 35 or even < 30. Available evidence on this topic is discussed in this mini-review.

  5. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies.

    Science.gov (United States)

    Wingerchuk, Dean M; Carter, Jonathan L

    2014-02-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating central nervous system disease that typically strikes young adults, especially women. The pathobiology of MS includes inflammatory and neurodegenerative mechanisms that affect both white and gray matter. These mechanisms underlie the relapsing, and often eventually progressive, course of MS, which is heterogeneous; confident prediction of long-term individual prognosis is not yet possible. However, because revised MS diagnostic criteria that incorporate neuroimaging data facilitate early diagnosis, most patients are faced with making important long-term treatment decisions, most notably the use and selection of disease-modifying therapy (DMT). Currently, there are 10 approved MS DMTs with varying degrees of efficacy for reducing relapse risk and preserving neurological function, but their long-term benefits remain unclear. Moreover, available DMTs differ with respect to the route and frequency of administration, tolerability and likelihood of treatment adherence, common adverse effects, risk of major toxicity, and pregnancy-related risks. Thorough understanding of the benefit-risk profiles of these therapies is necessary to establish logical and safe treatment plans for individuals with MS. We review the available evidence supporting risk-benefit profiles for available and emerging DMTs. We also assess the place of individual DMTs within the context of several different MS management strategies, including those currently in use (sequential monotherapy, escalation therapy, and induction and maintenance therapy) and others that may soon become feasible (combination approaches and "personalized medicine"). We conducted this review using a comprehensive search of MEDLINE, PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from January 1, 1990, to August 31, 2013. The following search terms were used: multiple sclerosis, randomized controlled trials

  6. Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications.

    Science.gov (United States)

    Charles, Ellen F; Lambert, Christophe G; Kerner, Berit

    2016-12-01

    Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors. In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly. A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review. We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2). Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes. The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex

  7. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Science.gov (United States)

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  8. An update on methotrexate pharmacogenetics in rheumatoid arthritis.

    Science.gov (United States)

    Ranganathan, Prabha

    2008-04-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disorder that mainly affects the joints. When left untreated, the disease can result in irreversible joint damage with high morbidity and mortality. Disease-modifying antirheumatic drugs are the cornerstones of treatment in RA. Disease-modifying antirheumatic drugs not only ameliorate the clinical signs and symptoms of disease, but also prevent the radiographic progression of joint damage. Methotrexate is one such disease-modifying antirheumatic drug that has been used in the treatment of RA for over two decades with excellent long-term efficacy and safety. However, there is significant variability in patients' response to methotrexate, both in terms of efficacy and toxicity. At the present time, there are no reliable means of predicting, a priori, an individual patient's response to methotrexate. In this review, recent published literature on the pharmacogenetics of methotrexate in RA is highlighted. Pharmacogenetics may be a powerful tool for optimizing methotrexate therapy in patients with RA.

  9. Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase Ⅱ clinical trial

    Institute of Scientific and Technical Information of China (English)

    鲍春德; 陈顺乐; 顾越英; 劳志英; 倪立青; 於强; 徐建华; 李向培; 刘嘉玲; 孙凌云; 何培根; 马骥良; 徐淑云; 丁长海

    2003-01-01

    Objective To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.Methods Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks.Results Both leflunomide and MTX could improve the symptoms, signs, and joint function, but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group, the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group, the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis, the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively, compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups (P>0.05). The adverse events in the leflunomide group were gastrointestinal symptoms, skin rash, alopecia, nervous system symptoms, decreased leukocyte count, and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%, significantly lower than that in MTX group (28.17%, P=0.002).Conclusions Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX, but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.

  10. Predicting the potential public health impact of disease-modifying HIV vaccines in South Africa: the problem of subtypes.

    Science.gov (United States)

    Blower, Sally M; Bodine, Erin N; Grovit-Ferbas, Kathie

    2005-06-01

    Current HIV vaccines in development appear unlikely to prevent infection, but could provide benefits by increasing survival; such vaccines are described as disease-modifying vaccines. We review the current status of vaccines and modeling vaccines. We also predict the impact that disease-modifying vaccines could have in South Africa, where multiple subtypes are co-circulating. We model transmissibility/fitness differences among subtypes. We used uncertainty analyses to model vaccines with four characteristics: (i) take, (ii) duration of immunity, (iii) reduction in transmissibility/fitness, and (iv) increase in survival. We reconstructed, and forecasted, the South African epidemic from 1940 to 2140 (assuming no vaccination). We predict that: (i) incidence will peak in 2014, decline, and stabilize, (ii) prevalence will continue to rise, and (iii) the AIDS death rate curve will peak in 2022. Our predictions show that (over the next 135 years) the epidemic in South Africa will switch from a predominantly Subtype C epidemic to an epidemic driven by other subtypes. We predict that the epidemic could remain unchanged, even with mass vaccination with a vaccine that is equally effective against all co-circulating subtypes. However, if the non-C subtypes are less (or equally) transmissible as Subtype C then disease-modifying vaccines could result in eradication. Thus, in countries where multiple-subtypes are co-circulating it is critical to realize that small biological differences among subtypes will have dramatic consequences for the effectiveness of HIV vaccination campaigns. A slight difference in fitness will determine whether a disease-modifying vaccine has almost no impact on the epidemic or can achieve eradication.

  11. Disease modifying and antiangiogenic activity of 2-methoxyestradiol in a murine model of rheumatoid arthritis.

    Science.gov (United States)

    Plum, Stacy M; Park, Eun J; Strawn, Steve J; Moore, Elizabeth G; Sidor, Carolyn F; Fogler, William E

    2009-05-01

    into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1beta, TNF-alpha, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2. These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.

  12. Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Moore Elizabeth G

    2009-05-01

    study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2. Conclusion These data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.

  13. Patient perspectives on switching disease-modifying therapies in the NARCOMS registry

    Directory of Open Access Journals (Sweden)

    Salter AR

    2014-07-01

    Full Text Available Amber R Salter,1 Ruth Ann Marrie,2,3 Neetu Agashivala,4 Daniel A Belletti,4 Edward Kim,4 Gary R Cutter,1 Stacey S Cofield,1 Tuula Tyry51Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Internal Medicine, 3Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada; 4Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 5Division of Neurology, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USAIntroduction: The evolving landscape of disease-modifying therapies (DMTs for multiple sclerosis raises important questions about why patients change DMTs. Physicians and patients could benefit from a better understanding of the reasons for switching therapy. Purpose: To investigate the reasons patients switch DMTs and identify characteristics associated with the decision to switch.Method: The North American Research Committee on Multiple Sclerosis (NARCOMS Registry conducted a supplemental survey among registry participants responding to the 2011 update survey. The supplemental survey investigated reasons for switching DMT, origin of the discussion of DMT change, and which factors influenced the decision. Chi-square tests, Fisher’s exact tests, and logistic regression were used for the analyses. Results: Of the 691 eligible candidates, 308 responded and met the inclusion criteria (relapsing disease course, switched DMT after September 2010. The responders were 83.4% female, on average 52 years old, with a median (interquartile range Patient-Determined Disease Steps score of 4 (2–5. The most recent prior therapy included first-line injectables (74.5%, infusions (18.1%, an oral DMT (3.4%, and other DMTs (4.0%. The discussion to switch DMT was initiated almost equally by physicians and participants. The primary reason for choosing the new DMT was based most frequently on physician’s recommendation (24.5% and patient perception of efficacy (13.7%. Conclusion

  14. Patient preferences for treatment of multiple sclerosis with disease-modifying therapies: a discrete choice experiment

    Directory of Open Access Journals (Sweden)

    Garcia-Dominguez JM

    2016-09-01

    Full Text Available José Manuel Garcia-Dominguez,1 Delicias Muñoz,2 Marta Comellas,3 Irmina Gonzalbo,3 Luis Lizán,3 Carlos Polanco Sánchez4 1Multiple Sclerosis Unit, Hospital General Universitario Gregorio Marañon, Madrid, 2Neurology Department, Hospital Universitario Alvaro Cunqueiro, Vigo, 3Outcomes’10, Jaime I University, Castellón, 4Health Economics & Outcomes Research, Merck, Madrid, Spain Objectives: To assess disease-modifying therapy (DMT preferences in a population of patients with multiple sclerosis (MS and to estimate the association between sociodemographic and clinical factors and these preferences. Methods: Preferences for DMTs attributes were measured using a discrete choice experiment. Analysis of preferences was assessed using mixed-logit hierarchical Bayes regression. A multilinear regression was used to evaluate the association between the preferences for each attribute and patients’ demographic and clinical characteristics. A Student’s t-test or Welch’s t-test was used for subgroup comparisons. Results: A total of 125 patients were included in the final analysis (62.9% female, mean age 44.5 years, 71.5% with relapsing-remitting MS diagnosis. The most important factor for patients was the possibility of suffering from the side effects of the treatment (relative importance [RI] =50%, followed by a delay in disease progression (RI =19.4%, and route and frequency of administration (RI =14.3%. According to maximum acceptable risk, patients were willing to accept an increase of 3.8% in severity of side effects, for a delay of 1 year in disease progression. Treatment duration was the most prevalent factor affecting preferences, followed by the age of patients, type of MS, level of education, and the type of current treatment. Patients treated orally were significantly more concerned about the route and frequency of administration (P=0.026 than patients on injectable therapy. Naïve patients stated significantly less importance to

  15. Patient preferences for treatment of multiple sclerosis with disease-modifying therapies: a discrete choice experiment

    Science.gov (United States)

    Garcia-Dominguez, José Manuel; Muñoz, Delicias; Comellas, Marta; Gonzalbo, Irmina; Lizán, Luis; Polanco Sánchez, Carlos

    2016-01-01

    Objectives To assess disease-modifying therapy (DMT) preferences in a population of patients with multiple sclerosis (MS) and to estimate the association between sociodemographic and clinical factors and these preferences. Methods Preferences for DMTs attributes were measured using a discrete choice experiment. Analysis of preferences was assessed using mixed-logit hierarchical Bayes regression. A multilinear regression was used to evaluate the association between the preferences for each attribute and patients’ demographic and clinical characteristics. A Student’s t-test or Welch’s t-test was used for subgroup comparisons. Results A total of 125 patients were included in the final analysis (62.9% female, mean age 44.5 years, 71.5% with relapsing-remitting MS diagnosis). The most important factor for patients was the possibility of suffering from the side effects of the treatment (relative importance [RI] =50%), followed by a delay in disease progression (RI =19.4%), and route and frequency of administration (RI =14.3%). According to maximum acceptable risk, patients were willing to accept an increase of 3.8% in severity of side effects, for a delay of 1 year in disease progression. Treatment duration was the most prevalent factor affecting preferences, followed by the age of patients, type of MS, level of education, and the type of current treatment. Patients treated orally were significantly more concerned about the route and frequency of administration (P=0.026) than patients on injectable therapy. Naïve patients stated significantly less importance to prevention of relapses (P=0.021) and deterioration of the capacity for performing usual daily life activities (P=0.015). Finally, patients with >5 years since diagnosis were significantly less concerned about preventing disease progression (P=0.021), and more concerned about treatment side effects (P=0.052) than compared with patients with <5 years of MS history. Conclusion The most important attribute for

  16. Drug: D00827 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available N) C14H10MgO6. 4H2O 370.075 370.5917 D00827.gif Analgesic; Antipyretic; Antirheumatic cyclooxygenase-1 (COX-...1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO:K11987] hsa00590(5742...P) Target-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase-1 (COX-1) [HSA:5...742] [KO:K00509] Magnesium salicylate D00827 Magnesium salicylate (USP) cyclooxygenase

  17. Drug: D00510 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00510.gif Antirheumatic Same as: C07440 ATC code: M01AA01 M02AA01 Pyrazolon derivative cyclooxygenase-1 (C...OX-1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO:K11987] hsa00590(5...ed classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase-1 (COX-1) [HSA:5742] [KO:K005...09] Phenylbutazone [ATC:M01AA01 M02AA01] D00510 Phenylbutazone (JP16/USP/INN) cyclooxygenase-2 (COX-2) [HSA:

  18. Drug: D05319 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05319.gif Anti-inflammatory; Antirheumatic ATC code: M01AA03 M02AA04 S01BC02 NSAIDs cyclooxygenase-1 (COX-...1) inhibitor [HSA:5742] [KO:K00509]; cyclooxygenase-2 (COX-2) inhibitor [HSA:5743] [KO:K11987] hsa00590(5742...05319 Oxyphenbutazone hydrate Target-based classification of drugs [BR:br08310] Enzymes Oxidoreductases cyclooxygenase...-1 (COX-1) [HSA:5742] [KO:K00509] Oxyphenbutazone [ATC:M01AA03] D05319 Oxyphenbutazone hydrate cyclooxygenase

  19. Drug: D04078 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04078 Drug Chondroitin sulfate sodium (JAN); Chondron (TN) (C14H20NO14S. Na)n D040...ng metabolism 399 Miscellaneous 3991 Chondroitins D04078 Chondroitin sulfate sodium (JAN) Anatomical Therape...X Other antiinflammatory and antirheumatic agents, non-steroids M01AX25 Chondroitin sulfate D04078 Chondroitin...ndroitin sulfate sodium (JAN) 3 Agents affecting metabolism 39 Other agents affecti... system and sensory organs 13 Agents affecting sensory organs 131 Ophthalmic agents 1319 Others D04078 Cho

  20. Drug: D04003 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04003 Drug Enolicam sodium (USAN); Enolicam sodium monohydrate C17H11Cl3NO4S. Na. ...H2O 470.9478 472.7026 D04003.gif Anti-inflammatory; Antirheumatic CAS: 73574-69-3 PubChem: 17397998 LigandBox: D0400...1855 -11.6538 24 O3c O 23.5775 -11.2349 25 O3c O 21.5976 -11.2349 26 X Cl 29.5390 -14.1231 27 Z Na 19.0400 -

  1. 77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

    Science.gov (United States)

    2012-10-01

    ... for Peripheral Neuropathy; Public Workshop; Request for Comments AGENCY: Food and Drug Administration...-modifying agents for the treatment of peripheral neuropathy. Discussion will focus on possible therapeutic targets for these agents, the types of painful peripheral neuropathies amenable to treatment with disease...

  2. [Treatment of rheumatoid arthritis by inhibition of tumor necrosis factor with infliximab or etanercept

    NARCIS (Netherlands)

    Tijhuis, G.J.; Putte, L.B.A. van de; Breedveld, F.C.

    2001-01-01

    The current pharmacotherapy of rheumatoid arthritis (RA) consists of non-steroidal anti inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) such as sulphasalazine, leflunomide and methotrexate. DMARDs can be given as monotherapy or in combination. However, not all patients

  3. A decade of biologic treatment observation in juvenile idiopathic arthritis: Lessons learned from the Dutch ABC Register

    NARCIS (Netherlands)

    M.H. Otten (Marieke)

    2012-01-01

    textabstractSince 1999, the treatment of juvenile idiopathic arthritis (JIA) has been extended with a new category of drugs: biologic agents (also known as biologicals or biologic disease modifying anti-rheumatic drugs). Biologic agents consist of natural proteins, like antibodies and cytokines, and

  4. What is animal experimentation telling us about new drug treatments of status epilepticus?

    Science.gov (United States)

    Nehlig, Astrid

    2007-01-01

    Basic research is mostly focused on the consequences of status epilepticus (SE) in terms of neuronal loss, behavior, epileptogenesis or disease-modifying effects such as preventing epilepsy or reducing seizure severity. Among the drugs tested, several were able to trigger neuroprotection but only a few had disease-modifying effects. At this point, many data are still missing, namely which drugs could efficiently stop SE or which mechanisms of action should be searched for to prevent the harmful consequences of SE.

  5. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use

    OpenAIRE

    Hazes, Johanna M.W.; Coulie, Pierre G; Geenen, Vincent; Vermeire, Severine; Carbonnel, Franck; Louis, Edouard; Masson, Pierre; de Keyser, Filip

    2011-01-01

    It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs aroun...

  6. Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera.

    Science.gov (United States)

    Casu, Carla; Oikonomidou, Paraskevi Rea; Chen, Huiyong; Nandi, Vijay; Ginzburg, Yelena; Prasad, Princy; Fleming, Robert E; Shah, Yatrik M; Valore, Erika V; Nemeth, Elizabeta; Ganz, Tomas; MacDonald, Brian; Rivella, Stefano

    2016-07-14

    In β-thalassemia and polycythemia vera (PV), disordered erythropoiesis triggers severe pathophysiological manifestations. β-Thalassemia is characterized by ineffective erythropoiesis, reduced production of erythrocytes, anemia, and iron overload and PV by erythrocytosis and thrombosis. Minihepcidins are hepcidin agonists that have been previously shown to prevent iron overload in murine models of hemochromatosis and induce iron-restricted erythropoiesis at higher doses. Here, we show that in young Hbb(th3/+) mice, which serve as a model of untransfused β-thalassemia, minihepcidin ameliorates ineffective erythropoiesis, anemia, and iron overload. In older mice with untransfused β-thalassemia, minihepcidin improves erythropoiesis and does not alter the beneficial effect of the iron chelator deferiprone on iron overload. In PV mice that express the orthologous JAK2 mutation causing human PV, administration of minihepcidin significantly reduces splenomegaly and normalizes hematocrit levels. These studies indicate that drug-like minihepcidins have a potential as future therapeutics for untransfused β-thalassemia and PV.

  7. Optimization of antiaggregant therapy in rheumatoid arthritis and coronary heart disease patients receiving nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Tatyana Vladimirovna Kropotina

    2012-01-01

    Full Text Available Objective: to study coagulative and vascular-thrombocytic hemostases in patients with rheumatoid arthritis (RA and coronary heart disease (CHD depending on therapy with different nonsteroidal anti-inflammatory drugs (NSAIDs alone and in combination with low-dose aspirin. Subjects and methods. The trial enrolled 58 patients (43 women and 15 men with a valid diagnosis of RA. The patients' mean age was 61.2 years; the disease duration averaged 10 years. All the patients received therapy with disease-modifying antirheumatic drugs (DMARDs and NSAIDs. All had CHD; 52 of the 58 patients presented with arterial hypertension; 30 had noncoronary atherosclerosis. Cardiovascular diseases were first identified in 18 patients. All took heart medications. Coagulative and vascular-thrombocytic hemostases were studied in all the patients and the results were compared depending on to the taken NSAID (diclofenac, tenoxicam, nimesulide, meloxicam. Thirty-seven patients who had not previously received antiaggregant therapy were given aspirin in a dose of 100 mg when they were found to have platelet hyperaggregation and aggregation was restudied on aspirin therapy days 7-8. A control group consisted of 26 healthy men (mean age 55 years who received no medications. Results. In patients with RA and CHD, activated coagulative hemostasis was identified in 65.5% of cases. The signs of hypercoagulation were observed in 35 of the 58 patients. When different NSAIDs were used, the coagulative hemostatic changes were unidirectional and no statistically significant differences were found between the groups. The patients taking diclofenac, nimesulide, or meloxicam were found to have activated vascular-thrombocytic hemostasis. Those receiving tenoxicam showed a tendency towards decreased adrenaline-induced platelet aggregation (the drug's aspirin-like effect; however, no statistical processing was made because of few cases. The use of aspirin in the patients taking diclofenac

  8. The impact of disease and antirheumatic therapy factors on growth retardation in children suffering from juvenile rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    T.M. Bzarova

    2006-01-01

    Full Text Available THE STUDY EVALUATED THE IMPACT OF REFRACTORY JUVENILE IDIOPATHIC ARTHRITIS (JIA AND INTERFERENCE OF ANTIRHEUMATIC THERAPY ON PHYSICAL STATURE AND GROWTH AND PHYSICAL DEVELOPMENT IN CHILDREN. WE OBSERVED 133 PATIENTS WITH JIA WITH AGE FROM 4.6 TO 18 YEARS. WE ASSESSED PATIENTS' PHYSICAL STATURE (DOCUMENTING HEIGHT AND WEIGHT AND FURTHER GROWTH AND DEVELOPMENT STARING FROM BIRTH, BEFORE THE ONSET OF JIA, AT THE FIRST YEAR FROM THE ONSET OF THE DISB EASE AND LATER ON. PHYSICAL RETARDATION WAS MARKED IN ALL CHILDREN IN THE FIRST YEAR FROM THE ONSET OF JIA. SYSTEMIC JIA, WHICH IS KNOWN FOR HIGH ACTIVITY AND POLYARTICULAR OR GENERALIZED JOINT LESION, WAS LINKED TO SIGNIFICANT PHYSICAL RETARDATION IN ALL CHILDREN WITH SYSBTEMIC JIA. LONGBTERM GLUCOCORTICOID ADMINISTRATION, EVEN AT LOW DOSES, ACCENTUATED THE NEGATIVE IMPACT OF JIA ON GROWTH RESULTING IN MARKED GROWTH DELAY OR ITS' TOTAL ARREST. WE HAVE ELABORATED RISK FACTORS FOR SHORT STATURE IN CHILDREN WITH JIA, WHICH SUGGEST THERAPY GUIDELINES, PRESENTED IN THIS ARTICLE.KEY WORDS: JUVENILE IDIOPATHIC ARTHRITIS, СHILDREN.

  9. A short history of anti-rheumatic therapy - VII. Biological agents

    Directory of Open Access Journals (Sweden)

    B. Gatto

    2011-11-01

    Full Text Available The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

  10. Drug: D06944 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06944 Formula, Drug Keishikajutsubuto Cinnamon bark [DR:D06712], Peony root [DR:D06739], Jujube [DR:D06758], Atractylodes lancea rhizome [DR:D06752], Glycyrrhiza [DR:D04365], Ginger [DR:D06744], Processed aconite root [DR:D06784] Arthralgia; Neuralgic Therapeutic category: 5200 Therapeutic category of drugs in Japan [BR:br08301] 5 Crude drugs and Chinese medicine formulations 52 Traditional Chinese medicines 520 Traditional Chinese medicines 5200 Traditional Chinese medicines D06944 Keishikajutsubuto Traditional Chinese Medicine in Japan [BR:br08304] Formulas Formulas for warming the interior Formulas for warming the interior D06944 *Keishikajutsubuto Formulas for dampness Antirheumatic formulas D06944 *Keishikajutsubuto PubChem: 51091286 ...

  11. Advances in the Development of Disease-Modifying Treatments for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Moujalled, Diane; White, Anthony R

    2016-03-01

    Amyotrophic lateral sclerosis (ALS) is a progressive adult-onset, neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Over recent years, numerous genes ha ve been identified that promote disease pathology, including SOD1, TARDBP, and the expanded hexanucleotide repeat (GGGGCC) within C9ORF72. However, despite these major advances in identifying genes contributing to ALS pathogenesis, there remains only one currently approved therapeutic: the glutamate antagonist, riluzole. Seminal breakthroughs in the pathomechanisms and genetic factors associated with ALS have heavily relied on the use of rodent models that recapitulate the ALS phenotype; however, while many therapeutics have proved to be significant in animal models by prolonging life and rescuing motor deficits, they have failed in human clinical trials. This may be due to fundamental differences between rodent models and human disease, the fact that animal models are based on overexpression of mutated genes, and confounding issues such as difficulties mimicking the dosing schedules and regimens implemented in mouse models to humans. Here, we review the major pathways associated with the pathology of ALS, the rodent models engineered to test efficacy of candidate drugs, the advancements being made in stem cell therapy for ALS, and what strategies may be important to circumvent the lack of successful translational studies in the clinic.

  12. The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Georgios Tsivgoulis

    Full Text Available The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS using available randomized-controlled trial (RCT data.We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4. The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001. We detected no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19 nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16. In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001 and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04; p<0.001. However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA.DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.

  13. Cognitive dysfunction in patients with multiple sclerosis treated with first-line disease-modifying therapy: a multi-center, controlled study using the BICAMS battery.

    Science.gov (United States)

    Cinar, Bilge Piri; Kösehasanoğulları, Görkem; Yigit, Pinar; Ozakbas, Serkan

    2017-02-01

    Multiple sclerosis (MS) can impair cognitive functions even in the early stages. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery is very short and highly sensitive and can be used to evaluate cognitive status in the disease. Several clinical trials have shown beneficial effects of disease-modifying drugs (DMDs) on long-term cognitive measures which may even reduce cognitive deficits in MS patients. Relapsing remitting MS patients using DMDs were enrolled in the study and monitored for 12 months. BICAMS and the Expanded Disability Status Scale were applied to the study group. We evaluated and monitored 161 newly diagnosed cases of definite MS by the end of the trial. 110 patients (68.2%) were female. One hundred and two healthy subjects (female to male ratio 68:34) were enrolled into the study. MS patients were categorized into three DMT groups: IFNB1-a SC, IFNB1-b, and GA. Mean scores of all three cognitive tests (SDMT, BVMT-R, and CVLT-II) were significantly higher in the control group than in the MS patients. The number of cognitively impaired patients decreased from 31.7 to 21.7% on the basis of CVLT (p = 0.024), and 42 (26.1%) to 30 (18.6%) on the basis of BVMT-R at month 12. A significant difference was determined in terms of cognitive status between MS patients using both IFNB and GA and the healthy control group. Ours is the first study to compare IFNB and GA in terms of evaluating cognitive involvement and to use the BICAMS battery in monitoring treatment.

  14. The Effect of Disease Modifying Therapies on Disease Progression in Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Georgios Tsivgoulis

    Full Text Available A number of officially approved disease-modifying drugs (DMD are currently available for the early intervention in patients with relapsing-remitting multiple sclerosis (RRMS. The aim of the present study was to systematically evaluate the effect of DMDs on disability progression in RRMS.We performed a systematic review on MEDLINE and SCOPUS databases to include all available placebo-controlled randomized clinical trials (RCTs of RRMS patients that reported absolute numbers or percentages of disability progression during each study period. Observational studies, case series, case reports, RCTs without placebo subgroups and studies reporting the use of RRMS therapies that are not still officially approved were excluded. Risk ratios (RRs were calculated in each study protocol to express the comparison of disability progression in RRMS patients treated with a DMD and those RRMS patients receiving placebo. The mixed-effects model was used to calculate both the pooled point estimate in each subgroup and the overall estimates.DMDs for RRMS were found to have a significantly lower risk of disability progression compared to placebo (RR = 0.72, 95%CI: 0.66-0.79; p20% rates of loss to follow-up were reported in many study protocols, while financial and/or other support from pharmaceutical industries with a clear conflict of interest on the study outcomes was documented in all included studies.Available DMD are effective in reducing disability progression in patients with RRMS, independently of the route of administration and their classification as "first" or "second" line therapies. Attrition bias needs to be taken into account in the interpretation of these findings.

  15. IMPACT OF THE SELECTIVITY AND HALF-LIFE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS ON THE DEVELOPMENT OF SUBCLINICAL KIDNEY INJURY

    Directory of Open Access Journals (Sweden)

    S. A. Zhigalov

    2016-01-01

    Full Text Available Objective: to investigate the impact of the selectivity and half-life of nonsteroidal anti-inflammatory drugs (NSAIDs on the development of subclinical kidney injury (SKI. A standard physical examination was made.Patients and methods. The study included 80 patients with a verified rheumatoid arthritis (RA diagnosis. The patients filled in a specially designed questionnaire to explore a history of drug use. As markers of SKI, the investigators determined the concentrations of albumin, α1-microglobulin (α1-MG, alanine aminotransferase (ALT, and alkaline phosphatase (ALP in urine. A control group consisted of 20 apparently healthy individuals matched for age and gender.Results. 80 patients suffering from RA received drug therapy. Of them, 82.5% and 87.5% took NSAIDs and disease-modifying antirheumatic drugs, respectively. The levels of SKI markers were compared in three groups of the examinees: 1 NSAID-treated patients; 2 NSAID-untreated patients; 3 a control group. There were statistically significant differences between all the groups (p<0.05. Comparison of the levels of SKI markers revealed no statistically significant difference in the groups receiving selective cyclooxygenase-2 (COX-2 inhibitors (n=18.6%, in those taking nonselective ones (n=68.6%, and the control group. Comparison of the levels of SKI markers demonstrated significantly higher >< 0.05. Comparison of the levels of SKI markers revealed no statistically significant difference in the groups receiving selective cyclooxygenase-2 (COX-2 inhibitors (n=18.6%, in those taking nonselective ones (n=68.6%, and the control group. Comparison of the levels of SKI markers demonstrated significantly higher α1-MG levels in the long-acting NSAID groups (n=8.6% than in the short-acting NSAID group (n=80%. ALT, ALP, and microalbuminuria showed a similar trend that failed to reach statistical significance.Conclusion: NSAIDs remain a group of medications with a certain nephrotoxic effect. At the

  16. Anti-tumor necrosis factor (TNF drugs for the treatment of psoriatic arthritis: an indirect comparison meta-analysis

    Directory of Open Access Journals (Sweden)

    Thorlund K

    2012-12-01

    Full Text Available Kristian Thorlund,1 Eric Druyts,2 J Antonio Aviña-Zubieta,3,4 Edward J Mills1,21Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; 2Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; 3Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 4Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, CanadaObjective: To evaluate the comparative effectiveness of available tumor necrosis factor-a inhibitors (anti-TNFs for the management of psoriatic arthritis (PsA in patients with an inadequate response to disease-modifying antirheumatic drugs (DMARDs.Methods: We used an exhaustive search strategy covering randomized clinical trials, systematic reviews and health technology assessments (HTA published on anti-TNFs for PsA. We performed indirect comparisons of the available anti-TNFs (adalimumab, etanercept, golimumab, and infliximab measuring relative risks (RR for the psoriatic arthritis response criteria (PsARC, mean differences (MDs for improvements from baseline for the Health Assessment Questionnaire (HAQ by PsARC responders and non-responders, and MD for the improvements from baseline for the psoriasis area and severity index (PASI. When the reporting of data on intervention group response rates and improvements were incomplete, we used straightforward conversions based on the available data.Results: We retrieved data from 20 publications representing seven trials, as well as two HTAs. All anti-TNFs were significantly better than control, but the indirect comparison did not reveal any statistically significant difference between the anti-TNFs. For PsARC response, golimumab yielded the highest RR and etanercept the second highest; adalimumab and infliximab both yielded notably smaller RRs. For HAQ improvement, etanercept and infliximab yielded the largest MD among PsARC responders

  17. The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.

    NARCIS (Netherlands)

    Flendrie, M.; Creemers, M.C.W.; Welsing, P.M.J.; Riel, P.L.C.M. van

    2005-01-01

    OBJECTIVE: To investigate the influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in rheumatoid arthritis (RA) and to compare it to infliximab in combination with other disease-modifying anti-rheumatic drugs. METHODS: RA patients starting infliximab the

  18. Lefunomide in combination therapy

    NARCIS (Netherlands)

    Kalden, J.R.; Smolen, J.S.; Emery, P.; Riel, P.L.C.M. van; Dougados, M.; Strand, C.V.; Breedveld, F.C.

    2004-01-01

    In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficaci

  19. End-stage rheumatoid arthritis: specific features of patient management

    Directory of Open Access Journals (Sweden)

    Nadezhda Aleksandrovna Shostak

    2013-01-01

    Full Text Available The paper provides data on the treatment of patients with end-stage rheumatoid arthritis (RA and a rationale for the long-term treatment with disease-modifying antirheumatic drugs, including leflunomide as a first-line agent. It describes a clinical case of a patient with end-stage RA during arava treatment.

  20. Vagal influences in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Rasmussen, S E; Pfeiffer-Jensen, M; Drewes, A M

    2017-01-01

    Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease with a prevalence of 0.5-1% in Western populations. Conventionally, it is treated with therapeutic interventions that include corticosteroids, disease-modifying anti-rheumatic drugs, and biological agents. RA exerts...

  1. Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)

    NARCIS (Netherlands)

    S. Ramiro; H. Radner; D. van der Heijde; A. van Tubergen; R. Buchbinder; D. Aletaha; R.B.M. Landewé

    2011-01-01

    Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA), ankylosi

  2. Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent

    DEFF Research Database (Denmark)

    Courvoisier, D S; Alpizar-Rodriguez, D; Gottenberg, J E;

    2016-01-01

    BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries...

  3. [The patient with arthritis: care by both general practitioners and rheumatologists].

    NARCIS (Netherlands)

    Janssens, H.; Lisdonk, E.H. van de; Janssen, M.

    2011-01-01

    Early aggressive treatment of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs such as TNF inhibitors prevents joint damage and improves the quality of life. There is increasing insight regarding the cardiovascular risks of patients suffering from RA or gout. These aspects and

  4. Non-canonical NF-κB signaling in rheumatoid arthritis and beyond

    NARCIS (Netherlands)

    Noort, A.R.

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, affecting the synovial joints. During the last 20 years the treatment of RA has markedly improved. Patients are nowadays not only treated with conventional disease-modifying antirheumatic drugs (DMARDs), but also with targeted

  5. Relevance of Tc-99m-HYNIC-tir-octreotide scintigraphy in a patient affected by sarcoidosis with lung and joints involvement and secondary Sjogren's syndrome treated with infliximab : Case report

    NARCIS (Netherlands)

    Migliore, A.; Signore, A.; Capuano, A.; Bizzi, E.; Massafra, U.; Vacca, F.; Todino, V.; Chianello, M.

    2008-01-01

    We report the case of a 59 years old woman affected by lung and joint sarcoidosis, secondary Sjogren's syndrome refractory to common disease-modifying antirheumatic drugs (DMARDs) that regressed with infliximab and methotrexate. Tc-99m-HYNIC- TOC scintigraphy was useful in diagnosis, choice of

  6. On the interactions of leflunomide and teriflunomide within receptor cavity — NMR studies and energy calculations

    OpenAIRE

    Kujawski, Jacek; Bernard, Marek K.; Jodłowska, Elżbieta; Czaja, Kornelia; Drabińska, Beata

    2015-01-01

    Leflunomide is a disease-modifying antirheumatic drug with antiinflammatory and immunosuppressive activity used for the treatment of psoriatic and rheumatoid arthritis. It undergoes rapid metabolization to teriflunomide, a metabolite that is responsible for the biological activity of leflunomide. Continuing our investigations on the interactions of biologically important azahetarenes with the environment, we focused on leflunomide and its active metabolite, teriflunomide, considering the inte...

  7. Glucocorticoids in early rheumatoid arthritis

    NARCIS (Netherlands)

    Everdingen, Amalia A. van

    2002-01-01

    For 50 years, glucocorticoids (GC) are used for symptomatic treatment of rheumatoid arthritis (RA). In the last decade, results from clinical studies of treatment with GC as additional therapy to long-acting antirheumatic drugs in patients with early RA suggested also disease-modifying properties of

  8. Proteasome inhibitors as experimental therapeutics of autoimmune diseases

    NARCIS (Netherlands)

    Verbrugge, Sue Ellen; Scheper, Rik J; Lems, Willem F; de Gruijl, Tanja D; Jansen, Gerrit

    2015-01-01

    Current treatment strategies for rheumatoid arthritis (RA) consisting of disease-modifying anti-rheumatic drugs or biological agents are not always effective, hence driving the demand for new experimental therapeutics. The antiproliferative capacity of proteasome inhibitors (PIs) has received consid

  9. [The patient with arthritis: care by both general practitioners and rheumatologists].

    NARCIS (Netherlands)

    Janssens, H.; Lisdonk, E.H. van de; Janssen, M.

    2011-01-01

    Early aggressive treatment of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs such as TNF inhibitors prevents joint damage and improves the quality of life. There is increasing insight regarding the cardiovascular risks of patients suffering from RA or gout. These aspects and ot

  10. Brief report

    DEFF Research Database (Denmark)

    Ammitzbøll, Christian G; Thiel, Steffen; Jensenius, Jens C

    2013-01-01

    To assess plasma M-ficolin concentrations in disease-modifying antirheumatic drug (DMARD)-naive patients with early rheumatoid arthritis (RA), to investigate the correlation of M-ficolin concentrations with disease activity markers, and to determine the predictive value of M-ficolin with respect ...

  11. Effect of IL-6R Inhibition with Tocilizumab on the Proteome of Peripheral Blood Mononuclear Cells from a Rheumatoid Arthritis Patient

    DEFF Research Database (Denmark)

    Meyer, Michael Kruse; Andersen, Marlene; Bennike, Tue Bjerg

    2015-01-01

    Abstract Objective: The availability of biological disease-modifying anti-rheumatic drugs (bDMARDs) has increased during the last decade, and while focus has been on treating clinical symptoms, the associated changes in the immune system remains poorly understood. Several key immunological regula...

  12. Effectiveness of a group-based intervention to change medication beliefs and improve medication adherence in patients with rheumatoid arthritis: a randomized controlled trial.

    NARCIS (Netherlands)

    Zwikker, H.E.; Ende, C.H. van den; Lankveld, W.G. van; Broeder, A.A. den; Hoogen, F.H. van den; Mosselaar, B. van de; Dulmen, S. van; Bemt, B.J. van den

    2014-01-01

    Objective: To assess the effect of a group-based intervention on the balance between necessity beliefs and concern beliefs about medication and on medication non-adherence in patients with rheumatoid arthritis (RA). Methods: Non-adherent RA patients using disease-modifying anti-rheumatic drugs (DMAR

  13. Early cost-utility analysis of general and cerebrospinal fluid-specific Alzheimer's disease biomarkers for hypothetical disease-modifying treatment decision in mild cognitive impairment

    NARCIS (Netherlands)

    Handels, Ron L. H.; Joore, Manuela A.; Tran-Duy, An; Wimo, Anders; Wolfs, Claire A. G.; Verhey, Frans R. J.; Severens, Johan L.

    2015-01-01

    Introduction: The study aimed to determine the room for improvement of a perfect cerebrospinal fluid (CSF) biomarker and the societal incremental net monetary benefit of CSF in subjects with mild cognitive impairment (MCI) assuming a hypothetical disease-modifying Alzheimer's disease (AD) treatment.

  14. Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

    Directory of Open Access Journals (Sweden)

    Raed Alroughani

    2016-01-01

    Full Text Available The burden of multiple sclerosis (MS in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs, which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

  15. Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

    Science.gov (United States)

    Altintas, Ayse; Al Jumah, Mohammed; Sahraian, Mohammadali; Alsharoqi, Issa; AlTahan, Abdurahman; Dahdaleh, Maurice; Deleu, Dirk; Fernandez, Oscar; Inshasi, Jihad; Karabudak, Rana; Taha, Karim; Totolyan, Natalia; Yamout, Bassem I.; Zakaria, Magd; Bohlega, Saeed

    2016-01-01

    The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation. PMID:28078140

  16. Relapsing-remitting multiple sclerosis: patterns of response to disease-modifying therapies and associated factors: a national survey.

    Science.gov (United States)

    Sá, Maria José; de Sá, João; Sousa, Lívia

    2014-12-01

    Current treatments for relapsing-remitting multiple sclerosis (RRMS) are only partially effective. The objective of this study was to characterize treatment response in RRMS patients in Portugal to 12-month therapy with first-line disease-modifying therapies. In this retrospective study, neurologists at participating centers completed survey questionnaires using records of patients with RRMS who had received first-line treatment with one of five European Medicine Agency-approved agents in the 12 months prior to inclusion in the survey. Sub-optimal responders included patients treated for at least 1 year, and who had ≥1 relapse(s) or an increase of 1.5 points on the Expanded Disability Status Scale (EDSS; if baseline EDSS was 0) or an increase of ≥0.5 points (baseline EDSS ≥1). Optimal responders included patients treated for at least 1 year without relapse and who had an increase of EDSS (if baseline EDSS was 0) or no increase in EDSS (baseline EDSS ≥1). Data for 1,131 patients from 15 centers were analyzed. Twenty-six percent (95% confidence interval 23-28%) of patients had sub-optimal treatment response. Duration of therapy (P EDSS score (P EDSS score at baseline and did not differ among therapies. Neurologists should closely monitor patients to optimize treatment strategies and better control disease, improving prognosis.

  17. The instrumented Timed Up and Go test: Potential outcome measure for disease modifying therapies in Parkinson's disease

    Science.gov (United States)

    Zampieri, Cris; Salarian, Arash; Carlson-Kuhta, Patricia; Aminian, Kamiar; Nutt, John G.; Horak, Fay B.

    2011-01-01

    The Timed Up and Go (TUG) test has been used to assess balance and mobility in Parkinson’s Disease (PD). However, it is not known if this test is sensitive to subtle abnormalities present in early stages of the disease, when balance and gait problems are not clinically evident but may be detected with instrumented analysis of movement. We hypothesize that postural transitions and arm swing during gait will be the most sensitive characteristics of the TUG for early PD. In the present study, we instrumented the TUG test (iTUG) using portable inertial sensors, and extended the walking distance from 3 meters (traditional TUG) to 7 meters. Twelve subjects with early-to-moderate, untreated PD and 12 healthy individuals participated. Our findings show that although the stopwatch measure of TUG duration did not detect abnormalities in early-to-mid stage PD, the peak arm swing velocity on the more affected side, average turning velocity, cadence and peak trunk rotation velocity were significantly slower. These iTUG parameters were also correlated with the UPDRS Motor Scale. Thus, the iTUG test is sensitive to untreated PD and could potentially detect progression of PD and response to symptomatic and disease-modifying treatments. PMID:19726406

  18. Investigational drugs for the management of Huntington's disease: are we there yet?

    Science.gov (United States)

    Kulkarni, Pushkar; Saxena, Uday

    2014-12-01

    Huntington's disease is a hereditary neurodegenerative disease. It is designated as a rare disease in the US, which means there are disease were not designed specifically for it but developed for other diseases. Presently, two classes of drugs are being developed; those that provide symptomatic relief and those that may modify course of the disease. This review is focused on seven selected drugs currently in clinical testing and describes their progress. Five of the seven drugs that are reviewed here, can be categorized as 'symptomatic' drugs, and, selisistat and PBT-2 are amongst the ones that would qualify as 'disease modifying' drugs. The authors believe that the future treatment paradigm for this disease is best met by using a disease-modifying drug that can be administered together with symptomatic drugs. Towards that end, it is important for the industry to focus on disease-modifying drugs by targeting unique pathways and targets. Furthermore, they propose that neuroprotective drugs, that is, drugs that directly work by preserving neuronal health and function is an opportunity for such disease-modifying drugs.

  19. Drug delivery options to increase patient adherence and satisfaction in the management of rheumatoid arthritis – focus on subcutaneous tocilizumab

    Directory of Open Access Journals (Sweden)

    Nakashima Y

    2014-07-01

    Full Text Available Yasuharu Nakashima,1 Masakazu Kondo,2 Hisaaki Miyahara,3 Yukihide Iwamoto11Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan; 2Kondo Clinic of Rheumatology and Orthopaedic Surgery, Fukuoka, Japan; 3Department of Orthopaedic Surgery and Rheumatology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanAbstract: Rheumatoid arthritis (RA is a chronic, progressive, inflammatory disease associated with joint destruction. Tocilizumab (TCZ is a humanized monoclonal anti-interleukin-6 receptor antibody that was initially developed for use as an intravenous (IV infusion. Previous studies have shown that TCZ-IV is an important treatment option in patients with moderate-to-severe RA. A subcutaneous (SC formulation of 162 mg TCZ that was recently developed and approved provides an additional treatment option for RA patients. In the present review, we provide an update on the efficacy and safety of TCZ-SC, compared with TCZ-IV. The TCZ-SC doses of 162 mg every 2 weeks (q2w or weekly (qw were selected based on pharmacokinetic and pharmacodynamic studies. Both TCZ-SC q2w and qw regimens showed equivalent effects to TCZ-IV in most patients; however, the TCZ-SC qw regimen consistently showed a more rapid effect in terms of C-reactive protein normalization. Randomized controlled studies showed that TCZ-SC monotherapy or combined with disease-modifying antirheumatic drugs demonstrated comparable efficacy to TCZ-IV in patients who were both biologic-naïve and refractory to tumor necrosis factor inhibitors. TCZ-SC at both qw and q2w were generally well-tolerated for up to 24 weeks. There was a low rate of withdrawal due to adverse events, and their incidence was comparable with that seen with TCZ-IV. An injection site reaction was seen in approximately 10% of patients who received the subcutaneous formulation. In conclusion, although clinical results are still limited, the currently available evidence

  20. A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies

    DEFF Research Database (Denmark)

    Ziemssen, Tjalf; Bajenaru, Ovidiu A; Carrá, Adriana;

    2014-01-01

    .32 (95 % CI 0.26-0.40; p disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p ...Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients...

  1. Applying the theory of planned behaviour to multiple sclerosis patients’ decisions on disease modifying therapy – questionnaire concept and validation

    Directory of Open Access Journals (Sweden)

    Kasper Jürgen

    2012-07-01

    Full Text Available Abstract Background Patients making important medical decisions need to evaluate complex information in the light of their own beliefs, attitudes and priorities. The process can be considered in terms of the theory of planned behaviour. Decision support technologies aim at helping patients making informed treatment choices. Instruments assessing informed choices need to include risk knowledge, attitude (towards therapy and actual uptake. However, mechanisms by which decision support achieves its goals are poorly understood. Our aim was therefore to develop and validate an instrument modeling the process of multiple sclerosis (MS patients’ decision making about whether to undergo disease modifying (immuno-therapies (DMT. Methods We constructed a 30-item patient administered questionnaire to access the elaboration of decisions about DMT in MS according to the theory of planned behaviour. MS-patients’ belief composites regarding immunotherapy were classified according to the domains “attitude”, “subjective social norm” and “control beliefs” and within each domain to either “expectations” or “values” yielding 6 sub-domains. A randomized controlled trial (n = 192 evaluating an evidence based educational intervention tested the instrument’s predictive power regarding intention to use immunotherapy and its sensitivity to the intervention. Results The psychometric properties of the questionnaire were satisfactory (mean item difficulty 62, mean SD 0.9, range 0–3. Responses explain up to 68% of the variability in the intention to use DMT was explained by up to 68% in the total sample. Four weeks after an educational intervention, predictive power was higher in the intervention (IG compared to the control group (CG (intention estimate: CG 56% / IG 69%, p = .179; three domains CG 56% / IG 74%, p = .047; six sub-domains CG 64% / IG 78%, p = .073. The IG held more critical beliefs towards immunotherapy (p = .002

  2. Epigenetic Modulation as a Therapeutic Prospect for Treatment of Autoimmune Rheumatic Diseases

    OpenAIRE

    Ciechomska, Marzena; O'Reilly, Steven

    2016-01-01

    Systemic inflammatory rheumatic diseases are considered as autoimmune diseases, meaning that the balance between recognition of pathogens and avoidance of self-attack is impaired and the immune system attacks and destroys its own healthy tissue. Treatment with conventional Disease Modifying Antirheumatic Drugs (DMARDs) and/or Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) is often associated with various adverse reactions due to unspecific and toxic properties of those drugs. Although biologic...

  3. Comparison of adherence and persistence among multiple sclerosis patients treated with disease-modifying therapies: a retrospective administrative claims analysis

    Directory of Open Access Journals (Sweden)

    Rachel Halpern

    2011-01-01

    Full Text Available Rachel Halpern1, Sonalee Agarwal2, Carole Dembek2, Leigh Borton1, Maria Lopez-Bresnahan31Health Economics and Outcomes Research, i3 Innovus, Eden Prairie, MN, USA; 2Health Outcomes and Pharmacoeconomics, Biogen Idec, Wellesley, MA, USA; 3Medical and Scientific Affairs, i3 Research, Waltham, MA, USAPurpose: To compare adherence and persistence among patients with multiple sclerosis (MS initiated on disease-modifying therapy (DMTs, including intramuscular (IM interferon beta-1a (IFNβ-1a, subcutaneous (SC IFNβ-1a, IFNβ-1b, or glatiramer acetate (GA.Methods: MS patients initiated on IM-IFNβ-1a, SC-IFNβ-1a, IFNβ-1b, or GA between January 1, 2000 and January 2, 2008 were identified from a retrospective claims database study associated with a large US health plan. The date of DMT initiation was the index date; patients were observed for 6 months before and 12–36 months after the index date. Adherence to the index DMT was measured with a medication possession ratio (MPR, the proportion of days patients possessed their index DMTs; MPR ≥0.80 was considered adherent. Persistence was time in days from index date until the earlier of a minimum 60-day gap in DMT therapy or the last DMT claim during follow-up. Adherence and persistence were modeled with logistic and Cox proportional hazard regressions, respectively.Results: The study population comprised 6,680 patients in the DMT cohorts: IM-IFNβ-1a (N = 2,305, 34.5%; IFNβ-1b (N = 894, 13.4%; GA (N = 2,270, 34.0%; and SC-IFNβ-1a (N = 1,211, 18.1%. The IM-IFNβ-1a cohort had significantly higher regression-adjusted odds of adherence relative to the other cohorts: 52.4% higher odds versus the IFNβ-1b cohort (OR = 0.656, CI = 0.561–0.768; 33.5% higher odds versus the GA cohort (OR = 0.749, CI = 0.665–0.844; and 20.6% higher odds versus the SC-IFNβ-1a cohort (OR = 0.829, CI = 0.719–0.957. There were no consistent differences in persistence between the cohorts.Conclusion: IM-IFNβ-1a patients

  4. Drug-specific risk and characteristics of lupus and vasculitis-like events in patients with rheumatoid arthritis treated with TNFi: results from BSRBR-RA

    Science.gov (United States)

    Dixon, William G; Kersley-Fleet, Lianne; Bruce, Ian N; Chinoy, Hector; Barton, Anne; Lunt, Mark; Watson, Kath; Hyrich, Kimme L

    2017-01-01

    Objective To compare the risk of lupus-like events (LLEs) and vasculitis-like events (VLEs) in tumour necrosis factor-α inhibitor (TNFi)-treated patients with rheumatoid arthritis (RA) to those receiving non-biological disease-modifying antirheumatic drugs (nbDMARDs). Methods Patients were recruited to the British Society for Rheumatology Biologics Register—RA, a national prospective cohort study. Two cohorts recruited between 2001 and 2015: (1) patients starting first TNFi (adalimumab, etanercept, infliximab and certolizumab) (n=12 937) and (2) biological-naïve comparison cohort receiving nbDMARDs (n=3673). The risk of an event was compared between the two cohorts using Cox proportional-hazard models, adjusted using propensity scores. Rates of LLE/VLE were compared between TNFi and nbDMARD patients. Results The crude incidence rates for LLEs were: TNFi 10/10 000 patient-years (pyrs) (95% CI 8 to 13) and nbDMARD 2/10 000 pyrs (95% CI 1 to 6); for VLEs: TNFi 15/10 000 pyrs (95% CI 12 to 19) and nbDMARD 7/10 000 pyrs (95% CI 4 to 12). The risk of both events was highest in the first year of TNFi treatment. After adjusting for differences in baseline characteristics, there was no difference in risk of LLEs (adjHR 1.86; 95% CI 0.52 to 6.58) or VLEs (adjHR 1.27; 95% CI 0.40 to 4.04) for TNFi compared to nbDMARD-treated patients. Infliximab conferred the highest overall risk, followed by etanercept, although 95% CIs overlapped following adjustment. Conclusions In one of the largest biological registers, the absolute risk of both events is low. The addition of TNFi to nbDMARD does not alter the risk of either event in patients with RA selected for TNFi. This is the first study to assess the risk of these outcomes in a prospective, observational cohort. PMID:28123776

  5. Drug: D00991 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available LETAL SYSTEM M01 ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS M01C SPECIFIC ANTIRHEU...1.gif Antirheumatic Same as: C08193 ATC code: M01CB04 Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] M MUSCULO-SKE

  6. Old and new therapeutics for Rheumatoid Arthritis: in vivo models and drug development

    DEFF Research Database (Denmark)

    Sardar, Samra; Andersson, Åsa

    2016-01-01

    Development of novel drugs for treatment of chronic inflammatory diseases is to a large extent dependent on the availability of good experimental in vivo models in order to perform preclinical tests of new drugs and for the identification of novel drug targets. Here, we review a number of existing...... of in vivo models during development of anti-rheumatic drugs; from Methotrexate to various antibody treatments, to novel drugs that are, or have recently been, in clinical trials. For novel drugs, we have explored websites for clinical trials. Although one Rheumatoid Arthritis in vivo model cannot mirror...... the complexity of disease development, there exist a number of good animal models for Rheumatoid Arthritis, each defining some parts in disease development, which are useful for studies of drug response. We find that many of the established drugs were not tested in in vivo models before being used in the clinic...

  7. CURRENT PHARMACOTHERAPY FOR KNEE OSTEOARTHRITIS: SPECIFIC FEATURES OF SYMPTOMATIC AND DISEASE MODIFYING EFFECTS. COMMUNICATION 1. SPECIFIC FEATURES OF THE SYMPTOMATIC EFFECTS OF CURRENT DRUGS TO TREAT KNEE OSTHEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    E. S. Tsvetkova

    2015-01-01

    Full Text Available Objective: to study the specific features of the symptomatic effect and tolerability of acetaminophen, glucosamine sulfate (GS, chondroitin sulfate (CS, and meloxicam in patents with knee osteoarthritis (OA. Subjects and methods. An 18-month open-label randomized prospective parallel-group trial enrolled 80 patients with knee OA who fulfilled the American College of Rheumatology criteria and signed the informed consent. They had Kellgren and Lawrence grades O-III OA with visual analogue scale pain intensity of ≥ 40 mm in the target knee, a body mass index of ≤ 35 kg/m2, and no clinical dysfunctions of vital organs and systems. The patients were randomized into 4 groups: 1 acetaminophen 2 g daily; 2 a standard GS regimen; 3 a standard CS regimen; 4 meloxicam 15 mg daily. The patients were followed up for 18 months. The effectiveness was evaluated by the WOMAC questionnaire, Leguesne index, and OMERACT-OARSI (D scenario during 8 visits. Laboratory and clinical examination as well as electrocardiography were performed. Adverse events were recorded during each visit.Results. After 4 weeks of treatment, symptomatic improvement was noted in all groups; however, the best effect was achieved by the use of meloxicam that ensured an obvious improvement in all patients. According to the OMERACT-OARSI criteria and changes in the WOMAC and Leguesne indices, the total efficacy of meloxicam was also highest. 20, 10, and 15% of the patients failed to respond to treatment in the acetaminophen, GS, and CS groups, respectively. Conclusion. The results of this trial suggest that it is expedient to use GS, CS, and meloxicam long, support the recent guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis and OA (ESCEO, and can give proofs of the efficiency and safety of GS, CS, and meloxicam used in the treatment of knee OA.

  8. Drugs affecting the eye.

    Science.gov (United States)

    Taylor, F

    1985-08-01

    This discussion reviews drugs that affect the eye, including antihyperglycemic agents; corticosteroids; antirheumatic drugs (quinolines, indomethacin, and allopurinol); psychiatric drugs (phenothiazine, thioridazine, and chlorpromazine); drugs used in cardiology (practolol, amiodarone, and digitalis gylcosides); drugs implicated in optic neuritis and atrophy, drugs with an anticholinergic action; oral contraceptives (OCs); and topical drugs and systemic effects. Refractive changes, either myopic or hypermetropic, can occur as a result of hyperglycemia, and variation in vision is sometimes a presenting symptom in diabetes mellitus. If it causes a change in the refraction, treatment of hyperglycemia almost always produces a temporary hypermetropia. A return to the original refractive state often takes weeks, sometimes months. There is some evidence that patients adequately treated with insulin improve more rapidly than those taking oral medication. Such patients always should be referred for opthalmological evaluation as other factors might be responsible, but it might not be possible to order the appropriate spectacle correction for some time. The most important ocular side effect of the systemic adiministration of corticosteroids is the formation of a posterior subcapsular cataract. Glaucoma also can result from corticosteroids, most often when they are applied topically. Corticosteroids have been implicated in the production of benign intracranial hypertension, which is paradoxical because they also are used in its treatment. The most important side effect of drugs such as chloroquine and hydroxychloroquine is an almost always irreversible maculopathy with resultant loss of central vision. Corneal and retinal changes similar to those caused by the quinolines have been reported with indomethacin, but there is some question about a cause and effect relationship. The National Registry of Drug Induced Ocular Side Effects in the US published 30 case histories of

  9. 新型抗风湿类药物戈利木单抗注射剂%A new anti-rheumatic drug: golimumab

    Institute of Scientific and Technical Information of China (English)

    邹羽真; 杜小莉

    2014-01-01

    肿瘤坏死因子(TNF)是一种细胞因子,在引发炎症反应中起重要介导作用,其抑制剂如英夫利昔单抗、阿达木单抗、依那西普,被相继批准用于慢性免疫性疾病如风湿性关节炎的治疗.戈利木单抗注射剂(golimumab)是一种新型TNF-α阻滞剂,与同类药物相比,其药理活性强,每月1次皮下注射给药更加方便.本文对其作用机制、药动学研究、临床试验、安全性评价等进行归纳总结.

  10. Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma

    DEFF Research Database (Denmark)

    Holgate, S T; Bousquet, J; Chung, K F

    2004-01-01

    With new drugs being introduced to treat asthma it is timely to review criteria that can be used to assess efficacy in clinical trials. Anti-asthma drugs are classified into symptoms-modifying, symptom preventers and disease modifying agents. Attention is drawn to the types of experimental eviden...

  11. [Current therapy of polyarticular forms of juvenile idiopathic arthritis].

    Science.gov (United States)

    Hospach, A; Rühlmann, J M; Weller-Heinemann, F

    2016-04-01

    Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA.

  12. Psoriatic arthritis: latest treatments and their place in therapy

    OpenAIRE

    Kang, Eun Jin; Kavanaugh, Arthur

    2015-01-01

    Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease that may affect peripheral and axial joints, entheses, skin and nails, and other organs. Treatment with nonsteroidal anti-inflammatory drugs, steroid and disease-modifying antirheumatic drugs had been the backbone of traditional management of PsA for many years. However, improvement in our understanding of immunopathogenesis of PsA has led to new immunomodulatory therapies. Introduction of novel agents has raised the ba...

  13. A history of the term “DMARD”

    OpenAIRE

    Buer, Jonas Kure

    2015-01-01

    The article outlines a history of the concept of “disease-modifying antirheumatic drugs” or DMARDs—from the emergence in the 1970s of the idea of drugs with decisive long-term effects on bone erosion in rheumatoid arthritis (RA), through the consolidation and popularisation in the term DMARD in 1980s and 1990s. It then examines the usage of the terms “remission-inducing drugs” (RIDs) and “slow-acting anti-rheumatic drugs” (SAARDs), which for some years offered competition to the term DMARDs, ...

  14. Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab

    Science.gov (United States)

    Benucci, Maurizio; Meacci, Francesca; Grossi, Valentina; Infantino, Maria; Manfredi, Mariangela; Bellio, Emanuele; Bellio, Valerio; Li Gobbi, Francesca; Bazzichi, Laura; Moscato, Paolo; Caputo, Dario; Saviola, Gianantonio; Talotta, Rossella; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola

    2016-01-01

    The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59±12 years, range 26–83; mean disease duration 11±5 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6±1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean dose 6.4±1.2 mg/day. They had a 28-joint Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR) of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-α; and IL-6. TCZ and anti-TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of 10 µg/mL high. After 6 months of treatment only one patient was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR, and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ levels of 10 µg/mL showed the following differences: DAS28: 3.09±1.32 vs 2.78±1.32, P=0.0005; ESR: 27±14.8 vs 14±12 mm/hour, P=0.0001; CRP: 1.47±1.05 vs 0.65±0.80 mg/dL, P=0.0086; TNF-α: 10.2±1.2 vs 9.9±1.1 pg/mL, P=0.999; IL-6: 3.65±4.75 vs 3.62±4.41 pg/mL, P=0.97; anti-citrullinated peptide antibody: 85.2±93.7 vs 86.7±90.3 IU/mL, P=0.94; RF IgM: 72.4±62.7 vs 68.3±61.6 IU/mL, P=0.754; RF IgA: 41.7±36.4 vs 47.8±42.1 U/mL, P=0.449; and RF IgG: 46.4±46.1 vs 59.3±58.2 U/mL, P=0.212. These findings show that the occurrence of anti-drug antibodies against TCZ is very rare and that

  15. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics.

    Science.gov (United States)

    Gottlieb, Alice; Korman, Neil J; Gordon, Kenneth B; Feldman, Steven R; Lebwohl, Mark; Koo, John Y M; Van Voorhees, Abby S; Elmets, Craig A; Leonardi, Craig L; Beutner, Karl R; Bhushan, Reva; Menter, Alan

    2008-05-01

    Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

  16. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes

    Directory of Open Access Journals (Sweden)

    Lior eGreenbaum

    2015-02-01

    Full Text Available Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP and tardive dyskinesia (TD. Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of Parkinson's disease (PD. Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD sub-phenotypes, such as age at onset, disease severity or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants may also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of L-dopa induced dyskinesia (LID, is an additional relevant sub-phenotype. LID may share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.

  17. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes.

    Science.gov (United States)

    Greenbaum, Lior; Lerer, Bernard

    2015-01-01

    Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson's disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.

  18. An overview of economic evaluations for drugs used in rheumatoid arthritis : focus on tumour necrosis factor-alpha antagonists.

    Science.gov (United States)

    Bansback, Nick J; Regier, Dean A; Ara, Roberta; Brennan, Alan; Shojania, Kamran; Esdaile, John M; Anis, Aslam H; Marra, Carlo A

    2005-01-01

    Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease that affects approximately 0.5-1% of the adult population. The introduction of new disease-modifying antirheumatic drugs (DMARDs) such as leflunomide, anakinra and the tumour necrosis factor (TNF)-alpha antagonists (infliximab, etanercept and adalimumab) have transformed the management of RA. In particular, the last class of agents has generated substantial controversy. Costing between 16,000 US dollars and 20,000 US dollars per patient-year (2001 values), the potential greater efficacy of treatment with TNFalpha antagonists comes at much higher drug costs, making these agents natural candidates for cost-effectiveness analyses (CEAs).A MEDLINE search (until 31 January 2004) identified six original CEAs evaluating TNFalpha antagonists in RA. The aim of a CEA is to facilitate the allocation of scarce health resources and to inform policy decisions. However, to enhance the reliability and relevance of these analyses to policy makers, there must be similarity between the methodologies used. Recently, the OMERACT (Outcome Measures in Rheumatoid Arthritis Clinical Trials) group produced a document to define such a reference case; the OMERACT document was used as a foundation to structure comparisons and highlight discrepancies. The methodologies employed in each analysis differed; in particular, disparate time horizons, comparators, quantities of drug and treatment sequences prohibit the comparison of cost effectiveness between studies. Outcomes also differed between the analyses. Most reported health-related quality of life (HR-QOL) in quality-adjusted life-years (QALYs). The QALYs metric was based on preference scores that were typically derived from linear regressions using the Health Assessment Questionnaire (HAQ). However, models also used American College of Rheumatology (ACR) criteria, as well as the disease activity score (DAS). Common to all studies was the lack of data from long

  19. Coexisting ankylosing spondylitis and rheumatoid arthritis: A case report with literature review

    Institute of Scientific and Technical Information of China (English)

    GUO Ying-ying; YANG Li-li; CUI Hua-dong; ZHAO Shuai; ZHANG Ning

    2011-01-01

    A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated.The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis.This patient was HLA-B27 and HLA-DR4 positive,and ankylosing spondylitis manifested before rheumatoid arthritis.After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby.One year later,she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis.We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis,and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.

  20. Coexisting ankylosing spondylitis and rheumatoid arthritis: a case report with literature review.

    Science.gov (United States)

    Guo, Ying-Ying; Yang, Li-Li; Cui, Hua-Dong; Zhao, Shuai; Zhang, Ning

    2011-10-01

    A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.

  1. Predictors of patient decision to discontinue anti-rheumatic medication in patients with rheumatoid arthritis: results from the Ontario best practices research initiative.

    Science.gov (United States)

    Ahluwalia, Vandana; Rampakakis, Emmanouil; Movahedi, Mohammad; Cesta, Angela; Li, Xiuying; Sampalis, John S; Bombardier, Claire

    2017-09-06

    Despite the availability of treatment guidelines and effective treatments, real-world effectiveness remains suboptimal partly due to poor patient medication adherence. We evaluated a comprehensive set of sociodemographic, health insurance, and disease-related factors for association with patient decision to discontinue anti-rheumatic medications (ARMs) in a large observational RA cohort in Ontario, Canada. Patients from the Ontario Best Practices Research Initiative registry were included. The following predictors of ARM discontinuation were evaluated with cox-regression: patient age, gender, education, income, smoking, health insurance type/coverage, RA duration, erosion presence, RF positivity, DAS28-ESR, physician global, HAQ-DI, comorbidity number, ARM types, and physician characteristics (gender, academic position, urban vs. rural, distance from patient's residence). Patients (1762) were included with a mean (SD) age of 57.4 years (13.0). Approximately 80% were female, 29% had early (≤ 1 year) RA, and 70% were RF-positive. Mean (SD) baseline DAS28-ESR and HAQ-DI were 4.5 (1.5) and 1.2 (0.76), respectively. In multivariate analysis, married status (HR [95%CI] 0.73 [0.56-0.96]), RF positivity (0.73 [0.56-0.96]), and higher comorbidity number (0.92 [0.85-0.99]) were significant predictors of ARMs continuation while higher physician global (1.10 [1.04-1.15]), NSAID use (1.75 [1.29-2.38]), and number of ARMs (1.23 [1.07-1.40]) were associated with ARMs discontinuation. In a subset analysis assessing conventional or biologic DMARD discontinuation, higher HAQ-DI and biologic use over time were associated with lower hazard for discontinuation. Several sociodemographic, disease, and treatment parameters were identified as independent predictors of patient discontinuation of ARMs. These results should be considered when developing patient adherence support programs and in the choice of treatment regimens.

  2. Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity

    OpenAIRE

    Ma, Lei-Lei; Wu, Zhi-tao; Wang, Le; Zhang, Xue-Feng; Wang, Jing; Chen, Chen; Ni, Xuan; Lin, Yun-fei; Cao, Yi-yi; Luan, Yang; Pan, Guo-yu

    2016-01-01

    Aim: Leflunomide is an immunosuppressive agent marketed as a disease-modifying antirheumatic drug. But it causes severe side effects, including fatal hepatitis and liver failure. In this study we investigated the contributions of hepatic metabolism and transport of leflunomide and its major metabolite teriflunomide to leflunomide induced hepatotoxicity in vitro and in vivo. Methods: The metabolism and toxicity of leflunomide and teriflunomide were evaluated in primary rat hepatocytes in vitro...

  3. Pulmonary Nodulosis Associated with Leflunomide Therapy in Rheumatoid Arthritis: Report of Four Cases and Review of the Literature

    OpenAIRE

    Ayse Balkarli; Veli Cobankara

    2016-01-01

    Rheumatoid arthritis (RA) is a multisystem inflamma­tory disease characterized by destructive synovitis and systemic extra-articular involvement. Leflunomide is a disease-modifying anti-rheumatic drug with anti-inflam­matory and anti-proliferative features. Leflunomide is an isoxazole immunomodulatory agent, which inhibits dihydroorotate dehydrogenase enzyme involved in de novo pyrimidine synthesis. It was shown that leflunomide can reduce signs and symptoms of rheumatoid arthritis (RA) with ...

  4. Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate

    DEFF Research Database (Denmark)

    Guyot, Patricia; Taylor, Peter; Christensen, Robin;

    2011-01-01

    The goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (<2.6) between abatacept and othe...... biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR)....

  5. Long-term safety of abatacept in patients with rheumatoid arthritis.

    Science.gov (United States)

    Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Mutti, Alessandra; Bugatti, Serena; Cavagna, Lorenzo; Caporali, Roberto

    2013-10-01

    Abatacept is a selective T cell co-stimulation modulator that was first approved by the Italian Medicines Agency and reimbursed by the Italian National Health Service when used to treat active rheumatoid arthritis "not sufficiently responsive to other disease-modifying anti-rheumatic drugs (DMARDs) including at least one TNF inhibitor", and is now also approved as a first line biological agent. The aim of this review is to summarise the safety data collected in clinical trials and observational studies.

  6. Proteasome inhibitors as experimental therapeutics of autoimmune diseases

    OpenAIRE

    Verbrugge, Sue Ellen; Scheper, Rik J.; Lems, Willem F.; Tanja D de Gruijl; Jansen, Gerrit

    2015-01-01

    Current treatment strategies for rheumatoid arthritis (RA) consisting of disease-modifying anti-rheumatic drugs or biological agents are not always effective, hence driving the demand for new experimental therapeutics. The antiproliferative capacity of proteasome inhibitors (PIs) has received considerable attention given the success of their first prototypical representative, bortezomib (BTZ), in the treatment of B cell and plasma cell-related hematological malignancies. Therapeutic applicati...

  7. Experience with tocilizumab in patients with rheumatoid arthritis (according to the data of the LORNET multicenter trial)

    OpenAIRE

    2013-01-01

    Objective: to estimate quality of life changes in patients with rheumatoid arthritis (RA) while adding tocilizumab (TCZ) to therapy with disease-modifying antirheumatic drugs (DMARDs) and to study the efficiency and safety of the therapy in RA patients with an inadequate response to previous DMARD treatment. Subjects and methods. 201 patients with RA were examined. All the patients received six intravenous infusions of TCZ 8 mg/kg at a 4-week interval during stable therapy with DMARDs and glu...

  8. Drug: D09092 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Atractylodes rhizome [DR:D06780]) Traditional Chinese Medicine in Japan [BR:br08304] Formulas Formulas for dampness Antirheumatic formulas D09092 Seishitsukatanto PubChem: 96025772 ...

  9. Drug: D10449 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available TORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS M01AE Propionic acid derivatives M01AE51 Ibuprofen, combinat...ions D10449 Ibuprofen - scopolamine butylbromide mixt PubChem: 172232542 ...

  10. Drug: D09967 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ide bridge: 23-89; 135-195; H230-L215, Dimer) Peptide Uveitis, rheumatoid arthritis, psoriasis ATC code: L04...teraction hsa05323(3605) Rheumatoid arthritis map07050 Antirheumatics - DMARDs and biological agents Anatomi

  11. Drug: D01049 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available PRODUCTS, NON-STEROIDS M01AX Other antiinflammatory and antirheumatic agents, non-steroids M01AX17 Nimesuli...INT AND MUSCULAR PAIN M02AA Antiinflammatory preparations, non-steroids for topic

  12. Prevalence of cutaneous adverse events associated with long-term disease-modifying therapy and their impact on health-related quality of life in patients with multiple sclerosis: A cross-sectional study

    NARCIS (Netherlands)

    D.M.W. Balak (Deepak); G. Hengstman (Gerald); E. Hajdarbegovic (Enes); R.J.P. van den Brule (Rob); R. Hupperts (Raymond); H.B. Thio (Bing)

    2013-01-01

    textabstractBackground: Glatiramer acetate (GA) and interferon-beta (IFN-β) are disease-modifying therapies (DMTs) for multiple sclerosis that are administered through subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated with DMTs are common and may influence patient's healt

  13. Prevalence of cutaneous adverse events associated with long-term disease-modifying therapy and their impact on health-related quality of life in patients with multiple sclerosis: A cross-sectional study

    NARCIS (Netherlands)

    D.M.W. Balak (Deepak); G. Hengstman (Gerald); E. Hajdarbegovic (Enes); R.J.P. van den Brule (Rob); R. Hupperts (Raymond); H.B. Thio (Bing)

    2013-01-01

    textabstractBackground: Glatiramer acetate (GA) and interferon-beta (IFN-β) are disease-modifying therapies (DMTs) for multiple sclerosis that are administered through subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated with DMTs are common and may influence patient's healt

  14. Pain mechanisms and ultrasonic inflammatory activity as prognostic factors in patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Christensen, Robin; Dreyer, Lene

    2016-01-01

    ) and erroneous treatments. Ultrasonography (US) is a highly sensitive method to detect tissue inflammation. Evaluating pain mechanisms in relation to US measures may prove valuable in predicting response to treatment in PsA. AIMS: To study the association and prognostic value of pain mechanisms, ultrasonic...... activity and clinical outcomes in patients with PsA who intensify antirheumatic treatment. METHODS AND ANALYSES: 100 participants >18 years of age with PsA who initiate or switch antirheumatic treatment (biologicals and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs......INTRODUCTION: Persistent pain is a major concern for patients with psoriatic arthritis (PsA). Pain may be due to inflammatory activity or augmented central pain processing. Unawareness of the origin and mechanisms of pain can lead to misinterpretation of disease activity (by composite scores...

  15. MS Disease-Modifying Medications

    Science.gov (United States)

    ... every 6 months Genentech (a member of the Roche Group) (first dose: 300 mg IV on day ... MS | National MS Society 26 Each of the pharmaceutical companies offers a program designed to help people ...

  16. MS Disease-Modifying Medications

    Science.gov (United States)

    ... pose risks to the developing fetus. Category B: Animal reproduction studies have failed to demonstrate a risk to ... well-controlled studies in pregnant women. Category C: Animal reproduction studies have shown an adverse effect on the ...

  17. The efficacy and tolerability of leflunomide (Arava® in therapy for psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available The paper gives data on differentiated disease-modifying anti-rheumatic therapy for psoriatic arthritis (PsA. When performing the therapy, account must be taken of the presence and magnitude of the major manifestations of this disease: the pattern of arthritis and spondylosis, the number of inflamed entheses, the number of swollen fingers or toes, the pattern of psoriasis in terms of its extent and stage, the presence and magnitude of systemic manifestations and the functional state of involved organs. There are data on the biological activity of leflunomide, its effect on the main manifestations of PsA with an analysis of its efficacy and tolerability, as well as the results of a comparative investigation of disease-modifying anti-rheumatic drugs used for the therapy of this disease.

  18. Staufen1 Regulates Multiple Alternative Splicing Events either Positively or Negatively in DM1 Indicating Its Role as a Disease Modifier.

    Directory of Open Access Journals (Sweden)

    Emma Bondy-Chorney

    2016-01-01

    Full Text Available Myotonic dystrophy type 1 (DM1 is a neuromuscular disorder caused by an expansion of CUG repeats in the 3' UTR of the DMPK gene. The CUG repeats form aggregates of mutant mRNA, which cause misregulation and/or sequestration of RNA-binding proteins, causing aberrant alternative splicing in cells. Previously, we showed that the multi-functional RNA-binding protein Staufen1 (Stau1 was increased in skeletal muscle of DM1 mouse models and patients. We also showed that Stau1 rescues the alternative splicing profile of pre-mRNAs, e.g. the INSR and CLC1, known to be aberrantly spliced in DM1. In order to explore further the potential of Stau1 as a therapeutic target for DM1, we first investigated the mechanism by which Stau1 regulates pre-mRNA alternative splicing. We report here that Stau1 regulates the alternative splicing of exon 11 of the human INSR via binding to Alu elements located in intron 10. Additionally, using a high-throughput RT-PCR screen, we have identified numerous Stau1-regulated alternative splicing events in both WT and DM1 myoblasts. A number of these aberrant ASEs in DM1, including INSR exon 11, are rescued by overexpression of Stau1. However, we find other ASEs in DM1 cells, where overexpression of Stau1 shifts the splicing patterns away from WT conditions. Moreover, we uncovered that Stau1-regulated ASEs harbour Alu elements in intronic regions flanking the alternative exon more than non-Stau1 targets. Taken together, these data highlight the broad impact of Stau1 as a splicing regulator and suggest that Stau1 may act as a disease modifier in DM1.

  19. Impact of specific Beers Criteria medications on associations between drug exposure and unplanned hospitalisation in elderly patients taking high-risk drugs: a case-time-control study in Western Australia.

    Science.gov (United States)

    Price, Sylvie D; Holman, C D'Arcy J; Sanfilippo, Frank M; Emery, Jon D

    2014-04-01

    Certain broad medication classes have previously been associated with high rates of hospitalisation due to related adverse events in elderly Western Australians, based on clinical coding recorded on inpatient summaries. Similarly, some medications from the Beers Criteria, considered potentially inappropriate in older people, have been linked with an increased risk of unplanned hospitalisation in this population. Our objective was to determine whether risk estimates of drug-related hospitalisations are altered in elderly patients taking 'high-risk drugs' (HRDs) when specific Beers potentially inappropriate medications (PIMS) are taken into consideration. Using the pharmaceutical claims of 251,305 Western Australians aged ≥65 years (1993-2005) linked with other health data, we applied a case-time-control design to estimate odds ratios (ORs) for unplanned hospitalisations associated with anticoagulants, antirheumatics, opioids, corticosteroids and four major cardiovascular drug groups, from which attributable fractions (AFs), number and proportion of drug-related admissions were derived. The analysis was repeated, taking into account exposure to eight specific PIMs, and results were compared. A total of 1,899,699 index hospitalisations were involved. Of index subjects, 12-57 % were exposed to each HRD at the time of admission, although the proportions taking both an HRD and one of the selected PIMs were much lower (generally ≤2 %, but as high as 8 % for combinations involving temazepam and for most PIMs combined with hypertension drugs). Included PIMs (indomethacin, naproxen, temazepam, oxazepam, diazepam, digoxin, amiodarone and ferrous sulphate) all tended to increase ORs, AFs and drug-related hospitalisation estimates in HRD combinations, although this was less evident for opioids and corticosteroids. Indomethacin had the greatest overall impact on HRD ORs/AFs. Indomethacin (OR 1.40; 95 % confidence interval [CI] 1.27-1.54) and naproxen (OR 1.22; 1

  20. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Kids Drug Use Hurts Unborn Children Drug Use Hurts Your Health Drug Use Hurts ... Find Treatment/Rehab Resources Prevent Drug Use Help Children and Teens Stay Drug-Free Talking to Kids ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  2. To stop the erosion of hope: the DMARD category and the place of semantics in modern rheumatology.

    Science.gov (United States)

    Buer, Jonas Kure

    2017-04-01

    The category of disease-modifying anti-rheumatic drugs (DMARDs) emerged in the 1970s to describe drugs capable of altering the long-term destructive course of arthritis. It became a core concept in rheumatology's reorientation towards pharmaceuticals in the late twentieth century. By examining the earliest use of the term "disease-modifying" in scientific publications, this paper identifies the drugs that the category described when it first emerged. Leaning on systematic reviews of each of these drugs towards the end of their career in rheumatology, it then establishes that posterity would not recognize any of these early DMARDs as capable of altering the long-term course of the disease. The notion of disease-modifying drugs was thus originally used to categorize drugs that were not disease-modifying. Instead of interpreting this inconsistency as an anomaly, the paper argues that the DMARD category may have gained currency because it allowed a number of actors to respond pragmatically to an ongoing crisis in the pharmacological approach to treating arthritis. The term offered to conjure prospects of disease-modifying effects regardless of drugs' actual capacities, and thus to semantically solve the tensions between needs and means that characterized rheumatology at the time. While shedding light on a pivotal moment in the history of rheumatology, the paper also models an approach to understanding drug categories as meaning-making mechanisms by which people can mediate the sometimes uneasy connections that exist between medical practice and science.

  3. Ethnopharmacology, Antibacterial and Antioxidant Activity of Dittrichia graveolens (L. W. Greuter. Which Has Been Used as Remedies Antirheumatic, Anti-inflammation and Antiinfection against Leishmaniasis in the Traditional Medicine of Gorgan, Iran

    Directory of Open Access Journals (Sweden)

    Mazandarani Masoumeh

    2014-10-01

    Full Text Available Objective: This study was survey to investigate of ethnopharmacology, antibacterial and antioxidant capacity of Dittrichia graveolens (L. W. Greuter extract in in vitro from waste ground region of Gorgan, Iran, which has been used in traditional as a strong anti-inflammation, antirheumatism, antitumor, antipathogene, and antiinfection. Materials and Methods: Ethnopharmacological data were obtained among well-known indigenous herbal practitioner (70 ages in Gorgan, Iran. Aerial parts of plant in blooming were collected from Gorgan waste ground (80 m in October 2013. Methanol and acetone extracts were obtained by maceration, antioxidant activity were evaluated spectrophotometrically by 1,1-diphenyl-2-picryl hydrazyl (DPPH, total antioxidant capacity and reducing power to compare of butylated hydroxytoluene and butylated hydroxyanisole antioxidant standard and antibacterial activity were determined by disc diffusion and minimal inhibitory concentrations (MICs method against tree Gram-positive and negative pathogenic bacteria. Results: D. graveolens (L. W. Greuteris is usually wild grow in Golestan Province and has been used in traditional medicine as a strong anti-inflammation, antirheumatism, antitumor, antipathogene and antiinfection specially in treat of leishmaniosis metanolic extract of plant has strong antioxidant activity against free radical scavenging specially in DPPH methode than aceton extract with IC50 (6.2 ± 0.13 μg/ml and Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Bacillus cereus with inhibition zone 35, 30, 26, 21 mm were the most sensitive bacteria, with MIC ranging from 12.6 to 112 μg/ml, respectively. Escherichia coli and Salmonella typhimurium have moderate sensitivity and other bacteria were resistant to the plant extract. Conclusion: Results demonstrate that the methanolic extract of D. graveolens can become good potential antioxidant and antibacterial activity for controlling certain Gram

  4. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use Hurts Other People Drug Use Hurts Families Drug Use Hurts Kids Drug Use Hurts Unborn ...

  5. Drug Facts

    Medline Plus

    Full Text Available ... Use Hurts Unborn Children Drug Use Hurts Your Health Drug Use Hurts Bodies Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  6. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use Hurts Other People Drug Use Hurts Families Drug Use Hurts Kids Drug Use Hurts Unborn ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... The Link Between Drug Use and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? ... and Family Can Help Find Treatment/Rehab Resources Prevent Drug Use Help Children and Teens Stay Drug- ...

  9. Old and new therapeutics for Rheumatoid Arthritis: in vivo models and drug development.

    Science.gov (United States)

    Sardar, Samra; Andersson, Åsa

    2016-01-01

    Development of novel drugs for treatment of chronic inflammatory diseases is to a large extent dependent on the availability of good experimental in vivo models in order to perform preclinical tests of new drugs and for the identification of novel drug targets. Here, we review a number of existing rodent models for Rheumatoid Arthritis in the context of how these models have been utilized for developing established therapy in Rheumatoid Arthritis and, furthermore, the present use of animal models for studies of novel drug candidates. We have studied the literature in the field for the use of in vivo models during development of anti-rheumatic drugs; from Methotrexate to various antibody treatments, to novel drugs that are, or have recently been, in clinical trials. For novel drugs, we have explored websites for clinical trials. Although a single Rheumatoid Arthritis in vivo model cannot mirror the complexity of disease development, there exist a number of good animal models for Rheumatoid Arthritis, each defining some parts in disease development, which are useful for studies of drug response. We find that many of the established drugs were not tested in in vivo models before being used in the clinic, but rather animal models have been subsequently used to find mechanisms for efficacy. Finally, we report a number of novel drugs, tested in preclinical in vivo models, presently in clinical trials.

  10. Risks and benefits of low-dosage cyclosporin in rheumatoid arthritis.

    Science.gov (United States)

    Pasero, G; Ferraccioli, G F; Portioli, I

    1997-05-01

    The effects of cyclosporin on the activity of rheumatoid arthritis have mainly been investigated in patients with active, refractory, long-standing disease. The data obtained in these trials suggest that cyclosporin is not only a symptomatic treatment for rheumatoid arthritis but can also be considered a disease-modifying antirheumatic drug (DMARD), since it seems to be capable of slowing the progression of cartilage and bone damage due to rheumatoid arthritis. The trials conducted so far have led to a better understanding of cyclosporin toxicity and, therefore, to better monitoring of patients in order to avoid it. The reasons for studying the role of cyclosporin in patients with early, active and potentially severe rheumatoid arthritis are the poor prognosis of the disease despite the use of the presently available DMARDs, and the hypothesis that the drug is more efficacious and better tolerated in early rheumatoid arthritis. A new classification of antirheumatic drugs proposes that disease-controlling antirheumatic therapies decrease inflammatory synovitis and prevent structural joint damage or significantly reduce its rate of progression. However, few existing drugs meet these criteria. The 12-month results of a disease-controlling antirheumatic therapy clinical trial with a blinded radiological end-point, named GRISAR (Gruppo Reumatologi Italiani Studio Artrite Reumatoide) comparing cyclosporin with conventional DMARDs in patients with early rheumatoid arthritis provide strong evidence that cyclosporin offers better control of ongoing joint damage than do conventional DMARDs.

  11. Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

    Science.gov (United States)

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2013-11-01

    Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients.

  12. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use.

    Science.gov (United States)

    Hazes, Johanna M W; Coulie, Pierre G; Geenen, Vincent; Vermeire, Séverine; Carbonnel, Franck; Louis, Edouard; Masson, Pierre; De Keyser, Filip

    2011-11-01

    It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn's disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant.

  13. New Therapeutic Approaches for the Treatment of Rheumatoid Arthritis may Rise from the Cholinergic Anti-Inflammatory Pathway and Antinociceptive Pathway

    Directory of Open Access Journals (Sweden)

    Xiao Hua Pan

    2010-01-01

    Full Text Available Due to the complex etiology of rheumatoid arthritis (RA, it is difficult to be completely cured at the current stage although many approaches have been applied in clinics, especially the wide application of nonsteroidal anti-inflammatory drugs (NSAIDs and disease-modifying antirheumatic drugs (DMARDs. New drug discovery and development via the recently discovered cholinergic anti-inflammatory and antinociceptive pathways should be promising. Based on the above, the nicotinic acetylcholine receptor agonists maintain the potential for the treatment of RA. Therefore, new therapeutic approaches may rise from these two newly discovered pathways. More preclinical experiments and clinical trials are required to confirm our viewpoint.

  14. Drugs and Drug Abuse.

    Science.gov (United States)

    Anastas, Robert, Comp.; And Others.

    GRADES OR AGES: Secondary grades. SUBJECT MATTER: Drugs and drug abuse. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into several sections, each of which is in outline or list form. It is xeroxed and spiral-bound with a paper cover. OBJECTIVES AND ACTIVITIES: No objectives are mentioned. The major portion of the guide contains a…

  15. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  16. Smoke and mirrors: Limited value of relative risk reductions for assessing the benefits of disease-modifying therapies for multiple sclerosis.

    Science.gov (United States)

    Zakaria, Magd

    2015-05-01

    A reduction in relapse rate is the main primary outcome in most clinical trials in patients with multiple sclerosis (MS), with the effect of a treatment commonly expressed as relative risk reduction for this outcome. Physicians often assume that a drug with a higher relative risk reduction demonstrated in one trial is more effective than a drug with a lower relative risk reduction in another, and may pass this idea on to younger physicians and to patients. The use of the relative risk reduction as a measure of drug efficacy can be misleading, as it depends on the nature of the population studied: a treatment effect characterized by a lower relative risk reduction may be more clinically meaningful than one with a higher relative risk reduction. This concept is especially important with regard to clinical trials in patients with MS, where relapse rates in placebo groups have been declining in recent decades. Direct, head-to-head comparisons are the only way to compare the efficacy of the different treatments for MS.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  18. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? Do You or a Loved One Have a Drug Use Problem? Signs of Drug Use and Addiction How Does Drug Use Become Addiction? Addiction Risk ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  1. Drug adherence and multidisciplinary care in patients with multiple sclerosis: Protocol of a prospective, web-based, patient-centred, nation-wide, Dutch cohort study in glatiramer acetate treated patients (CAIR study)

    NARCIS (Netherlands)

    P.J. Jongen (Peter); G. Hengstman (Gerald); R. Hupperts (Raymond); H. Schrijver (Hans); J. Gilhuis (Job); J.H. Vliegen (Joseph); E. Hoogervorst (Erwin); M. van Huizen (Marc); E. van Munster (Eric); J. Samijn (Johnny); E.L.L.M. de Schryver (Els); T.A.M. Siepman (Theodora); M. Tonk (Martijn); E. Zandbergen (Eveline); J. ten Holter (Jacques); R. van der Kruijk (Ruud); G.F. Borm (George Florimond)

    2011-01-01

    textabstractBackground: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability p

  2. Drug adherence and multidisciplinary care in patients with multiple sclerosis: protocol of a prospective, web-based, patient-centred, nation-wide, Dutch cohort study in glatiramer acetate treated patients (CAIR study).

    NARCIS (Netherlands)

    Jongen, P.J.H.; Hengstman, G.J.D.; Hupperts, R.; Schrijver, H.; Gilhuis, J.; Vliegen, J.H.; Hoogervorst, E.; Huizen, M. van; Munster, E. van; Samijn, J.; Schryver, E. de; Siepman, T.; Tonk, M.; Zandbergen, E.; Holter, J. ten; Kruijk, R. van der; Borm, G.F.

    2011-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, for which no definitive treatment is available. Most patients start with a relapsing-remitting course (RRMS). Disease-modifying drugs (DMDs) reduce relapses and disability progression.

  3. Benefit and Risk of Tofacitinib in the Treatment of Rheumatoid Arthritis: A Focus on Herpes Zoster.

    Science.gov (United States)

    Yamaoka, Kunihiro

    2016-09-01

    The biologics have revolutionized the treatment of rheumatoid arthritis (RA). However, there are still patients that are difficult to control and a cure is still not achievable. Tofacitinib, a Janus kinase (JAK) inhibitor is an orally available, new-in-class, disease-modifying anti-rheumatic drug with similar efficacy to biologics. JAK is activated by multiple cytokines involved in the pathology of RA, and affects non-immune and immune cells, mainly the lymphocytes. Besides its anti-rheumatic effect, the recent focus has been on adverse events. As with other biologics, serious infections have been observed especially with patients with lymphopenia, consistent with the mechanism of action. The major difference in adverse events from other disease-modifying anti-rheumatic drugs is the prominent increase in the occurrence of herpes zoster; it is increased worldwide, especially in Asia. There are other concerns such as malignancies and hyperlipidemia that may cause cardiovascular events that deserve further attention. The first JAK inhibitor for RA is demonstrating great benefit along with some risk, providing insights into the post-biologic era.

  4. Drug: D04334 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available [BR:br08303] M MUSCULO-SKELETAL SYSTEM M01 ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS M01A ANTIINFLAMMATOR....gif Pharmaceutic aid Same as: C00329 ATC code: M01AX05 Anatomical Therapeutic Chemical (ATC) classification

  5. Drug: D00238 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 2 277.2626 D00238.gif Immunosuppressant [DS:H00080 H00083] Same as: C06837 Therapeutic category: 3999 ATC code: L04AX01 Genomic bioma...rker: TPMT [HSA:7172] map07046 Immunosuppressive agents map07050 Antirheumatics - D

  6. Drug: D04358 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available i (TN) C6530H10068N1752O2026S44 146852.6362 146943.1937 Treatment of inflammatory disorders, rheumatoid arthritis...a05323(7124) Rheumatoid arthritis map07050 Antirheumatics - DMARDs and biological...124) Fc epsilon RI signaling pathway hsa04920(7124) Adipocytokine signaling pathway hsa05310(7124) Asthma hs

  7. Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab

    Directory of Open Access Journals (Sweden)

    Benucci M

    2016-03-01

    Full Text Available Maurizio Benucci,1 Francesca Meacci,2 Valentina Grossi,2 Maria Infantino,2 Mariangela Manfredi,2 Emanuele Bellio,2 Valerio Bellio,2 Francesca Li Gobbi,1 Laura Bazzichi,3 Paolo Moscato,4 Dario Caputo,4 Gianantonio Saviola,5 Rossella Talotta,6 Piercarlo Sarzi-Puttini,6 Fabiola Atzeni71Rheumatology Unit, Ospedale San Giovanni di Dio, Florence, Italy; 2Allergology and Immunology Laboratory, Ospedale San Giovanni di Dio, Florence, Italy; 3Rheumatology Unit, University of Pisa, Pisa, Italy; 4Internal Medicine and Rheumatology Unit, University of Salerno, Salerno, Italy; 5Rheumatology Unit, Salvatore Maugeri Foundation, Mantua, Italy; 6Rheumatology Unit, Ospedale Luigi Sacco, Milan, Italy; 7IRCCS Galeazzi Orthopedic Institute, Milan, ItalyAbstract: The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ. We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59±12 years, range 26–83; mean disease duration 11±5 years with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6±1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean dose 6.4±1.2 mg/day. They had a 28-joint Disease Activity Score (DAS28 of >3.2, an erythrocyte sedimentation rate (ESR of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-α; and IL-6. TCZ and anti-TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of <10 µg/mL were considered low and >10 µg/mL high. After

  8. Management of pregnancy in women with rheumatoid arthritis.

    Science.gov (United States)

    Ngian, Gene-Siew; Briggs, Andrew M; Ackerman, Ilana N; Van Doornum, Sharon

    2016-02-01

    Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal-fetal medicine specialist for risk assessment and advice.

  9. Giant cell arteritis. Part II. Treatment

    Directory of Open Access Journals (Sweden)

    Azamat Makhmudovich Satybaldyev

    2012-01-01

    Full Text Available Treatment options for giant cell arteritis (GCA and its complications are considered. GCA is treatable with glucocorticoids (GC. The data available in the literature suggest that it is necessary to hospitalize GCA patients with acute vision loss or brain ischemia to administer intravenous megadose methylprednisolone and to control and prevent complications of GC therapy. It is expedient to use aspirin in these cases. The evidence for the use of methotrexate and other disease-modifying antirheumatic and genetically engineered drugs as GC-saving drugs is discussed.

  10. Surgical management of the juvenile idiopathic arthritis patient with multiple joint involvement.

    Science.gov (United States)

    Abdel, Matthew P; Figgie, Mark P

    2014-10-01

    Juvenile idiopathic arthritis (JIA) is recognized as a heterogenous group of disorders in which the common factor is persistent arthritis in at least 1 joint occurring before the age of 16 years. Although conservative management with nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs can be effective, approximately 10% of JIA patients have end-stage degenerative changes requiring total hip arthroplasties (THAs) and total knee arthroplasties (TKAs). This article discusses the overall epidemiology, coordination of care, and medical and surgical management of JIA patients undergoing THA and TKA.

  11. Investigational new drugs for focal epilepsy.

    Science.gov (United States)

    Mula, Marco

    2016-01-01

    For more than 30 years, antiepileptic drug development has been based on specific assumptions regarding the neurobiology of epilepsy but all marketed drugs have not changed the proportion of drug refractory patients. It is, therefore, evident that new molecular targets need to be identified. Advances in neurobiology and molecular pharmacology are bringing into the epilepsy field new neurochemical functions such as those modulated by cannabinoid, serotonin, melatonin and galanin receptors. Among all the different compounds, the melatonin type 3 receptor agonist beprodone and cannabidiol are those at the more advanced stage of development. Interestingly, despite the structural analogies with tetrahydrocannabinol, the anticonvulsant activity of cannabidiol is not mediated by an interaction with cannabinoid receptors. Neurosteroids represent another remarkable class of drugs, and among them, ganaxolone is at the most advanced stage of development. Furthermore, for the first time, potential disease-modifying agents and techniques are entering the epilepsy market. Rapalogues such as everolimus and the antibiotic minocycline are currently under development for specific epileptic syndromes like tuberous sclerosis or Angelman syndrome. Finally, optogenetics, though still at an early stage of development, represents a futuristic therapeutic strategy for drug-refractory epilepsy.

  12. Alzheimer's disease drug development: translational neuroscience strategies.

    Science.gov (United States)

    Cummings, Jeffrey L; Banks, Sarah J; Gary, Ronald K; Kinney, Jefferson W; Lombardo, Joseph M; Walsh, Ryan R; Zhong, Kate

    2013-06-01

    Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.

  13. Drug Facts

    Medline Plus

    Full Text Available ... and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of ... to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? Effects of ...

  14. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  15. Drug Resistance

    Science.gov (United States)

    HIV Treatment Drug Resistance (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  16. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Germing, Ulrich; List, Alan; MacBeth, Kyle J

    2014-01-01

    Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians' ability to predict/monitor response and identify patients at risk of relapse.

  17. Palmitoylethanolamide Is a Disease-Modifying Agent in Peripheral Neuropathy: Pain Relief and Neuroprotection Share a PPAR-Alpha-Mediated Mechanism

    Directory of Open Access Journals (Sweden)

    L. Di Cesare Mannelli

    2013-01-01

    Full Text Available Neuropathic syndromes which are evoked by lesions to the peripheral or central nervous system are extremely difficult to treat, and available drugs rarely joint an antihyperalgesic with a neurorestorative effect. N-Palmitoylethanolamine (PEA exerts antinociceptive effects in several animal models and inhibits peripheral inflammation in rodents. Aimed to evaluate the antineuropathic properties of PEA, a damage of the sciatic nerve was induced in mice by chronic constriction injury (CCI and a subcutaneous daily treatment with 30 mg kg−1 PEA was performed. On the day 14, PEA prevented pain threshold alterations. Histological studies highlighted that CCI induced oedema and an important infiltrate of CD86 positive cells in the sciatic nerve. Moreover, osmicated preparations revealed a decrease in axon diameter and myelin thickness. Repeated treatments with PEA reduced the presence of oedema and macrophage infiltrate, and a significant higher myelin sheath, axonal diameter, and a number of fibers were observable. In PPAR-α null mice PEA treatment failed to induce pain relief as well as to rescue the peripheral nerve from inflammation and structural derangement. These results strongly suggest that PEA, via a PPAR-α-mediated mechanism, can directly intervene in the nervous tissue alterations responsible for pain, starting to prevent macrophage infiltration.

  18. Carbohydrate metabolism disorders in patients with rheumatoid arthritis and ankylosing spondylitis – impact of treatment

    Directory of Open Access Journals (Sweden)

    Piotr Dąbrowski

    2014-06-01

    Full Text Available Chronic inflammation – the crucial pathogenic mechanism of rheumatoid arthritis and ankylosing spondylitis – is the main cause of accelerated atherosclerosis, insulin resistance and well-known consequences related to it. The conservative treatment of rheumatoid arthritis and ankylosing spondylitis may provide a significant influence on glucose metabolism. The paper is a literature overview concerning insulin resistance and impaired glucose metabolism during treatment with disease-modifying drugs including biologic DMARDs (disease-modifying antirheumatic drugs, corticosteroids and commonly used non-steroidal anti-inflammatory drugs (NSAID. It has been found that the risk of carbohydrate disorders among those patients is much lower after therapy with hydroxychloroquine, methotrexate and TNF blockers – particularly with infliximab. The NSAID may play an important protective role in reducing risk of diabetes. The recent data show, contrary to general opinion, the advantageous outcome for glucose metabolism after treatment with corticosteroids, especially in the early active stage of rheumatoid arthritis.

  19. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth Varghese

    2014-11-01

    Full Text Available Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca2+]i in breast cancer cells (MCF-7. Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca2+]i was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM with a strong negative correlation (r = −0.713 to viability. Pharmacological modulators 2-APB (50 μM, Nimodipine (10 μM, Caffeine (10 mM, SKF 96365(20 μM were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca2+]i in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca2+]i. Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca2+]i should be considered as a crucial factor for the induction of cell death in cancer cells.

  20. Pharmacogenetics of multiple sclerosis: personalized therapy with immunomodulatory drugs.

    Science.gov (United States)

    Tsareva, Ekaterina; Kulakova, Olga; Boyko, Alexey; Favorova, Olga

    2016-03-01

    Pharmacogenetic (PG) studies aim to discover the individual genetic background that underlies the heterogeneity of treatment response, and thus find biomarkers for identification of individual patients who will benefit the most from the therapy administered or urgently require the alternate drug. Over the last decade, PG studies have made progress in terms of multiple sclerosis (MS), which is one of the most severe neurodegenerative diseases of the central nervous system. With the understanding of the role of the immune system in the pathogenesis of MS, a number of immunomodulatory drugs were developed for MS treatment management. However, clinical response to these disease-modifying therapies varies in individual patients. Interferon-β and glatiramer acetate showed the most reliable long-term safety and remain among the first-line disease-modifying therapies for MS worldwide. Here, we will review the results of interferon-β and glatiramer acetate PG studies with a detailed analysis of study design and approaches, their advantages and limitations, and future perspectives.

  1. TIME COURSE OF CHANGES IN BLOOD LIPID PARAMETERS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS DURING TREAT-TO-TARGET ANTIRHEUMATIC THERAPY: ACCORDING TO 18-MONTH FOLLOW-UP FINDINGS

    Directory of Open Access Journals (Sweden)

    E. V. Udachkina

    2016-01-01

    Full Text Available The mechanisms for lowering a cardiovascular risk (CVR in patients with early rheumatoid arthritis (RA when implementing the treat-to-target strategy remain inadequately investigated.Objective: to estimate the time course of changes in blood lipid parameters in patients with early RA during Treat-totarget antirheumatic therapy at an 18-month follow-up.Subjects and methods. Seventy-four patients (73% women; median age, 56 years with early RA meeting the respective 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR classification criteria and moderate or high activity (median DAS28-ESR score of 5.4 were examined within the framework of the REMARCA trial. After 6-month treatment, RA activity significantly reduced (p < 0.05. At months 6 to 18, no significant change in RA activity was recorded. After 18 months, remission was observed in 31 (42% patients: in 17 (55% on methotrexate (MTX monotherapy and in 14 (45% on combined therapy with MTX and a biological agent. Blood lipid levels were determined at inclusion in the investigation, 6 and 18 months later. The values of lipid parameters were estimated in terms of the total CVR. 67.6% of the patients were classified as at very high CVR. At 18 months of treatment, 34 (46% patients were treated with statins (median atorvastatin and rosuvastatin doses were 10 mg/day each.Results and discussion. Only 12% of the patients had optimal baseline values of just all lipid parameters. The concentration of total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and high-density lipoprotein cholesterol (HDL-C correlated negatively with C-reactive protein (CRP levels, DAS28-ESR, DAS28-CRP, and HAQ (p < 0.05. After 6-month treatment, there were increases in TC by 7%, LDL-C by 12.5%, and HDL-C by 19.7%, and a decrease in the atherogenic index by 16% (p < 0.05. ΔCRP negatively correlated with ΔTC, ΔLDL-C, and ΔHDL-C (r = -0.3; p < 0.05. A correlation of TC and LDL-C with

  2. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca{sup 2+}]{sub i}) in MCF-7 Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Varghese, Elizabeth; Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144 Doha (Qatar)

    2014-11-06

    Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in breast cancer cells (MCF-7). Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca{sup 2+}]{sub i}) was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM) with a strong negative correlation (r = −0.713) to viability. Pharmacological modulators 2-APB (50 μM), Nimodipine (10 μM), Caffeine (10 mM), SKF 96365(20 μM) were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca{sup 2+}]{sub i} in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca{sup 2+}]{sub i}. Overall, elevation of [Ca{sup 2+}]{sub i} by Auranofin might be crucial for triggering Ca{sup 2+}-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca{sup 2+}]{sub i} should be considered as a crucial factor for the induction of cell death in cancer cells.

  3. A reprofiled drug, auranofin, is effective against metronidazole-resistant Giardia lamblia.

    Science.gov (United States)

    Tejman-Yarden, Noa; Miyamoto, Yukiko; Leitsch, David; Santini, Jennifer; Debnath, Anjan; Gut, Jiri; McKerrow, James H; Reed, Sharon L; Eckmann, Lars

    2013-05-01

    Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 compounds that caused significant inhibition of G. lamblia growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent G. lamblia isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious in vivo, as it eradicated infection with different G. lamblia isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains.

  4. Severe cutaneous adverse drug reactions:a review on epidemiology,etiology,clinical manifestation and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Tomy Martin; LI Hui

    2008-01-01

    Purpose To review the current progress in epidemiology, etiology, clinical manifestation, and pathophysiology of severe cutaneous adverse drug reactions(SCADRs). Data sources Data were acquired by using Blackwell-Synergy, PubMed, original articles published in the main Chinese journals and related medical textbooks materials. Study-selection and date extraction Throughout the literature review 49 articles were selected. Results SCADRs cases are rare, however, the implication is life threatening with significant mortatity rates. Epidemiology studies have shown various incidences from different regions, gender, age, race and concurrent illness. There are typical signs and symptoms for each type of SCADRs, but this is not always so. Drugs associated with inducing SCADRs are anticonvulsants, antibiotics, NSAIDs and antirheumatic drugs. In some countries, especially in Asia, traditional drugs are offen the cause of SCADRs. Genetic polymorphisms and viral infections are predisposition factors of SCADRs. Patients with certain genetic alleles and underlying diseases are vulnerable to SCADRs. The exact pathogenesis of SCADRs is not well defined. Nonetheless, recent study showed that reactive metabolites and immunological processes have a significant role in SCADRs. Conclusions The different SCADRs reactions are attributed by different intrinsic factors, such as genetic polymorphisms, gender, age and race as well as extrinsic factors, such as underlying diseases. Different regions and culprit drugs also play a role in the various types of SCADRs.

  5. A treat-to-target strategy with methotrexate and intra-articular triamcinolone with or without adalimumab effectively reduces MRI synovitis, osteitis and tenosynovitis and halts structural damage progression in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Axelsen, Mette Bjørndal; Eshed, Iris; Hørslev-Petersen, Kim

    2014-01-01

    OBJECTIVES: To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional...... effect. METHODS: In a double-blind, placebo-controlled trial, 85 disease-modifying antirheumatic drug-naïve patients with ERA were randomised to receive methotrexate, intra-articular glucocorticosteroid injections and placebo/adalimumab (43/42). Contrast-enhanced MRI of the right hand was performed...

  6. Psoriatic arthritis management update - biotherapeutic options.

    LENUS (Irish Health Repository)

    Saber, Tajvur P

    2012-02-01

    Psoriatic arthritis (PsA) is a seronegative spondyloarthropathy (SpA) occurring in up to 30% of patients with psoriasis. It has a wide variation of annual incidence (median 6.4, range 0.1-3.1 per 10(5) people), based on analysis of 13 incidence and prevalence reviews published between 1987 and December 2006. Conventional treatments with antiinflammatory and disease modifying or antirheumatic drugs are not efficacious in all patients, in particular those with axial disease. This review examines new pharmacological developments in the treatment of PsA with a focus on biologic therapies.

  7. Cardiovascular disease in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel

    2008-01-01

    ABSTRACT: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross......-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire...

  8. Patients with seronegative RA have more inflammatory activity compared with patients with seropositive RA in an inception cohort of DMARD-naïve patients classified according to the 2010 ACR/EULAR criteria.

    Science.gov (United States)

    Nordberg, Lena Bugge; Lillegraven, Siri; Lie, Elisabeth; Aga, Anna-Birgitte; Olsen, Inge Christoffer; Hammer, Hilde Berner; Uhlig, Till; Jonsson, Maria Karolina; van der Heijde, Désirée; Kvien, Tore K; Haavardsholm, Espen Andre

    2017-02-01

    To compare the presentation of seropositive and seronegative early rheumatoid arthritis (RA) in disease-modifying antirheumatic drug (DMARD)-naïve patients classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. All patients had symptom duration from first swollen joint EULAR classification criteria for RA. NCT01205854; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Monitoring patients with rheumatoid arthritis in routine care

    DEFF Research Database (Denmark)

    Hetland, Merete Lund; Jensen, Dorte Vendelbo; Krogh, Niels Steen

    2014-01-01

    , little is known about the feasibility of a T2T strategy in patients with rheumatoid arthritis (RA) treated in routine care. The aim of the present study was to (i) present the annual number of patients included in DANBIO between 2006 and 2013 and their disease characteristics and (ii) estimate coverage......OBJECTIVES: Advances in aggressive use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) as well as biological DMARDs (bDMARDs) have improved the treatment armamentarium for rheumatologists, and modern treatment principles include a treat-to-target (T2T) strategy. However...

  10. Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Christensen, Anton Wulf; Tarp, Simon; Furst, Daniel E;

    2015-01-01

    )) for rheumatoid arthritis (RA). METHODS: We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design......OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs...

  11. Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, Niels; Hubeck-Graudal, Thorbjørn; Faurschou, Mikkel;

    2015-01-01

    OBJECTIVE: The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared...... the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. METHODS: Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials...

  12. Psoriatic onycho-pachydermo periostitis.

    Science.gov (United States)

    Srivastava, Monika; Solomon, Gary; Strober, Bruce

    2007-01-27

    A 46-year-old woman presented with onycholysis and swollen, painful digits. No other stigmata of psoriasis were present. Magnetic resonance imaging of the hands showed an extensive periosteal reaction of the phalangeal tuft. Psoriatic onycho-pachydermo periostitis (POPP) is a rare subset of psoriatic arthritis that is characterized by psoriatic onychodystrophy, connective-tissue thickening above the distal phalanx, and a periosteal reaction. Treatment of POPP is difficult; however, low-dose methotrexate and anti-TNF-alpha agents may be beneficial. In patients who are unresponsive or intolerant of these medications, other biologic and non-biologic disease modifying anti-rheumatic drugs need to be considered.

  13. Recurrent Pneumothorax after Etanercept Therapy in a Rheumatoid Arthritis Patient: A Case Report

    Science.gov (United States)

    Kim, Sang Hoon; Seo, Young Ho; Kim, Ji Hyoung; Jeong, Il Woo; Sohn, Sung Birm

    2014-01-01

    The use of anti-tumor necrosis factor (anti-TNF) agents for rheumatoid arthritis (RA) patients who are refractory to disease-modifying anti-rheumatic drugs is gradually increasing. Etanercept is the first anti-TNF agent to be approved for RA treatment and is also the most widely used. However, aggravation of interstitial lung disease after etanercept treatment in RA patients has been reported recently. We report the first case of recurrent spontaneous pneumothorax with progression of interstitial lung disease after initiating etanercept therapy. The withdrawal of etanercept and a change to adalimumab, a different class of TNF inhibitor, achieved clinical stabilization. PMID:25568848

  14. MonitorNet: studio italiano osservazionale multicentrico per la valutazione del profilo rischio-beneficio dei farmaci biologici nella pratica clinica reumatologica

    Directory of Open Access Journals (Sweden)

    S. Bombardieri

    2011-06-01

    Full Text Available Over the last decade, several new biologic agents have become available for the treatment of patients with rheumatoid arthritis (RA, psoriatic arthritis (PsA, ankylosing spondylitis (AS and psoriasis (Ps. In contrast to conventional disease modifying anti-rheumatic drugs (DMARDs, these biological agents have rapid onset of action and pronounced disease reducing activity when administered as monotherapy or in combination with MTX. Pre-registration randomised clinical trials have compared biological agents against placebo over a limited time span (1-3. Wider use of biologics has resulted in reports of a wide range of adverse events (4, including evidence of reactivation of latent tuberculosis, increased incidence...

  15. Pharmacologic Therapies for Rheumatologic and Autoimmune Conditions.

    Science.gov (United States)

    Bays, Alison M; Gardner, Gregory

    2016-07-01

    Disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed by rheumatologists to reduce disease activity and induce remission in autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis. Steroids are sometimes used in combination with DMARD therapy and should be used at the lowest effective dose for the least amount of time. There are many biologic agents available for use for inflammatory arthritis and other autoimmune conditions. Care should be taken when prescribing and managing DMARDS, steroids and biologic agents medications with a careful eye towards screening for infectious disease, vaccination, bone heath and lab monitoring.

  16. Magnetic resonance imaging applications in early rheumatoid arthritis diagnosis and management.

    Science.gov (United States)

    Troum, Orrin M; Pimienta, Olga; Olech, Ewa

    2012-05-01

    Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is a sensitive modality that can assess both inflammatory and structural lesions. MRI can assist in following the disease course in patients treated with traditional disease-modifying antirheumatic drugs and biological therapies both in the clinic and in research trials. Therefore, it is anticipated that MRI becomes the diagnostic imaging modality of choice in RA clinical trials while remaining a useful tool for clinicians evaluating patients with RA.

  17. Three-dimensional morphological condylar and mandibular changes in a patient with juvenile idiopathic arthritis: interdisciplinary treatment

    Directory of Open Access Journals (Sweden)

    G. Farronato

    2014-11-01

    Full Text Available Temporomandibular joint (TMJ involvement is common but usually delayed in patients with juvenile idiopathic arthritis (JIA. We describe the case of a JIA patient with bilateral TMJ involvement, mandibular retrognathia, bone erosion, and severely restricted mouth opening. The use of cone beam computed tomography and a 3D diagnostic protocol in young patients with JIA provides reliable, accurate and precise quantitative data and images of the condylar structures and their dimensional relationships. Analgesics and conventional disease modifying antirheumatic drugs were ineffective, but interdisciplinary treatment with etanercept and a Herbst functional appliance improved functional TMJ movement and bone resorption.

  18. Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate.

    Science.gov (United States)

    Reina, Delia; Cerdà, Dacia; Güell, Elena; Martínez Montauti, Joaquín; Pineda, Antonio; Corominas, Hèctor

    2016-08-11

    Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. [Skin symptoms of psoriasis associated with spondylarthropathies].

    Science.gov (United States)

    Menzinger, Sébastien; Boehncke, Wolf-Henning

    2016-03-01

    The term spondylarthropathy summarizes a heterogenous group of diseases with spinal involvement as the common denominator. In this paper, we will primarily focus on cutaneous manifestations of psoriasis, as this dermatosis is associated with psoriatic artrhritis, one of the major diseases classified as spondylarthropathy. We will describe the clinical manifestations of psoriasis as well as the underlying pathophysiology, the latter allowing to understand the differences in efficacy of numerous Disease Modifying Anti-Rheumatic Drugs (DMARDs) on joint versus skin symptoms. Additionally, we address the exacerbation of pre-existing psoriasis under DMARD therapy.

  20. Drug Facts

    Medline Plus

    Full Text Available ... Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts ... Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs ...

  1. Drugged Driving

    Science.gov (United States)

    ... Parents & Educators Children & Teens Search Connect with NIDA : Google Plus Facebook LinkedIn Twitter YouTube Flickr RSS Menu ... misuse of prescription drugs can make driving a car unsafe—just like driving after drinking alcohol. Drugged ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  5. Study Drugs

    Science.gov (United States)

    ... study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta Most people get study ... How Much Sleep Do I Need? Prescription Drug Abuse How to Make Homework Less Work Organizing Schoolwork & ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  8. Drugs (image)

    Science.gov (United States)

    ... Drugs for fever, cough, stuffy nose, runny nose, diarrhea, and allergies are common drugs which are especially helpful during times of illness. All medications should be kept out of the reach of children.

  9. Drug Facts

    Science.gov (United States)

    ... drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different people around me. To stop using marijuana, "Cristina" is making positive changes in her life. She finds support from ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to ...

  11. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  12. Urinary excretion of alpha-GST and albumin in rheumatoid arthritis patients treated with methotrexate or other DMARDs alone or in combination with NSAIDs

    DEFF Research Database (Denmark)

    Svendsen, K B; Ellingsen, T; Bech, J N

    2005-01-01

    OBJECTIVE: To evaluate the effect of methotrexate (MTX) and other disease-modifying anti-rheumatic drugs (DMARDs) alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the urinary excretion of alpha-glutathione S-transferase (alpha-GST) and albumin in rheumatoid arthritis......, and none had proteinuria using urine dipstick methods. CONCLUSION: DMARD-treated RA patients with normal serum creatinine had no detectable renal injuries assessed by the urinary excretions of alpha-GST and albumin.......OBJECTIVE: To evaluate the effect of methotrexate (MTX) and other disease-modifying anti-rheumatic drugs (DMARDs) alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the urinary excretion of alpha-glutathione S-transferase (alpha-GST) and albumin in rheumatoid arthritis...... (RA) patients. METHODS: Nineteen RA patients starting treatment with MTX were followed for 1 year with measurements of urinary alpha-GST, urinary albumin, and urinary and plasma creatinine at the start of treatment, and after 16, 28, and 52 weeks. A larger group of RA patients (n = 72) undergoing long...

  13. Orphan drugs

    Directory of Open Access Journals (Sweden)

    Goločorbin-Kon Svetlana

    2013-01-01

    Full Text Available Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. The beginning of orphan drugs development. This problem was first recognized by Congress of the United States of America in January 1983, and when the ”Orphan Drug Act” was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. Conclusion. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs. [Projekat Ministarstva nauke Republike Srbije, br. III 41012

  14. Club Drugs

    Science.gov (United States)

    ... Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ...

  15. Herbal drugs and drug interactions

    OpenAIRE

    Gül Dülger

    2014-01-01

    Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions ...

  16. Drugged Driving

    Science.gov (United States)

    ... Age Adults in 2015 Teens and E-cigarettes Abuse of Prescription (Rx) Drugs Affects Young Adults Most Substance Use in Women and Men View All NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home ...

  17. Drug treatment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010263 Drug resistance mechanism of non-small cell lung cancer PC9/AB2 cell line with acquired drug resistance to gefitinib.JU Lixia(鞠立霞),et al. Dept Oncol,Shanghai Pulm Hosp,Tongji Univ,Shanghai 200433. Chin J Tuberc Respir Dis 2010;33(5):354-358. Objective To

  18. Drug Education.

    Science.gov (United States)

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  19. Update on the use of steroids in rheumatoid arthritis.

    Science.gov (United States)

    García-Magallón, Blanca; Silva-Fernández, Lucía; Andreu-Sánchez, José Luis

    2013-01-01

    Corticosteroids are a mainstay in the therapy of rheumatoid arthritis (RA). In recent years, a number of high-quality controlled clinical trials have shown their effect as a disease-modifying anti-rheumatic drug (DMARD) and a favourable safety profile in recent-onset RA. Despite this, they are more frequently used as bridge therapy while other DMARDs initiate their action than as true disease-modifying agents. Low-dose corticosteroid use during the first two years of disease slows radiologic damage and reduces the need of biologic therapy aimed at reaching a state of clinical remission in recent-onset RA. Thus, their systematic use in this clinical scenario should be considered. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Link Between Drug Use and HIV/AIDS Treatment & Recovery What is Treatment? Why Does a Person Need ... Work? What Are the Treatment Options? What Is Recovery? What Is a Relapse? How Can Friends and ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco ... Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  5. Drug Addiction

    Science.gov (United States)

    ... stimulants Stimulants include amphetamines, meth (methamphetamine), cocaine and methylphenidate (Ritalin). They are often used and abused in ... a medication, talk to your doctor. Preventing drug abuse in children and teenagers Take these steps to ...

  6. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  7. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and ... Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  9. Prescription Drugs

    Science.gov (United States)

    ... Jackets, Yellows, and Zombie Pills Stimulants: Bennies, Black Beauties, Hearts, Roses, Skippy, The Smart Drug, Speed, and ... used to relieve anxiety or help a person sleep, such as Valium or Xanax Stimulants — used for ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  11. Drug discovery from Chinese medicine against neurodegeneration in Alzheimer's and vascular dementia

    Directory of Open Access Journals (Sweden)

    So Kwok-Fai

    2011-04-01

    Full Text Available Abstract Alzheimer's disease and vascular dementia are two major diseases associated with dementia, which is common among the elderly. While the etiology of dementia is multi-factorial and complex, neurodegeneration may be the major cause of these two diseases. Effective drugs for treating dementia are still to be discovered. Current western pharmacological approaches against neurodegeneration in dementia develop symptom-relieving and disease-modifying drugs. Current integrative and holistic approaches of Chinese medicine to discovering drugs for neurodegeneration in dementia include (1 single molecules from the herbs, (2 standardized extracts from a single herb, and (3 herbal formula with definite composition. This article not only reviews the concept of dementia in western medicine and Chinese medicine but also evaluates the advantages and disadvantages of these approaches.

  12. Duchenne muscular dystrophy drugs face tough path to approval.

    Science.gov (United States)

    Hodgkinson, L; Sorbera, L; Graul, A I

    2016-03-01

    Highly anticipated as new disease-modifying treatments for Duchenne muscular dystrophy (DMD), therapeutics by BioMarin Pharmaceutical (Kyndrisa™; drisapersen) and Sarepta Therapeutics (eteplirsen; AVI-4658) both recently received negative FDA reviews and are now facing battles for approval in the U.S. At present, BioMarin is committed to working with the FDA to forge a pathway to approval following the failure of its NDA, while Sarepta awaits the formal decision on its NDA, which is expected by late May 2016. Despite the critical nature of both reviews, analysts consider that there is still a narrow possibility of approval of both drugs. According to Consensus forecasts from Thomson Reuters Cortellis for Competitive Intelligence, Kyndrisa is forecast to achieve sales of USD 533.71 million in 2021.

  13. Drug-drug interactions: antiretroviral drugs and recreational drugs.

    Science.gov (United States)

    Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

  14. Randomized, open-label study to evaluate patient-reported outcomes with fingolimod after changing from prior disease-modifying therapy for relapsing multiple sclerosis: EPOC study rationale and design.

    Science.gov (United States)

    Cascione, Mark; Wynn, Daniel; Barbato, Luigi M; Pestreich, Linda; Schofield, Lesley; McCague, Kevin

    2013-07-01

    The study to Evaluate Patient OutComes, Safety, and Tolerability of Fingolimod (EPOC; NCT01216072) aimed to test the hypothesis that therapy change to oral Gilenya (Novartis AG, Stein, Switzerland) (fingolimod) improves patient-reported outcomes compared with standard-of-care disease-modifying therapy (DMT) in patients with relapsing multiple sclerosis; safety and tolerability were also assessed. This communication describes the study rationale and design. EPOC is a phase 4, open-label, multi-center study conducted in the US and Canada of patients with relapsing forms of multiple sclerosis who are candidates for therapy change. Therapy change eligibility was determined by the treating physician (US patients) or required an inadequate response to or poor tolerance for at least 1 MS therapy (Canadian patients). Patients were randomly assigned in a 3:1 ratio to 6 months of treatment with once-daily oral fingolimod 0.5 mg or standard-of-care DMTs. The primary study end-point was the change from baseline in treatment satisfaction as determined by the global satisfaction sub-scale of the Treatment Satisfaction Questionnaire for Medication. Secondary end-points included changes from baseline in perceived effectiveness and side-effects, and measures of activities of daily living, fatigue, depression, and quality-of-life. A 3-month open-label fingolimod extension was available for patients randomly assigned to the DMT group who successfully completed all study visits. Enrollment has been completed with 1053 patients; the patient population is generally older and has a longer duration of disease compared with populations from phase 3 studies of fingolimod. Inclusion criteria selected for patients with a sub-optimal experience with a previous DMT, limiting the collection of data on therapy change in patients who were satisfied with their previous DMT. Results of the EPOC study are anticipated in early 2013 and will inform treatment selection by providing patient

  15. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - ...

  16. Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

    Directory of Open Access Journals (Sweden)

    Jones G

    2012-07-01

    Full Text Available Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression. A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference and abatacept (no effect on odds of progression. This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

  17. Protecting Bone Health in Pediatric Rheumatic Diseases: Pharmacological Considerations.

    Science.gov (United States)

    Zhang, Yujuan; Milojevic, Diana

    2017-06-01

    Bone health in children with rheumatic conditions may be compromised due to several factors related to the inflammatory disease state, delayed puberty, altered life style, including decreased physical activities, sun avoidance, suboptimal calcium and vitamin D intake, and medical treatments, mainly glucocorticoids and possibly some disease-modifying anti-rheumatic drugs. Low bone density or even fragility fractures could be asymptomatic; therefore, children with diseases of high inflammatory load, such as systemic onset juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, and those requiring chronic glucocorticoids may benefit from routine screening of bone health. Most commonly used assessment tools are laboratory testing including serum 25-OH-vitamin D measurement and bone mineral density measurement by a variety of methods, dual-energy X-ray absorptiometry as the most widely used. Early disease control, use of steroid-sparing medications such as disease-modifying anti-rheumatic drugs and biologics, supplemental vitamin D and calcium, and promotion of weight-bearing physical activities can help optimize bone health. Additional treatment options for osteoporosis such as bisphosphonates are still controversial in children with chronic rheumatic diseases, especially those with decreased bone density without fragility fractures. This article reviews common risk factors leading to compromised bone health in children with chronic rheumatic diseases and discusses the general approach to prevention and treatment of bone fragility.

  18. Herbal drugs and drug interactions

    Directory of Open Access Journals (Sweden)

    Gül Dülger

    2012-01-01

    Full Text Available Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions of some most commanly used herbals (St John's wort, ginkgo biloba, ginseng, ginger, garlic, echinacea, ephedra and valerian with the conventional drugs were reviewed. Pharmacokinetic interactions involve mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoproteins by the herbal medicine, thus changing the absorption and/or elimination rate and consequently the efficacy of the concommitantly used drugs. St John's wort, a well known enzyme inducer, decreases the efficacy of most of the other drugs that are known to be the substrates of these enzymes.Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

  19. Pharmacogenetics and pharmacogenomics in rheumatology.

    Science.gov (United States)

    Szekanecz, Zoltán; Meskó, Bertalan; Poliska, Szilard; Váncsa, Andrea; Szamosi, Szilvia; Végh, Edit; Simkovics, Enikö; Laki, Judit; Kurkó, Júlia; Besenyei, Timea; Mikecz, Katalin; Glant, Tibor T; Nagy, László

    2013-07-01

    Pharmacogenetics and pharmacogenomics deal with possible associations of a single genetic polymorphism or those of multiple gene profiles with responses to drugs. In rheumatology, genes and gene signatures may be associated with altered efficacy and/or safety of anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) and biologics. In brief, genes of cytochrome P450, other enzymes involved in drug metabolism, transporters and some cytokines have been associated with responses to and toxicity of non-steroidal anti-inflammatory drugs, corticosteroids and DMARDs. The efficacy of biologics may be related to alterations in cytokine, chemokine and FcγR genes. Numerous studies reported multiple genetic signatures in association with responses to biologics; however, data are inconclusive. More, focused studies carried out in larger patient cohorts, using pre-selected genes, may be needed in order to determine the future of pharmacogenetics and pharmacogenomics as tools for personalized medicine in rheumatology.

  20. Advancing drug delivery systems for the treatment of multiple sclerosis.

    Science.gov (United States)

    Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

    2015-12-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

  1. Antineoplastic Drugs.

    Science.gov (United States)

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  2. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  3. Mucoactive drugs

    Directory of Open Access Journals (Sweden)

    R. Balsamo

    2010-06-01

    Full Text Available Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal infection and/or inflammation associated with these diseases often gives rise to inflammatory products, including neutrophil-derived DNA and filamentous actin, in addition to bacteria, apoptotic cells and cellular debris, that may collectively increase mucus production and viscosity. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical complication. The main purpose of mucoactive drugs is to increase the ability to expectorate sputum and/or decrease mucus hypersecretion. Many mucoactive drugs are currently available and can be classified according to their putative mechanism of action. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. By developing our understanding of the specific effects of mucoactive agents, we may result in improved therapeutic use of these drugs. The present review provides a summary of the most clinically relevant mucoactive drugs in addition to their potential mechanism of action.

  4. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  5. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure f

  6. Advances in tau-based drug discovery

    Science.gov (United States)

    Noble, Wendy; Pooler, Amy M.; Hanger, Diane P.

    2011-01-01

    Introduction Tauopathies, including Alzheimer’s disease (AD) and some frontotemporal dementias, are neurodegenerative diseases characterised by pathological lesions comprised of tau protein. There is currently a significant and urgent unmet need for disease-modifying therapies for these conditions and recently attention has turned to tau as a potential target for intervention. Areas covered Increasing evidence has highlighted pathways associated with tau-mediated neurodegeneration as important targets for drug development. Here, the authors review recently published papers in this area and summarise the genetic and pharmacological approaches that have shown efficacy in reducing tau-associated neurodegeneration. These include the use of agents to prevent abnormal tau processing and increase tau clearance, therapies targeting the immune system, and the manipulation of tau pre-mRNA to modify tau isoform expression. Expert opinion Several small molecule tau-based treatments are currently being assessed in clinical trials, the outcomes of which are eagerly awaited. Current evidence suggests that therapies targeting tau are likely, at least in part, to form the basis of an effective and safe treatment for Alzheimer’s disease and related neurodegenerative disorders in which tau deposition is evident. PMID:22003359

  7. The impact of patient heterogeneity and socioeconomic factors on abatacept retention in rheumatoid arthritis across nine European countries

    DEFF Research Database (Denmark)

    Finckh, A; Neto, D; Iannone, F

    2015-01-01

    BACKGROUND: There are substantial differences in accessibility to biological disease modifying antirheumatic drugs (bDMARDs) across countries. The objective of this study was to analyse the impact of patient demographics, disease characteristics and gross domestic product (GDP) on abatacept (ABA...... retention differed between countries, with median drug retention rates ranging from 1.2 to more than 6 years. The differences in drug retention were marginally explained by disparities in disease characteristics, while the national GDP per capita was strongly associated with drug retention (correlation...... characteristics. Lower ABA retention was observed in countries with a more liberal access to bDMARDs and higher GDP. National differences need to be accounted for when pooling data on treatment with bDMARDs from various countries....

  8. Optimal drug use and rational drug policy.

    Science.gov (United States)

    Miller, Geoffrey F

    2011-12-01

    The Müller & Schumann (M&S) view of drug use is courageous and compelling, with radical implications for drug policy and research. It implies that most nations prohibit most drugs that could promote happiness, social capital, and economic growth; that most individuals underuse rather than overuse drugs; and that behavioral scientists could use drugs more effectively in generating hypotheses and collaborating empathically.

  9. Nanomaterials for the Local and Targeted Delivery of Osteoarthritis Drugs

    Directory of Open Access Journals (Sweden)

    Parthiban Chinnagounder Periyasamy

    2012-01-01

    Full Text Available Nanotechnology has found its potential in every possible field of science and engineering. It offers a plethora of options to design tools at the nanometer scale, which can be expected to function more effectively than micro- and macrosystems for specific applications. Although the debate regarding the safety of synthetic nanomaterials for clinical applications endures, it is a promising technology due to its potential to augment current treatments. Various materials such as synthetic polymer, biopolymers, or naturally occurring materials such as proteins and peptides can serve as building blocks for adaptive nanoscale formulations. The choice of materials depends highly on the application. We focus on the use of nanoparticles for the treatment of degenerative cartilage diseases, such as osteoarthritis (OA. Current therapies for OA focus on treating the symptoms rather than modifying the disease. The usefulness of OA disease modifying drugs is hampered by side effects and lack of suitable drug delivery systems that target, deliver, and retain drugs locally. This challenge can be overcome by using nanotechnological formulations. We describe the different nanodrug delivery systems and their potential for cartilage repair. This paper provides the reader basal understanding of nanomaterials and aims at drawing new perspectives on the use of existing nanotechnological formulations for the treatment of osteoarthritis.

  10. The Ocular Manifestations of Drugs Used to Treat Multiple Sclerosis.

    Science.gov (United States)

    Heath, Gregory; Airody, Archana; Gale, Richard Peter

    2017-03-01

    Recent times have seen an increase in the number of options to treat multiple sclerosis. Ocular manifestations of multiple sclerosis are well known to treating physicians; however, the medications used to treat multiple sclerosis can also have ocular side effects. This review article focuses on the ocular manifestations of corticosteroids and disease-modifying agents such as interferon, fingolomod, natalizumab, alemtuzumab and mitoxantron used to treat the disease. The ocular manifestations of multiple sclerosis treatments can be varied depending on the drug used, and include retinopathy, chronic central serous chorioretinopathy, macular oedema, Graves' ophthalmopathy and cortical blindness. These effects may be specific to the drug or secondary to their immunosuppressive effect. The association of macular oedema with fingolomod is clear and merits ocular screening for toxicity. The immunosuppressive nature of the treatments makes patients prone to acquired infections. Hence, if a patient with multiple sclerosis presents with vision loss, infectious and drug-induced aetiology should be considered alongside relapses of multiple sclerosis itself as a cause.

  11. [Emergent drugs (I): smart drugs].

    Science.gov (United States)

    Burillo-Putze, G; Díaz, B Climent; Pazos, J L Echarte; Mas, P Munné; Miró, O; Puiguriguer, J; Dargan, P

    2011-01-01

    In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects.

  12. Drug resistance and antiretroviral drug development

    OpenAIRE

    Shafer, Robert W.; Jonathan M Schapiro

    2005-01-01

    As more drugs for treating HIV have become available, drug resistance profiles within antiretroviral drug classes have become increasingly important for researchers developing new drugs and for clinicians integrating new drugs into their clinical practice. In vitro passage experiments and comprehensive phenotypic susceptibility testing are used for the pre-clinical evaluation of drug resistance. Clinical studies are required, however, to delineate the full spectrum of mutations responsible fo...

  13. Drug Coverage (Part D)

    Science.gov (United States)

    ... insurance Find health & drug plans Drug coverage (Part D) How to get drug coverage Get Medicare prescription drug coverage either from a Part D plan or a Medicare Advantage Plan offering Medicare ...

  14. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs...

  15. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  16. Prescription Drug Abuse

    Science.gov (United States)

    ... over-the-counter medications. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/drugfacts/prescription-over-counter- ... 2015. Prescription drug abuse. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/prescription-drugs/ ...

  17. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  18. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  19. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  20. Urine drug screen

    Science.gov (United States)

    Drug screen -- urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence indicates that you recently used these drugs. Some drugs may remain in your system for ...

  1. Medication/Drug Allergy

    Science.gov (United States)

    ... Science Education & Training Home Conditions Medication/Drug Allergy Medication/Drug Allergy Make an Appointment Find a Doctor ... immediate or delayed. What Is an Allergy to Medication/Drugs? Allergies to drugs/medications are complicated, because ...

  2. From Leflunomide to Teriflunomide: Drug development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2016-12-08

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, the increased number of approved substances and the possibility of an oral availability of some immunomodulators improve the therapeutic repertory and increase patient satisfaction and compliance. Teriflunomide is indicated as first line oral disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Its immunosuppressive capacity results from an inhibition of de novo pyrimidine synthesis in rapidly proliferating lymphocytes. While Teriflunomide has been approved for the treatment of RRMS only since 2012, there is substantial therapeutic experience with its prodrug Leflunomide used in the treatment of rheumatoid arthritis (RA). In MS, a daily dose of 14 mg Teriflunomide reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo while it provides a reasonable safety profile. This review presents an overview on oral immunosuppressants used in the treatment of MS. With an emphasis on Teriflunomide it summarizes discovery, mechanism of action and clinical effectiveness in phase II and III trials as well as important aspects for treating physicians.

  3. Use of a Cholestyramine Washout in a Patient With Septic Shock on Leflunomide Therapy: A Case Report and Review of the Literature.

    Science.gov (United States)

    Laub, Melissa; Fraser, Robert; Kurche, Jonathan; Lara, Abigail; Kiser, Tyree H; Reynolds, Paul M

    2016-07-01

    Patients presenting with infections while receiving disease-modifying antirheumatic agents (DMARD) may be predisposed to a higher degree illness due to immunosuppression. This can be particularly problematic in patients who are receiving DMARDs with prolonged pharmacokinetic profiles. Leflunomide is a DMARD that has a prolonged half-life due to enterohepatic recirculation. We report a case of a patient with severe septic shock secondary to a prosthetic joint infection in which therapeutic levels of leflunomide were discovered, despite the patient ceasing therapy several weeks prior to admission. An orogastric cholestyramine washout was given to the patient to expedite the removal of the drug. Serum levels rapidly declined over the next several days, corresponding with resolution of her sepsis. A review of the literature relevant to the incidence of DMARD-related infections was conducted as well as discussion regarding the role of leflunomide drug monitoring and cholestyramine-facilitated removal of the drug in episodes of acute infectious syndromes.

  4. Smoking and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Kathleen Chang

    2014-12-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs, there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper.

  5. The dark side of SAPHO syndrome.

    Science.gov (United States)

    Henriques, Celia Coelho; Sousa, Mónica; Panarra, António; Riso, Nuno

    2011-12-21

    SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a relatively rare entity. The therapeutic approach of patients with SAPHO syndrome has included multiple drugs with varying success and incoherence responses. The therapy is still empirical today. SAPHO syndrome is commonly treated with non-steroidal anti-inflammatory drugs, bisphophonates and non-biologic disease modifying antirheumatic drugs. Recent reports showed successful treatment with tumour necrosis factor α (TNF α) antagonists, but there is still a dark side of SAPHO syndrome including a subgroup of patient's refractory to all the treatments that have been empirically experienced. A clinical report of a patient with SAPHO syndrome with 12 years of evolution is described. All the therapeutic approaches, including anti TNF α therapy, have not prevented the clinical and radiographic progression of the disease. Given that the disease affects mostly younger patients, new therapeutic strategies are necessary in order to avoid potentially irreversible joint and bone lesions.

  6. Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action

    Directory of Open Access Journals (Sweden)

    Damal K

    2013-11-01

    Full Text Available Kavitha Damal, Emily Stoker, John F FoleyRocky Mountain Multiple Sclerosis Research Group, Salt Lake City, UT, USAAbstract: Multiple sclerosis (MS is a debilitating neurological disorder that affects nearly 2 million adults, mostly in their prime of youth. An environmental trigger, such as a viral infection, is hypothesized to initiate the abnormal behavior of host immune cells: to attack and damage the myelin sheath surrounding the neurons of the central nervous system. While several other pathways and disease triggers are still being investigated, it is nonetheless clear that MS is a heterogeneous disease with multifactorial etiologies that works independently or synergistically to initiate the aberrant immune responses to myelin. Although there are still no definitive markers to diagnose the disease or to cure the disease per se, research on management of MS has improved many fold over the past decade. New disease-modifying therapeutics are poised to decrease immune inflammatory responses and consequently decelerate the progression of MS disease activity, reduce the exacerbations of MS symptoms, and stabilize the physical and mental status of individuals. In this review, we describe the mechanism of action, optimal dosing, drug administration, safety, and efficacy of the disease-modifying therapeutics that are currently approved for MS therapy. We also briefly touch upon the new drugs currently under investigation, and discuss the future of MS therapeutics.Keywords: multiple sclerosis, immunomodulation, interferons, glatiramer acetate, monoclonal antibodies, dimethyl fumarate

  7. DrugCentral: online drug compendium.

    Science.gov (United States)

    Ursu, Oleg; Holmes, Jayme; Knockel, Jeffrey; Bologa, Cristian G; Yang, Jeremy J; Mathias, Stephen L; Nelson, Stuart J; Oprea, Tudor I

    2017-01-04

    DrugCentral (http://drugcentral.org) is an open-access online drug compendium. DrugCentral integrates structure, bioactivity, regulatory, pharmacologic actions and indications for active pharmaceutical ingredients approved by FDA and other regulatory agencies. Monitoring of regulatory agencies for new drugs approvals ensures the resource is up-to-date. DrugCentral integrates content for active ingredients with pharmaceutical formulations, indexing drugs and drug label annotations, complementing similar resources available online. Its complementarity with other online resources is facilitated by cross referencing to external resources. At the molecular level, DrugCentral bridges drug-target interactions with pharmacological action and indications. The integration with FDA drug labels enables text mining applications for drug adverse events and clinical trial information. Chemical structure overlap between DrugCentral and five online drug resources, and the overlap between DrugCentral FDA-approved drugs and their presence in four different chemical collections, are discussed. DrugCentral can be accessed via the web application or downloaded in relational database format. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Drug Preferences of Multiple Drug Abusers.

    Science.gov (United States)

    Harford, Robert J.

    1978-01-01

    Examined drug preferences of a group of active multiple drug abusers referred for treatment. Nearly half the respondents preferred drugs other than type they most frequently used. Preferences were related to method of administration. Results suggest preference is one among several determinants of drug use. (Author/BEF)

  9. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  10. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  11. Drugs in development for relapsing multiple sclerosis.

    Science.gov (United States)

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral

  12. Multiple sclerosis: Therapeutic applications of advancing drug delivery systems.

    Science.gov (United States)

    Dolati, Sanam; Babaloo, Zohreh; Jadidi-Niaragh, Farhad; Ayromlou, Hormoz; Sadreddini, Sanam; Yousefi, Mehdi

    2017-02-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood-brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs suppress circulating immune cells, inhibit passing the BBB and decrease the inflammatory responses. Recent advances have remarkably delayed disease development and improved the quality of life for numerous patients. In spite of major improvements in therapeutic options, there are some limitations regarding the routes of administration and the necessity for repeated and long-term dosing in which cause to systemic disadvantageous consequences and patient non-compliance. Nanotechnology presents promising approaches to improve autoimmune disease treatment with the capability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we emphasis on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis. This comprehensive review details the most successful drugs in MS therapy and also focuses on conceptions and clinical potential of novel nanomedicine attitudes for inducing immunosuppression and immunological tolerance in MS to modulate abnormal and pathologic immune responses.

  13. AIDSinfo Drug Database

    Science.gov (United States)

    ... U V W X Y Z All Drugs Drug News Thursday, February 2, 2017 Sustiva Drug Label Updated ... Drug Label Updated Tuesday, January 31, 2017 Stribild Drug Label Updated More News Mobile Apps iPhone/iPad App Android App Back ...

  14. Current treatment approaches in patients with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Bilal Elbey

    2015-03-01

    Full Text Available Ankylosing spondylitis (AS is a chronic, inflammatory, rheumatic disease that mainly affects sacroiliac joints and spine. AS predominantly occurs more often in males and typically begins in the second or third decade. The mainstay of therapy in AS are nonsteroidal anti-inflammatory drugs, which reduce inflammation and pain. Disease modifying antirheumatic drugs (DMARD did not have enough evidence to prove their effect in AS treatment. The use of DMARD may not sufficient to improve the treatment and symptoms. Currently, TNF-blockers such as, Golimumab Etanersept Adalimumab İnfliksimab have promising results in the treatment of AS. TNF-blockers improve the clinical signs and symptoms, and improve the patients’ physical function and quality of life. This manuscript is focused that Current pharmacological treatments in patients with ankylosing spondylitis.

  15. Sulfasalazine plus Chloroquine-Induced Mood Disorder in a Patient with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Gulcan Gulec

    2009-03-01

    Full Text Available Rheumatoid arthritis is a chronic systemic inflammatory diseasethat affects approximately 0.5-1% of the world population.The current approach to this disease is to start an intensivetreatment without delay once the disease has developed.Various studies in the literature have shown that combinationof disease modifying antirheumatic drugs such as sulfasalazineand chloroquine offers a more advantageous treatment.Although these drugs may cause central nervous system adverseeffects such as serious psychiatric problems includingmania and psychosis, these symptoms have been reported tooccur only infrequently. The present case study reports a femalepatient who was hospitalized due to bipolar affective disorder-mixed episode. She had been receiving 250 mg/daychloroquine for 9 months for rheumatoid arthritis without exhibitingany adverse psychiatric effects. However, upon receivinga combination of 250 mg/day chloroquine and 2 gr/day sulfasalazine,she developed serious psychiatric symptoms.

  16. Treatment of psoriasis and psoriatic arthritis during pregnancy and breastfeeding.

    Science.gov (United States)

    Kurizky, Patricia Shu; Ferreira, Clarissa de Castro; Nogueira, Lucas Souza Carmo; Mota, Licia Maria Henrique da

    2015-01-01

    Psoriasis is a chronic inflammatory disease that affects primarily the skin and joints, with a worldwide incidence of 2-3%. Fifty percent of patients are women, most still diagnosed during childbearing years. Currently,the estimate is that up to 107 thousand deliveries are performed annually in women with psoriasis, a percentage of them in women with moderate to severe disease. Fetal risks in pregnant women with psoriasis derive both from maternal disease and the medications used to control the illness. The purpose of this review is to study the effect of the main drugs used in the treatment of psoriasis and psoriatic arthritis during pregnancy and lactation, with particular focus on disease-modifying anti-rheumatic biological drugs, biological therapies, immunobiologics or biologics.

  17. One year in an Alaskan arthritis clinic.

    Science.gov (United States)

    Templin, D

    1999-10-01

    During 1997 visits were made by 852 individuals to an arthritis clinic in Alaska serving predominantly Alaska Natives. Three hundred twenty- seven of these were seen for the first time. The ratio of women to men was 3:1. Rheumatoid Arthritis was the most common arthritic condition seen, followed by Degenerative Joint Disease and Spondyloarthropathies. Three hundred five Tlingit and 246 Eskimo made up 65% of the patients seen that year. Methotrexate was the most frequently used Disease Modifying Antirheumatic Drug but the other such drugs were prescribed as well. Recording demographic and clinical information on a portable computer at the time of visit provided record linkage and the data for this report and was used in Health Care Planning.

  18. Remission-induction therapies for early rheumatoid arthritis: evidence to date and clinical implications.

    Science.gov (United States)

    Espinoza, Francisco; Fabre, Sylvie; Pers, Yves-Marie

    2016-08-01

    Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a 'window of opportunity' for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission.

  19. Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story.

    Science.gov (United States)

    Malaviya, Anand N

    2016-09-01

    This review highlights the story of how methotrexate (MTX), a drug discovered for the treatment of childhood leukemia, became the mainstay of treatment and the standard-of-care for rheumatoid arthritis (RA) and was also found useful for several additional related rheumatological diseases. As against several synthetic disease-modifying antirheumatic drugs (csDMARDs) for treating RA that were discovered serendipitously, the use of low-dose MTX (LD-MTX) was based on sound reasoning and astute observations made in the 1940s and 1950s. The difference between high-dose MTX (HD-MTX) used in the treatment of childhood leukaemia and other malignancies as against LD-MTX used in rheumatology is emphasized.

  20. Diagnosis and treatment of enthesitis-related arthritis

    Directory of Open Access Journals (Sweden)

    Weiss PF

    2012-06-01

    Full Text Available Pamela F WeissDivision of Rheumatology and Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Departments of Pediatrics and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Juvenile idiopathic arthritis (JIA is a chronic, inflammatory disease of unknown etiology. The enthesitis-related arthritis (ERA JIA category describes a clinically heterogeneous group of children including some who have predominately enthesitis, enthesitis and arthritis, juvenile ankylosing spondylitis, or inflammatory bowel disease-associated arthropathy. ERA accounts for 10%–20% of JIA. Common clinical manifestations of ERA include arthritis, enthesitis, and acute anterior uveitis. Axial disease is also common in children with established ERA. Treatment regimens for ERA, many of them based on adults with rheumatoid arthritis and ankylosing spondylitis, include the use of nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologic agents either individually or in combination.Keywords: juvenile arthritis, enthesitis, sacroillitis, epidemiology, therapy

  1. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    Science.gov (United States)

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine.

  2. KEGG DRUG / Acutect (TN) [KEGG DRUG

    Lifescience Database Archive (English)

    Full Text Available DRUG: D06027 Entry D06027Drug Name Technetium Tc 99m apcitide (USP); Acutect (TN) F... 1 838085 1 848586 1 857781 1 868182 1 878280 1 888687 1 898288 2 908689 2 918390 1 929091 2 939092 1 949495 2 KEGG DRUG / Acutect (TN) ...

  3. Attitudes towards drug legalization among drug users.

    Science.gov (United States)

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  4. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  5. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  6. Drug Plan Coverage Rules

    Science.gov (United States)

    ... get about Medicare Lost/incorrect Medicare card Report fraud & abuse File a complaint Identity theft: protect yourself ... drug plan How Part D works with other insurance Find health & drug plans Drug plan coverage rules ...

  7. Drugs: Shatter the Myths

    Science.gov (United States)

    ... ML. Tobacco, alcohol, and other risk behaviors in film: how well do MPAA ratings distinguish content? J ... about drugs and drug abuse. NDFW includes local school and community events and Drug Facts Chat Day, ...

  8. Drug-induced hepatitis

    Science.gov (United States)

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  9. Drugs Approved for Melanoma

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Melanoma This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome ( ...

  10. Drug Retention Times

    Energy Technology Data Exchange (ETDEWEB)

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  11. Prescription Drug Abuse

    Science.gov (United States)

    ... Whether they're using street drugs or medications, drug abusers often have trouble at school, at home, with ... a short period of time may make a drug abuser aggressive or paranoid. Although stimulant abuse might not ...

  12. Drug Development Process

    Science.gov (United States)

    ... Device Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Step 1 Discovery and Development Discovery and Development Research for a new drug ...

  13. Drug: D06912 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nese Medicine in Japan [BR:br08304] Crude Drugs Drugs for blood Drugs for removing blood stasis D06912 *Quercus cortex; Bokusoku Drug...s for external use Drugs for external use D06912 *Quercu

  14. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    Directory of Open Access Journals (Sweden)

    Chandra Prakash

    2015-12-01

    Full Text Available Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs, and transport proteins coordinate drug influx (phase 0 and drug/drug-metabolite efflux (phase III. Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs, i.e. PXR (pregnane X receptor and CAR (constitutive androstane receptor, and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR, due to transactivation of xenobiotic-response elements (XREs present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug's impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse

  15. Small-Molecule Anticonvulsant Agents with Potent in vitro Neuroprotection and Favorable Drug-like Properties

    Science.gov (United States)

    Smith, Garry R.; Brenneman, Douglas E.; Zhang, Yan; Du, Yanming; Reitz, Allen B.

    2014-01-01

    Severe seizure activity is associated with reoccurring cycles of excitotoxicity and oxidative stress that result in progressive neuronal damage and death. Intervention with these pathological processes is a compelling disease-modifying strategy for the treatment of seizure disorders. We have optimized a series of small molecules for neuroprotective and anticonvulsant activity as well as altered their physical properties to address potential metabolic liabilities, to improve CNS penetration and to prolong the duration of action in vivo. Utilizing phenotypic screening of hippocampal cultures with nutrient medium depleted of antioxidants as a disease model, cell death and decreased neuronal viability produced by acute treatment with glutamate or hydrogen peroxide were prevented. Modifications to our previously reported proof of concept compounds have resulted in a lead which has full neuroprotective action at anticonvulsants are feasible within a single molecular entity which also possesses favorable CNS-active drug properties in vitro and in vivo. PMID:24277343

  16. Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.

    Science.gov (United States)

    Maurer, H H; Tauvel, F X; Kraemer, T

    2001-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesic and anti-rheumatic drugs, and they are often misused. A gas chromatographic-mass spectrometric (GC-MS) screening procedure was developed for their detection in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons after extractive methylation. The compounds were separated by capillary GC and identified by computerized MS in the full-scan mode. Using mass chromatography with the ions m/z 119, 135, 139, 152, 165, 229, 244, 266, 272, and 326, the possible presence of NSAIDs and their metabolites could be indicated. The identity of positive signals in such mass chromatograms was confirmed by comparison of the peaks underlying full mass spectra with the reference spectra recorded during this study. This method allowed the detection of therapeutic concentrations of acemetacin, acetaminophen (paracetamol), acetylsalicylic acid, diclofenac, diflunisal, etodolac, fenbufen, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, indometacin, kebuzone, ketoprofen, lonazolac, meclofenamic acid, mefenamic acid, mofebutazone, naproxen, niflumic acid, phenylbutazone, suxibuzone, tiaprofenic acid, tolfenamic acid, and tolmetin in urine samples. The overall recoveries of the different NSAIDs ranged between 50 and 80% with coefficients of variation of less than 15% (n = 5), and the limits of detection of the different NSAIDs were between 10 and 50 ng/mL (S/N = 3) in the full-scan mode. Extractive methylation has proved to be a versatile method for STA of various acidic drugs, poisons, and their metabolites in urine. It has also successfully been used for plasma analysis.

  17. Assessment of disease activity in rheumatoid arthritis: recommendations and practice

    Directory of Open Access Journals (Sweden)

    Yu.A. Olyunin

    2014-01-01

    Full Text Available The results of studies conducted over the past two decades were used to elaborate EULAR recommendations for the management of rheumatoid arthritis (RA; the updated recommendations have recently been published. In accordance with these recommendations, the tactics in management of each patient is determined by the disease activity. This indicator determines the frequency of examination for the patient, selection of an anti-rheumatic drug, and the need for therapy correction. Methotrexate is recommended to patients with active RA (high or moderate activity naÏve to disease-modifying anti-rheumatic drugs (DMARDs. Another DMARD can be used for patients with lower activity of RA. Therapy effectiveness is evaluated as soon as 3 months after its prescription. Clinical improvement (decrease in RA activity from high to moderate needs to be achieved by this time. However, the aim of therapy is to achieve low disease activity or remission (that needs to be achieved earlier than 6 month after the therapy was started rather than clinical improvement only. If the maximum dose of a drug results neither in clinical improvement after 3 months nor in low activity after 6 months, the therapy should be corrected. EULAR experts recommend using the overall score that includes joint score indices (DAS28, SDAI or CDAI to assess the level of RA activity. 

  18. Assessment of disease activity in rheumatoid arthritis: recommendations and practice

    Directory of Open Access Journals (Sweden)

    Yu.A. Olyunin

    2014-05-01

    Full Text Available The results of studies conducted over the past two decades were used to elaborate EULAR recommendations for the management of rheumatoid arthritis (RA; the updated recommendations have recently been published. In accordance with these recommendations, the tactics in management of each patient is determined by the disease activity. This indicator determines the frequency of examination for the patient, selection of an anti-rheumatic drug, and the need for therapy correction. Methotrexate is recommended to patients with active RA (high or moderate activity naÏve to disease-modifying anti-rheumatic drugs (DMARDs. Another DMARD can be used for patients with lower activity of RA. Therapy effectiveness is evaluated as soon as 3 months after its prescription. Clinical improvement (decrease in RA activity from high to moderate needs to be achieved by this time. However, the aim of therapy is to achieve low disease activity or remission (that needs to be achieved earlier than 6 month after the therapy was started rather than clinical improvement only. If the maximum dose of a drug results neither in clinical improvement after 3 months nor in low activity after 6 months, the therapy should be corrected. EULAR experts recommend using the overall score that includes joint score indices (DAS28, SDAI or CDAI to assess the level of RA activity. 

  19. An experimental evaluation of patient decision aid design to communicate the effects of medications on the rate of progression of structural joint damage in rheumatoid arthritis.

    Science.gov (United States)

    Martin, Richard W; Brower, Matthew E; Geralds, Alexander; Gallagher, Patience J; Tellinghuisen, Donald J

    2012-03-01

    To explore how effectively information presentation formats used in a patient decision aid communicated the ability of a disease modifying anti-rheumatic drug to slow the rate of progression of rheumatoid arthritis related structural joint damage (SJD). 91 first year psychology students and 91 RA patients participated in a prospective randomized, single blind, factorial experimental design evaluating the effect of four information formats on: satisfaction with risk communication, verbatim and gist recall of a hypothetical anti-rheumatic drug's ability to slow the rate of progression of SJD. Both groups underestimated the hypothetical drug's ability to slow SJD. Formats that supported the narrative statement with a reinforcing graphic element resulted in recall closer to the true value. Comparison of the results from testing of RA patients and college students were remarkably similar across formats. Rate of progression as communicated by narrative statement plus a graphic element (i.e. speedometer metaphor or pictograph) aided recall better than a narrative statement alone. Our results suggest that testing decision aid components with non-patients may provide data generalizable to patient populations. Graphics must be used carefully in patient decision aids as they can enhance recall, but may also introduce unintended recall bias. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Drug: D06722 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ranthes bidentata root Major component: Ecdysterone [CPD:C02633] Therapeutic category of drugs in Japan [BR:br08301] 5 Crude drugs... and Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D06...ude Drugs Drugs for blood Drugs for removing blood stasis D06722 Achyranthes root; Achyranthese root Crude drugs

  1. Drug: D06697 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ceae (buckwheat family) Polygonum tuber Major component: Chrysophanol [CPD:C10315] Therapeutic category of drugs... in Japan [BR:br08301] 5 Crude drugs and Chinese medicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs... [BR:br08304] Crude Drugs Drugs for blood Drugs for replenishing blood D06697 Polygonum root Crude drugs [BR

  2. CONCEPT OF DRUG INTERACTION

    Directory of Open Access Journals (Sweden)

    Singh Nidhi

    2012-07-01

    Full Text Available Drug interaction is an increasingly important cause of adverse reactions (ADR, and is the modification of the effect of one drug (object by the prior or concomitant administration of another drug (precipitant drug. Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. The aim of present review is to throw light on the concept of drug interaction.

  3. Synthesis, structural, optical and anti-rheumatic activity of metal complexes derived from (E)-2-amino-N-(1-(2-aminophenyl)ethylidene)benzohydrazide (2-AAB) with Ru(III), Pd(II) and Zr(IV).

    Science.gov (United States)

    Hosny, Nasser Mohammed; Sherif, Yousery E

    2015-02-05

    Three new metal complexes derived from Pd(II), Ru(III) and Zr(IV) with (E)-2-amino-N-(1-(2-aminophenyl)ethylidene)benzohydrazide (2-AAB) have been synthesized. The isolated complexes were characterized by elemental analyses, FT-IR, UV-Vis, ES-MS, (1)H NMR, XRD, thermal analyses (TGA and DTA) and conductance. The morphology and the particle size were determined by transmittance electron microscope (TEM). The results showed that, the ligand coordinates to Pd(II) in the enol form, while it coordinates to Ru(III) and Zr(IV) in the keto form. A square planar geometry is suggested for Pd(II) complex and octahedral geometries are suggested for Ru(III) and Zr(IV) complexes. The optical band gaps of the isolated complexes were measured and indicated the semi-conductivity nature of the complexes. The anti-inflammatory and analgesic activities of the ligand and its complexes showed that, Ru(III) complex has higher effect than the well known drug "meloxicam".

  4. Simultaneous Determination of Thirteen Chemical Materials Illegally Added in Antirheumatic Health Products by HPLC-DAD%HPLC-DAD法同时测定抗风湿类保健食品中非法添加的13种化学成分

    Institute of Scientific and Technical Information of China (English)

    金舒

    2016-01-01

    Objective: To simultaneously detect 13 anti-rheumatic chemical components added illegally in health food. Methods: Using HPLC-DAD, the separation was performed on the XBridge C18 (4.6 mm×250 mm, 5μm) column by gradient elution at a flow rate of 1.0 mL·min-1. The mobile phase consisted of ace-tonitril-0.02 mol·L-1 ammonium acetate (including 0.075% acetic acid) and the detection wavelength was 230 nm. Results: The correlation coefficients of the equation of linear regression were above 0.9999. The average recoveries were 95.6%-102.5% and the relative standard deviations were less than 1.6% (n=3). U-PLC-QTOF-MS was used to further confirm. Conclusion: The method is simple and reliable, and can be used for simultaneously detecting 13 anti-rheumatic chemical components (acetaminophen, aspirin, trimetho-prim, aminopyrine, hydrocortisone, piroxicam, dexamethasone, naproxen, prednisone acetate, diclofenac sodi-um, indometacin, phenylbutazone and ibuprofen) in health food.%目的:同时检测抗风湿类保健食品中非法添加的13种化学成分。方法:采用高效液相色谱串联二极管阵列检测器法,使用XBridge C18(4.6 mm×250 mm,5μm)色谱柱进行分离,流动相为乙腈-0.02 mol·L-1醋酸铵(含0.075%乙酸),梯度洗脱,流速为1.0 mL·min-1,检测波长为230 nm。结果:各化学成分线性回归方程的相关系数均大于0.9999,平均回收率为95.6%~102.5%, RSD均小于1.6%(n=3),并用UPLC-QTOF-MS法进一步确证。结论:该方法操作简便可靠,能同时测定抗风湿类保健食品中非法添加的13种化学成分,分别为对乙酰氨基酚、阿司匹林、甲氧苄啶、氨基比林、氢化可的松、吡罗昔康、地塞米松、萘普生、醋酸泼尼松、双氯芬酸钠、吲哚美辛、保泰松、布洛芬。

  5. Fighting the Drug War.

    Science.gov (United States)

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan…

  6. Drugs and Young People

    Science.gov (United States)

    ... fully developed. As a result, the brains of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs include Amphetamines Anabolic ... better to prevent drug abuse in the first place. NIH: National Institute on Drug Abuse

  7. Utah Drug Use Questionnaire.

    Science.gov (United States)

    Governor's Citizen Advisory Committee on Drugs, Salt Lake City, UT.

    This questionnaire assesses drug use practices in junior and senior high school students. The 21 multiple choice items pertain to drug use practices, use history, available of drugs, main reason for drug use, and demographic data. The questionnaire is untimed, group administered, and may be given by the classroom teacher in about 10 minutes. Item…

  8. Drug: D06758 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available component: Zizyphus saponin Therapeutic category of drugs in Japan [BR:br08301] 5 Crude drugs and Chinese m...edicine formulations 51 Crude drugs 510 Crude drugs 5100 Crude drugs D06758 Jujub...e (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Stomachic and antidiarrheal drugs St...omachic and antidiarrheal drugs D06758 *Jujube; Jujube Drugs for Qi Drugs for replenishing Qi D06758 *Jujube; Jujube Crude drugs

  9. Knee osteoarthritis a pathological basis for use of newer drug therapies

    Directory of Open Access Journals (Sweden)

    Mukundraj S. Keny

    2014-06-01

    Full Text Available Knee osteoarthritis (OA is a disease of the whole knee joint occurring due to an interaction between inflammatory, hypoxic, and mechanical pathways. Initial management includes monotherapy with analgesics or anti and #8209;inflammatory agents, eventually switching over to combination therapy with steroids and/or newer drugs. Cardiovascular risks associated with non and #8209;steroidal anti and #8209;inflammatory drugs (NSAIDs limit their long term use. Hence, novel target receptors or pathways, which remain unaffected by conventional therapy and modify disease are being increasingly looked for. Newer drugs such as glucosamine, chondroitin, methylsulfonylmethane, diacerein along with vitamins/minerals are commonly used as adjuncts to NSAIDs or as monotherapy. Because of their novel mechanisms of action and better safety profile they seem to be promising as disease modifying agents in the treatment of OA. Google, PubMed, Cochrane databases and Science Direct search was performed, and relevant articles were identified. This review focuses on the pathological targets which these drugs modify in order to bring about a symptom modifying effect. [Int J Basic Clin Pharmacol 2014; 3(3.000: 424-430

  10. Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis.

    Science.gov (United States)

    Dekkers, J S; Schoones, J W; Huizinga, T W; Toes, R E; van der Helm-van Mil, A H

    2017-02-01

    Current research in rheumatoid arthritis focuses on preclinical disease phases as it is hypothesised that early preclinical treatment might prevent progression to full-blown disease. Since performance of studies in prearthritis phases in humans is challenging, animal models offer an opportunity to evaluate preventive treatments. We performed a systematic literature review and summarised treatment effects during different stages of arthritis development in animal models. Eight medical literature databases were systematically searched. Studies were selected if they reported effects of synthetic or biological disease-modifying antirheumatic drugs in animal models of arthritis (collagen-induced arthritis and adjuvant-induced arthritis) on arthritis severity, as measured with arthritis severity scores, paw swelling or paw volume. Quality was assessed using an 11-item checklist. Study characteristics were extracted and effect sizes obtained in high-quality studies were summarised in meta-analyses. Studies were categorised into three groups: prophylactic (prior to generation of autoantibody response), prearthritis (after induction of autoantibody response) and therapeutic intervention (after arthritis development). Out of 1415 screened articles, 22 studies (including n=712 animals) were eligible of good quality and included in meta-analyses. Prophylactic (16 experiments, n=312 animals) and prearthritis treatment (9 experiments, n=156 animals) both were associated with a reduction of arthritis severity (p<0.001 and p=0.005, respectively). Stratified analyses for different antirheumatic drugs initiated in the prearthritis phase suggested higher efficacy of methotrexate than of anti-tumour necrosis factor. Data of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs. Published by the BMJ Publishing Group Limited. For permission to use

  11. New drug update: 2010.

    Science.gov (United States)

    Hussar, Daniel A

    2010-10-01

    Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  12. 2016 New Drug Update.

    Science.gov (United States)

    Hussar, Daniel A

    2016-04-01

    Six new drugs marketed within the last year, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating. The drugs include a hypnotic, an anticoagulant, two drugs for heart failure, and two drugs to reduce low-density lipoprotein cholesterol.

  13. New drug update: 2011.

    Science.gov (United States)

    Hussar, Daniel A

    2012-04-01

    Five new drugs that are used for medical problems often encountered in the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined using the New Drug Comparison Rating (NDCR) system developed by the author. In the NDCR system, a rating from 1 to 5 (5 being the highest rating) is assigned for each new drug. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  14. Food and drugs

    OpenAIRE

    Đaković-Švajcer Kornelija

    2002-01-01

    Food can exert a significant influence on the effects of certain drugs. The interactions between food and drugs can be pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions most often take place on absorption and drug metabolism levels. Absorption can be either accelerated or delayed, increased or decreased, while drug metabolism can be either stimulated or inhibited. The factors which influence food-drug interactions are as follows: composition and physic-chemical properties of d...

  15. New drug update: 2012.

    Science.gov (United States)

    Hussar, Daniel A

    2013-04-01

    Five new drugs that are used for medical problems often experienced by the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

  16. Drug interactions with oral sulphonylurea hypoglycaemic drugs.

    Science.gov (United States)

    Hansen, J M; Christensen, L K

    1977-01-01

    The effect of the oral sulphonylurea hypoglycaemic drugs may be influenced by a large number of other drugs. Some of these combinations (e.g. phenylbutazone, sulphaphenazole) may result in cases of severe hypoglycaemic collapse. Tolbutamide and chlorpropamide should never be given to a patient without a prior careful check of which medicaments are already being given. Similarly, no drug should be given to a diabetic treated with tolbutamide and chlorpropamide without consideration of the possibility of interaction phenomena.

  17. Drug Products in the Medicaid Drug Rebate Program

    Data.gov (United States)

    U.S. Department of Health & Human Services — Active drugs that have been reported by participating drug manufacturers under the Medicaid Drug Rebate Program. All drugs are identified by National Drug Code...

  18. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2017-07-14

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  19. Drug: D06742 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Crude drugs D06742 Houttuynia herb (JP16) Traditional Chinese Medicine in Japan [BR:br08304] Crude Drugs Drugs for clearing heat Drug...s for clearing heat D06742 *Houttuynia herb; Houttuynia harb Drugs... for pus discharge Drugs for pus discharge D06742 *Houttuynia herb; Houttuynia harb Crude drugs [B

  20. Medicaid Drug Rebate Program Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Product Data for Drugs in the Medicaid Drug Rebate Program. The rebate drug product data file contains the active drugs that have been reported by participating drug...