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  1. Cognitive impairment in relapsing remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Saška Roškar

    2003-06-01

    Full Text Available The purpose of the study was to identify changes in cognitive abilities that affect patients with relapsing remitting form of multiple sclerosis (MS and to find out which instrument manifests them best. The performance of MS patients was compared to a matched group of healthy people using three neuropsychological tests: Wisconsin card sorting test (WCST, Stroop color and word test and Trail making test (TMT part B. Results on all three tests indicate general cognitive impairments in the group of patients. Compared to the group of healthy people patients with MS exhibited impaired ability of abstract reasoning (WCST, impaired cognitive flexibility and less resistance to irrelevant stimuli (Stroop color and word test, slowed information processing and impaired ability of shifting attention from one symbol to another (TMT. The largest differences between groups occured in Stroop color and word test as well as in TMT. The estimation of cognitive abilities of MS patients is of high importance and sistematicaly observing of changes in those abilities should be considered.

  2. Dimethyl fumarate for relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    2014-09-01

    For many years the only drugs licensed for the treatment of multiple sclerosis (MS) were administered by injection (interferon beta, glatiramer and ▼natalizumab). Recently, three oral drugs have become available. We have previously reviewed the use of ▼fingolimod for highly active relapsing-remitting MS1 and ▼teriflunomide for the management of relapsing-remitting MS in adults.2 Here, we review the evidence for ▼dimethyl fumarate (Tecfidera-Biogen Idec Ltd) for the treatment of adults with relapsing-remitting MS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Cladribine tablets for relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Rammohan, Kottil; Giovannoni, Gavin; Comi, Giancarlo

    2012-01-01

    BACKGROUND: In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses....../>40 years); disease duration (10 years); prior disease-modifying drug treatment (treated/naïve); relapses in the prior year (≤1/2/≥3); Expanded Disability Status Scale score (median) at baseline (all P≤0...

  4. Teriflunomide for the treatment of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Miller, Aaron E

    2015-02-01

    Teriflunomide, a once-daily, oral disease-modifying therapy, is a valuable new treatment option for the management of patients with relapsing-remitting multiple sclerosis. This article reviews key efficacy and safety data arising from pivotal teriflunomide studies that demonstrate the utility in treating both treatment-naïve patients and those previously treated with another disease-modifying therapy who, for a variety of reasons, may require an alternative treatment.

  5. [Vestibular rehabilitation in patients with relapsing-remitting multiple sclerosis].

    Science.gov (United States)

    Pavan, Karina; Marangoni, Bruna E M; Schmidt, Kizi B; Cobe, Fernanda A; Matuti, Gabriela S; Nishino, Lúcia K; Thomaz, Rodrigo B; Mendes, Maria Fernanda; Lianza, Sérgio; Tilbery, Charles Peter

    2007-06-01

    Multiple sclerosis (MS) is a demyelinating, inflammatory illness, that attack the white matter of the central nervous system, and abnormal vestibular sensations (vertigo, disequilibrium) are frequent. The vestibular rehabilitation (VR) is determined by mechanisms of adaptations, neural substitutions and compensations. This study evaluated the improvement of the central or peripheral vertigo in patients with relapsing-remitting MS submitted to the VR (exercises of Cawthorne-Cooksey), through the scale of Berg and Dizziness Handicap Inventory (DHI). In this sample of 4 cases the VR, carried through in a period of 2 months, demonstrated the improvement in 3 patients according to the Berg scale and in 2 patients considering that of the DHI.

  6. Brain atrophy in clinically early relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Chard, D T; Griffin, C M; Parker, G J M; Kapoor, R; Thompson, A J; Miller, D H

    2002-02-01

    Brain atrophy measured by MRI is a potentially useful tool for monitoring disease progression in multiple sclerosis. The location, extent and mechanisms of brain atrophy in early disease are not well documented. Using quantitative MRI, this study investigated whole brain, grey and white matter atrophy in clinically early relapsing-remitting multiple sclerosis and its relationship to lesion measures. Data came from 27 normal control subjects (14 females and 13 males, mean age 36.1 years) and 26 subjects with clinically definite multiple sclerosis (18 females and eight males, mean age 35.1 years, mean delay from first symptom to scan 1.8 years, median Expanded Disability Status Scale score 1.0). All had three-dimensional fast spoiled gradient recall (3D FSPGR), T(1)-weighted pre- and post-gadolinium-enhanced and T(2)-weighted scans. The 3D FSPGR images were automatically segmented into grey and white matter and cerebrospinal fluid using SPM99. 3D FSPGR hypo-intense, T(2) hyper-intense, T(1) hypo-intense and T(1) post-gadolinium-enhancing lesion volumes were determined by semi-automatic lesion segmentation. The SPM99 output was combined with the 3D FSPGR lesion segmentations to quantify tissue volumes as fractions of total intracranial volumes, producing values for the brain parenchymal fraction (BPF), white matter fraction (WMF) and grey matter fraction (GMF). Comparing multiple sclerosis with control subjects, BPF, GMF and WMF were significantly reduced (P lesion volumes were inversely related to BPF (T(2) r = -0.78, P lesion volumes were not correlated with any fractional volumes. These results indicate that significant brain atrophy, affecting both grey and white matter, occurs early in the clinical course of multiple sclerosis. The lack of correlation between lesion load measures and WMF suggests that pathological changes in white matter may occur by mechanisms which are at least partly independent from overt lesion genesis in early multiple sclerosis.

  7. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

    2003-01-01

    Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies.......Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

  8. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Fuqing Zhou

    Full Text Available Brain entropy (BEN mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI, reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS, a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

  9. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

    Science.gov (United States)

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

    2016-01-01

    Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

  10. Motor callosal disconnection in early relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Wahl, Mathias; Hübers, Annemarie; Lauterbach-Soon, Birgit; Hattingen, Elke; Jung, Patrick; Cohen, Leonardo G; Ziemann, Ulf

    2011-06-01

    In relapsing-remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0-2.0) to an age-matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA-CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short-interval interhemispheric inhibition (S-IHI), an established measure of CMF effective connectivity. FA-CC and S-IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA-CC) and function (S-IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine-hole-peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S-IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion. Copyright © 2010 Wiley-Liss, Inc.

  11. Relapsing-Remitting MS (RRMS)

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  12. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Genaro Gabriel Ortiz

    2009-01-01

    Full Text Available Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old and 7 men (5 aged from 20 to 30 and 2 were > 40 years old fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites, lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals, and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.

  13. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    Science.gov (United States)

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

  14. Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

    Science.gov (United States)

    Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

    2009-01-01

    This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

  15. Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab.

    Science.gov (United States)

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg; Sellebjerg, Finn; Oturai, Annette Bang

    2016-11-01

    Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity. To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in patients with relapsing-remitting MS (RRMS) and to examine the clinical effects associated with changes in 25(OH)D levels. In this prospective cohort study, baseline blood samples were collected from 170 natalizumab-treated RRMS patients during winter 2009-2010 and were repeated the following winter. Vitamin D supplements were recommended according to standard clinical practice in our clinic to patients with serum 25(OH)Dvitamin D supplements in patients with vitamin D insufficiency was associated with a significant increase in serum 25(OH)D concentrations (p=5.1×10-10), which was significantly related with decreases in ARR; for each nmol/l increase in Δ25(OH)D a -0.014 (95% CI -0.026 to -0.003) decrease in ΔARR was observed, p=0.02. Correction of hypovitaminosis D in clinical practice by recommending oral D3 supplements resulted in increases in 25(OH)D levels in serum, which were associated with decreases in ARR in RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Advances in the treatment of relapsing - Remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Radu Tanasescu

    2014-04-01

    Full Text Available This article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS. MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1 the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2 oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate; (3 monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab; and (4 immunosuppressive agents (e.g. mitoxantrone. The place of each drug in the therapeutic algorithm is dependent on its specific risk-benefit profile. Patients' clinical and paraclinical phenotypes and biomarker profile may help to elucidate disease subtypes and response to therapy in the future, thus allowing treatment individualization.

  17. Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

    Science.gov (United States)

    Sotelo, Julio; Corona, Teresa

    2011-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS. PMID:22096629

  18. Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates.

    OpenAIRE

    Barak, Y; Achiron, A.; Elizur, A; Gabbay, U; Noy, S; Sarova-Pinhas, I

    1996-01-01

    The purpose of this study was to examine the sexual complaints and severity of sexual dysfunction in relapsing-remitting multiple sclerosis patients and to correlate them with psychological, neurological, and radiological variables. Frequency and characteristics of sexual disturbances were reported by 41 multiple sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical neurologic variables tested were disease duration, exacerbation rate, and disability; psychological varia...

  19. Relapsing-Remitting MS (RRMS)

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  20. Subcutaneous IFN-β1a to treat relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Thouvenot, Eric; Carlander, Bertrand; Camu, William

    2012-11-01

    Multiple sclerosis (MS) is the main nontraumatic cause of handicap in young adults. Immunomodulators and treatments limiting lymphocyte migration have been proven efficient to treat relapsing-remitting MS. Subcutaneous IFN-β1a improve relapse rate and MRI parameters in a series of double-blind, placebo-controlled trials in relapsing-remitting MS patients. Similar results, and with a greater extent, were obtained when treating patients with a first demyelinating event suggestive of MS. Except for the rare liver toxicity, the drug is well tolerated and has no severe adverse reaction. When compared with intramuscular IFN-β1a, both relapse rate and MRI parameters were modulated in favor of the subcutaneous administration. Although the effect of subcutaneous IFN-β1a on disability progression is limited, the good tolerance profile together with the efficiency of the drug explain why this treatment, as well as the other interferons and glatiramer acetate, is a first-line therapy for relapsing-remitting MS.

  1. Teriflunomide in Patients with Relapsing?Remitting Forms of Multiple Sclerosis

    OpenAIRE

    Chan, Andrew; de Seze, Jérôme; Comabella, Manuel

    2016-01-01

    Teriflunomide is a once-daily oral agent that has been licensed in the EU since August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). More recently (September 2014), the EU summary of product characteristics (SmPC) was updated to include data from patients with a first clinical demyelinating event. This review examines the EU SmPC for teriflunomide, with reference to key clinical and safety outcomes and practical considerations for prescribing phy...

  2. Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis

    OpenAIRE

    MacKenzie-Graham, A; Kurth, F.; Itoh, Y.; Wang, H-J; Montag, MJ; Elashoff, R.; Voskuhl, RR

    2016-01-01

    Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown.To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS.In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using vo...

  3. Sensitivity to glucocorticoids is decreased in relapsing remitting multiple sclerosis

    NARCIS (Netherlands)

    van Winsen, Lisa M. L.; Muris, Daan F. R.; Polman, Chris H.; Dijkstra, Christine D.; van den Berg, Timo K.; Uitdehaag, Bernard M. J.

    2005-01-01

    Endogenous glucocorticoids (GC), which are under control of the hypothalamic-pituitary-adrenal axis, play an important role in controlling chronic inflammatory demyelinating diseases, like multiple sclerosis (MS). Increased hypothalamic-pituitary-adrenal axis activity has been found in MS patients

  4. The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Madsen, Claus

    2017-01-01

    The introduction of interferon beta therapies more than 20 years ago marked a milestone in the treatment of relapsing-remitting multiple sclerosis (RRMS) with a significant impact on the approach to modern multiple sclerosis (MS) care. Key learnings and perspectives from the early days of disease...... modifying therapies in MS have improved the knowledge base of MS, need for treatment, and patient care. The continuous development of interferons over the past two decades outlines a journey with increased understanding of the pharmacodynamics and pharmacokinetic mechanisms of interferons, leading...

  5. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

    DEFF Research Database (Denmark)

    Fazekas, F.; Lublin, F.D.; Li, D.

    2008-01-01

    therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety. METHODS: One hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo......OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We......-controlled trial. Forty-four and 42 patients received treatment with 0.2 and 0.4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0.1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity...

  6. Alemtuzumab: a review of efficacy and risks in the treatment of relapsing remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Guarnera C

    2017-07-01

    Full Text Available Cristina Guarnera, Placido Bramanti, Emanuela Mazzon Experimental Neurology Laboratory, IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, Messina, Italy Abstract: Alemtuzumab is a selective humanized monoclonal antibody directed against the CD52 antigen, and has been found to be a powerful treatment for relapsing remitting multiple sclerosis. Alemtuzumab demonstrated high efficacy in several clinical studies. The risk of relapse and sustained accumulation of disability showed significant reduction in the Phase II CAMMS223 and the Phase III clinical trials CARE MS I and CARE MS II. The data presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis confirmed these results. After completion of a 1-year treatment cycle, alemtuzumab showed a sustained effect. Although the efficacy of alemtuzumab has been widely proven, several severe adverse effects have been reported with its use. Infusion-associated reactions, increased risk of infections, and secondary autoimmunity have been associated with alemtuzumab. Autoimmune disease – mainly of the thyroid – has been reported. Immune thrombocytopenic purpura and autoimmune nephropathies have been observed less frequently. These adverse effects, given the short period of alemtuzumab marketing for relapsing remitting multiple sclerosis, require strict monitoring. Keywords: effectiveness, clinical studies, follow-up, adverse events

  7. Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

    DEFF Research Database (Denmark)

    Lyksborg, Mark; Siebner, Hartwig R.; Sørensen, Per S.

    2014-01-01

    Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy...... with clinical disability as reflected by the expanded disability status scale (EDSS). The correlation between these statistics and EDSS was either similar to or stronger than the correlation between FA statistics and the EDSS. Together, the results reveal an improved relationship between ACM, the clinical...

  8. Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Bieniek, M; Altmann, D R; Davies, G R; Ingle, G T; Rashid, W; Sastre-Garriga, J; Thompson, A J; Miller, D H

    2006-09-01

    The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.

  9. Relapsing-Remitting MS (RRMS)

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  10. Relapsing-Remitting MS (RRMS)

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  11. Predicting relapsing-remitting dynamics in multiple sclerosis using discrete distribution models: a population approach.

    Directory of Open Access Journals (Sweden)

    Nieves Velez de Mendizabal

    Full Text Available Relapsing-remitting dynamics are a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. A clinical relapse in MS reflects an acute focal inflammatory event in the central nervous system that affects signal conduction by damaging myelinated axons. Those events are evident in T1-weighted post-contrast magnetic resonance imaging (MRI as contrast enhancing lesions (CEL. CEL dynamics are considered unpredictable and are characterized by high intra- and inter-patient variability. Here, a population approach (nonlinear mixed-effects models was applied to analyse of CEL progression, aiming to propose a model that adequately captures CEL dynamics.We explored several discrete distribution models to CEL counts observed in nine MS patients undergoing a monthly MRI for 48 months. All patients were enrolled in the study free of immunosuppressive drugs, except for intravenous methylprednisolone or oral prednisone taper for a clinical relapse. Analyses were performed with the nonlinear mixed-effect modelling software NONMEM 7.2. Although several models were able to adequately characterize the observed CEL dynamics, the negative binomial distribution model had the best predictive ability. Significant improvements in fitting were observed when the CEL counts from previous months were incorporated to predict the current month's CEL count. The predictive capacity of the model was validated using a second cohort of fourteen patients who underwent monthly MRIs during 6-months. This analysis also identified and quantified the effect of steroids for the relapse treatment.The model was able to characterize the observed relapsing-remitting CEL dynamic and to quantify the inter-patient variability. Moreover, the nature of the effect of steroid treatment suggested that this therapy helps resolve older CELs yet does not affect newly appearing active lesions in that month. This model could be used for design of future longitudinal studies and clinical trials, as

  12. Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Karin van der Hiele

    Full Text Available The majority of patients with Multiple Sclerosis (MS are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed. Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53=2.76, p=0.008 and reported more organising and planning problems (χ2(1=6.3, p=0.012, higher distractibility (Kendall's tau-b= -0.24, p=0.03 and more cognitive fatigue (U=205.0, p=0.028, r=-0.30 than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28. Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

  13. Teriflunomide in Patients with Relapsing-Remitting Forms of Multiple Sclerosis.

    Science.gov (United States)

    Chan, Andrew; de Seze, Jérôme; Comabella, Manuel

    2016-01-01

    Teriflunomide is a once-daily oral agent that has been licensed in the EU since August 2013 for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS). More recently (September 2014), the EU summary of product characteristics (SmPC) was updated to include data from patients with a first clinical demyelinating event. This review examines the EU SmPC for teriflunomide, with reference to key clinical and safety outcomes and practical considerations for prescribing physicians. In two phase III trials (TEMSO and TOWER) in patients with relapsing forms of MS, teriflunomide 14 mg significantly reduced the annualized relapse rate and the risk of confirmed disability progression sustained for at least 12 weeks. Magnetic resonance imaging (MRI) total lesion volume, gadolinium-enhancing lesions, and unique active lesions were reduced with teriflunomide treatment in TEMSO. In the TOPIC study, in patients with a first clinical demyelinating event, teriflunomide treatment significantly reduced the time to a second clinical episode (relapse). Across the clinical studies, teriflunomide was generally well tolerated; adverse events reported in ≥ 10% of teriflunomide-treated patients were diarrhea, nausea, increased alanine aminotransferase, and alopecia. Data from the clinical development program support the use of teriflunomide in a broad spectrum of patients with RRMS.

  14. Lateral and escalation therapy in relapsing-remitting multiple sclerosis: a comparative study.

    Science.gov (United States)

    D'Amico, Emanuele; Leone, Carmela; Zanghì, Aurora; Fermo, Salvatore Lo; Patti, Francesco

    2016-09-01

    Performing a therapeutic switch in MS is still a matter of debate. Objective of our study is to compare switching to another first-line therapy with switching to a second-line therapy in persons with relapsing-remitting multiple sclerosis (pwRRMS). A retrospective analysis of data prospectively collected was performed. PwRRMS experiencing on-treatment disease activity were included. No clinical relapse, no sustained disability progression by the Expanded Disability Status Scale (EDSS), and no radiological activity (new T2 and/or gadolinium-enhanced brain lesions) were used as indicators of no disease activity (NEDA 3). Time to reach the first relapse after switch and time to reach an EDSS of 4.0 were also evaluated. Ninety-one pwRRMS were enrolled. Forty-eight (52.7 %) were on lateral switch, and 43 (47.3 %) on escalation switch. At baseline, the two groups differed for T2 and T1 brain lesions number (higher in the escalation group, p < 0.005). The proportion of pwRRMS who were NEDA 3 after 24 months from the switch was similar in the two groups (20.8 % in lateral group and 18.6 % in escalation group). No difference in timing to reach the first relapse after switch and an EDSS of 4.0 were found. Therefore, in selected pwRRMS, lateral and escalation strategies showed similar efficacy in delaying MS progression.

  15. Vitamin D and disability in relapsing-remitting multiple sclerosis in patients with a Mexican background.

    Science.gov (United States)

    Rito, Yamel; Flores, Jesus; Fernández-Aguilar, Angeles; Escalante-Membrillo, Carmen; Barboza, Miguel A; Amezcua, Lilyana; Corona, Teresa

    2017-10-03

    Previous studies of multiple sclerosis (MS) patients have reported an inverse correlation between disability, the number of relapses and vitamin D levels in mostly white patients. It is unclear if this relationship has the same behavior in individuals with Hispanic backgrounds. To determine the relationship between vitamin D serum levels and disability in a sample of Hispanics of a Mexican background with relapsing-remitting multiple sclerosis (RRMS). A cross-sectional study was conducted on 50 RRMS individuals of Mexican background. The Expanded Disability Status Scale (EDSS) score, progression index (PI) and annual relapse rate (ARR) were recorded for each patient. Vitamin D levels were assessed during the summer. Pearson's test was used to evaluate the relationship between vitamin D and EDSS, PI, ARR, and duration of disease evolution. Most patients were females (n = 29, 58%). The mean vitamin D level was 22.3 (± 6.4) ng/ml; the mean EDSS score was 2.2 (± 0.7), ARR 1.3 (± 0.5) and PI1.08 (± 0.6). No correlation was found between vitamin D levels and EDSS scores, ARR, PI or duration of disease. Moderate negative association between vitamin D levels and EDSS was found just in females (vitamin D levels and disability was found in this sample of RRMS Mexicans. Longitudinal studies are needed to better understand the impact of Vitamin D in disability and multiple time points.

  16. [Clinical guidelines for the use of dimethyl fumarate in relapsing-remitting multiple sclerosis].

    Science.gov (United States)

    Alifirova, V M; Boiko, A N; Vlasov, Ya V; Davydovskaya, M V; Zakharova, M N; Malkova, N A; Popova, E V; Sivertseva, S A; Spirin, N N; Khachanova, N V; Shmidt, Т Е

    Multiple sclerosis is a chronic demyelinating and neurodegenerative disease of the central nervous system, in which autoimmune inflammation and oxidative stress play essential pathogenetic roles. Activation and infiltration of immune cells in brain tissues, lipid peroxidation products, mitochondrial dysfunction, defective antioxidant protection, and many other pathological factors result in demyelination, axonal injury and death, and apoptosis of oligodendrocytes and neurons, all of which causes constant progression of the disease. The new oral agent for the treatment of relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate (DMF), helps change the pathogenetic mechanisms of the disease, thus decreasing the rate of exacerbations, slowing down disease progression, and reducing the risk of radiological progression of the disease.

  17. Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

    Directory of Open Access Journals (Sweden)

    Julie Chevalier

    Full Text Available The paper aimed to estimate the incremental cost-effectiveness ratio (ICER at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015.The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results.From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY of 0.281, corresponding to an ICER of €13,110/QALY.Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

  18. Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

    Science.gov (United States)

    Chevalier, Julie; Chamoux, Catherine; Hammès, Florence; Chicoye, Annie

    2016-01-01

    The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015. The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results. From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY. Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

  19. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Clinically Isolated Syndrome (CIS) Relapsing-remitting MS (RRMS) Primary progressive MS (PPMS) Secondary progressive MS (SPMS) d ... these lesions contain more inflammatory cells. People with primary progressive MS (PPMS) tend to have more spinal ...

  20. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Clinically Isolated Syndrome (CIS) Relapsing-remitting MS (RRMS) Primary progressive MS (PPMS) ... Treating MS d Comprehensive Care Developing a Healthcare Team Make the Most of ...

  1. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined by inflammatory ... exactly the same symptoms. Why are modifiers used to characterize RRMS? Disease activity and progression should be ...

  2. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Stimulation (FES) d Complementary & Alternative Medicines Chiropractic Therapy Marijuana Massage and Bodywork Acupuncture Low-Dose Naltrexone d ... without symptoms of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined ...

  3. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... MS Symptoms Diagnosing MS Possible MS Clinically Isolated Syndrome (CIS) Newly Diagnosed Diagnosing Tools Other Conditions to ... Sclerosis FAQs d Types of MS Clinically Isolated Syndrome (CIS) Relapsing-remitting MS (RRMS) Primary progressive MS ( ...

  4. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... most common disease course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These ... What happens in RRMS? Relapsing-remitting MS is defined by inflammatory attacks on myelin (the layers of ...

  5. Metabolic response to epigallocatechin-3-gallate in relapsing-remitting multiple sclerosis: a randomized clinical trial.

    Science.gov (United States)

    Mähler, Anja; Steiniger, Jochen; Bock, Markus; Klug, Lars; Parreidt, Nadine; Lorenz, Mario; Zimmermann, Benno F; Krannich, Alexander; Paul, Friedemann; Boschmann, Michael

    2015-03-01

    Muscle weakness and fatigue are common symptoms in multiple sclerosis (MS). Green tea catechins such as (-)epigallocatechin-3-gallate (EGCG) are known to improve energy metabolism at rest and during exercise. We tested the hypothesis that EGCG improves energy metabolism and substrate utilization in patients with MS. Eighteen patients (8 men) with relapsing-remitting MS (expanded disability status scale score women). After placebo, exercise EE was mainly fueled by FAOx in both men and women. After EGCG, there was a shift to a higher and more stable CHOx during exercise in men but not in women. Our data indicate that EGCG given to patients with MS over 12 wk improves muscle metabolism during moderate exercise to a greater extent in men than in women, possibly because of sex-specific effects on autonomic and endocrine control. © 2015 American Society for Nutrition.

  6. Predictors of driving in individuals with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Akinwuntan, Abiodun Emmanuel; Devos, Hannes; Stepleman, Lara; Casillas, Rhonda; Rahn, Rebecca; Smith, Suzanne; Williams, Mitzi Joi

    2013-03-01

    We previously reported that performance on the Stroke Driver Screening Assessment (SDSA), a battery of four cognitive tests that takes less than 30 min to administer, predicted the driving performance of participants with multiple sclerosis (MS) on a road test with 86% accuracy, 80% sensitivity, and 88% specificity. In this study, we further investigated if the addition of driving-related physical and visual tests and other previously identified cognitive predictors, including performance on the Useful Field of View test, will result in a better accuracy of predicting participants' on-road driving performance. Forty-four individuals with relapsing-remitting MS (age = 46 ± 11 years, 37 females) and Expanded Disability Status Scale values between 1 and 7 were administered selected physical, visual and cognitive tests including the SDSA. The model that explained the highest variance of participants' performance on a standardized road test was identified using multiple regression analysis. A discriminant equation containing the tests included in the best model was used to predict pass or fail performance on the test. Performance on 12 cognitive and three visual tests were significantly associated with performance on the road test. Five of the tests together explained 59% of the variance and predicted the pass or fail outcome of the road test with 91% accuracy, 70% sensitivity, and 97% specificity. Participants' on-road performance was more accurately predicted by the model identified in this study than using only performance on the SDSA test battery. The five psychometric/off-road tests should be used as a screening battery, after which a follow-up road test should be conducted to finally decide the fitness to drive of individuals with relapsing-remitting MS. Future studies are needed to confirm and validate the findings in this study.

  7. Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Diego Cadavid

    Full Text Available There is an unmet need for disease-modifying therapies to improve ambulatory function in disabled subjects with multiple sclerosis.Assess the effects of natalizumab on ambulatory function in disabled subjects with relapsing-remitting multiple sclerosis (RRMS or secondary progressive multiple sclerosis (SPMS.We retrospectively reviewed ambulatory function as measured by timed 25-foot walk (T25FW in clinical trial subjects with an Expanded Disability Status Scale score ≥3.5, including RRMS subjects from the phase 3 AFFIRM and SENTINEL trials, relapsing SPMS subjects from the phase 2 MS231 study, and nonrelapsing SPMS subjects from the phase 1b DELIVER study. For comparison, SPMS subjects from the intramuscular interferon beta-1a (IM IFNβ-1a IMPACT study were also analyzed. Improvement in ambulation was measured using T25FW responder status; response was defined as faster walking times over shorter (6-9-month or longer (24-30-month treatment periods relative to subjects' best predose walking times.There were two to four times more T25FW responders among disabled MS subjects in the natalizumab arms than in the placebo or IM IFNβ-1a arms. Responders walked 25 feet an average of 24%-45% faster than nonresponders.Natalizumab improves ambulatory function in disabled RRMS subjects and may have efficacy in disabled SPMS subjects. Confirmation of the latter finding in a prospective SPMS study is warranted.

  8. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Stein, M S; Liu, Y; Gray, O M; Baker, J E; Kolbe, S C; Ditchfield, M R; Egan, G F; Mitchell, P J; Harrison, L C; Butzkueven, H; Kilpatrick, T J

    2011-10-25

    Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months' double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.

  9. Dimethyl fumarate: a review of its use in patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Burness, Celeste B; Deeks, Emma D

    2014-04-01

    Dimethyl fumarate (Tecfidera®) is a novel oral therapy that has recently been approved for the treatment of relapsing forms of multiple sclerosis (MS) and relapsing-remitting MS (RRMS). In preclinical studies, dimethyl fumarate exhibited anti-inflammatory and cytoprotective properties that are generally thought to be mediated via activation of the nuclear factor (erythroid-derived 2)-like 2 transcriptional pathway, which is involved in the cellular response to oxidative stress. In the large, double-blind, multinational, 2-year DEFINE and CONFIRM trials conducted in over 2,600 adult patients with RRMS, twice-daily oral dimethyl fumarate 240 mg was effective in reducing the proportion of patients with MS relapse at 2 years (primary endpoint of DEFINE) and the annualized relapse rate (primary endpoint of CONFIRM) compared with placebo, with reduced disability progression also observed with the drug versus placebo in DEFINE. Dimethyl fumarate also reduced disease activity measures relative to placebo in these trials, as assessed by magnetic resonance imaging. Dimethyl fumarate was generally well tolerated in patients with RRMS; adverse events that occurred more frequently in dimethyl fumarate than in placebo recipients included flushing and gastrointestinal events. The long-term efficacy and tolerability of dimethyl fumarate is currently being investigated in the ENDORSE trial, with interim results demonstrating that dimethyl fumarate was associated with continued efficacy for up to 4 years of treatment, with no new tolerability concerns. In conclusion, although more comparative data are needed to fully establish the relative efficacy and tolerability of dimethyl fumarate compared with other therapies, oral dimethyl fumarate is an important addition to the therapeutic options available for RRMS.

  10. Cost-Effectiveness of Peginterferon Beta-1a and Alemtuzumab in Relapsing-Remitting Multiple Sclerosis.

    Science.gov (United States)

    Dashputre, Ankur A; Kamal, Khalid M; Pawar, Gauri

    2017-06-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, affecting 2.5 million people globally and 400,000 people in the United States. While no cure exists for MS, the goal is to manage the disease using disease-modifying therapies (DMTs), which have been shown to slow disease progression and prevent relapses. Relapsing-remitting MS (RRMS) is the most common form of MS at the time of diagnosis. Peginterferon beta-1a (PEG) and alemtuzumab (ALT) were recently approved and have demonstrated good clinical outcomes, including reduced relapse rates in clinical trials. High costs associated with these DMTs necessitates cost-effectiveness analyses to understand their overall value in RRMS management. To assess the cost-effectiveness of (a) Model 1: PEG relative to intramuscular interferon beta-1a (IM IFN), subcutaneous interferon beta-1b (SC IFN), glatiramer acetate 20 mg per mL (GA), fingolimod (FIN), natalizumab (NAT), and dimethyl fumarate (DMF), and (b) Model 2: ALT relative to subcutaneous interferon beta-1a 44 μg (IFN beta-1a 44 μg). Both analyses were conducted from a U.S. third-party payer perspective. Two static decision models were used to compare the cost-effectiveness of PEG and ALT over a 1-year and a 2-year time horizon, respectively. Model inputs were drug acquisition costs (wholesale acquisition cost from RED BOOK); drug administration and monitoring costs (package inserts and Centers for Medicare & Medicaid Services 2015 Physician Fee Schedule); relapse rates and relapse rate reduction (clinical trials); and cost of managing relapses (published literature). All costs were adjusted to 2015 U.S. dollars using the medical care component of the Consumer Price Index. Outcomes measured were total cost of therapy per patient, cost per relapse avoided, and incremental cost-effectiveness ratios (ICERs) calculated as cost per relapse avoided. Sensitivity analysis was conducted to test model robustness given the uncertainty of

  11. Intrinsic functional plasticity of the sensorimotor network in relapsing-remitting multiple sclerosis: evidence from a centrality analysis.

    Science.gov (United States)

    Zhuang, Ying; Zhou, Fuqing; Gong, Honghan

    2015-01-01

    Advanced MRI studies have revealed regional alterations in the sensorimotor cortex of patients with relapsing-remitting multiple sclerosis (RRMS). However, the organizational features underlying the relapsing phase and the subsequent remitting phase have not been directly shown at the functional network or the connectome level. Therefore, this study aimed to characterize MS-related centrality disturbances of the sensorimotor network (SMN) and to assess network integrity and connectedness. Thirty-four patients with clinically definite RRMS and well-matched healthy controls participated in the study. Twenty-three patients in the remitting phase underwent one resting-state functional MRI, and 11 patients in the relapsing-remitting phase underwent two different MRIs. We measured voxel-wise centrality metrics to determine direct (degree centrality, DC) and global (eigenvector centrality, EC) functional relationships across the entire SMN. In the relapsing phase, DC was significantly decreased in the bilateral primary motor and somatosensory cortex (M1/S1), left dorsal premotor (PMd), and operculum-integrated regions. However, DC was increased in the peripheral SMN areas. The decrease in DC in the bilateral M1/S1 was associated with the expanded disability status scale (EDSS) and total white matter lesion loads (TWMLLs), suggesting that this adaptive response is related to the extent of brain damage in the rapid-onset attack stage. During the remission process, these alterations in centrality were restored in the bilateral M1/S1 and peripheral SMN areas. In the remitting phase, DC was reduced in the premotor, supplementary motor, and operculum-integrated regions, reflecting an adaptive response due to brain atrophy. However, DC was enhanced in the right M1 and left parietal-integrated regions, indicating chronic reorganization. In both the relapsing and remitting phases, the changes in EC and DC were similar. The alterations in centrality within the SMN indicate rapid

  12. Intrinsic functional plasticity of the sensorimotor network in relapsing-remitting multiple sclerosis: evidence from a centrality analysis.

    Directory of Open Access Journals (Sweden)

    Ying Zhuang

    Full Text Available Advanced MRI studies have revealed regional alterations in the sensorimotor cortex of patients with relapsing-remitting multiple sclerosis (RRMS. However, the organizational features underlying the relapsing phase and the subsequent remitting phase have not been directly shown at the functional network or the connectome level. Therefore, this study aimed to characterize MS-related centrality disturbances of the sensorimotor network (SMN and to assess network integrity and connectedness.Thirty-four patients with clinically definite RRMS and well-matched healthy controls participated in the study. Twenty-three patients in the remitting phase underwent one resting-state functional MRI, and 11 patients in the relapsing-remitting phase underwent two different MRIs. We measured voxel-wise centrality metrics to determine direct (degree centrality, DC and global (eigenvector centrality, EC functional relationships across the entire SMN.In the relapsing phase, DC was significantly decreased in the bilateral primary motor and somatosensory cortex (M1/S1, left dorsal premotor (PMd, and operculum-integrated regions. However, DC was increased in the peripheral SMN areas. The decrease in DC in the bilateral M1/S1 was associated with the expanded disability status scale (EDSS and total white matter lesion loads (TWMLLs, suggesting that this adaptive response is related to the extent of brain damage in the rapid-onset attack stage. During the remission process, these alterations in centrality were restored in the bilateral M1/S1 and peripheral SMN areas. In the remitting phase, DC was reduced in the premotor, supplementary motor, and operculum-integrated regions, reflecting an adaptive response due to brain atrophy. However, DC was enhanced in the right M1 and left parietal-integrated regions, indicating chronic reorganization. In both the relapsing and remitting phases, the changes in EC and DC were similar.The alterations in centrality within the SMN indicate

  13. Indoleamine 2,3 Dioxygenase (IDO Expression and Activity in Relapsing-Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Roberta Mancuso

    Full Text Available Interferon gamma (IFN-γ production induces the transcription of indoleamine 2,3 dioxygenase (IDO resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS patients.IDO and interferon-γ (IFN-γ gene expression, serum IDO activity (Kynurenine/Tryptophan ratio and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS and 15 healthy controls (HC. PBMCs samples in AMS patients were collected before (BT-AMS and during glucocorticoids-based therapy (DT-AMS.IDO expression was increased and IFN-γ was decreased (p<0.001 in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001. Serum neopterin concentration followed the same trend as IDO expression and activity.Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS.

  14. The clinical importance of neutralizing antibodies in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Namaka, Mike; Pollitt-Smith, Merinda; Gupta, Aneri; Klowak, Meghann; Vasconcelos, Marcus; Turcotte, Dana; Gong, Yuewen; Melanson, Maria

    2006-02-01

    Neutralizing antibodies (NAbs) develop in patients receiving interferon beta (IFN-beta) for multiple sclerosis (MS). Debate continues concerning the relevance of NAb development on treatment efficacy. To determine the incidence and clinical importance of NAbs in patients with relapsing-remitting MS (RRMS). A comprehensive literature review was conducted using PubMed (accessed from 1983 to June 2005), Cochrane MS Group trials register (accessed June 2005), MEDLINE (accessed 1983 to June 2005), and Toxnet (accessed June 2005) databases. NAb-induced changes in clinical efficacy and disease progression were evaluated according to the clinical guidelines established by the American Academy of Neurology. Currently, there is no standardized assay to comparatively assess NAbs among different treatments. NAbs develop independent of age, sex, disease duration and progression index at the onset of treatment. The occurrence of NAbs varies from 2-45% depending on the treatment initiated. NAb+ patients demonstrate accelerated disease progression as confirmed by an approximate 1-point increase in the Expanded Disability Status Scale score. The odds of relapse during a NAb+ period are between 1.51 and 1.58 (p < 0.03) with the time to first relapse being shortened by an average of 244 days after 12 months of IFN-beta therapy. NAb+ patients experience an approximately four-fold increase (p = 0.009) in the median number of active T2 magnetic resonance imaging (MRI) lesions compared to NAb-negative patients (1.4 vs. 0.3 respectively, p < 0.01). The induction of NAbs in IFN-beta treated patients reduce clinical effect and accelerate disease progression.

  15. [Extending therapeutic possibilities in relapsing-remitting multiple sclerosis: dimethyl fumarate].

    Science.gov (United States)

    Matolcsi, Judit; Rózsa, Csilla

    2015-01-30

    Dimethyl fumarate (DMF) is a novel oral therapy that has recently been approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Dimethyl fumarate shows anti-inflammatory and cytoprotective properties that are thought to be mediated primarily via activation of the nuclear factor (erythroid-derived 2)-like 2- Nrf2 transcriptional pathway, which up-regulates the genes involved in the cellular response to oxidative stress. The drug was evaluated in 2 large, randomized, double-blind, multicentric, multinational, 2-year, phase III clinical trials. The DEFINE and CONFIRM trials, conducted with over 2600 adult patients suffering from RRMS, unequivocally confirmed the efficacy of DMF (2 x 240 mg daily) in reducing the annualized relapse rate (ARR) and reducing the proportion of patients with MS relapse at 2 years. Significantly reduced sustained disability progression was observed with the drug versus placebo in DEFINE, while the same tendency was seen in CONFIRM. The MRI results of the studies were also convincing: DMF significantly reduced the number of new/enlarging T2-hyperintense lesions and the number of Gd-enhancing lesions compared to placebo. Dimethyl fumarate was generally well tolerated and no safety concern has been raised. Adverse events that occurred most frequently included flushing and gastrointestinal events. The long-term efficacy and tolerability of dimethyl fumarate is currently being investigated in the ENDORSE trial, with interim results demonstrating the same results as the two previous studies. In conclusion, although further, mostly comparative data are needed to fully establish the relative efficacy and tolerability of dimethyl fumarate compared with other therapies, dimethyl-fumarate is a valuable addition to the therapeutic options available for RRMS.

  16. Disability-Specific Atlases of Gray Matter Loss in Relapsing-Remitting Multiple Sclerosis.

    Science.gov (United States)

    MacKenzie-Graham, Allan; Kurth, Florian; Itoh, Yuichiro; Wang, He-Jing; Montag, Michael J; Elashoff, Robert; Voskuhl, Rhonda R

    2016-08-01

    Multiple sclerosis (MS) is characterized by progressive gray matter (GM) atrophy that strongly correlates with clinical disability. However, whether localized GM atrophy correlates with specific disabilities in patients with MS remains unknown. To understand the association between localized GM atrophy and clinical disability in a biology-driven analysis of MS. In this cross-sectional study, magnetic resonance images were acquired from 133 women with relapsing-remitting MS and analyzed using voxel-based morphometry and volumetry. A regression analysis was used to determine whether voxelwise GM atrophy was associated with specific clinical deficits. Data were collected from June 28, 2007, to January 9, 2014. Voxelwise correlation of GM change with clinical outcome measures (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores). Among the 133 female patients (mean [SD] age, 37.4 [7.5] years), worse performance on the Multiple Sclerosis Functional Composite correlated with voxelwise GM volume loss in the middle cingulate cortex (P disability (P = .03). Thus, deficits in specific clinical test results were directly associated with localized GM loss in clinically eloquent locations. These biology-driven data indicate that specific disabilities in MS are associated with voxelwise GM loss in distinct locations. This approach may be used to develop disability-specific biomarkers for use in future clinical trials of neuroprotective treatments in MS.

  17. Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Gschwind, Markus; Hardmeier, Martin; Van De Ville, Dimitri; Tomescu, Miralena I; Penner, Iris-Katharina; Naegelin, Yvonne; Fuhr, Peter; Michel, Christoph M; Seeck, Margitta

    2016-01-01

    Spontaneous fluctuations of neuronal activity in large-scale distributed networks are a hallmark of the resting brain. In relapsing-remitting multiple sclerosis (RRMS) several fMRI studies have suggested altered resting-state connectivity patterns. Topographical EEG analysis reveals much faster temporal fluctuations in the tens of milliseconds time range (termed "microstates"), which showed altered properties in a number of neuropsychiatric conditions. We investigated whether these microstates were altered in patients with RRMS, and if the microstates' temporal properties reflected a link to the patients' clinical features. We acquired 256-channel EEG in 53 patients (mean age 37.6 years, 45 females, mean disease duration 9.99 years, Expanded Disability Status Scale ≤ 4, mean 2.2) and 49 healthy controls (mean age 36.4 years, 33 females). We analyzed segments of a total of 5 min of EEG during resting wakefulness and determined for both groups the four predominant microstates using established clustering methods. We found significant differences in the temporal dynamics of two of the four microstates between healthy controls and patients with RRMS in terms of increased appearance and prolonged duration. Using stepwise multiple linear regression models with 8-fold cross-validation, we found evidence that these electrophysiological measures predicted a patient's total disease duration, annual relapse rate, disability score, as well as depression score, and cognitive fatigue measure. In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.

  18. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

    Science.gov (United States)

    Kalincik, Tomas; Brown, J William L; Robertson, Neil; Willis, Mark; Scolding, Neil; Rice, Claire M; Wilkins, Alastair; Pearson, Owen; Ziemssen, Tjalf; Hutchinson, Michael; McGuigan, Christopher; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Alroughani, Raed; Pucci, Eugenio; Sola, Patrizia; Hupperts, Raymond; Lechner-Scott, Jeannette; Terzi, Murat; Van Pesch, Vincent; Rozsa, Csilla; Grand'Maison, François; Boz, Cavit; Granella, Franco; Slee, Mark; Spitaleri, Daniele; Olascoaga, Javier; Bergamaschi, Roberto; Verheul, Freek; Vucic, Steve; McCombe, Pamela; Hodgkinson, Suzanne; Sanchez-Menoyo, Jose Luis; Ampapa, Radek; Simo, Magdolna; Csepany, Tunde; Ramo, Cristina; Cristiano, Edgardo; Barnett, Michael; Butzkueven, Helmut; Coles, Alasdair

    2017-04-01

    Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], pmultiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly

  19. Dimethyl fumarate treatment of relapsing-remitting multiple sclerosis influences B-cell subsets

    Science.gov (United States)

    Lundy, Steven K.; Wu, Qi; Wang, Qin; Dowling, Catherine A.; Taitano, Sophina H.; Mao, Guangmei

    2016-01-01

    Objective: To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Peripheral blood B cells were compared for surface marker expression in patients with RRMS prior to initiation of treatment, after 4–6 months, and at more than 1 year of treatment with BG-12. Production of interleukin (IL)–10 by RRMS patient B cells was also analyzed. Results: Total numbers of peripheral blood B lymphocytes declined after 4–6 months of BG-12 treatment, due to losses in both the CD27+ memory B cells and CD27neg B-cell subsets. Some interpatient variability was observed. In contrast, circulating CD24highCD38high (T2-MZP) B cells increased in percentage in the majority of patients with RRMS after 4–6 months and were present in higher numbers in all of the patients after 12 months of treatment. The CD43+CD27+ B-1 B cells also increased at the later time point in most patients but were unchanged at 4–6 months compared to pretreatment levels. Purified B cells from 7 of the 9 patients with RRMS tested after 4–6 months of treatment were able to produce IL-10 following CD40 ligand stimulation, and the amount corresponded with the combined levels of T2-MZP and B-1 B cells in the sample. None of the patients with RRMS in this study have had a relapse while taking BG-12. Conclusions: These data suggest that BG-12 differentially affects B-cell subsets in patients with RRMS, resulting in increased numbers of circulating B lymphocytes with regulatory capacity. PMID:27006972

  20. Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    M.A. Moreira

    2006-04-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF of 23 relapsing-remitting MS patients under interferon-ß-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean ± SEM, 369.5 ± 69.3 pg/mL when compared with controls (178.5 ± 29.1 pg/mL, P < 0.05. CSF levels of CCL2 were significantly lower in active MS (144.7 ± 14.4 pg/mL than in controls (237.1 ± 16.4 pg/mL, P < 0.01. There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

  1. Hypovitaminosis D association with disease activity in relapsing remitting multiple sclerosis in Brazil.

    Science.gov (United States)

    Becker, Jefferson; Callegaro, Dagoberto; Lana-Peixoto, Marco Aurélio; Talim, Natália; Vidaletti, Tamara; de Paula Corrêa, Marcelo; Gomes, Irenio

    2016-04-15

    Multiple sclerosis (MS) onset is believed to result from a combination of environmental and genetic factors. A prevailing theory addresses the influence of hypovitaminosis D in the development of MS. This research aimed to study the association between vitamin D serum levels and MS, as a prognostic and risk factor for the development and progression of the disease. A cross-sectional multicenter study was conducted in patients with relapsing-remitting MS (n=67), according to the revised McDonald criteria (2010), accompanied in three MS centers in different Brazilian states. A control group consisted of healthy volunteers (n=61). Blood collections were carried out in late summer and late winter. This seems to be the first study of this kind in Latin America. The vitamin D serum levels for MS patients (29.63±8.08) in summer were similar to the controls (29.71±8.28); however, in winter they were lower than the healthy individuals (24.05±7.47 vs 26.56±8.01). No significant difference between the three cities was observed. No association was noted between vitamin D serum levels and gender, race and age, nor correlation of these levels with the EDSS or disease duration. In contrast, a significant association was seen between deficient vitamin D serum levels in late winter with disease activity, characterized by the onset of relapses (19.73±5.69 vs 25.30±6.22) or Gd+ lesions (17.22±3.11 vs 22.79±7.22). Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Perception of affective prosody in patients at an early stage of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Kraemer, Markus; Herold, Michele; Uekermann, Jennifer; Kis, Bernhard; Daum, Irene; Wiltfang, Jens; Berlit, Peter; Diehl, Rolf R; Abdel-Hamid, Mona

    2013-03-01

    Cognitive dysfunction is well known in patients suffering from multiple sclerosis (MS) and has been described for many years. Cognitive impairment, memory, and attention deficits seem to be features of advanced MS stages, whereas depression and emotional instability already occur in early stages of the disease. However, little is known about processing of affective prosody in patients in early stages of relapsing-remitting MS (RRMS). In this study, tests assessing attention, memory, and processing of affective prosody were administered to 25 adult patients with a diagnosis of RRMS at an early stage and to 25 healthy controls (HC). Early stages of the disease were defined as being diagnosed with RRMS in the last 2 years and having an Expanded Disability Status Scale (EDSS) of 2 or lower. Patients and HC were comparable in intelligence quotient (IQ), educational level, age, handedness, and gender. Patients with early stages of RRMS performed below the control group with respect to the subtests 'discrimination of affective prosody' and 'matching of affective prosody to facial expression' for the emotion 'angry' of the 'Tübingen Affect Battery'. These deficits were not related to executive performance. Our findings suggest that emotional prosody comprehension is deficient in young patients with early stages of RRMS. Deficits in discriminating affective prosody early in the disease may make misunderstandings and poor communication more likely. This might negatively influence interpersonal relationships and quality of life in patients with RRMS. © 2012 The British Psychological Society.

  3. Quantitative diffusion tensor deterministic and probabilistic fiber tractography in relapsing-remitting multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Hu Bing [Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Road Tianhe 600, 510630 Guangdong, Guangzhou (China); Ye Binbin [Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou (China); Yang Yang [Department of Information Technology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou (China); Zhu Kangshun [Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou (China); Kang Zhuang; Kuang Sichi; Luo Lin [Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Road Tianhe 600, 510630 Guangdong, Guangzhou (China); Shan Hong, E-mail: shanhong5@gmail.com [Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Road Tianhe 600, 510630 Guangdong, Guangzhou (China)

    2011-07-15

    Purpose: Our aim was to study the quantitative fiber tractography variations and patterns in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the correlation between quantitative fiber tractography and Expanded Disability Status Scale (EDSS). Material and methods: Twenty-eight patients with RRMS and 28 age-matched healthy volunteers underwent a diffusion tensor MR imaging study. Quantitative deterministic and probabilistic fiber tractography were generated in all subjects. And mean numbers of tracked lines and fiber density were counted. Paired-samples t tests were used to compare tracked lines and fiber density in RRMS patients with those in controls. Bivariate linear regression model was used to determine the relationship between quantitative fiber tractography and EDSS in RRMS. Results: Both deterministic and probabilistic tractography's tracked lines and fiber density in RRMS patients were less than those in controls (P < .001). Both deterministic and probabilistic tractography's tracked lines and fiber density were found negative correlations with EDSS in RRMS (P < .001). The fiber tract disruptions and reductions in RRMS were directly visualized on fiber tractography. Conclusion: Changes of white matter tracts can be detected by quantitative diffusion tensor fiber tractography, and correlate with clinical impairment in RRMS.

  4. Cortical thickness and surface area relate to specific symptoms in early relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Nygaard, Gro O; Walhovd, Kristine B; Sowa, Piotr; Chepkoech, Joy-Loi; Bjørnerud, Atle; Due-Tønnessen, Paulina; Landrø, Nils I; Damangir, Soheil; Spulber, Gabriela; Storsve, Andreas B; Beyer, Mona K; Fjell, Anders M; Celius, Elisabeth G; Harbo, Hanne F

    2015-04-01

    Cortical atrophy is common in early relapsing-remitting multiple sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness or cortical surface area is not known, nor is their separate contributions to clinical symptoms. To investigate the difference in cortical surface area, thickness and volume between early RRMS patients and healthy controls; and the relationship between these measures and neurological disability, cognitive decline, fatigue and depression. RRMS patients (n = 61) underwent magnetic resonance imaging (MRI), neurological and neuropsychological examinations. We estimated cortical surface area, thickness and volume and compared them with matched healthy controls (n = 61). We estimated the correlations between clinical symptoms and cortical measures within the patient group. We found no differences in cortical surface area, but widespread differences in cortical thickness and volume between the groups. Neurological disability was related to regionally smaller cortical thickness and volume. Better verbal memory was related to regionally larger surface area; and better visuo-spatial memory, to regionally larger cortical volume. Higher depression scores and fatigue were associated with regionally smaller cortical surface area and volume. We found that cortical thickness, but not cortical surface area, is affected in early RRMS. We identified specific structural correlates to the main clinical symptoms in early RRMS. © The Author(s), 2014.

  5. Social cognitive predictors of physical activity in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Suh, Yoojin; Joshi, Ina; Olsen, Conner; Motl, Robert W

    2014-12-01

    Persons with relapsing-remitting multiple sclerosis (RRMS) are often sedentary, despite the benefits of the regular physical activity. This has motivated the search for variables that act as determinants of physical activity. Such variables are derived from theory and presumably represent targets of behavioral interventions for increasing physical activity. This prospective, observational study examined variables from social cognitive theory as determinants of physical activity 6 weeks later in persons with RRMS. Persons (N = 68) with RRMS initially completed a questionnaire battery that included measures of self-efficacy, physical, social, and self-evaluative outcome expectations, functional limitations as an impediment, social support as a facilitator, and goal setting for physical activity. The participants wore an accelerometer and completed a self-reported physical activity measure 6 weeks later. Data were analyzed using path analysis in Mplus 3.0. Self-efficacy (path coefficient = 0.19, p path coefficient = -0.33, p goal setting (path coefficient = 0.26, p path coefficient = 0.12, p goal setting (path coefficient = 0.02, p = 0.66). This model explained 28 % of the variance in physical activity. This prospective study suggests that self-efficacy, functional limitations, and goal setting might represent modifiable targets of behavioral interventions for increasing physical activity among persons with RRMS.

  6. Normal plasma antithrombin activity in patients with relapsing-remitting and secondary progressive multiple sclerosis.

    Science.gov (United States)

    Campos-de-Magalhães, Marilza; de Almeida, Adilson José; Papaiz-Alvarenga, Regina Maria; Gadelha, Telma; Morais-de-Sá, Carlos Alberto; Alves-Leon, Soniza Vieira

    2009-06-01

    Multiple sclerosis (MS) is an inflammatory disease characterized by multifocal areas of central nervous system (CNS) demyelination. Activation of coagulation factors and fibrin deposition are observed around CNS blood vessels in experimental autoimmune encephalomyelitis, an animal model of MS. Antithrombin (AT) is a potent anticoagulant with remarkable anti-inflammatory properties, and its inhibitory effects on coagulation and inflammation may play a role in the pathogenesis and clinical course of MS. We studied the association between plasma AT activity and clinical forms of MS. A total of 69 patients, 37 with relapsing-remitting and 32 with secondary progressive MS, were included in the study. A control group (CG) of 34 normal subjects was also studied. Plasma AT activity (Stachrom ATIII) was quantified using a chromogenic activity assay with normal reference values ranging from 70% to 120% of AT activity. We found no difference between plasma AT levels in patients and those in CG. We also found no association of AT levels with activity of disease, duration of disease progression, level of neurological disability, and treatment. We found no association between plasma AT activity and RRMS or SPMS. It remains to be studied whether exists or not an association between abnormal plasma AT activity and other MS forms.

  7. Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Yu Chunshui [Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing (China); Education Ministry Key Laboratory for Neurodegenerative Disease, Beijing (China); Lin Fuchun [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan (China); Liu Yaou; Duan Yunyun [Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing (China); Lei Hao [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan (China); Li Kuncheng [Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing (China); Education Ministry Key Laboratory for Neurodegenerative Disease, Beijing (China)], E-mail: kunchengli1955@yahoo.com.cn

    2008-11-15

    Objective: The purposes of our study were to employ diffusion tensor imaging (DTI)-based histogram analysis to determine the presence of occult damage in clinically isolated syndrome (CIS), to compare its severity with relapsing-remitting multiple sclerosis (RRMS), and to determine correlations between DTI histogram measures and clinical and MRI indices in these two diseases. Materials and methods: DTI scans were performed in 19 CIS and 19 RRMS patients and 19 matched healthy volunteers. Histogram analyses of mean diffusivity and fractional anisotropy were performed in normal-appearing brain tissue (NABT), normal-appearing white matter (NAWM) and gray matter (NAGM). Correlations were analyzed between these measures and expanded disability status scale (EDSS) scores, T{sub 2}WI lesion volumes (LV) and normalized brain tissue volumes (NBTV) in CIS and RRMS patients. Results: Significant differences were found among CIS, RRMS and control groups in the NBTV and most of the DTI histogram measures of the NABT, NAWM and NAGM. In CIS patients, some DTI histogram measures showed significant correlations with LV and NBTV, but none of them with EDSS. In RRMS patients, however, some DTI histogram measures were significantly correlated with LV, NBTV and EDSS. Conclusion: Occult damage occurs in both NAGM and NAWM in CIS, but the severity is milder than that in RRMS. In CIS and RRMS, the occult damage might be related to both T2 lesion load and brain tissue atrophy. Some DTI histogram measures might be useful for assessing the disease progression in RRMS patients.

  8. Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

    Science.gov (United States)

    Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

    2016-01-01

    The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

  9. Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9 production in relapsing-remitting multiple sclerosis

    Science.gov (United States)

    Shinto, L.; Marracci, G.; Baldauf-Wagner, S.; Strehlow, A.; Yadav, V.; Stuber, L.; Bourdette, D.

    2009-01-01

    Objectives The primary objective was to evaluate the effect of omega-3 fatty acids (omega-3 FA) on matrix metalloproteinase-9 (MMP-9) production by immune cells in multiple sclerosis (MS). Quality of life, fatty acid levels, and safety were also evaluated. Materials and Methods Ten participants with relapsing-remitting MS (RRMS) received omega-3 FA supplementation (9.6 grams/day fish oil) in an open-label study. Participants were evaluated at four time points, baseline, after 1-month of omega-3 FA supplementation, after 3-months of omega-3 FA supplementation, and after a 3-month wash out. Results Immune cell secretion of MMP-9 decreased by 58% after 3-months of omega-3 FA supplementation when compared to baseline levels (p < 0.01). This effect was coupled with a significant increase in omega-3 FA levels in red blood cell membranes. Conclusions Omega-3 FA significantly decreased MMP-9 levels in RRMS and may act as immune-modulator that has potential therapeutic benefit in MS patients. PMID:19171471

  10. Prediction of Driving Ability in People with Relapsing-Remitting Multiple Sclerosis Using the Stroke Driver Screening Assessment

    OpenAIRE

    AKINWUNTAN, Abiodun Emmanuel; O'Connor, Christina; McGonegal, Erin; Turchi, Kristen; Smith, Suzanne; Williams, Mitzi; Wachtel, Jerry

    2012-01-01

    The ability to drive is often affected in individuals with multiple sclerosis (MS) because of the motor, visual, or cognitive deficits commonly associated with the condition. In this study, we investigated the accuracy with which the Stroke Driver Screening Assessment (SDSA), an established battery for the prediction of driving performance of stroke survivors, would predict driving performance of individuals with MS. Driving performance of 44 individuals with relapsing-remitting MS (mean ± SD...

  11. Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab

    DEFF Research Database (Denmark)

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

    2016-01-01

    Background Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity.  Objective To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels...... winter. Vitamin D supplements were recommended according to standard clinical practice in our clinic to patients with serum 25(OH)D... vitamin D supplements in patients with vitamin D insufficiency was associated with a significant increase in serum 25(OH)D concentrations (p=5.1×10−10), which was significantly related with decreases in ARR; for each nmol/l increase in Δ25(OH)D a −0.014 (95% CI −0.026 to −0.003) decrease in ΔARR...

  12. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Us Clinical Fellows d Careers in MS Clinical Care Research Have you met? d Our Healthcare Voice Home What Is MS? Types of MS Relapsing-remitting MS (RRMS) Share this ... time helps you and your MS care provider discuss your treatment options and expected outcomes. ...

  13. Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates.

    Science.gov (United States)

    Barak, Y; Achiron, A; Elizur, A; Gabbay, U; Noy, S; Sarova-Pinhas, I

    1996-01-01

    The purpose of this study was to examine the sexual complaints and severity of sexual dysfunction in relapsing-remitting multiple sclerosis patients and to correlate them with psychological, neurological, and radiological variables. Frequency and characteristics of sexual disturbances were reported by 41 multiple sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical neurologic variables tested were disease duration, exacerbation rate, and disability; psychological variables tested were anxiety and depression. All patients underwent a brain magnetic resonance imaging (MRI) scan at the time of this study. The sexual dysfunction questionnaire included items based on the 3 phases of human sexual response: loss of libido, excitement (arousal difficulties, impotence, premature ejaculation), and anorgasmia. Five males (55.5%) and 16 females (50.0%) reported at least 1 sexual disturbance. The most frequent dysfunctions were loss of libido (26.8%) and arousal difficulties (19.5%). Females rated their difficulties as more severe. Sexual dysfunctions correlated with depression, (r = 0.68, P = 0.001). No correlation between MRI score and depression was found. Anorgasmia correlated with brain stem and pyramidal abnormalities (r = 0.56, P = 0.011; r = 0.56, P = 0.012, respectively). The total area of lesions (plaques) on the brain MRI scan also correlated with anorgasmia (r = 0.41, P = 0.02). Sexual dysfunctions in multiple sclerosis patients are frequent, are mild to moderate in severity, correlate with depression and in some cases central nervous system (CNS) demyelinating process, and thus may be related either to the psychological impact of this disease or to specific organic lesions in the brain. PMID:8754594

  14. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

    2007-01-01

    Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar to...

  15. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

    Science.gov (United States)

    Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

    2014-01-01

    For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of

  16. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Duque Pablo

    2008-11-01

    Full Text Available Abstract Background A possible method of finding physiological markers of multiple sclerosis (MS is the application of EEG quantification (QEEG of brain activity when the subject is stressed by the demands of a cognitive task. In particular, modulations of the spectral content that take place in the EEG of patients with multiple sclerosis remitting-relapsing (RRMS and benign multiple sclerosis (BMS during a visuo-spatial task need to be observed. Methods The sample consisted of 19 patients with RRMS, 10 with BMS, and 21 control subjects. All patients were free of medication and had not relapsed within the last month. The power spectral density (PSD of different EEG bands was calculated by Fast-Fourier-Transformation (FFT, those analysed being delta, theta, alpha, beta and gamma. Z-transformation was performed to observe individual profiles in each experimental group for spectral modulations. Lastly, correlation analyses was performed between QEEG values and other variables from participants in the study (age, EDSS, years of evolution and cognitive performance. Results Nearly half (42% the RRMS patients showed a statistically significant increase of two or more standard deviations (SD compared to the control mean value for the beta-2 and gamma bands (F = 2.074, p = 0.004. These alterations were localized to the anterior regions of the right hemisphere, and bilaterally to the posterior areas of the scalp. None of the BMS patients or control subjects had values outside the range of ± 2 SD. There were no significant correlations between these values and the other variables analysed (age, EDSS, years of evolution or behavioural performance. Conclusion During the attentional processing, changes in the high EEG spectrum (beta-2 and gamma in MS patients exhibit physiological alterations that are not normally detected by spontaneous EEG analysis. The different spectral pattern between pathological and controls groups could represent specific changes for

  17. Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

    2017-07-01

    The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

  18. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Van Haren, Keith; Tomooka, Beren H; Kidd, Brian A; Banwell, Brenda; Bar-Or, Amit; Chitnis, Tanuja; Tenembaum, Silvia N; Pohl, Daniela; Rostasy, Kevin; Dale, Russell C; O'Connor, Kevin C; Hafler, David A; Steinman, Lawrence; Robinson, William H

    2013-11-01

    Acute disseminated encephalomyelitis (ADEM) and relapsing-remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them. We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles. ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62-86%; specificity 56-79%) from MS serum (sensitivity 40-87%; specificity 62-86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides. Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.

  19. Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Lycke, Jan; Erälinna, Juha-Pekka

    2011-01-01

    Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy.......Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy....

  20. Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Lund, Henrik; Krakauer, Martin; Skimminge, Arnold

    2013-01-01

    and after the intravenous injection of a paramagnetic contrast agent to assess BBB permeability in the normal appearing white matter (NAWM) in patients with relapsing-remitting MS (RR-MS). Methodology/Principal Findings: Fifty-nine patients (38 females) with RR-MS undergoing immunomodulatory treatment...... and nine healthy controls (4 females) underwent quantitative T1 measurements at 3 tesla before and after injection of a paramagnetic contrast agent (0.2 mmol/kg Gd-DTPA). Mean T1 values were calculated for NAWM in patients and total cerebral white matter in healthy subjects for the T1 measurements before...

  1. Lymphocyte subtypes in relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.

    Science.gov (United States)

    Chaves, C; Ganguly, R; Ceresia, C; Camac, A

    2017-01-01

    Recent data suggest that lymphopenia is more prevalent than reported in relapsing-remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF). The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia. A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1, n  = 35) and normal lymphocyte counts (G2, n  = 24). Fifty-nine patients were identified, with mean age 49, 71.2% females, and average DMF duration 20 months. Age, sex, baseline white blood count, disease and treatment durations were similar between groups. Prior interferon therapy and baseline lower normal lymphocyte counts were more frequent in G1. Mean lymphocyte counts were 0.8 ± 0.2 × 10 9 /L in G1 and 1.6 ± 0.3 × 10 9 /L in G2. CD3 + , CD4 + , and CD8 + T cell mean counts were lower ( p  < 0.0001), while CD4/CD8 ratio higher ( p  = 0.03) in G1 than G2. Mean CD19  +  B cell counts were normal; however, values were lower in G1 ( p  = 0.04). After adjusting for confounders, significantly positive correlations were noted between lymphocyte counts and CD3  +  , CD4 + , CD8 + T, and B cell counts. Negative correlation was observed between lymphocyte counts and CD4/CD8 ratio driven by low CD8 + T cell counts. DMF treatment predominantly impacts T cells, in particular CD8 + subtype. This finding may have implications in this population's immunocompetence.

  2. Multimodal quantitative MRI assessment of cortical damage in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Gracien, René-Maxime; Jurcoane, Alina; Wagner, Marlies; Reitz, Sarah C; Mayer, Christoph; Volz, Steffen; Hof, Stephanie-Michelle; Fleischer, Vinzenz; Droby, Amgad; Steinmetz, Helmuth; Groppa, Sergiu; Hattingen, Elke; Deichmann, Ralf; Klein, Johannes C

    2016-12-01

    To investigate magnetization transfer ratio (MTR), T1 relaxation time, and proton density (PD) as indicators of gray matter damage in relapsing-remitting multiple sclerosis (RRMS), reflecting different aspects of microstructural damage and as imaging correlates of clinical disability. We aimed to determine which of these parameters may optimally quantify cortical damage, and serve as an imaging surrogate of clinical disability. In this study, cortical values of MTR, a surrogate for demyelination in MS, of PD, reflecting replacement of neural tissue by water, and of T1 , indicating a complex array of microstructural changes, were assessed in a group of RRMS patients in comparison to healthy controls (HC). 22 RRMS patients with varying disease duration (4.0 ± 6.54 years) and 10 HC received quantitative 3T magnetic resonance imaging (MRI) with MTR, T1 , and PD mapping. We tested for differences in cortical measurements between patients and HC. Additionally, correlation with disability as quantified by the Expanded Disability Status Scale was investigated. Cortical parameter values were significantly altered in the RRMS group, with increased values of T1 (P = 0.008) and PD (P = 0.028) and reduced values of MTR (P = 0.043). Only cortical T1 was correlated with clinical disability measurements (P = 0.001, r = 0.65). Receiver operating characteristic analysis demonstrated the best discriminatory power for T1 (area under the curve 0.79, PD: 0.75, MTR 0.73). Out of the parameters studied, cortical T1 is best suited to detect cortical damage as an imaging surrogate of clinical disability in RRMS. J. Magn. Reson. Imaging 2016;44:1600-1607. © 2016 International Society for Magnetic Resonance in Medicine.

  3. Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Røsjø, Egil; Steffensen, Linn H; Jørgensen, Lone; Lindstrøm, Jonas C; Šaltytė Benth, Jūratė; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Kampman, Margitta T; Torkildsen, Øivind; Holmøy, Trygve

    2015-12-01

    Observational studies have suggested that vitamin D may reduce inflammation in relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly confirmed in randomized controlled trials. To further explore the possible anti-inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose oral vitamin D3 on eleven markers of systemic inflammation in 68 RRMS patients enrolled in a double-blinded randomized placebo-controlled trial of vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25-hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no restrictions were set on additional standard immunomodulatory treatment for RRMS. The mean 25(OH)D level rose from 56 ± 29 to 123 ± 34 nmol/L among patients receiving vitamin D3 supplementation, whereas only a minor increase from 57 ± 22 to 63 ± 24 nmol/L was seen in the placebo group. However, no significant differences appeared between the vitamin D group and the placebo group for any of the inflammation markers. Patients on immunomodulatory therapy had significantly higher levels of interleukin-1 receptor antagonist and chemokine (C-X-C motif) ligand 16 than patients without immunomodulatory treatment, but there were no clear synergistic effects between immunomodulatory therapy and vitamin D3 supplementation on any of the inflammation markers. The rise in 25(OH)D levels after vitamin D3 supplementation was unaffected by immunomodulatory treatment. We conclude that in this study of RRMS patients, high-dose oral vitamin D3 supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment.

  4. Vitamin D is associated with degree of disability in patients with fully ambulatory relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Thouvenot, E; Orsini, M; Daures, J-P; Camu, W

    2015-03-01

    Vitamin D deficiency is a recognized risk factor for multiple sclerosis (MS) and is associated with increased disease activity. It has also been proposed that the lower the vitamin D levels are, the higher is the handicap. To refine the links between vitamin D insufficiency and disability in MS patients, a retrospective cohort analysis was performed including 181 patients prospectively followed without previous vitamin D supplementation, and age, gender, age at MS onset, MS type, MS activity, Expanded Disability Status Scale (EDSS) were analysed in correlation with plasma vitamin D levels. Vitamin D levels were significantly higher in relapsing-remitting MS than in progressive forms of MS in multivariate analyses adjusted for age, ethnicity, gender, disease duration and season (P = 0.0487). Overall, there was a negative correlation between vitamin D level and EDSS score (P = 0.0001, r = -0.33). In relapsing-remitting MS, vitamin D levels were only correlated with disability scores for EDSS 20 ng/ml of vitamin D were 2.78 times more likely to have an EDSS vitamin D deficiency is associated with higher risk of disability in MS. Vitamin D levels also correlated with the degree of disability in fully ambulatory patients with relapsing-remitting MS. These additional results support the pertinence of randomized controlled trials analysing the interest of an early vitamin D supplementation in MS patients to influence evolution of disability. © 2014 EAN.

  5. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study.

    Science.gov (United States)

    Riccio, Paolo; Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

    2016-03-01

    The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. © 2016 by the Society for Experimental Biology and Medicine.

  6. Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study

    Science.gov (United States)

    Rossano, Rocco; Larocca, Marilena; Trotta, Vincenzo; Mennella, Ilario; Vitaglione, Paola; Ettorre, Michele; Graverini, Antonio; De Santis, Alessandro; Di Monte, Elisabetta; Coniglio, Maria Gabriella

    2016-01-01

    The aim of this work was to assess the influence of nutritional intervention on inflammatory status and wellness in people with multiple sclerosis. To this end, in a seven-month pilot study we investigated the effects of a calorie-restricted, semi-vegetarian diet and administration of vitamin D and other dietary supplements (fish oil, lipoic acid, omega-3 polyunsaturated fatty acids, resveratrol and multivitamin complex) in 33 patients with relapsing-remitting multiple sclerosis and 10 patients with primary-progressive multiple sclerosis. At 0/3/6 months, patients had neurological examination, filled questionnaires and underwent anthropometric measurements and biochemical analyses. Serum fatty acids and vitamin D levels were measured as markers of dietary compliance and nutritional efficacy of treatment, whereas serum gelatinase levels were analyzed as markers of inflammatory status. All patients had insufficient levels of vitamin D at baseline, but their values did not ameliorate following a weekly administration of 5000  IU, and rather decreased over time. Conversely, omega-3 polyunsaturated fatty acids increased already after three months, even under dietary restriction only. Co-treatment with interferon-beta in relapsing-remitting multiple sclerosis was irrelevant to vitamin D levels. After six months nutritional treatment, no significant changes in neurological signs were observed in any group. However, serum levels of the activated isoforms of gelatinase matrix metalloproteinase-9 decreased by 59% in primary-progressive multiple sclerosis and by 51% in relapsing-remitting multiple sclerosis patients under nutritional intervention, including dietary supplements. This study indicates that a healthy nutritional intervention is well accepted by people with multiple sclerosis and may ameliorate their physical and inflammatory status. PMID:26785711

  7. Do coping styles mediate the relationship between disability status and psychosocial loss in people with relapsing remitting multiple sclerosis?

    Science.gov (United States)

    Gedik, Zumrut; Sorias, Oya; Idiman, Egemen

    2017-05-01

    The main aim of this cross-sectional study was to analyse the degree to which coping may act as a mediator between disability and psychosocial loss in people with relapsing remitting multiple sclerosis. Participants ( N = 158) completed measures of psychosocial loss and ways of coping. Disability status was evaluated by attending neurologists. Coping partially mediated the relationship between disability and psychosocial loss. Disability leads to the experience of psychosocial loss but it is not the sole factor determining the formation of psychosocial loss. Coping is also associated with such losses in multiple sclerosis.

  8. Trace elements in scalp hair samples from patients with relapsing-remitting multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Elisa Tamburo

    Full Text Available Epidemiological studies have suggested a possible role of trace elements (TE in the etiology of several neurological diseases including Multiple Sclerosis (MS. Hair analysis provides an easy tool to quantify TE in human subjects, including patients with neurodegenerative diseases.To compare TE levels in scalp hair from patients with MS and healthy controls from the same geographic area (Sicily.ICP-MS was used to determine the concentrations of 21 elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn in scalp hair of 48 patients with relapsing-remitting Multiple Sclerosis compared with 51 healthy controls.MS patients showed a significantly lower hair concentration of aluminum and rubidium (median values: Al = 3.76 μg/g vs. 4.49 μg/g and Rb = 0.007 μg/g vs. 0.01 μg/g; and higher hair concentration of U (median values U: 0.014 μg/g vs. 0.007 μg/g compared to healthy controls. The percentages of MS patients showing hair elemental concentrations greater than the 95th percentile of controls were 20% for Ni, 19% for Ba and U, and 15% for Ag, Mo and Se. Conversely, the percentages of MS patients showing hair elemental concentrations lower than the 5th percentile of healthy controls were 27% for Al, 25% for Rb, 22% for Ag, 19% for Fe, and 16% for Pb. No significant association was found between levels of each TE and age, disease duration or Expanded Disability Status Scale (EDSS score. After stratification by gender, healthy subjects did not show any significant difference in trace element levels, while MS patients showed significant differences (p<0.01 for the concentrations of Ag, Cr, Fe, Ni and Sr. No significant differences were also found, at p<0.01, in relation to the use of cigarettes, consume of water, vegetables and place of living.The different distributions of TE in hair of MS patients compared to controls provides an additional indirect evidence of metabolic imbalance of chemical elements in the

  9. "Always looking for a new balance": toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Meide, Hanneke van der; Gorp, Dennis van; van der Hiele, Karin; Visser, Leo

    2017-06-22

    The aim of this study was to gain insight into the meaning of work in the everyday lives of people with relapsing-remitting multiple sclerosis, and the barriers and facilitators to staying in work. Nineteen employed adults diagnosed with relapsing-remitting multiple sclerosis participated in narrative interviews. All interviews were transcribed and coded for thematic analysis. For people with relapsing-remitting multiple sclerosis, continuing to work was a precarious balancing act. Five themes influenced this balance: becoming familiar with the disease, adjusting expectations, having an understanding and realistic line manager, seeing work as meaningful life activity and strategic considerations. People receiving a diagnosis of relapsing-remitting multiple sclerosis have to refamiliarize themselves with their own body in a meaningful way to be able to continue their work. Rehabilitation professionals can support them herein by taking into account not merely functional capabilities but also identity aspects of the body. Medication that stabilizes symptoms supports making the necessary adjustments. A trusting relationship with the line manager is vital for this adaptation process. Additionally, a match between being adequately challenged by work, while still having the capacity to meet those work demands, is needed, as is long-term financial stability. Implications for rehabilitation Rehabilitation professionals can support employees with relapsing-remitting multiple sclerosis by taking into account not merely functional capabilities but also identity aspects of the body. A trusting relationship with the line manager, including a timely disclosure of the diagnosis, is vital for people with relapsing-remitting multiple sclerosis to remain at work. For people with relapsing-remitting multiple sclerosis, there is a delicate balance between being adequately challenged by work while still having the capacity to meet work demands.

  10. Alemtuzumab: a new therapy for active relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Hartung, Hans-Peter; Aktas, Orhan; Boyko, Alexey N

    2015-01-01

    Alemtuzumab is a humanized monoclonal antibody directed against CD52 to deplete circulating T and B lymphocytes; lymphocyte depletion is followed by a distinctive pattern of T- and B-cell repopulation, changing the balance of the immune system. This review reports the efficacy and safety findings of the phase 2 CAMMS223 trial and the phase 3 CARE-MS I and II trials investigating alemtuzumab for the treatment of active relapsing-remitting MS. Alemtuzumab, administered intravenously, was shown to improve relapse rate versus subcutaneous interferon beta-1a in patients who were treatment-naive (CAMMS223 and CARE-MS I) or had relapsed on prior therapy (CARE-MS II), and to reduce sustained accumulation of disability (CAMMS223 and CARE-MS II). Important adverse events were infusion-associated reactions, serious infections and autoimmune events. A safety monitoring program allowed for early detection and management of autoimmune events. Recommendations for the monitoring of adverse events are made. Alemtuzumab's mechanism of action, pharmacodynamics and opportunities for future research are discussed. © The Author(s), 2015.

  11. Assessment of Definitions of Sustained Disease Progression in Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Brian C. Healy

    2013-01-01

    Full Text Available Sustained progression on the expanded disability status scale (EDSS is a common outcome measure of disease progression in clinical studies of MS. Unfortunately, this outcome may not accurately measure long-term and irreversible disease progression. To assess the performance of definitions of sustained progression, patients with relapsing-remitting MS (RRMS or a clinically isolated syndrome with evidence of lesions on a brain MRI were included in our study. Fifteen definitions of sustained progression using both the EDSS and the functional system (FS scales were investigated. The impact of both relapses and changes in provider on the probability of maintaining progression was also evaluated. Although the provider scoring the EDSS sometimes changed during followup, the provider had access to previous EDSS scores. Between 15.8% and 42.2% of patients experienced sustained progression based on the definitions using EDSS as the outcome, but nearly 50% of these patients failed to maintain sustained progression for the duration of followup. When FS scales were used, progression was most common on the pyramidal and sensory scales. Unfortunately, progression on specific FS scales failed to be more sensitive to irreversible disability. Relapses or changes in provider did not explain the poor performance of the measures. Short-term changes in the EDSS or FS scores may not be an accurate marker of irreversible change in RRMS.

  12. Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lugaresi A

    2013-06-01

    Full Text Available Alessandra Lugaresi,1 Maria di Ioia,1 Daniela Travaglini,1 Erika Pietrolongo,1 Eugenio Pucci,2 Marco Onofrj11Department of Neuroscience and Imaging, University “G d’Annunzio”, Chieti, 2Operative Unit Neurologia ASUR Marche Area Vasta 3, Macerata, ItalyAbstract: Multiple sclerosis (MS is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics

  13. Interferon-beta for relapsing-remitting multiple sclerosis: a systematic review

    Directory of Open Access Journals (Sweden)

    Dian HE

    2014-09-01

    Full Text Available Objective To assess the efficacy and safety of interferon-beta (IFN-β as monotherapy versus placebo for patients with relapsing-remitting multiple sclerosis (RRMS.  Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL, PubMed, EMBASE, CINAHL, LILACS, PEDRO, China Biology Medicine Disc (CBMDisc, as well as clinical trial registries and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, retrieval deadline: June 2014. Furthermore, we checked reference lists of published reviews and retrieved articles, and communicated personally with investigators and biotechnology companies participating in trials of IFN-β in an effort to identify further studies or unpublished data. Two review authors independently screened studies, extracted data and evaluated the risk of bias. Formal Meta-analysis were conducted by using Review Manager software (Version 5.3.3 and the impacts of limitations in study design or execution (risk of bias, inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the quality of the body of evidence were assessed.  Results A total of 576 articles were retrieved. After screening of titles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for further assessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS (high-dose IFN-β group: N = 1076; placebo group: N = 1053. All studies were randomized, double-blind, controlled, parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo as monotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk of attrition bias. Moreover, the intention to treat (ITT principle was not used in data analysis. Data from only 919 patients (43.17% were available to calculate the primary outcomes at 2 years of follow-up. Meta-analysis indicated

  14. Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

    Science.gov (United States)

    O'Day, Ken; Meyer, Kellie; Stafkey-Mailey, Dana; Watson, Crystal

    2015-04-01

    To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly

  15. Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

    Science.gov (United States)

    Tramacere, Irene; Del Giovane, Cinzia; Salanti, Georgia; D'Amico, Roberto; Filippini, Graziella

    2015-09-18

    Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biologics. Although there is consensus that these therapies reduce the frequency of relapses, their relative benefit in delaying new relapses or disability worsening remains unclear due to the limited number of direct comparison trials. To compare the benefit and acceptability of interferon beta-1b, interferon beta-1a (Avonex, Rebif), glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine and immunoglobulins for the treatment of people with RRMS and to provide a ranking of these treatments according to their benefit and acceptability, defined as the proportion of participants who withdrew due to any adverse event. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, which contains trials from CENTRAL (2014, Issue 9), MEDLINE (1966 to 2014), EMBASE (1974 to 2014), CINAHL (1981 to 2014), LILACS (1982 to 2014), clinicaltrials.gov and the WHO trials registry, and US Food and Drug Administration (FDA) reports. We ran the most recent search in September 2014. Randomised controlled trials (RCTs) that studied one or more of the 15 treatments as monotherapy, compared to placebo or to another active agent, for use in adults with RRMS. Two authors independently identified studies from the search results and performed data extraction. We performed data synthesis by pairwise meta-analysis and network meta-analysis. We assessed the quality of the body of evidence for outcomes within the network meta-analysis according to GRADE, as very low, low, moderate or high. We included 39 studies in this review, in which 25,113 participants were randomised. The majority of the included trials were short-term studies, with a median duration of 24 months

  16. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

    Science.gov (United States)

    Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

    2017-07-01

    The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

  17. Oral available agents in the treatment of relapsing remitting multiple sclerosis an overview of merits and culprits

    Directory of Open Access Journals (Sweden)

    Thöne J

    2013-02-01

    Full Text Available Jan Thöne, Gisa Ellrichmann Department of Neurology, St Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany Abstract: Multiple sclerosis (MS is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Major therapeutic progress has occurred during the past decade, in particular since the introduction of immunomodulatory agents, however, MS is still an incurable disease. In addition, parenteral application of the currently licensed drugs is associated with injection-related adverse events (AEs and low patient compliance. Thus, there remains an unmet need for the development of more effective and well tolerated oral therapies for the treatment of MS. A number of new orally administered agents including fingolimod, laquinimod, teriflunomide, cladribine, and BG-12 have been licensed recently or are currently under investigation in relapsing remitting MS patients. In multi-center, randomized, placebo-controlled phase III clinical studies, all of these agents have already shown their efficacy on both clinical disease parameters and magnetic resonance imaging-based measures of disease activity in patients with relapsing remitting MS. However, there are essential differences concerning their clinical efficacy and side-effect profiles. Additionally, the mechanisms by which these substances exert clinical efficacy have not been fully elucidated. In this article, we review the pharmaceutical properties of fingolimod, laquinimod, teriflunomide, cladribine, and BG-12; and their suggested mechanisms of action, clinical efficacy, and side-effect profiles. Keywords: cladribine, fingolimod (FTY, fumaric acid esters (BG-12, laquinimod, teriflunomide

  18. Cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis with EDSS < or = 3.5.

    Science.gov (United States)

    Ruggieri, R M; Palermo, R; Vitello, G; Gennuso, M; Settipani, N; Piccoli, F

    2003-11-01

    Previous papers have mainly demonstrated the presence and the frequency of cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis. The purpose of this study was to investigate subjects with the relapsing-remitting form of the disease and mild clinical disability (EDSS Aphasie Test (AAT). They also underwent Clinical Depression Scale (CDQ) and State-Trait Anxiety Inventory (STAI). The results show the presence of significant memory impairment on both WMS (P = 0.000) and BVRT (P = 0.000) in patients compared with controls. Patients were also impaired in abstract reasoning and problem-solving deficit (KT P = 0.003; RCPM P = 0.000) and in FR (P = 0.019). Cognitive decline correlated with illness duration (r = 0.761), but was independent of EDSS (r = 0.085). Cognitive decline was present even when physical disability was not yet severe, but it was mild and did not limit patients' ability to work. The cognitive impairment outlined was of the subcortical type and correlated with illness duration. This study emphasizes the importance of cognitive examination in clinical practice. It is suggested that a complete neurological examination include tests on memory and abstract reasoning.

  19. Prediction of driving ability in people with relapsing-remitting multiple sclerosis using the stroke driver screening assessment.

    Science.gov (United States)

    Akinwuntan, Abiodun Emmanuel; O'Connor, Christina; McGonegal, Erin; Turchi, Kristen; Smith, Suzanne; Williams, Mitzi; Wachtel, Jerry

    2012-01-01

    The ability to drive is often affected in individuals with multiple sclerosis (MS) because of the motor, visual, or cognitive deficits commonly associated with the condition. In this study, we investigated the accuracy with which the Stroke Driver Screening Assessment (SDSA), an established battery for the prediction of driving performance of stroke survivors, would predict driving performance of individuals with MS. Driving performance of 44 individuals with relapsing-remitting MS (mean ± SD age, 46 ± 11 years; 37 females and 7 males) who were currently driving at least once a month was predicted using their performance on the SDSA. Outcomes of a road test and the Useful Field of View (UFOV) test were used as measures of driving ability. Participants' performance on both the road and UFOV tests was predicted with more than 80% accuracy. The SDSA was more accurate in predicting who would pass the two tests than who would fail the tests. The SDSA battery appears to be a good predictor of driving performance of individuals with relapsing-remitting MS, especially those who have sufficient cognitive skills to continue driving. Larger studies are needed to definitively establish its predictive accuracy and confirm the validity of the predictions.

  20. Cladribine tablets for relapsing-remitting multiple sclerosis: Efficacy across patient subgroups from the phase III CLARITY study.

    Science.gov (United States)

    Rammohan, Kottil; Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart; Rieckmann, Peter; Soelberg Sørensen, Per; Vermersch, Patrick; Hamlett, Anthony; Kurukulasuriya, Nuwan

    2012-01-01

    In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses of CLARITY study data were conducted to determine the efficacy of cladribine tablets across patient subgroups stratified by baseline characteristics. Relapse rates over the 96-week CLARITY study were analyzed in cohorts stratified by demographics; disease duration; treatment history and disease activity at baseline. In the intent-to-treat population (n=437, 433 and 456 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively), treatment with cladribine tablets 3.5 and 5.25mg/kg led to consistent improvements in ARR versus placebo in patients stratified by gender; age (≤40/>40 years); disease duration (10 years); prior disease-modifying drug treatment (treated/naïve); relapses in the prior year (≤1/2/≥3); Expanded Disability Status Scale score (median) at baseline (all P≤0.05 for reduction in the relative risk of relapse [cladribine tablets versus placebo]). Significant effects were also observed in patients who had only one relapse in the year prior to study entry (n=306, 303 and 323 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively) and who were further stratified according to other measures of disease activity at baseline. Treatment with cladribine tablets provides consistent reductions in ARR compared with placebo across the spectrum of baseline demographics and disease characteristics represented in the CLARITY study. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. EBV and vitamin D status in relapsing-remitting multiple sclerosis patients with a unique cytokine signature.

    Science.gov (United States)

    Nejati, Ahmad; Shoja, Zabihollah; Shahmahmoodi, Shohreh; Tafakhori, Abbas; Mollaei-Kandelous, Yaghoub; Rezaei, Farhad; Hamid, Kabir Magaji; Mirshafiey, Abbas; Doosti, Rozita; Sahraian, Mohammad Ali; Mahmoudi, Mahmood; Shokri, Fazel; Emery, Vince; Marashi, Sayed Mahdi

    2016-04-01

    Multiple sclerosis, a debilitating autoimmune and inflammatory disease of the central nervous system, is associated with both infectious and non-infectious factors. We investigated the role of EBV infection, vitamin D level, and cytokine signature in MS patients. Molecular and serological assays were used to investigate immune biomarkers, vitamin D level, and EBV status in 83 patients with relapsing-remitting multiple sclerosis and 62 healthy controls. In total, 98.8 % of MS patients showed a history of EBV exposure compared to 88.6 % in the healthy group (p = 0.005). EBV DNA load was significantly higher in MS patients than healthy subjects (p vitamin D concentration and EBV load, but not EBNA-1 IgG antibody levels. Our data highlight biomarker correlates in MS patients together with a complex interplay between EBV replication and vitamin D levels.

  2. High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS)

    Science.gov (United States)

    Nash, Richard A.; Hutton, George J.; Racke, Michael K.; Popat, Uday; Devine, Steven M.; Griffith, Linda M.; Muraro, Paolo A.; Openshaw, Harry; Sayre, Peter H.; Stüve, Olaf; Arnold, Douglas L.; Spychala, Meagan E.; McConville, Kaitlyn C.; Harris, Kristina M.; Phippard, Deborah; Georges, George E.; Wundes, Annette; Kraft, George H.; Bowen, James D.

    2016-01-01

    IMPORTANCE Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS. OBJECTIVE To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT. DESIGN, SETTING, AND PARTICIPANTS Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled. INTERVENTIONS Autologous peripheral blood stem cell grafts were CD34+ selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT. MAIN OUTCOMES AND MEASURES The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176–250) weeks). Overall event-free survival was 78.4% (90% CI, 60.1%–89.0%) at 3 years. Progression-free survival and clinical relapse

  3. Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS).

    Science.gov (United States)

    Gold, Ralf; Giovannoni, Gavin; Phillips, J Theodore; Fox, Robert J; Zhang, Annie; Meltzer, Leslie; Kurukulasuriya, Nuwan C

    2015-01-01

    Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials. To evaluate delayed-release DMF in newly diagnosed relapsing-remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM. Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy. The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF. Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients. © The Author(s), 2015.

  4. Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Guilherme Sciascia do Olival

    2013-08-01

    Full Text Available This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease-modifying therapy (DMT withdrawn. Forty patients, which had made continuous use of one immunomodulator and had remained free of disease for at least 5 years, had their DMT withdrawn and were observed from 13 to 86 months. Out of the followed patients, 4 (10% patients presented with new attacks. In addition to these patients, 2 (5% patients had new lesions revealed by magnetic resonance imaging that did not correspond to clinical attacks. Despite these results, the difficult decision to withdraw medication requires careful analysis. Withdrawal, however, should not be viewed as simply the suspension of treatment because these patients should be evaluated periodically, and the immunomodulators should be readily reintroduced if new attacks occur. Nonetheless, medication withdrawal is an option for a select group of patients.

  5. Contrasting responses to interferon β-1b treatment in relapsing-remitting multiple sclerosis: Does baseline interleukin- 12p35 messenger RNA predict the efficacy of treatment?

    NARCIS (Netherlands)

    Boxel van-Dezaire, A.H.H.; Trigt van-Hoff, S.C.J.; Killestein, J.; Schrijver, H.M.; Houwelingen, J.C. van; Polman, C.H.; Nagelkerken, L.

    2000-01-01

    Interferon (IFN)-β treatment is effective in relapsing-remitting multiple sclerosis (RR-MS) via an as yet unidentified mechanism. In the present study, we investigated whether the expression of messenger RNA (mRNA) encoding the interleukin (IL)-12 subunits p40 and p35, IL-12 receptor chains, IL-18,

  6. Improvement of health-related quality of life in relapsing remitting multiple sclerosis patients after 2 years of treatment with intramuscular interferon-beta-1a.

    NARCIS (Netherlands)

    Jongen, P.J.H.; Sindic, C.; Carton, H.; Zwanikken, C.P.; Lemmens, W.A.J.G.; Borm, G.F.

    2010-01-01

    In patients with relapsing remitting multiple sclerosis (RRMS), the effect of interferon-beta (INFb) on health-related quality of life (HR-QoL) is not firmly documented. The objective of this study is to assess HR-QoL during 2 years of treatment with intramuscular INFb and its correlation with

  7. Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

    2014-05-01

    At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  8. Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study.

    Directory of Open Access Journals (Sweden)

    Gabriel Bsteh

    Full Text Available Multiple sclerosis (MS has a highly heterogenic course making prediction of long term outcome very difficult.The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset.This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5, moderate (EDSS 3.0-5.5 or severe (EDSS ≥6.0 disability were calculated to correct for confounders.Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1; p<0.001. Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005, while depression (HR 3.59; CI 1.14-11.24; p = 0.028 and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability.We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms.

  9. Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy

    Directory of Open Access Journals (Sweden)

    Foronda Jesus

    2004-06-01

    Full Text Available Abstract Background What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. Methods Thirty one patients (9 male and 22 female with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0–5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. Results A statistically significant correlation was found (r = -0.38 p Conclusions There is correlation between disability (measured by Expanded Disability Scale Score and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor.

  10. NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Mellgren, Svein Ivar; Svenningsson, Anders

    2009-01-01

    BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce...... the yearly relapse rate in patients with relapsing-remitting multiple sclerosis. METHODS: NORMIMS (NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis) was a randomised, placebo-controlled trial done in 29 neurology....... INTERPRETATION: Oral methylprednisolone given in pulses every 4 weeks as an add-on therapy to subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis leads to a significant reduction in relapse rate. However, because of the small number of patients and the high dropout rate...

  11. Trace Elements in Scalp Hair Samples from Patients with Relapsing-Remitting Multiple Sclerosis

    Science.gov (United States)

    Tamburo, Elisa; Varrica, Daniela; Dongarrà, Gaetano; Grimaldi, Luigi Maria Edoardo

    2015-01-01

    Background Epidemiological studies have suggested a possible role of trace elements (TE) in the etiology of several neurological diseases including Multiple Sclerosis (MS). Hair analysis provides an easy tool to quantify TE in human subjects, including patients with neurodegenerative diseases. Objective To compare TE levels in scalp hair from patients with MS and healthy controls from the same geographic area (Sicily). Methods ICP-MS was used to determine the concentrations of 21 elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn) in scalp hair of 48 patients with relapsing–remitting Multiple Sclerosis compared with 51 healthy controls. Results MS patients showed a significantly lower hair concentration of aluminum and rubidium (median values: Al = 3.76 μg/g vs. 4.49 μg/g and Rb = 0.007 μg/g vs. 0.01 μg/g;) and higher hair concentration of U (median values U: 0.014 μg/g vs. 0.007 μg/g) compared to healthy controls. The percentages of MS patients showing hair elemental concentrations greater than the 95th percentile of controls were 20% for Ni, 19% for Ba and U, and 15% for Ag, Mo and Se. Conversely, the percentages of MS patients showing hair elemental concentrations lower than the 5th percentile of healthy controls were 27% for Al, 25% for Rb, 22% for Ag, 19% for Fe, and 16% for Pb. No significant association was found between levels of each TE and age, disease duration or Expanded Disability Status Scale (EDSS) score. After stratification by gender, healthy subjects did not show any significant difference in trace element levels, while MS patients showed significant differences (p<0.01) for the concentrations of Ag, Cr, Fe, Ni and Sr. No significant differences were also found, at p<0.01, in relation to the use of cigarettes, consume of water, vegetables and place of living. Conclusion The different distributions of TE in hair of MS patients compared to controls provides an additional indirect evidence of

  12. Quality of life outcomes with BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: the DEFINE study.

    Science.gov (United States)

    Kappos, Ludwig; Gold, Ralf; Arnold, Douglas L; Bar-Or, Amit; Giovannoni, Gavin; Selmaj, Krzysztof; Sarda, Sujata P; Agarwal, Sonalee; Zhang, Annie; Sheikh, Sarah I; Seidman, Emily; Dawson, Katherine T

    2014-02-01

    Oral BG-12 (dimethyl fumarate), approved for the treatment of the relapsing forms of MS, has demonstrated clinical efficacy with an acceptable safety profile in the Phase III "Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (RRMS)" (DEFINE) and "Comparator and an Oral Fumarate in RRMS" (CONFIRM) studies. To evaluate the health-related quality of life (HRQoL) impairment that is associated with RRMS and to assess the effects of BG-12 on HRQoL in the DEFINE study. Patients with RRMS were randomized to BG-12 240 mg twice (BID) or three times (TID) daily, or placebo, for 2 years. HRQoL was assessed by the Short Form-36 (SF-36), global assessment of well-being visual analog scale and the EuroQol-5D. In the 1237 patients from DEFINE, HRQoL impairment was greatest in patients who had higher disability scores and in those who had experienced relapse. Change in SF-36 physical component summary scores during 2 years' treatment significantly favored BG-12 over placebo (both doses: p < 0.001). We saw similar benefits in other measures of functioning and general well-being as early as Week 24. These benefits were maintained during the study. Our results add to evidence for a negative impact of RRMS on HRQoL and they demonstrate the benefits of BG-12 on HRQoL measures, which coupled with significant clinical efficacy, further support its use as a new treatment for RRMS.

  13. Safety of teriflunomide for the management of relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Papadopoulou, Athina; Kappos, Ludwig; Sprenger, Till

    2015-05-01

    Teriflunomide is a new oral disease-modifying drug (DMD), recently approved for the first-line treatment of relapsing multiple sclerosis (MS). Since MS is a chronic disease, which often necessitates long-term treatment, data not only on efficacy but also on long-term safety, including pregnancy-related issues, are very important. In this review article, we outline the key preclinical and clinical data on teriflunomide with a focus on its safety profile. We summarize adverse events observed in the Phase II and III clinical trials and the safety data from the long-term extension phases as well as the > 15-year post-marketing experience with the parent drug, leflunomide. We also consider the evidence regarding immune competence and potential fetal risks of the drug. Teriflunomide has the advantage of a convenient once-daily oral administration scheme and a large body of evidence suggesting a manageable safety profile (clinical development program with > 6800 patient-years of exposure and post-marketing experience with leflunomide). Further post-marketing data, especially regarding pregnancy outcomes and risks of infections, will help to define the exact place of teriflunomide in the treatment of MS in the future, especially compared with the other oral DMDs.

  14. Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Natalia Niedziela

    2016-01-01

    Full Text Available The role of nitric oxide and its reactive derivatives (NOx is well known in the pathogenesis of multiple sclerosis, which is an inflammatory disease while NOx seems to be important in coordinating inflammatory response. The purpose of the present study was to assess serum NOx as one of the nitrogen species and inflammatory parameters in relapsing-remitting multiple sclerosis patients and to compare the effectiveness of various types of disease-modifying therapies that reduce nitric oxide and inflammatory biomarkers. Elevated NOx level was observed in patients who received the first-line disease-modifying therapy (interferons beta-1a and beta-1b in comparison with the subjects treated with the second-line disease-modifying therapy (natalizumab; fingolimod and healthy controls without significant differences in C-reactive protein and interleukin-1 beta. A negative correlation was observed between serum NOx level and the duration of multiple sclerosis confirmed in the whole study population and in subjects treated with the first-line agents. Only serum NOx, concentration could reveal a potential efficacy of disease-modifying therapy with a better reduction in NOx level due to the second-line agents of disease-modifying therapy.

  15. Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2012-08-01

    Full Text Available OBJECTIVE: To determine if the presence of oligoclonal bands (OB at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF were included. SIENAX was used for total brain volume (TBV, gray matter volume (GMV, and white matter volume (WMV. RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS, treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6 compared with 1.64 mm³ x 10(6 in the negative ones (p=0.02. GMV was 0.51 mm³ x 10(6 in positive IgG-OB compared with 0.62 mm³ x 10(6 in negative ones (p=0.002. No differences in WMV (p=0.09 were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR markers in early RRMS.

  16. Long-term safety and efficacy of natalizumab in relapsing-remitting multiple sclerosis: impact on quality of life

    Directory of Open Access Journals (Sweden)

    Planas R

    2014-04-01

    Full Text Available Raquel Planas, Roland Martin, Mireia Sospedra Neuroimmunology and MS Research, Department of Neurology, University of Zurich, Zurich, Switzerland Abstract: Natalizumab was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS based on its short-term efficacy and overall tolerability. However, the incidence of treatment-associated progressive multifocal leukoencephalopathy (PML, an infection of the brain caused by the John Cunningham virus, jeopardized this efficacious treatment from the beginning. Eight years after licensing of natalizumab, long-term studies confirm the considerable and sustained efficacy of natalizumab, although the PML complication still threatens one of the most successful treatments available for RRMS. During these years, considerable progress has been made in identification of risk factors that allow more effective management of PML risk. In addition, long-term studies to define better when to start or stop treatment and to optimize treatment strategies after cessation of natalizumab are ongoing, and hopefully will improve management and will allow natalizumab to remain as a valuable therapeutic option for patients with highly active RRMS. Keywords: therapy, progressive multifocal leukoencephalopathy, multiple sclerosis

  17. Impact of daclizumab versus interferon beta-1a on patient-reported outcomes in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Liu, Ying; Vollmer, Timothy; Havrdova, Eva; Riester, Katherine; Lee, Andrew; Phillips, Glenn; Wang, Ping; Sabatella, Guido

    2017-01-01

    Patient-reported outcomes (PROs) provide information on treatment effects from the patient's perspective that complement outcomes on clinical measures. In DECIDE, daclizumab demonstrated superior efficacy in reducing relapses, 24-week confirmed disability progression, and brain lesions (assessed by magnetic resonance imaging [MRI]) versus intramuscular interferon beta-1a in relapsing-remitting multiple sclerosis. To examine the impact of daclizumab versus interferon beta-1a on PROs in DECIDE. DECIDE was a randomized, double-blind, active-controlled, phase 3 study comparing daclizumab 150mg subcutaneous every 4 weeks with interferon beta-1a 30mcg intramuscular once weekly. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) and EuroQoL 5-Dimensions (EQ-5D) were assessed at baseline and every 24 weeks. Mean changes from baseline were analyzed using analysis of covariance models. Individual items for the MSIS-29 physical (PHYS) and psychological (PSYCH) subscales were analyzed post hoc. Daclizumab treatment resulted in greater mean improvements relative to baseline in MSIS-29 PHYS and PSYCH scores starting at week 24 that persisted over 96 weeks. Mean improvements from baseline in MSIS-29 PHYS and PSYCH scores were significantly greater for daclizumab versus intramuscular interferon beta-1a at week 96. Daclizumab-treated patients showed steady improvements in EQ-5D health utility index and EQ-5D visual analog scale scores over the study period, with significantly greater improvements versus intramuscular interferon beta-1a at week 96 (p=0.0048 and p=0.0006, respectively). Improvements in patient-reported physical and psychological functioning and general health status with daclizumab compared with intramuscular interferon beta-1a are consistent with outcomes on clinical and brain MRI lesion measures in DECIDE (NCT01064401). Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

    Directory of Open Access Journals (Sweden)

    Simon Zhornitsky

    Full Text Available Disease modifying therapies (DMTs reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS. Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA or interferon-β 1a/1b (IFN-β between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2% were lost to follow-up and 160 (11% moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54% started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

  19. Pregnancy outcomes following maternal and paternal exposure to teriflunomide during treatment for relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Kieseier, Bernd C; Benamor, Myriam

    2014-12-01

    Teriflunomide, indicated for the treatment of relapsing-remitting multiple sclerosis, is contraindicated in pregnancy based on signs of developmental toxicity in the offspring of rats and rabbits; developmental toxicity has also been observed in preclinical studies of other disease-modifying therapies. Despite the requirement to use reliable contraception in clinical trials evaluating the safety and efficacy of teriflunomide, a number of pregnancies have been reported. This work reports pregnancy outcomes in teriflunomide clinical trials. Pregnancy outcomes were evaluated in a retrospective analysis of the global pharmacovigilance database. The following information was collected from the pharmacovigilance database or individual patient files: treatment allocation, pregnancy outcome, teriflunomide exposure, and use of the accelerated elimination procedure. At data cut-off, 83 pregnancies were reported in female patients and 22 pregnancies were documented in partners of male patients. All newborns were healthy and did not have any structural or functional abnormalities at birth. Available data do not indicate any teratogenic signals in patients treated with teriflunomide.

  20. Natural killer cell subpopulations are associated with MRI activity in a relapsing-remitting multiple sclerosis patient cohort from Australia.

    Science.gov (United States)

    Caruana, P; Lemmert, K; Ribbons, K; Lea, R; Lechner-Scott, J

    2017-10-01

    The importance of the innate immune system in multiple sclerosis (MS) is increasingly recognized and the role of natural killer (NK) cells in controlling autoimmunity may be an important modulator of disease activity. To examine NK subsets in MS patients on different treatments and to evaluate the role of NK subsets as indicators for disease activity. We measured NK subset levels in blood obtained from 110 relapsing-remitting MS patients. Patients were either off treatment or on treatment with natalizumab, fingolimod, glatiramer acetate or beta-interferon. Disease activity was defined according to 'No Evidence of Disease Activity' (NEDA) criteria within an observation period of up to 2.4 years. The mean NK subset levels were compared among treatment groups using multivariate analysis of variance (ANOVA) and association analysis with disease activity performed using multi-factor logistic regression. Our analysis revealed differences in NK cells and subsets on treatment compared to off treatment ( p < 0.0005). A high proportion of bright NK cells were significantly associated with stable magnetic resonance imaging (MRI) imaging after adjusting for treatment effects ( p < 0.05). The independent association of NK subsets with MRI stability needs to be confirmed in prospective studies to test their usefulness in predicting disease activity in MS patients.

  1. Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis?

    Science.gov (United States)

    Jongen, Peter Joseph; Wesnes, Keith; van Geel, Björn; Pop, Paul; Schrijver, Hans; Visser, Leo H.; Gilhuis, H. Jacobus; Sinnige, Ludovicus G.; Brands, Augustina M.

    2015-01-01

    In persons with multiple sclerosis (MS) a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting MS (eRRMS) were assessed for self-efficacy (MSSES-18), cognition (CDR System), fatigue (MFIS-5), depressive symptoms (BDI), disease impact (MSIS-29), and disability (EDSS). Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (r= 0.65; P< 0.001), Reaction Time Variability (r= 0.57; P< 0.001), and Speed of Memory (r= 0.53; P< 0.01), and between control self-efficacy and Reaction Time Variability (r= 0.55; P< 0.01). Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy. PMID:26064686

  2. Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis?

    Directory of Open Access Journals (Sweden)

    Peter Joseph Jongen

    2015-01-01

    Full Text Available In persons with multiple sclerosis (MS a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS and early Relapsing Remitting MS (eRRMS were assessed for self-efficacy (MSSES-18, cognition (CDR System, fatigue (MFIS-5, depressive symptoms (BDI, disease impact (MSIS-29, and disability (EDSS. Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (r= 0.65; P< 0.001, Reaction Time Variability (r= 0.57; P< 0.001, and Speed of Memory (r= 0.53; P< 0.01, and between control self-efficacy and Reaction Time Variability (r= 0.55; P< 0.01. Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy.

  3. Gray Matter Correlates of Cognitive Performance Differ between Relapsing-Remitting and Primary-Progressive Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Laura E Jonkman

    Full Text Available Multiple Sclerosis (MS is a chronic inflammatory/demyelinating and neurodegenerative disease of the central nervous system (CNS. Most patients experience a relapsing-remitting (RR course, while about 15-20% of patients experience a primary progressive (PP course. Cognitive impairment affects approximately 40-70% of all MS patients and differences in cognitive impairment between RR-MS and PP-MS have been found. We aimed to compare RR-MS and PP-MS patients in terms of cognitive performance, and to investigate the MRI correlates of cognitive impairment in the two groups using measures of brain volumes and cortical thickness. Fifty-seven patients (42 RR-MS, 15 PP-MS and thirty-eight matched controls underwent neuropsychological (NP testing and MRI. PP-MS patients scored lower than RR-MS patients on most of the NP tests in absence of any specific pattern. PP-MS patients showed significantly lower caudate volume. There was no significant difference in MRI correlates of cognitive impairment between the two groups except for a prevalent association with MRI measures of cortical GM injury in RR-MS patients and with MRI measures of subcortical GM injury in PP-MS patients. This suggests that although cognitive impairment results from several factors, cortical and subcortical GM injury may play a different role depending on the disease course.

  4. Fadiga na forma remitente recorrente da esclerose múltipla Fatigue in multiple sclerosis relapsing-remitting form

    Directory of Open Access Journals (Sweden)

    MARIA FERNANDA MENDES

    2000-06-01

    Full Text Available Foram avaliados 95 pacientes com forma remitente-recorrente da esclerose múltipla quanto à presença de fadiga. A Escala de Severidade de Fadiga foi aplicada em todos os pacientes. Em 64 pacientes (67,4% a fadiga foi encontrada. Não observamos diferenças clínicas quanto ao gênero, idade, grau de incapacidade funcional e depressão, nos pacientes com e sem fadiga. Foi encontrada correlação entre ansiedade e tempo de doença com a presença de fadiga. Ao analisarmos estas variáveis quanto à intensidade da fadiga, observamos haver associação entre fadiga grave e maior incapacidade funcional.In 95 patients with the remitting-relapsing form of multiple sclerosis we investigated fatigue. All of them were evaluated with the Fatigue Severity Scale and we found it in 64 patients (67.4%. Gender, age, depression and fuctional incapacity was not predictive of fatigue occurrence, while anxiety and time of disease seems to be correlated with it. When we analysed the fatigue severity, a correlation between the EDSS and the increasing fatigue severity was found.

  5. P300 amplitude and response speed relate to preserved cognitive function in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Sundgren, Mathias; Nikulin, Vadim V; Maurex, Liselotte; Wahlin, Åke; Piehl, Fredrik; Brismar, Tom

    2015-04-01

    To explore if cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) is associated with abnormal neural function and if there is evidence of neural compensatory mechanisms. Seventy-two RRMS patients and 89 healthy control subjects were included in a cross-sectional study. Event-related brain potential (P300) and response time (RT) were recorded with visual and auditory choice reaction tasks. Cognitive function was evaluated with an 18 item test battery. Patients had a decrease in cognitive function (pP300 amplitude frontally. P300 amplitude was normal in other brain areas and RT was normal. P300 latency was normal except for an increase in auditory latency occipitally. Cognitive performance correlated positively with parietal P300 amplitude in patients but not in controls. Cognition had stronger correlation (negative) with RT in patients than in controls. Patients with low P300 amplitude and long RT were more often cognitively impaired. This indicates that general factors such as signal amplitude and speed are limiting for cognitive function in RRMS patients. The increase in frontal P300 amplitude may be a compensatory effect. Our findings suggest that high amplitude and fast speed may be protective against cognitive impairment. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Subcutaneous Interferon ?-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study

    OpenAIRE

    J?rvinen, Elina; Multanen, Juha; Atula, Sari

    2017-01-01

    The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS), using an electronic auto-injector Rebismart® to self-inject interferon β-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart® for selfinjecting interferon β-1a subcutaneously three times weekly were included in a reallife clinical multicenter study for 24 weeks...

  7. Effects of Interferon β-1a and Interferon β-1b Monotherapies on Selected Serum Cytokines and Nitrite Levels in Patients with Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Stępień, Adam; Chalimoniuk, Ma?gorzata; Lubina-Dąbrowska, Natalia

    2013-01-01

    Interferon (IFN)β treatment is a mainstay of relapsing-remitting multiple sclerosis (RRMS) immunotherapy. Its efficacy is supposedly a consequence of impaired trafficking of inflammatory cells into the central nervous system and modification of the proinflammatory/antiinflammatory cytokine balance....... However, the effects of long-term monotherapy using various IFNβ preparations on cytokine profiles and the relevance of these effects for the therapy outcome have not yet been elucidated....

  8. Cognitive correlates of under-ambiguity and under-risk decision making in high-functioning patients with relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Cogo, Martina Gaia; Rota, Stefania; Fusco, Maria Letizia; Mapelli, Cristina; Ferri, Francesca; Appollonio, Ildebrando Marco; Isella, Valeria

    2014-01-01

    Impairment of decision making in relapsing remitting multiple sclerosis is still controversial, and its neuropsychological correlates have never been explored thoroughly, especially in patients with minimal physical and cognitive deficits. In the present study we investigated the cognitive underpinnings of decision making under ambiguous and explicit conditions in patients with very mild relapsing remitting multiple sclerosis, using a dice and a card gambling game. The study sample included 60 patients and 35 healthy subjects. In the Game of Dice Task, winning and losing probabilities are obvious to the subject, while in the Iowa Gambling Task they are initially ambiguous and have to be gradually identified. Performance at the two tasks was correlated with scores obtained at tests investigating cognitive processing speed, memory, language and executive functions. Patients' performance did not differ from that of controls at either gambling task. There was only a trend for them to be significantly slower than healthy subjects in progressively recognizing advantageous decks in the Iowa Gambling Task. While the Game of Dice was unrelated to neuropsychological tests, predictors of performance at the Iowa task were Letter Fluency and the Symbol Digit Modalities Test for the initial, under-ambiguity, trials and the Wisconsin Card Sorting Test for the last, purely under-risk, trials. Our results suggest that high-functioning patients with relapsing remitting multiple sclerosis are substantially capable of making advantageous decisions, even if they may be slower in processing options and shifting strategy when selection criteria are not explicit.

  9. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2013-09-01

    In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

  10. Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients.

    Science.gov (United States)

    Le Page, Emmanuelle; Leray, Emmanuelle; Taurin, Grégory; Coustans, Marc; Chaperon, Jacques; Morrissey, Sean P; Edan, Gilles

    2008-01-01

    Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS). To report the long term effectiveness and safety of mitoxantrone as induction therapy in patients with aggressive relapsing-remitting MS, and to assess treatment response factors. 100 consecutive patients with aggressive relapsing-remitting MS received mitoxantrone 20 mg monthly combined with methylprednisolone 1 g for 6 months. Relapses, Expanded Disability Status Scale (EDSS) and drug safety were assessed every 6 months for up to at least 5 years. Within 6 months after induction, 73 patients received maintenance therapy (mitoxantrone every 3 months (n = 21); interferon beta (n = 25); azathioprine (n = 15); methotrexate (n = 7); glatiramer acetate (n = 5)). During the 12 months following initiation of mitoxantrone, the annual relapse rate (ARR) was reduced by 91%, 78% of patients remained relapse free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p<10(-6)) and 64% of patients improved by 1 point or more on the EDSS. In the longer term, the ARR reduction was sustained (0.29-0.42 for up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved after 5 years. Younger age and lower EDSS score at the start of mitoxantrone treatment were predictive of better treatment response. Three patients presented with an asymptomatic decrease in left ventricular ejection fraction to less than 50% (one reversible). One patient was diagnosed with acute myeloid leukaemia (remission 5 years after diagnosis). Mitoxantrone monthly for 6 months as induction therapy followed by maintenance treatment showed sustained clinical benefit for up to 5 years with an acceptable adverse events profile in patients with aggressive relapsing-remitting MS.

  11. MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Simioni, Samanta; Amarù, Fabio; Bonnier, Guillaume; Kober, Tobias; Rotzinger, David; Du Pasquier, Renaud; Schluep, Myriam; Meuli, Reto; Sbarbati, Andrea; Thiran, Jean-Philippe; Krueger, Gunnar; Granziera, Cristina

    2014-08-01

    Despite that cognitive impairment is a known early feature present in multiple sclerosis (MS) patients, the biological substrate of cognitive deficits in MS remains elusive. In this study, we assessed whether T1 relaxometry, as obtained in clinically acceptable scan times by the recent Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) sequence, may help identifying the structural correlate of cognitive deficits in relapsing-remitting MS patients (RRMS). Twenty-nine healthy controls (HC) and forty-nine RRMS patients underwent high-resolution 3T magnetic resonance imaging to obtain optimal cortical lesion (CL) and white matter lesion (WML) count/volume and T1 relaxation times. T1 z scores were then obtained between T1 relaxation times in lesion and the corresponding HC tissue. Patient cognitive performance was tested using the Brief Repeatable Battery of Neuro-psychological Tests. Multivariate analysis was applied to assess the contribution of MRI variables (T1 z scores, lesion count/volume) to cognition in patients and Bonferroni correction was applied for multiple comparison. T1 z scores were higher in WML (p memory; (2) T1 z scores in CL-I (β = 0.3; p = 0.03) were independent determinants of long-term memory storage, and (3) lesion volume did not significantly influenced cognitive performances in patients. Our study supports evidence that T1 relaxometry from MP2RAGE provides information about microstructural properties in CL and WML and improves correlation with cognition in RRMS patients, compared to conventional measures of disease burden.

  12. [Mitoxantrone as induction therapy in aggressive relapsing remitting multiple sclerosis: a descriptive analysis of 100 consecutive patients].

    Science.gov (United States)

    Le Page, E; Leray, E; Taurin, G; Coustans, M; Chaperon, J; Edan, G

    2006-02-01

    On the basis of the French and British (FB) MS Trial, Mitoxantrone (MITOX) was approved by the AFSAPPS in October 2003 in patients with aggressive multiple sclerosis (MS), given as induction therapy monthly for 6 months (ELSEP). We report an observational study of 100 aggressive relapsing remitting (RR) MS patients treated by induction therapy with MITOX and followed up to 5 years. One hundred patients with aggressive RR MS received an induction therapy with MITOX 20 mg monthly combined with methylprednisolone 1 g for 6 months. MRI data within 12 months before and 6 months after MITOX induction were collected (mean cumulative dose 65 mg/m2). Clinical evaluation was performed every 6 months and data (relapses and EDSS scores) were prospectively recorded in the EDMUS Database. After MITOX, a maintenance therapy was given to 57 patients (MITOX every 3 months: 21; Interferon beta: 13; Azathioprine: 14; Methotrexate: 7; Glatiramer acetate: 2). The mean follow-up period was of 3.8 years. Patients were treated at a mean age of 27 +/- 9 years after 5 +/- 3 years of MS duration. Within the 12 months preceding MITOX onset, the annual relapse rate (ARR) was 3.2, the mean EDSS increased by 2.2 +/- 1 points (to a score of 4 at M0), 87 patients worsened by 1 point EDSS or more and 85 percent of patients had Gd enhancing lesions on MRI. During the 12 months following MITOX onset, the inflammatory activity of the disease dropped dramatically with a reduction of the ARR by 91 percent whereas 76 percent of patients were free of new relapse and MRI activity was reduced by 89 percent. In addition, the mean EDSS decreased by 1.2 points (p<10-6) and 60 percent of patients improved by 1 point EDSS or more. At a longer term, the reduction of the ARR was confirmed (0.28-0.37 up to 5 years) and the median time to the first relapse was 2.8 years. A significant improvement of disability was maintained until 4 years and got back to the initial level at year 5. The ARR was significantly lower

  13. Investigating the Relationship Between Selective Attention and Cognitive Flexibility With Balance in Patients With Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Vali Shiri

    2018-01-01

    Conclusion A significant relationship between selective attentions to balance demonstrates that appropriately designed interventions to repair the attention, can decrease the balance problem in patients with MS. One of the possible reasons for this relationship can be found in the brain system that attention circuits are interacting with equilibrium systems, and any defect in selective attention leads to a loss of balance. Patients with MS experience constant imbalance due to cerebral plaques and relapsing-remitting periods, and in addition to rehabilitation of the balance system, cognitive systems such as attention should be treated.

  14. Cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate and intramuscular interferon-β1a in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Zhang, Xinke; Hay, Joel W; Niu, Xiaoli

    2015-01-01

    The aim of the study was to compare the cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate, and intramuscular (IM) interferon (IFN)-β(1a) as first-line therapies in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). A Markov model was developed to evaluate the cost effectiveness of disease-modifying drugs (DMDs) from a US societal perspective. The time horizon in the base case was 5 years. The primary outcome was incremental net monetary benefit (INMB), and the secondary outcome was incremental cost-effectiveness ratio (ICER). The base case INMB willingness-to-pay (WTP) threshold was assumed to be US$150,000 per quality-adjusted life year (QALY), and the costs were in 2012 US dollars. One-way sensitivity analyses and probabilistic sensitivity analysis were conducted to test the robustness of the model results. Dimethyl fumarate dominated all other therapies over the range of WTPs, from US$0 to US$180,000. Compared with IM IFN-β(1a), at a WTP of US$150,000, INMBs were estimated at US$36,567, US$49,780, and US$80,611 for fingolimod, teriflunomide, and dimethyl fumarate, respectively. The ICER of fingolimod versus teriflunomide was US$3,201,672. One-way sensitivity analyses demonstrated the model results were sensitive to the acquisition costs of DMDs and the time horizon, but in most scenarios, cost-effectiveness rankings remained stable. Probabilistic sensitivity analysis showed that for more than 90% of the simulations, dimethyl fumarate was the optimal therapy across all WTP values. The three oral therapies were favored in the cost-effectiveness analysis. Of the four DMDs, dimethyl fumarate was a dominant therapy to manage RRMS. Apart from dimethyl fumarate, teriflunomide was the most cost-effective therapy compared with IM IFN-β(1a), with an ICER of US$7,115.

  15. Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Hesse, Dan

    2012-01-01

    Numerous cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS), but studies are often limited to whole blood (WB) or peripheral blood mononuclear cells (PBMCs), thereby omitting important information about the cellular origin of the cytokines. Knowledge about the relation...... between blood and cerebrospinal fluid (CSF) cell expression of cytokines and the cellular source of CSF cytokines is even more scarce....

  16. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... as well as worsening (a confirmed increase in disability over a specified period of time following a relapse) or not worsening . An increase in disability is confirmed when the person exhibits the same ...

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... in RRMS; however, each person's experience with RRMS will be unique. Following a relapse, the new symptoms ... and worsening, you and your MS care provider will likely want to consider a more aggressive treatment ...

  18. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... the periods of remission. At different points in time, RRMS can be further characterized as either active ( ... increase in disability over a specified period of time following a relapse) or not worsening . An increase ...

  19. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Employer Matching Gifts d Gifts of Stock or Securities d Giving Circles Golden Circle Circle of Distinction ... time, RRMS can be further characterized as either active (with relapses and/or evidence of new MRI ...

  20. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Disasters d Relationships Disclosure Family Matters Parenting Intimacy Self Advocacy in the Family Preventing Abuse d Research ... well as worsening (a confirmed increase in disability over a specified period of time following a relapse) ...

  1. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... been affected—or may be affected—by a hurricane, wildfire, or other natural disaster, we can help. ... attacks of inflammation (relapses) in the CNS, progressive forms of MS involve much less of this type ...

  2. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... disappear, resulting in an increase in disability. New lesions on MRI, as shown by the arrows, often ... as part of a relapse. However, new MRI lesions indicating MS activity may also occur without symptoms ...

  3. Sample size estimates for determining treatment effects in high-risk patients with early relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Scott, Thomas F; Schramke, Carol J; Cutter, Gary

    2003-06-01

    Risk factors for short-term progression in early relapsing remitting MS have been identified recently. Previously we determined potential risk factors for rapid progression of early relapsing remitting MS and identified three groups of high-risk patients. These non-mutually exclusive groups of patients were drawn from a consecutively studied sample of 98 patients with newly diagnosed MS. High-risk patients had a history of either poor recovery from initial attacks, more than two attacks in the first two years of disease, or a combination of at least four other risk factors. To determine differences in sample sizes required to show a meaningful treatment effect when using a high-risk sample versus a random sample of patients. Power analyses were used to calculate the different sample sizes needed for hypothetical treatment trials. We found that substantially smaller numbers of patients should be needed to show a significant treatment effect by employing these high-risk groups of patients as compared to a random population of MS patients (e.g., 58% reduction in sample size in one model). The use of patients at higher risk of progression to perform drug treatment trials can be considered as a means to reduce the number of patients needed to show a significant treatment effect for patients with very early MS.

  4. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Siemonsen, Susanne; Wenzel, Damian

    2017-01-01

    BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic...... lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did...... not differ between groups. PBVC tended to differ between groups and higher absolute cortical thickness values were observed in 19 of 74 investigated cortical regions after PRT. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups for four areas...

  5. Persistence with dimethyl fumarate in relapsing-remitting multiple sclerosis: a population-based cohort study.

    Science.gov (United States)

    Eriksson, Irene; Cars, Thomas; Piehl, Fredrik; Malmström, Rickard E; Wettermark, Björn; von Euler, Mia

    2018-02-01

    To describe patients initiating dimethyl fumarate (DMF) and measure persistence with DMF, discontinuation, and switching in treatment-naïve DMF patients and patients switching to DMF from other multiple sclerosis disease-modifying treatments (DMTs). A population-based cohort study of all Stockholm County residents initiating DMF from 9 May 2014 until 31 May 2017. All data were derived from a regional database that collects individual-level data on healthcare and drug utilization of all residents. The study outcomes were persistence with DMF and DMF discontinuation and switching to other DMTs. Persistence was measured as the number of days until either DMF discontinuation (treatment gap ≥ 60 days) or switching to another DMT. The study included 400 patients (median follow-up = 2.5 years). The majority had previously been treated with other DMTs (61%). Throughout the follow-up period, 124 patients (31%) discontinued DMF and 114 patients (29%) switched treatment. Overall, 34% of patients initiating DMF stopped treatment within 1 year and only 43% of patients remained on DMF at 2 years from treatment initiation. DMF had a rapid market uptake likely due to high expectations held by both patients and clinicians. However, persistence with DMF in routine clinical practice was found to be low.

  6. Anti lingo 1 (opicinumab) a new monoclonal antibody tested in relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Ruggieri, Serena; Tortorella, Carla; Gasperini, Claudio

    2017-11-01

    Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The modern treatment era for MS witnessed a growing pool of drugs now available for use in clinical practice. These therapies work at different levels, however there is a lack of treatments acting on the neurodegenerative component or improving mechanism of repair. Areas covered: The latest knowledge about the pathophysiological changes occurring in MS have translated into novel treatments at different stages of development. Drugs for MS work mainly through modulating the inflammatory factors of the disease, but enhancing remyelination may be more successful in reducing long-term disability. Anti-LINGO-1 (opicinumab) is the first investigational product that achieved phase I trial with the aim of remyelination and axonal protection and/or repair in MS. Expert commentary: Over the past decade considerable strength has been applied to find more reliable strategies to improve myelin repair. The anti-LINGO-1 trial showed that the drug is safe and tolerable. A future phase II trial will provide more insights regarding the compound. The greatest challenge for myelin repair therapies will be how to monitor their efficacy. Eventually research will need to focus on consistent tools to assess the grade of remyelination in vivo.

  7. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Live Well Knowledge Is Power Everyday Matters You CAN! Webcasts DVDs Books For Kids: Keep S'myelin Información ... of remission. At different points in time, RRMS can be further characterized as either active (with relapses ...

  8. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Your Life d Cognitive Health d Work, Home & Leisure Employment ... during the periods of remission. At different points in time, RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity) or not active , as well as worsening (a ...

  9. Cognitive performance in relapsing remitting multiple sclerosis: A longitudinal study in daily practice using a brief computerized cognitive battery

    Directory of Open Access Journals (Sweden)

    Jacquerye Philippe

    2011-06-01

    Full Text Available Abstract Background There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS. In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR battery, we longitudinally assessed cognition in patients with relapsing remitting (RR MS. Methods Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST, Paced Auditory Serial Addition Test (PASAT and five composite scores derived from the CDR computerized cognitive test system (CDR System: Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC and Expanded Disability Status Scale (EDSS measured disability. Results The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT and were also strongly related to disability (EDSS and MSFC. Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention], and a moderate impairment both to sustained attention (Continuity of Attention d 0.6 and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory], when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory and episodic memory (Quality of Episodic Memory

  10. Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: findings from the CONFIRM study.

    Science.gov (United States)

    Kita, Mariko; Fox, Robert J; Phillips, J Theodore; Hutchinson, Michael; Havrdova, Eva; Sarda, Sujata P; Agarwal, Sonalee; Kong, Jessica; Zhang, Annie; Viglietta, Vissia; Sheikh, Sarah I; Seidman, Emily; Dawson, Katherine T

    2014-02-01

    Multiple sclerosis (MS) has a significant impact on health-related quality of life (HRQoL) with symptoms adversely affecting many aspects of everyday living. BG-12 (dimethyl fumarate) demonstrated significant efficacy in the phase III studies DEFINE and CONFIRM in patients with relapsing-remitting MS. In CONFIRM, HRQoL was worse in patients with greater disability at baseline, and who relapsed during the study, and improved with BG-12 treatment. Mean Short Form-36 Physical Component Summary scores for BG-12 increased over 2 years and scores for placebo decreased. Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS.

  11. Treatment satisfaction with injectable disease-modifying therapies in patients with relapsing-remitting multiple sclerosis (the STICK study.

    Directory of Open Access Journals (Sweden)

    Oscar Fernández

    Full Text Available Treatment satisfaction in patients with relapsing-remitting multiple sclerosis (RRMS may impact adherence and thus clinical outcomes. The objective of this study was to measure the satisfaction of patients with RRMS with injectable disease-modifying therapies (DMTs and to evaluate the factors associated with treatment satisfaction.In this observational retrospective study conducted in the neurology departments of 35 hospitals throughout Spain, demographic data, disease characteristics, and information on treatment with injectable DMTs were collected at a single scheduled visit. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM, version 1.4. Patients also answered complementary questions about the factors that might affect treatment satisfaction. The data collected were analyzed descriptively. A regression model was used to explore the factors associated with treatment satisfaction.The study included 445 patients (mean±SD age, 41±10.2 years; two-thirds women. The percentages treated with each DMT were Avonex 28.5%, Rebif 44 μg 24.5%, Copaxone 22.5%, Betaferon 13.0%, Rebif22 μg 8.3% and Extavia 3.1%. The mean±SD overall satisfaction according to the TSQM was 68.8±18.6 and the highest overall satisfaction was reported for Rebif 22 μg (72.4±20.3 and the lowest for Extavia (61.7±23.7. In the regression analysis, rehabilitation, interference with social life, pain on injection and number of MS treatments received were significantly associated with a decrease in overall TSMQ score. A small but significant negative correlation was found between EDSS scores and TSMQ scores (rho = -0.11, p = 0.02 and effectiveness (rho = -0.17, p<0.001. A perceived inconvenience of injections was reflected by the stated preference of 83% for once-daily oral treatment over other administration routes.Patients on stable injectable DMT therapy were reasonably satisfied with their treatment. Our results suggest

  12. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  13. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In Upstate New York Change Location ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  14. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... topics that may interest you Living with MS (.pdf) Download Brochure Focus on Employment (.pdf) Download Brochure Working with MS (.pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple ...

  15. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Find Support Advanced Care Needs Resources for Specific Populations Find Programs & Services in Your Area Living Well ... Services: Questions to Ask d Resources for Specific Populations Pediatric MS Support Veterans with Multiple Sclerosis d ...

  16. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Lawry d Cultural Values d Financials Annual Reports Sources of Support d News d Press Room Events ... Brochure Working with MS (.pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (. ...

  17. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... tend to have more brain lesions — also called plaques or scars — on magnetic resonance imaging (MRI) scans, ... Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying ...

  18. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate Search v ... Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis MS Symptoms Diagnosing MS Possible MS Clinically Isolated ...

  19. Relapsing-Remitting MS (RRMS)

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  20. Relapsing-Remitting MS (RRMS)

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  1. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Gets MS? Pediatric MS African Americans Hispanics & Latino/as d Multiple Sclerosis FAQs d Types of MS ... Clinicians d Treating MS d Comprehensive Care Developing a Healthcare Team Make the Most of Your Doctor ...

  2. An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol.

    Science.gov (United States)

    Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Evers, Silvia; Duyverman, Lotte; Valkenburg-Vissers, Joyce; Cornelissen, Job; Bos, Michel; van Droffelaar, Maarten; Lemmens, Wim A; Donders, Rogier; van der Zande, Anneke; Visser, Leo H

    2016-05-28

    In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-related quality of life 6 months after treatment in those people with MS who had relapsing remitting disease and low disability. CDT is a sociologically oriented approach, its goal is to uncover and promote existing capabilities, and the notion "stressor" is the central concept. CDT's components are plenary group sessions, small group sessions, consultations, a theatre evening, and start of the day with a joint activity. The small group sessions form the actual training. Depending on their individual goals the participants join the training groups 'Body', 'Feeling' or 'Life', to work out their aims and to reduce their stressors. The multidisciplinary team includes a psychiatrist, psychiatric nurse, neurologist, specialized MS nurse, physiotherapist, dance therapist, and a person with MS. To evaluate the (cost)effectiveness of CDT in persons with relapsing remitting MS and low disability we perform a single-centre, randomized controlled trial in 140 patients, with or without support partners. The primary outcome is self-efficacy control. The secondary outcomes are self-efficacy function, health-related quality of life, autonomy and participation, anxiety, depression, cost effectiveness and cost utility. The tertiary outcome is care-related strain to support partners. Outcomes are assessed at baseline and at 1, 3 and 6 months after CDT. This randomized controlled trial will adequately evaluate the clinical and cost effectiveness of a 3-day intensive social cognitive program in people with

  3. Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

    Science.gov (United States)

    Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

    2017-08-01

    What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26

  4. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying Therapies Overview (.pdf) Download Document Pediatric MS Learn More Transverse Myelitis Learn More Neuromyelitis Optica (NMO) Learn More HTLV-I ... Learn More Acute Disseminated Encephalomyelitis (ADEM) Learn More ...

  5. [The influence of age and illness duration on cognitive impairment in aging patients with relapsing-remitting multiple sclerosis (RR-MS)].

    Science.gov (United States)

    Leclercq, Eugénie; Cabaret, Maryline; Guilbert, Alma; Jougleux, Caroline; Vermersch, Patrick; Moroni, Christine

    2014-09-01

    The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.

  6. Decreased Frequency of Circulating Myelin Oligodendrocyte Glycoprotein B Lymphocytes in Patients with Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Annie Elong Ngono

    2015-01-01

    Full Text Available Although there is no evidence for a role of anti-MOG antibodies in adult MS, no information on B lymphocytes with MOG-committed BCR is available. We report here on the frequency of anti-MOG B cells forming rosettes with polystyrene beads (BBR covalently bound to the extracellular domain of rhMOG in 38 relapsing-remitting patients (RRMS and 50 healthy individuals (HI. We show a substantial proportion of circulating anti-MOG-BBR in both RRMS and HI. Strikingly, MOG-specific B cells frequencies were lower in MS than in HI. Anti-MOG antibodies measured by a cell-based assay were not different between MS patients and controls, suggesting a specific alteration of anti-MOG B cells in MS. Although anti-MOG-BBR were higher in CNS fluid than in blood, no difference was observed between MS and controls. Lower frequency of MOG-BBR in MS was not explained by an increased apoptosis, but a trend for lower proliferative capacity was noted. Despite an efficient B cell transmigration across brain derived endothelial cells, total and anti-MOG B cells transmigration was similar between MS and HI. The striking alteration in MOG-specific B cells, independent of anti-MOG antibody titers, challenges our view on the role of MOG-specific B cells in MS.

  7. Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting Multiple Sclerosis Progression: Preliminary Findings of a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Vahid Shaygannejad

    2012-01-01

    Full Text Available The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS. A phase II double-blind placebo-controlled randomized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were randomly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy. Response to treatment was assessed at eight-week intervals. In both groups, the mean relapse rate decreased significantly (P<0.001. In the 25 patients treated with placebo, the mean (SD Expanded Disability Status Scale (EDSS increased from 1.70 (1.21 at baseline to 1.94 (1.41 at the end of study period (P<0.01. Average EDSS and relapse rate at the end of trial did not differ between groups. Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate. A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention.

  8. Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM.

    Science.gov (United States)

    Fernández, Óscar; Giovannoni, Gavin; Fox, Robert J; Gold, Ralf; Phillips, J Theodore; Potts, James; Okwuokenye, Macaulay; Marantz, Jing L

    2017-08-01

    In Phase III studies (DEFINE [Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the effect of DMF in patients previously treated with interferon (IFN) beta. Patients (age 18-55 years; Expanded Disability Status Scale score, 0-5.0) were randomized to receive DMF 240 mg BID or TID, placebo, or glatiramer acetate (CONFIRM only) for up to 2 years. Previous IFN users received at least 1 IFN treatment >3 months before randomization. Data for DMF 240 mg BID (approved dosing regimen) are reported. In the integrated intention-to-treat population, 172 and 169 patients receiving DMF or placebo, respectively, had received ≥1 prior IFN. In this subgroup, significant reductions with DMF versus placebo were observed for the annualized relapse rate (rate ratio, 0.55 [95% CI, 0.40-0.77]), new/newly enlarging T2-hyperintense lesions (lesion mean ratio, 0.16 [95% CI, 0.09-0.29]), odds of having more gadolinium-enhancing lesions (odds ratio, 0.17 [95% CI, 0.07-0.44]), and new T1-hypointense lesions (lesion mean ratio, 0.25 [95% CI, 0.14-0.45]). Median Expanded Disability Status Scale scores remained stable during the study period. Adverse events associated with DMF included flushing and gastrointestinal events. In this post hoc analysis in patients with previous IFN treatment, DMF demonstrated significant efficacy over 2 years versus placebo and an adverse event profile consistent with the overall population of DEFINE/CONFIRM. ClinicalTrials.gov identifiers: DEFINE, NCT00420212; and CONFIRM, NCT00451451. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  9. No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).

    Science.gov (United States)

    Lanzillo, Roberta; Quarantelli, Mario; Pozzilli, Carlo; Trojano, Maria; Amato, Maria Pia; Marrosu, Maria G; Francia, Ada; Florio, Ciro; Orefice, Giuseppe; Tedeschi, Gioacchino; Bellantonio, Paolo; Annunziata, Pasquale; Grimaldi, Luigi M; Comerci, Marco; Brunetti, Arturo; Bonavita, Vincenzo; Alfano, Bruno; Marini, Stefano; Brescia Morra, Vincenzo

    2016-08-01

    A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis. The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis. This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months. Brain magnetic resonance imaging, multiple sclerosis functional composite score, Rao neuropsychological battery and expanded disability status scale were evaluated over 24 months. A total of 154 patients were randomly assigned, 75 in the atorvastatin and 79 in the placebo arms, with a comparable drop-out rate (overall 23.4%). Brain atrophy over 2 years was not different in the two arms (-0.38% and -0.32% for the atorvastatin and placebo groups, respectively). Relapse rate, expanded disability status scale, multiple sclerosis functional composite score or cognitive changes were not different in the two arms. Patients withdrawing from the study had a higher number of relapses in the previous 2 years (P=0.04) and a greater probability of relapsing within 12 months. Our results suggest that the combination of atorvastatin and interferon β1b is not justified in early relapsing-remitting multiple sclerosis and adds to the body of evidence indicating an absence of significant radiological and clinical benefit of statins in relapsing-remitting multiple sclerosis. © The Author(s), 2015.

  10. Vitamin D status and effect of interferon-β1a treatment on MRI activity and serum inflammation markers in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Røsjø, Egil; Myhr, Kjell-Morten; Løken-Amsrud, Kristin I; Bakke, Søren J; Beiske, Antonie G; Bjerve, Kristian S; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Šaltytė Benth, Jūratė; Torkildsen, Øivind; Wergeland, Stig; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Holmøy, Trygve

    2015-03-15

    To explore if vitamin D modulates interferon-β1a treatment effects in relapsing-remitting multiple sclerosis, we examined relationships between serum vitamin D and magnetic resonance imaging (MRI) activity and ten systemic inflammation markers in 88 patients, before and during treatment. Odds ratios for all MRI parameters were negatively associated with vitamin D levels before therapy, but converged to equally low values irrespective of vitamin D status during treatment. During therapy, similar alterations of MRI activity and inflammation markers were found across patients categorized by mean vitamin D values. This suggests that vitamin D status has no major influence on interferon-β1a treatment effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Long-Term Adherence to IFN Beta-1a Treatment when Using RebiSmart® Device in Patients with Relapsing-Remitting Multiple Sclerosis

    Science.gov (United States)

    Fernández, O.; Arroyo, R.; Martínez-Yélamos, S.; Marco, M.; Merino, J. A. García; Muñoz, D.; Merino, E.; Roque, A.

    2016-01-01

    The effectiveness of disease-modifying drugs in the treatment of multiple sclerosis is associated with adherence. RebiSmart® electronic device provides useful information about adherence to the treatment with subcutaneous (sc) interferon (IFN) β-1a (Rebif®). The aim of the study was to determine long-term adherence to this treatment in patients with relapsing-remitting multiple sclerosis (RRMS). This retrospective multicentre observational study analysed 258 patients with RRMS who were receiving sc IFN β-1a (Rebif®) treatment by using RebiSmart® until replacement (36 months maximum lifetime) or treatment discontinuation. Adherence was calculated with data (injection dosage, time, and date) automatically recorded by RebiSmart®. Patients in the study had a mean age of 41 years with a female proportion of 68%. Mean EDSS score at start of treatment was 1.8 (95% CI, 1.6–1.9). Overall adherence was 92.6% (95% CI, 90.6–94.5%). A total of 30.2% of patients achieved an adherence rate of 100%, 80.6% at least 90%, and only 13.2% of patients showed a suboptimal adherence (<80%). A total of 59.9% of subjects were relapse-free after treatment initiation. Among 106 subjects (41.1%) who experienced, on average, 1.4 relapses, the majority were mild (40.6%) or moderate (47.2%). Having experienced relapses from the beginning of the treatment was the only variable significantly related to achieving an adherence of at least 80% (OR = 3.06, 1.28–7.31). Results of this study indicate that sc IFN β-1a administration facilitated by RebiSmart® could lead to high rates of adherence to a prescribed dose regimen over 36 months. PMID:27526201

  12. Long-Term Cost Effectiveness of Interferon-beta-1a in the Treatment of Relapsing-Remitting Multiple Sclerosis : An Econometric Model.

    Science.gov (United States)

    Lepen, Claude; Coyle, Patricia; Vollmer, Timothy; Blumhardt, Lance; Lilliu, Hervé; Beresniak, Ariel

    2003-01-01

    To evaluate the cost effectiveness of subcutaneous interferon-beta-1a (IFNbeta-1a) 44mug three times weekly in relapsing-remitting multiple sclerosis (RRMS) using an econometric model. Data on RRMS patients treated with IFNbeta-1a 22 or 44mug subcutaneously three times weekly or placebo for up to 4 years were obtained from the Prevention of Relapses and disability by Interferon-beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study. The area under the Expanded Disability Status Scale (EDSS) score-time curve was used as a measure of disability and the effectiveness of therapy was expressed as EDSS-months of disability prevented. Costs were calculated for the UK and France, and results were projected to 10 and 20 years using a time series regression model. Over 10 years, treatment with IFNbeta-1a 44mug subcutaneously three times weekly prevented 121 EDSS-months of additional disability at a cost of Euros (euro)732 each (year of costing 2000). Over 20 years, 321 EDSS-months were saved at a cost of euro359 per month (year of costing 2000). This analysis indicated that IFNbeta-1a 44mug subcutaneously three times weekly is cost effective in RRMS and that treatment becomes increasingly cost effective over time.

  13. Reduction in Healthcare and Societal Resource Utilization Associated with Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis: Analysis of Economic Data from the CLARITY Study

    DEFF Research Database (Denmark)

    Ali, Shehzad; Paracha, Noman; Cook, Stuart

    2012-01-01

    burden. Objective: This study aimed to compare health and societal resource use and productivity in patients with relapsing-remitting MS (RRMS) receiving cladribine tablets versus placebo over 96 weeks in the CLARITY study. Methods: The CLARITY study was a 96-week, randomized, double-blind, placebo...

  14. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cohen, Jeffrey A; Coles, Alasdair J

    2016-01-01

    OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CAR...

  15. Safety and Tolerability of Delayed-Release Dimethyl Fumarate Administered with Interferon Beta or Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis

    Science.gov (United States)

    Calkwood, Jonathan; Vollmer, Timothy; Fox, Robert J.; Zhang, Ray; Novas, Mark; Sheikh, Sarah I.

    2016-01-01

    Background: Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for relapsing multiple sclerosis (MS). The objective of this study was to explore the safety and tolerability of DMF when administered with interferon beta (IFNβ) or glatiramer acetate (GA). Methods: Patients with relapsing-remitting MS receiving established therapy with the same dose of IFNβ or GA for at least 12 months continued their prescribed therapy for 2 months (monotherapy period) and then received DMF 240 mg three times daily in addition to their prescribed MS therapy for 6 months (add-on therapy period). Safety and magnetic resonance imaging outcomes were monitored monthly. Results: During the add-on therapy period, in the DMF+IFNβ (n = 57) and DMF+GA (n = 47) groups, the overall incidence of adverse events was 95% and 100%, respectively; the most common adverse events were flushing, diarrhea, and abdominal pain. In both groups, mean lymphocyte counts decreased but remained within normal limits, and hepatic transaminase levels increased transiently; no case met Hy's law criteria. There was no overall increased risk of infection. In both groups, gadolinium-enhancing lesion activity and new/enlarging T2 lesions decreased compared with the monotherapy period (exploratory endpoints). Conclusions: The safety profile of DMF taken with IFNβ or GA was acceptable and consistent with the known safety profile of DMF monotherapy. PMID:27252601

  16. The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Koch-Henriksen, N.; Sorensen, P.S.; Bendtzen, K.

    2009-01-01

    OBJECTIVE: To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFN beta) depends on the type of IFNbeta (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS). INTRODUCTION: NAbs against IFN beta-1b appear faster...... and may be more evenly distributed on IgG subclasses, whereas NAbs against IFN beta-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs. DESIGN/PATIENTS: All Danish MS-patients who had started first-time treatment with IFNbeta-1a 22 microg s.c tiw (Rebif...... was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFN beta-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable. RESULTS: In 1,309 patients, who were observed for 21,958 months...

  17. 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

  18. Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial.

    Science.gov (United States)

    Saida, Takahiko; Kira, Jun-Ichi; Kishida, Shuji; Yamamura, Takashi; Ohtsuka, Nobuhisa; Ling, Yan; Torii, Shinichi; Lucas, Nisha; Kuesters, Geoffrey; Steiner, Deb; Tibung, J T

    2017-06-01

    The efficacy of natalizumab was evaluated in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) in a 24-week, phase 2 bridging study. An open-label, 2-year extension study from this trial was conducted to assess the safety and efficacy of natalizumab treatment in Japanese patients. A total of 97 patients (43 previously on placebo; 54 previously on natalizumab) who had completed the bridging study were treated with 300 mg natalizumab every 4 weeks. Multiple sclerosis relapses, changes in Expanded Disability Status Scale (EDSS) scores, and adverse events were assessed at regular intervals. Anti-natalizumab and anti-JC virus (JCV) antibodies were measured. After 2 years of natalizumab treatment, the mean adjusted annualized relapse rate was 0.30 (95% confidence interval [CI]: 0.18-0.52) among previously-on-placebo patients and 0.13 (95% CI: 0.05-0.29) among previously-on-natalizumab patients. The mean change in EDSS score from baseline to week 120 was -0.03 among previously-on-placebo patients and -0.18 among previously-on-natalizumab patients. In both groups, >90% of patients experienced ≥1 adverse event. Two previously-on-placebo patients developed persistently positive anti-natalizumab antibodies. Approximately 65% of all patients tested positive for anti-JCV antibodies at open-label treatment initiation. No deaths or progressive multifocal leukoencephalopathy cases were reported. The efficacy and safety findings from this 2-year open-label extension study are comparable to and confirm the results of other clinical trials of natalizumab conducted in non-Asian patient populations, and provide longer-term evidence of efficacy and safety in Japanese patients. ClinicalTrials.gov identifier NCT01416155. Biogen.

  19. No evidence of disease activity in patients receiving daclizumab versus intramuscular interferon beta-1a for relapsing-remitting multiple sclerosis in the DECIDE study.

    Science.gov (United States)

    Kappos, Ludwig; Havrdova, Eva; Giovannoni, Gavin; Khatri, Bhupendra O; Gauthier, Susan A; Greenberg, Steven J; You, Xiaojun; Wang, Ping; Giannattasio, Giorgio

    2017-11-01

    No evidence of disease activity (NEDA) is a composite endpoint being increasingly applied as an outcome measure in clinical trials as well as proposed for individual therapeutic decisions in multiple sclerosis (MS). Assess the proportion of patients with relapsing-remitting MS achieving NEDA in the DECIDE study of daclizumab 150 mg subcutaneous versus intramuscular interferon beta-1a 30 µg for 96-144 weeks. NEDA was defined as no relapses, no onset of 12-week confirmed disability progression (CDP), no new/newly enlarging T2 hyperintense lesions (NET2), and no gadolinium-enhancing (Gd+) lesions. Logistic regression models adjusted for baseline covariates compared treatment groups for baseline to week 96, weeks 0-24, and weeks 24-96. From baseline to week 96, more daclizumab versus intramuscular interferon beta-1a patients achieved NEDA (24.6% vs 14.2%; odds ratio (OR; 95% confidence interval): 2.059 (1.592-2.661); p < 0.0001). ORs for clinical NEDA (no relapses, no CDP) and magnetic resonance imaging (MRI) NEDA (no NET2, no Gd+ lesions) were 1.651 (1.357-2.007; p < 0.0001) and 2.051 (1.628-2.582; p < 0.0001), respectively. ORs in favor of daclizumab for weeks 24-96 were consistently higher than for weeks 0-24. More daclizumab versus intramuscular interferon beta-1a patients achieved NEDA early in DECIDE, with effects increasing over time.

  20. The experience of transitioning from relapsing remitting to secondary progressive multiple sclerosis: views of patients and health professionals.

    Science.gov (United States)

    O'Loughlin, Emer; Hourihan, Susan; Chataway, Jeremy; Playford, E Diane; Riazi, Afsane

    2017-09-01

    The majority of people with multiple sclerosis (pwMS) initially present with discreet periods of relapses followed by partial remission of symptoms (RRMS). Over time, most pwMS transition to secondary progressive MS (SPMS), characterized by a gradual accumulation of disability. This study aimed to explore the experiences, coping and needs associated with transitioning from RRMS to SPMS. Data were collected via semi-structured interviews with nine pwMS and seven specialist MS health professionals (HPs). Thematic analysis was used to analyze the data. Four major themes were identified: "Is this really happening?"; "Becoming a reality"; "A life of struggle"; and "Brushing oneself off and moving on." Findings suggested a process of moving from uncertainty towards confirmation of one's diagnostic label. Being reclassified with SPMS served as a turning point for many, and was accompanied by a range of cognitive, emotional and behavioral responses. The value of adequate information and support surrounding the transition, and the potential benefit of education and support for health professionals in relation to the transition were indicated. Understanding pwMS' experiences of the transition is essential if clinicians are to provide pwMS with appropriate support during the transition. Implications for Rehabilitation The timing and delivery of preparatory education for patients about the transition to SPMS should be carefully considered. Sufficient information and follow-up support following the reclassification of SPMS is crucial but sometimes lacking. The importance of sensitive communication of the reclassification of SPMS was highlighted. MS Specialist health professionals may potentially benefit from training and support around communication of the reclassification of SPMS. Given the potential negative psychological impact of the transition, the psychological wellbeing of the patients during the transition to SPMS should be monitored and responded to appropriately.

  1. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

    Energy Technology Data Exchange (ETDEWEB)

    Bellmann-Strobl, J.; Paul, F.; Aktas, O.; Zipp, F. [Charite - University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Cecilie Vogt Clinic for Neurology, Berlin (Germany); Stiepani, H.; Bohner, G.; Klingebiel, R. [Charite - University Medicine Berlin, Department of Neuroradiology, Berlin (Germany); Wuerfel, J. [Charite - University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Cecilie Vogt Clinic for Neurology, Berlin (Germany); University Schleswig-Holstein, Institute of Neuroradiology, Campus Luebeck, Kiel (Germany); Warmuth, C. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Wandinger, K.P. [Charite - University Medicine Berlin, Department of Neurology, Berlin (Germany)

    2009-08-15

    The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0{+-}7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon {beta}-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p<0.05) and correlated to the MSFC score (r=0.476, p<0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p<0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects. (orig.)

  2. Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

    Science.gov (United States)

    2011-01-01

    Background Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile. Methods We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis. Results Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to

  3. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study.

    Science.gov (United States)

    Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Adeniji, Abidemi K; Vermersch, Patrick

    2017-08-01

    In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.

  4. 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.

  5. Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Røsjø, Egil; Lossius, Andreas; Abdelmagid, Nada; Lindstrøm, Jonas C; Kampman, Margitta T; Jørgensen, Lone; Sundström, Peter; Olsson, Tomas; Steffensen, Linn H; Torkildsen, Øivind; Holmøy, Trygve

    2017-03-01

    Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV. The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

  6. High dose Vitamin D intake and quality of life in relapsing-remitting multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Ashtari, Fereshteh; Toghianifar, Nafiseh; Zarkesh-Esfahani, Sayyed Hamid; Mansourian, Marjan

    2016-10-01

    Low level of vitamin D is associated with a more severe course and low quality of life in relapsing-remitting multiple sclerosis (RRMS). Low dose vitamin D intake has improved quality of life in RRMS patients. This study explored the effect of high dose vitamin D intake on quality of life in RRMS patients in a double blind randomized clinical trial. 94 RRMS patients were randomized to two groups. One group received 50,000 IU vitamin D3 every five days for 3 months. The other group received placebo. Interferon-β (IFN-β) continued as the main treatment in both groups. Quality of life was assessed using MSQOL-54 Persian version at the beginning and at the end of the study. After 3 months, the vitamin D group had a significant difference in mental health composite with placebo group, 62.41 ± 13.99 vs. 60.99 ± 17.99 (p-value = 0.041). Change in health was 75.74 ± 25.73 and 70.59 ± 26.45 in vitamin D and placebo group, respectively (p-value = 0.036). Mental QOL improved significantly after taking high dose vitamin D for 3 months in vitamin D group relative to placebo.

  7. Real-World Safety and Patient Profile of Fingolimod in Relapsing-Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina.

    Science.gov (United States)

    Rojas, Juan Ignacio; Patrucco, Liliana; Miguez, Jimena; Cristiano, Edgardo

    The aim was to evaluate fingolimod safety and patient profiles in a real-world setting in Buenos Aires, Argentina. Relapsing-remitting patients with multiple sclerosis who had been prescribed fingolimod and at least 18 months or more of follow-up were included. Demographic, clinical, and safety issues were described during first dose and follow-up. A total of 145 patients were included, 68% female; mean age, 30 ± 10.5 years; mean disease duration, 6.5 ± 3.1 years; mean fingolimod use, 25 ± 13 months. Eleven patients (7.6%) discontinued fingolimod (7 owing to disease activity/4 owing to desire of pregnancy and personal decisions). Forty-two percent of patients experienced adverse events: headache, fatigue, liver enzyme elevation, and lymphopenia were the most commonly found. No serious cardiac event was reported during the first dose. The safety and patient profile of fingolimod in a new real-world setting were consistent with information provided from phase III clinical trials.

  8. Lesion-to-ventricle distance and other risk factors for the persistence of newly formed black holes in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Papadopoulou, Athina; Menegola, Milena; Kuhle, Jens; Ramagopalan, Sreeram V; D'Souza, Marcus; Sprenger, Till; Radue, Ernst-Wilhelm; Kappos, Ludwig; Yaldizli, Özgür

    2014-03-01

    Progenitor cells from the subventricular zone (SVZ) of the lateral ventricles are assumed to contribute to remyelination and resolution of black holes (BHs) in multiple sclerosis (MS). This process may depend on the distance between the lesion and the SVZ. The objective of this paper is to investigate the relationship between lesion-to-ventricle (LV) distance and persistence of new BHs. We analysed the magnetic resonance images (MRIs) of 289 relapsing-remitting (RR) MS patients, obtained during a multi-centre, placebo-controlled phase II trial over one year. Overall, 112/289 patients showed 367 new BHs at the beginning of the trial. Of these, 225 were located in 94/112 patients at the level of the lateral ventricles on axial MRIs and included in this analysis. In total, 86/225 (38%) BHs persisted at month 12. LV distance in persistent BHs (PBHs) was not longer than in transient BHs. In fact PBHs tended to be closer to the SVZ than transient BHs. A generalised linear mixed multivariate model adjusted for BHs clustered within a patient and including patient- as well as lesion-specific factors revealed size, ring contrast enhancement, and shorter LV distance as independent predictors for BH persistence. Location of BHs close to the lateral ventricles does not appear to favourably influence the resolution of new BHs in RRMS.

  9. Event related potential and response time give evidence for a physiological reserve in cognitive functioning in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Sundgren, Mathias; Wahlin, Åke; Maurex, Liselotte; Brismar, Tom

    2015-09-15

    Cognitive dysfunction is common in multiple sclerosis (MS). Different factors may moderate the degree of cognitive deficit. The aim of the present study was to distinguish different mechanisms for cognitive reserve in relapsing-remitting MS (RRMS). The effects of clinical variables (physical disability, depression), premorbid intelligence (years of education, vocabulary knowledge), visual event-related potential measures (P300) and response time (RT) were studied in RRMS patients (n=71) and healthy subjects (n=89). Patients with high P300 amplitude and short RT had better cognitive performance. This effect was significantly weaker in controls. High P300 and short RT may be physiological markers of a cognitive reserve in RRMS. In contrast, the association between cognitive scores and premorbid intelligence was similar in patients and in control subjects. The effects of physiological reserve and clinical variables were studied in a hierarchical linear regression model of cognitive performance in RRMS. P300 amplitude and RT explained a considerable amount of variance in global cognitive performance (34%, pP300 and RT were not moderated by premorbid intelligence. Physical disability and depression added significantly to explained variance, and the final model accounted for 44% (p<0.001) of the variation. We conclude that physiological reserve is the strongest moderator of cognitive impairment in RRMS. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Arroyo González, Rafael; Kita, Mariko; Crayton, Heidi; Havrdova, Eva; Margolin, David H; Lake, Stephen L; Giovannoni, Gavin

    2017-09-01

    Alemtuzumab was superior on clinical and magnetic resonance imaging (MRI) outcomes versus subcutaneous interferon beta-1a in phase 3 trials in patients with relapsing-remitting multiple sclerosis. To examine quality-of-life (QoL) outcomes in the alemtuzumab phase 3 trials. Patients who were treatment naive (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis I [CARE-MS I]) or had an inadequate response to prior therapy (CARE-MS II) received annual courses of alemtuzumab 12 mg/day at baseline (5 days) and Month 12 (3 days) or subcutaneous interferon beta-1a 44 µg three times/week. QoL was measured every 6 or 12 months using Functional Assessment of Multiple Sclerosis (FAMS), European Quality of Life-5 Dimensions (EQ-5D) and its visual analog scale (EQ-VAS), and 36-Item Short-Form Survey (SF-36). Statistically significant improvements from baseline with alemtuzumab were observed on all three QoL instruments at the earliest post-baseline assessment and sustained through Year 2. Statistically significant greater QoL improvements over subcutaneous interferon beta-1a were seen at all time points in CARE-MS II with FAMS, EQ-VAS and SF-36 physical component summary, and in CARE-MS I with FAMS. Patients treated with alemtuzumab had improvements in physical, mental, and emotional QoL regardless of treatment history. Improvements were significantly greater with alemtuzumab versus subcutaneous interferon beta-1a on both disease-specific and general measures of QoL.

  11. Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Rolf, Linda; Muris, Anne-Hilde; Mathias, Amandine; Du Pasquier, Renaud; Koneczny, Inga; Disanto, Giulio; Kuhle, Jens; Ramagopalan, Sreeram; Damoiseaux, Jan; Smolders, Joost; Hupperts, Raymond

    2017-07-01

    Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored. The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures. High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism.

  12. Composite Marker of Cognitive Dysfunction and Brain Atrophy is Highly Accurate in Discriminating Between Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.

    Science.gov (United States)

    Kizlaitienė, Rasa; Kaubrys, Gintaras; Giedraitienė, Nataša; Ramanauskas, Naglis; Dementavičienė, Jūratė

    2017-02-01

    BACKGROUND With the advent of numerous new-generation disease-modifying drugs for multiple sclerosis (MS), the discrimination between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) has become a problem of high importance. The aim of our study was to find a simple way to accurately discriminate between RRMS and SPMS that is applicable in clinical practice as a composite marker, using the linear measures of magnetic resonance imaging (MRI) and the results of cognitive tests. MATERIAL AND METHODS We included 88 MS patients in the study: 43 participants had RRMS and 45 had SPMS. A battery consisting of 11 tests was used to evaluate cognitive function. We used 11 linear MRI measures and 7 indexes to assess brain atrophy. RESULTS Four cognitive tests and 3 linear MRI measures were able to distinguish RRMS from SPMS with the AUC >0.8 based on ROC analysis. Multiple logistic regression models were constructed to identify the best set of cognitive and MRI markers. The model, using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Huckman Index, showed the highest predictive ability: AUC=0.921 (p<0.001). We constructed a simple remission-progression index from the same 3 variables, which discriminated well between RRMS and SPMS: AUC=0.920 (p<0.001), maximal Youden Index=0.702, cut-off=1.68, sensitivity=79.1%, and specificity=91.1%. CONCLUSIONS The composite remission-progression index, using the RAVLT test, DSST test, and MRI Huckman Index, is highly accurate in discriminating between RRMS and SPMS.

  13. Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis.

    Science.gov (United States)

    González Gómez, A; García-Ben, A; Soler García, A; García-Basterra, I; Padilla Parrado, F; García-Campos, J M

    2017-03-15

    The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

  14. Relationship between working hours and power of attention, memory, fatigue, depression and self-efficacy one year after diagnosis of clinically isolated syndrome and relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Jongen, Peter Joseph; Wesnes, Keith; van Geel, Björn; Pop, Paul; Sanders, Evert; Schrijver, Hans; Visser, Leo H; Gilhuis, H Jacobus; Sinnige, Ludovicus G; Brands, Augustina M

    2014-01-01

    The role of cognitive domain dysfunction with respect to vocational changes in persons with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting Multiple Sclerosis (eRRMS) is insufficiently known. We investigated thirty-three patients--14 CIS, 19 eRRMS -, mean (standard deviation [SD]) time since diagnosis 13.5 (4.8) months and mean (SD) Expanded Disability Status Scale (EDSS) score 1.3 (1.1). Patients were assessed on the CDR System, a set of automated tests of cognitive function, which yielded scores for Power of Attention (ms), Continuity of Attention (#), Working Memory (SI), Episodic Memory (#) and Speed of Memory (ms). Work-related items and the confounding variables fatigue, depression, disease impact and self-efficacy, were assessed by self-report questionnaires. Patients had poorer Power of Attention compared to normative data (1187 [161.5] vs. 1070 [98.6]; PMemory (4043 [830.6]) vs. 2937 [586.1]; PAttention (Pearson r =  -0.42; PWorking Memory (r = 0.42; Pworked per week. Fatigue (r =  -0.56; Pworked per week. Persons who wished to work less had poorer Power of Attention (1247 vs. 1116 ms; PMemory (1.35 vs. 1.57; pworking hours within 12 months after diagnosis had higher fatigue and disease impact, and lower self-efficacy. The findings of this pilot study indicate that one year after the diagnosis of CIS and RRMS Power of Attention and Speed of Memory are reduced, that Power of Attention and Memory are associated with a capability of working less hours, and that fatigue, depression and disease impact may negatively, and self-efficacy positively affect working hours.

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

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    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.

  16. A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients

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    Ann J. Ligocki

    2015-10-01

    Full Text Available * These authors contributed equally to the work in this manuscript.We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF of early and established relapsing remitting multiple sclerosis (RRMS patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS. In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate whether AGS+ antibodies bind to brain tissue antigens. Single B cells were isolated from the CSF of 10 patients with early or established RRMS. We chose 32 of these B cells that expressed antibodies enriched for the AGS for further study. We generated monoclonal full-length recombinant human antibodies (rhAbs and used both immunological assays and immunohistochemistry to investigate the capacity of these AGS+ rhAbs to bind brain tissue antigens. AGS+ rhAbs did not recognize myelin tracts in the corpus callosum. Instead, AGS+ rhAbs recognized neuronal nuclei and/or astrocytes, which are prevalent in the cortical gray matter. This pattern was unique to the AGS+ antibodies from early and established RRMS patients, as AGS+ antibodies from an early neuromyelitis optica patient did not display the same reactivity. Prevalence of CSF-derived B cells expressing AGS+ antibodies that bind to these cell types may be an indicator of gray matter-directed autoimmunity in early and established RRMS patients.

  17. Cognitive profile of patients with relapsing remitting multiple sclerosis Perfil cognitivo de pacientes com esclerose múltipla do tipo surto-remissão

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    VIVIAN M. ANDRADE

    1999-09-01

    Full Text Available Multiple sclerosis (MS is a common disease in Western countries of temperate/cold climate, but in tropical countries an increasing number of cases have been diagnosticated. Moved by the lack of information about cognitive dysfunction of Brazilian MS patients, the present study attempted to describe features of neuropsychological alterations in patients with relapsing remitting MS living in the city of São Paulo. They were compared to healthy volunteers, matched for age and education. In the absence of global intellectual deterioration, the patients had a deficit: a in learning and verbal long-term memory tasks and in visual long-term memory of complex figure; b in timed tasks, accounted for by a slowness of mental processes; c in tasks with a motor component. Tendency to depression was observed; anxiety levels were normal.A esclerose múltipla (EM é doença comum em países de clima temperado/frio, mas também em países tropicais um crescente número de casos tem sido diagnosticado. Motivado pela escassez de informações acerca da cognição dos portadores de EM em nosso país, o presente estudo procurou traçar o perfil neuropsicológico de pacientes com EM da forma surto-remissão, residentes no município de São Paulo, os quais foram comparados a pessoas sadias, com idade e escolaridade semelhantes. A inteligência geral dos pacientes estava preservada mas foram detectados déficits: a em tarefas de aprendizagem e de memória verbal e visual de figura complexa, ambas de longo prazo; b em tarefas cronometradas, explicados por lentificação do processamento mental; c em tarefas com componente motor. Tendência a depressão foi observada; os níveis de ansiedade encontravam-se normais.

  18. Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study.

    Science.gov (United States)

    Muris, Anne-Hilde; Smolders, Joost; Rolf, Linda; Thewissen, Marielle; Hupperts, Raymond; Damoiseaux, Jan

    2016-11-15

    Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study. Thirty Dutch relapsing remitting (RR) MS patients treated with IFNβ-1a received high dose vitamin D3 supplementation and 23 patients received placebo during a period of 48weeks. Lymphocytes were phenotypically characterized by flow cytometry and in vitro cytokine secretion was assessed in the presence or absence of 1,25(OH)2D3 using Luminex technology. Changes in immune regulatory parameters were determined within subjects as well as between treatment groups. The proportion of cells in the immune regulatory cell compartment (nTreg, iTreg and Breg) was not altered upon high dose vitamin D3 supplementation. Proportions of T helper subsets were not affected by vitamin D3, except for the proportion of IL4+ Th cells, which decreased in the placebo but not in the vitamin D3 group. T cell cytokine secretion increased, most pronounced for IL5 and latency activated protein of TGFβ, in the placebo group but not in the vitamin D3 group. Lymphocytes remained equally reactive to in vitro 1,25(OH)2D3. In conclusion, high dose vitamin D3 supplementation did not result in a relative increase in lymphocytes with a regulatory phenotype. However, this study supports the hypothesis that vitamin D contributes to the maintenance of immune homeostasis by preventing further disturbance of the T cell compartment early in the disease course of MS. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Reabilitação vestibular em pacientes com esclerose múltipla remitente-recorrente Vestibular rehabilitation in patients with relapsing- remitting multiple sclerosis

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    Karina Pavan

    2007-06-01

    Full Text Available A esclerose múltipla (EM é doença desmielinizante, inflamatória, que acomete a substância branca do sistema nervoso central, e sensações vestibulares anormais (vertigem, desequilíbrio são freqüentes. A reabilitação vestibular (RV é determinada por mecanismos de adaptações, substituições e compensações neurais. Este estudo avaliou a melhora da vertigem central ou periférica em pacientes com EM remitente-recorrente submetidos à RV (exercícios de Cawthorne-Cooksey, através da escala de Berg e Dizziness Handicap Inventory (DHI. Nesta amostra de 4 casos a RV, realizada em um período de 2 meses, demonstrou a melhora em 3 pacientes avaliados pela escala de Berg e em 2 pacientes quando avaliados pela DHI.Multiple sclerosis (MS is a demyelinating, inflammatory illness, that attack the white matter of the central nervous system, and abnormal vestibular sensations (vertigo, disequilibrium are frequent. The vestibular rehabilitation (VR is determined by mechanisms of adaptations, neural substitutions and compensations. This study evaluated the improvement of the central or peripheral vertigo in patients with relapsing-remitting MS submitted to the VR (exercises of Cawthorne-Cooksey, through the scale of Berg and Dizziness Handicap Inventory (DHI. In this sample of 4 cases the VR, carried through in a period of 2 months, demonstrated the improvement in 3 patients according to the Berg scale and in 2 patients considering that of the DHI.

  20. Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

    Science.gov (United States)

    Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

    2017-12-01

    To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

  1. An initial validation of the Italian Mishel Uncertainty Illness Scale (MUIS) for relapsing remitting multiple sclerosis patients.

    Science.gov (United States)

    Giammanco, Maria Daniela; Polimeni, Giovanni; Spadaro, Letteria; Gitto, Lara; Buccafusca, Maria; Bramanti, Placido

    2014-09-01

    Multiple sclerosis is a chronic disease, likely to condition patients' daily living and quality of life: given the unpredictability of frequency and severity of the attacks, patients experience a high level of uncertainty. While there have been many analyses whose purpose was to monitor multiple sclerosis (MS) patients' quality of life, the role of uncertainty, that is peculiar to the disease, has not been adequately considered so far. The present study is aimed at filling this gap by validating for Italian MS patients the Mishel's Uncertainty Illness Scale (MUIS). The MUIS has been developed in the USA context in order to assess four aspects of uncertainty: ambiguity, complexity, inconsistency and unpredictability. It has been largely applied in the cancer, cardiac and chronic illness population. Data employed in this study have been collected at two neurological centres in Messina (IRCCS Centro Studi Neurolesi "Bonino Pulejo" and Policlinico di Messina) in the first semester of 2013 and refer to 120 MS patients. The confirmatory factor analysis described in this study validates two of the four dimensions of MUIS, namely ambiguity and inconsistency. The validation, though partial, of the MUIS, allows the use of this instrument in studies investigating quality of life for Italian patients.

  2. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

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    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  3. Immune and Epstein-Barr virus gene expression in cerebrospinal fluid and peripheral blood mononuclear cells from patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Veroni, Caterina; Marnetto, Fabiana; Granieri, Letizia; Bertolotto, Antonio; Ballerini, Clara; Repice, Anna Maria; Schirru, Lucia; Coghe, Giancarlo; Cocco, Eleonora; Anastasiadou, Eleni; Puopolo, Maria; Aloisi, Francesca

    2015-07-14

    Gene expression analyses in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) from patients with multiple sclerosis (MS) are restrained by the low RNA amounts from CSF cells and low expression levels of certain genes. Here, we applied a Taqman-based pre-amplification real-time reverse-transcription polymerase chain reaction (RT-PCR) (PreAmp RT-PCR) to cDNA from CSF cells and PBMC of MS patients and analyzed multiple genes related to immune system function and genes expressed by Epstein-Barr virus (EBV), a herpesvirus showing strong association with MS. Using this enhanced RT-PCR method, we aimed at the following: (1) identifying gene signatures potentially useful for patient stratification, (2) understanding whether EBV infection is perturbed in CSF and/or blood, and (3) finding a link between immune and EBV infection status. Thirty-one therapy-free patients with relapsing-remitting MS were included in the study. Paired CSF cells and PBMC were collected and expression of 41 immune-related cellular genes and 7 EBV genes associated with latent or lytic viral infection were determined by PreAmp RT-PCR. Clinical, radiological, CSF, and gene expression data were analyzed using univariate and multivariate (cluster analysis, factor analysis) statistical approaches. Several immune-related genes were differentially expressed between CSF cells and PBMC from the whole MS cohort. By univariate analysis, no or only minor differences in gene expression were found associated with sex, clinical, or radiological condition. Cluster analysis on CSF gene expression data grouped patients into three clusters; clusters 1 and 2 differed by expression of genes that are related mainly to innate immunity, irrespective of sex and disease characteristics. By factor analysis, two factors grouping genes involved in antiviral immunity and immune regulation, respectively, accurately discriminated cluster 1 and cluster 2 patients. Despite the use of an enhanced RT

  4. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    On the basis of various clinical and MRI measurements, the phase 3 Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study in patients with relapsing-remitting multiple sclerosis (RRMS) showed that short-course oral treatment with cladribine at cumulative doses of 3·5 and 5·25 mg....../kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study....

  5. Improved self-efficacy in persons with relapsing remitting multiple sclerosis after an intensive social cognitive wellness program with participation of support partners: a 6-months observational study.

    Science.gov (United States)

    Jongen, Peter Joseph; Ruimschotel, Rob; Heerings, Marco; Hussaarts, Astrid; Duyverman, Lotte; van der Zande, Anneke; Valkenburg-Vissers, Joyce; Wolper, Hanne; van Droffelaar, Maarten; Lemmens, Wim; Donders, Rogier; Visser, Leo H

    2014-03-19

    For persons with multiple sclerosis (MS) it is important to preserve their autonomy, in spite of increasing disability. A major factor mediating autonomy is self-efficacy. According to the social cognitive theory stressors are crucial determinants of self-efficacy, as well as the interaction with partners. In an explorative observational study we assessed in 47 persons with MS (PwMS) the effect of an intense, multidisciplinary, 3-day, social cognitive wellness program with the participation of support partners, after 1, 3 and 6 months. self-efficacy-control and -function (Multiple Sclerosis Self-Efficacy Scale [MSSES]),limitations to and problems with participation and autonomy (Impact on Participation and Autonomy [IPA] scale). health-related quality of life (HRQoL) (MS Quality of Life-54 Items [MSQoL-54] questionnaire), anxiety, depression (Hospital Anxiety and Depression Scale [HADS]), and fatigue (Modified Fatigue Impact Scale-5 Items [MFIS-5]). Disability was measured with the Expanded Disability Status Scale (EDSS). Percentage changes from baseline were tested with T-tests, level of significance 0.05. In the whole group the MSQoL-54 Mental score was increased at 1, 3 and 6 months (+16.0%, +13.2%, +12.2%), and the MSQoL-54 Physical (+10.2%) at 6 months, with no changes in other outcomes. The relapsing remitting (RR) subgroup (n = 20) had at 6 months an increase in the MSSES-Control score (+24.8%) and in the MSQoL54 Mental and Physical scores (+22.3%, +17.6%). Progressive patients (n = 22) only showed an increase in the MSQoL-54 Mental score (+11.5%) at 1 month. In the low-disability (EDSS  =4.0) subgroup no significant changes occurred. Results from this observational study suggest that 6 months after an intense, 3-day, multidisciplinary, social cognitive wellness program with support partners, PwMS with a RR course or low disability may experience an improved self-efficacy-control and HRQoL.

  6. Relationship between Working Hours and Power of Attention, Memory, Fatigue, Depression and Self-Efficacy One Year after Diagnosis of Clinically Isolated Syndrome and Relapsing Remitting Multiple Sclerosis

    Science.gov (United States)

    Jongen, Peter Joseph; Wesnes, Keith; van Geel, Björn; Pop, Paul; Schrijver, Hans; Visser, Leo H.; Gilhuis, H. Jacobus; Sinnige, Ludovicus G.; Brands, Augustina M.

    2014-01-01

    The role of cognitive domain dysfunction with respect to vocational changes in persons with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting Multiple Sclerosis (eRRMS) is insufficiently known. We investigated thirty-three patients - 14 CIS, 19 eRRMS -, mean (standard deviation [SD]) time since diagnosis 13.5 (4.8) months and mean (SD) Expanded Disability Status Scale (EDSS) score 1.3 (1.1). Patients were assessed on the CDR System, a set of automated tests of cognitive function, which yielded scores for Power of Attention (ms), Continuity of Attention (#), Working Memory (SI), Episodic Memory (#) and Speed of Memory (ms). Work-related items and the confounding variables fatigue, depression, disease impact and self-efficacy, were assessed by self-report questionnaires. Patients had poorer Power of Attention compared to normative data (1187 [161.5] vs. 1070 [98.6]; P<0.0001) and slower Speed of Memory (4043 [830.6]) vs. 2937 [586.1]; P<0.0001). Power of Attention (Pearson r = −0.42; P<0.04), Working Memory (r = 0.42; P<0.04) and depression r = −0.41; P<0.05) correlated with number of days worked per week. Fatigue (r = −0.56; P<0.005), self-efficacy (r = 0.56; P<0.005) and disease impact (r = −0.46; P<0.05) correlated with number of hours worked per week. Persons who wished to work less had poorer Power of Attention (1247 vs. 1116 ms; P<0.02), those who wished to change job had poorer Episodic Memory (1.35 vs. 1.57; p<0.03). People who reduced working hours within 12 months after diagnosis had higher fatigue and disease impact, and lower self-efficacy. The findings of this pilot study indicate that one year after the diagnosis of CIS and RRMS Power of Attention and Speed of Memory are reduced, that Power of Attention and Memory are associated with a capability of working less hours, and that fatigue, depression and disease impact may negatively, and self-efficacy positively affect working hours. PMID:24787714

  7. Altered inter-subregion connectivity of the default mode network in relapsing remitting multiple sclerosis: a functional and structural connectivity study.

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    Fuqing Zhou

    Full Text Available BACKGROUND AND PURPOSE: Little is known about the interactions between the default mode network (DMN subregions in relapsing-remitting multiple sclerosis (RRMS. This study used diffusion tensor imaging (DTI and resting-state functional MRI (rs-fMRI to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients. METHODS: Twenty-four RRMS patients and 24 healthy subjects participated in this study. The fiber connections derived from DTI tractography and the temporal correlation coefficient derived from rs-fMRI were combined to examine the inter-subregion structural-functional connectivity (SC-FC within the DMN and its correlations with clinical markers. RESULTS: Compared with healthy subjects, the RRMS patients showed the following: 1 significantly decreased SC and increased FC in the pair-wise subregions; 2 two significant correlations in SC-FC coupling patterns, including the positive correlation between slightly increased FC value and long white matter tract damage in the PCC/PCUN-MPFC connection, and the negative correlations between significantly increased FC values and long white matter tract damage in the PCC/PCUN-bilateral mTL connections; 3 SC alterations [log(N track of the PCC/PCUN-left IPL, RD value of the MPFC-left IPL, FA value of the PCC/PCUN-left mTL connections] correlated with EDSS, increases in the RD value of MPFC-left IPL connection was positively correlated to the MFIS; and decreases in the FA value of PCC/PCUN-right IPL connection was negatively correlated with the PASAT; 4 decreased SC (FA value of the MPFC-left IPL, track volume of the PCC/PCUN-MPFC, and log(N track of PCC/PCUN-left mTL connections was positively correlated with brain atrophy. CONCLUSIONS: In the connections of paired DMN subregions, we observed decreased SC and increased FC in RRMS patients. The relationship between MS-related structural abnormalities and clinical markers suggests that the

  8. Altered inter-subregion connectivity of the default mode network in relapsing remitting multiple sclerosis: a functional and structural connectivity study.

    Science.gov (United States)

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Wang, Bo; Wang, Xing; Chen, Qi; Wu, Lin; Wan, Hui

    2014-01-01

    Little is known about the interactions between the default mode network (DMN) subregions in relapsing-remitting multiple sclerosis (RRMS). This study used diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to examine alterations of long white matter tracts in paired DMN subregions and their functional connectivity in RRMS patients. Twenty-four RRMS patients and 24 healthy subjects participated in this study. The fiber connections derived from DTI tractography and the temporal correlation coefficient derived from rs-fMRI were combined to examine the inter-subregion structural-functional connectivity (SC-FC) within the DMN and its correlations with clinical markers. Compared with healthy subjects, the RRMS patients showed the following: 1) significantly decreased SC and increased FC in the pair-wise subregions; 2) two significant correlations in SC-FC coupling patterns, including the positive correlation between slightly increased FC value and long white matter tract damage in the PCC/PCUN-MPFC connection, and the negative correlations between significantly increased FC values and long white matter tract damage in the PCC/PCUN-bilateral mTL connections; 3) SC alterations [log(N track) of the PCC/PCUN-left IPL, RD value of the MPFC-left IPL, FA value of the PCC/PCUN-left mTL connections] correlated with EDSS, increases in the RD value of MPFC-left IPL connection was positively correlated to the MFIS; and decreases in the FA value of PCC/PCUN-right IPL connection was negatively correlated with the PASAT; 4) decreased SC (FA value of the MPFC-left IPL, track volume of the PCC/PCUN-MPFC, and log(N track) of PCC/PCUN-left mTL connections) was positively correlated with brain atrophy. In the connections of paired DMN subregions, we observed decreased SC and increased FC in RRMS patients. The relationship between MS-related structural abnormalities and clinical markers suggests that the disruption of this long-distance "inter-subregion" connectivity

  9. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

    DEFF Research Database (Denmark)

    Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus

    2010-01-01

    over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. FINDINGS: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients...... therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. METHODS: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination...

  10. Quantitative detection of epstein-barr virus DNA in cerebrospinal fluid and blood samples of patients with relapsing-remitting multiple sclerosis.

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    Clementina E Cocuzza

    Full Text Available The presence of Epstein-Barr Virus (EBV DNA in cerebrospinal fluid (CSF and peripheral blood (PB samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.

  11. Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.

    Science.gov (United States)

    Havrdova, E; Giovannoni, G; Gold, R; Fox, R J; Kappos, L; Phillips, J Theodore; Okwuokenye, M; Marantz, J L

    2017-05-01

    Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years. A time-to-event method was used to estimate the percentage of patients achieving NEDA. Clinical NEDA (no relapses/no 12-week confirmed disability progression) was analysed in the intention-to-treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium-enhancing lesions) and overall NEDA (clinical and neuroradiological NEDA) were analysed in the magnetic resonance imaging (MRI) cohort. The ITT and MRI populations comprised 1540 and 692 patients, respectively. The percentage of patients with clinical NEDA (ITT population) and neuroradiological NEDA (MRI cohort) was higher with DMF versus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52-0.72; P < 0.0001; neuroradiological NEDA: 40.0% relative reduction; HR, 0.60; 95% CI, 0.49-0.73; P < 0.0001]. The percentage of patients achieving overall NEDA (MRI cohort) was also higher with DMF (26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48-0.69; P < 0.0001). A significantly higher percentage of patients treated with DMF achieved NEDA status over 2 years compared with placebo. © 2017 Biogen. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  12. Paroxysmal dysarthria-ataxia in remitting-relapsing Bickerstaff's-like encephalitis.

    Science.gov (United States)

    Piffer, Silvio; Turri, Giulia; Acler, Michele; Richelli, Silvia; Cerini, Roberto; Fiaschi, Antonio; Monaco, Salvatore; Bonetti, Bruno

    2014-06-15

    Paroxysmal dysarthria-ataxia is a rare neurological condition due to ephaptic transmission, generally appearing in multiple sclerosis patients characterized by stereotyped attacks of slurred speech usually accompanied by ataxia, appearing many times a day. Here we describe a patient with an unusual remitting-relapsing form of Bickerstaff's-like brainstem encephalitis who manifested PDA after a relapse with the involvement of a peculiar region below the red nuclei and benefited from lamotrigine. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Börnsen, Lars; Sellebjerg, Finn

    2016-01-01

    with reduced ability of B cells to produce IL-10 after stimulation with MBP, indicative of diminished B-cell immune regulatory function in patients with the most severe disease. Moreover, EDSS correlated positively with the frequencies of TNF-α, IL-6 and IL-10 producing B cells after polyclonal stimulation......B cells are involved in driving relapsing-remitting multiple sclerosis (RRMS), as demonstrated by the positive effect of therapeutic B-cell depletion. Aside from producing antibodies, B cells are efficient antigen-presenting and cytokine-secreting cells. Diverse polyclonal stimuli have been used...... to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize...

  14. Efficacy of fingolimod and interferon beta-1b on cognitive, MRI, and clinical outcomes in relapsing-remitting multiple sclerosis: an 18-month, open-label, rater-blinded, randomised, multicentre study (the GOLDEN study).

    Science.gov (United States)

    Comi, Giancarlo; Patti, Francesco; Rocca, Maria Assunta; Mattioli, Flavia Caterina; Amato, Maria Pia; Gallo, Paolo; Centonze, Diego; Pozzilli, Carlo; Saccà, Francesco; Bergh, Florian Then; Bartezaghi, Marta; Turrini, Renato; Filippi, Massimo

    2017-12-01

    Cognitive impairment (CI) affects 40-65% of multiple sclerosis (MS) patients. This study attempted evaluating the effects of fingolimod and interferon beta-1b (IFN β-1b) on CI progression, magnetic resonance imaging (MRI) and clinical outcomes in relapsing-remitting MS (RRMS) patients over 18 months. The GOLDEN study was a pilot study including RRMS patients with CI randomised (2:1) to fingolimod (0.5 mg daily)/IFN β-1b (250 µg every other day). CI was assessed via Rao's Brief Repeatable Battery and Delis-Kaplan Executive Function System test. MRI parameters, Expanded Disability Status Scale scores and relapses were measured. Overall, 157 patients were randomised, of whom 30 discontinued the study (fingolimod, 8.49%; IFN β-1b, 41.18%; p ≤ 0.0001). Patients randomised to fingolimod had more severe clinical and MRI disease characteristics at baseline compared with IFN β-1b. At Month (M) 18, both treatment groups showed improvements in all cognitive parameters. At M18, relapse rate, total number and volume of T2/T1 gadolinium-enhancing lesions were higher with IFN β-1b, as well as the percentage brain volume change during the study. Safety and tolerability of both treatments were similar to previous studies. Both treatments showed improvements in cognitive parameters. Fingolimod demonstrated significantly better effects on MRI parameters and relapse rate. Imbalance in baseline characteristics and the drop-out pattern may have favoured IFN β-1b. A longer duration trial may be needed to observe the complete expression of differential effects on CI scales reflecting the between-groups differences on MRI. Although limited in size, the GOLDEN study confirms the favourable benefit-risk profile of fingolimod reported in previous studies.

  15. RESULTS OF AN OPEN-LABEL COMPARATIVE RANDOMIZED CLINICAL TRIAL OF AXOGLATIRAN® FS (F-SINTEZ, RUSSIA EFFICIENCY AND SAFETY IN COMPARISON WITH COPAXONE®-TEVA (TEVA PHARMACEUTICAL INDUSTRIES LTD., ISRAEL IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    F. A. Khabirov

    2016-01-01

    Full Text Available Objective. Comparison of Axoglatiran® FS (F-Sintez,  Russia and Copaxone®-Teva (Teva Pharmaceutical Industries Ltd.,  Israel efficiency and safety in patients with relapsing-remitting multiple sclerosis. Materials and methods. In the study 150 patients with relapsing-remitting multiple sclerosis were randomized into 2 groups: patients in the 1st group (n = 100 received treatment with Axoglatiran® FS, patients in the 2nd group (n = 50 received treatment with Copaxone®-Teva. Vital signs of every patient in the study were monitored accompanied by physical examinations, neurological examinations with EDSS (Expanded Disability Status Scale and MSFC (Multiple Sclerosis Functional Composite evaluations, magnetic resonance imaging of the brain and lab tests. Results. Mean age (M ± SD of the patients in the 1st group was 32.8 ± 8.7 years (20–54  years, percentages of men and women were 34 and 66 % respectively, mean age of multiple sclerosis onset was 27.93 ± 7.72 years (11–48 years. Median (Me, lower and upper quartiles estimates [LQ; UQ] on the EDSS scale were 2 [1.5; 3.0] steps (1.0–4.5  steps. In the 2nd group mean age of the patients was 35.2 ± 9.5 years (18–57  years, percentages of men and women were 24 and 76 % respectively, mean age of multiple sclerosis onset was 26.5 ± 6.9 years (18–47  years, EDSS estimates were 2.25 [1.5; 3.5] steps (1–5  steps. In the 1st group 88 (88 % patients completed the study, in the 2nd  group 44 (88 % patients completed the study. Among them in 73 (82.95 % patients in the 1st group and 34 (77.27 % patients in the 2nd  group the disease didn’t exacerbate (p > 0.05. In both groups no progression according to the EDSS and MSFC scale was observed (p > 0.05. Magnetic resonance imaging data showed that dynamics of the total number of T2 lesions, contrast-enhancing T1 lesions, atrophy degree estimated using internuclear index were comparable in both groups (p > 0.05. Safety profiles of

  16. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan A. [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Clinical Center Nis, Center for Radiology, Nis (Serbia); Vojinovic, Slobodan; Ljubisavljevic, Srdjan [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Clinic for Neurology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-03-15

    To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

  17. Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes

    KAUST Repository

    Ruhrmann, Sabrina

    2017-08-02

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes.Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

  18. Subcutaneous interferon β-1a administration by electronic auto-injector is associated with high adherence in patients with relapsing remitting multiple sclerosis in a real-life study

    Directory of Open Access Journals (Sweden)

    Elina Järvinen

    2017-02-01

    Full Text Available The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS, using an electronic auto-injector Rebismart® to self-inject interferon β-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart® for selfinjecting interferon β-1a subcutaneously three times weekly were included in a reallife clinical multicenter study for 24 weeks in Finland. Mean adherence reported by the device and mean self-assessment of adherence were studied. Reasons for missing injections and treatment convenience were assessed. Association between adherence and gender and age were studied. The mean adherence calculated from the device data was 93.5%. The mean self-assessment of adherence was 96.6%. The most common reason for missing an injection was forgetfulness. Adherence (measured by the device was not changed over time. In the high adherence group there were more females and young patients (<30 years of age. The auto-injector was found to substantially ease the treatment by 90% of the patients. The electronic auto-injector was associated with high adherence to treatment. The device was found to ease the patient’s treatment and it was perceived as easy to use. It is a convenient tool to assess patient’s adherence to treatment.

  19. Subcutaneous Interferon β-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study.

    Science.gov (United States)

    Järvinen, Elina; Multanen, Juha; Atula, Sari

    2017-02-20

    The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS), using an electronic auto-injector Rebismart® to self-inject interferon β-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart® for self-injecting interferon β-1a subcutaneously three times weekly were included in a real-life clinical multicenter study for 24 weeks in Finland. Mean adherence reported by the device and mean self-assessment of adherence were studied. Reasons for missing injections and treatment convenience were assessed. Association between adherence and gender and age were studied. The mean adherence calculated from the device data was 93.5%. The mean self-assessment of adherence was 96.6%. The most common reason for missing an injection was forget-fulness. Adherence (measured by the device) was not changed over time. In the high adherence group there were more females and young patients (auto-injector was found to substantially ease the treatment by 90% of the patients. The electronic auto-injector was associated with high adherence to treatment. The device was found to ease the patient's treatment and it was perceived as easy to use. It is a convenient tool to assess patient's adherence to treatment.

  20. Memory B cells from a subset of treatment naïve relapsing remitting multiple sclerosis patients elicit CD4+ T cell proliferation and IFN-γ production in response to MBP and MOG

    Science.gov (United States)

    Harp, Christopher T.; Ireland, Sara; Davis, Laurie S.; Remington, Gina; Cassidy, Bonnie; Cravens, Petra D.; Stuve, Olaf; Lovett-Racke, Amy E.; Eagar, Todd N.; Greenberg, Benjamin M.; Racke, Michael K.; Cowell, Lindsay G.; Karandikar, Nitin J.; Frohman, Elliot M.; Monson, Nancy L.

    2011-01-01

    Recent evidence suggests that B and T cell interactions may be paramount in relapsing remitting multiple sclerosis (RRMS) disease pathogenesis. We hypothesized that memory B cell pools from RRMS patients may specifically harbor a subset of potent neuro-antigen presenting cells that support neuro-antigen reactive T cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and LTα secretion, neuro-antigen binding capacity, and neuro-antigen presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4+ T cell proliferation and IFN-γ secretion in response to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Notwithstanding the fact that the phenotypic parameters that promote efficient antigen presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4+ T cell proliferation in response to MBP and MOG was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B cell pool in RRMS harbors neuro-antigen specific B cells that can activate T cells. PMID:20812237

  1. 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

    converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included...... in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0...

  2. Intensive social cognitive treatment (can do treatment) with participation of support partners in persons with relapsing remitting multiple sclerosis: observation of improved self-efficacy, quality of life, anxiety and depression 1 year later.

    Science.gov (United States)

    Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Duyverman, Lotte; van der Zande, Anneke; Valkenburg-Vissers, Joyce; van Droffelaar, Maarten; Lemmens, Wim; Donders, Rogier; Visser, Leo H

    2016-07-29

    In persons with multiple sclerosis (MS) self-efficacy positively affects health-related quality of life (HRQoL) and physical activity. In a previous study we observed that 6 months after an intensive 3-day social cognitive treatment (Can Do treatment) with the participation of support partners, self-efficacy and HRQoL had improved in persons with relapsing remitting MS (RRMS). Given the chronic nature of the disease, it is important to know whether these beneficial changes may last. Can Do treatment was given to 60 persons with MS and their support partners. At baseline and 12 months after treatment self-efficacy control, self-efficacy function, physical and mental HRQoL, anxiety, depression and fatigue were assessed via self-report questionnaires. Differences were tested via a paired t test. Of the 57 persons with MS that completed the baseline assessment and the 3-day treatment, 38 filled in the 12th month questionnaires (response rate 66.7 %), 22 with RRMS and 14 with progressive MS. In the RR group self-efficacy control had increased by 20.2 % and physical HRQoL by 15.0 %, and depression and anxiety had decreased by 29.8 and 25.9 %, respectively (all P social cognitive treatment (Can Do treatment) with the participation of support partners may have long lasting beneficial effects on the self-efficacy and HRQoL in persons with RRMS; and that improvements in anxiety and depression, not seen in the 6-month study, may yet develop at 12 months.

  3. Validity and reliability of the multidimensional assessment of fatigue scale in Iranian patients with relapsing-remitting subtype of multiple sclerosis.

    Science.gov (United States)

    Behrangrad, Shabnam; Kordi Yoosefinejad, Amin

    2017-03-21

    The purpose of this study is to investigate the validity and reliability of the Persian version of the Multidimensional Assessment of Fatigue Scale (MAFS) in an Iranian population with multiple sclerosis. A self-reported survey on fatigue including the MAFS, Fatigue Impact Scale and demographic measures was completed by 130 patients with multiple sclerosis and 60 healthy persons sampled with a convenience method. Test-retest reliability and validity were evaluated 3 days apart. Construct validity of the MAFS was assessed with the Fatigue Impact Scale. The MAFS had high internal consistency (Cronbach's alpha >0.9) and 3-d test-retest reliability (intraclass correlation coefficient = 0.99). Correlation between the Fatigue Impact Scale and MAFS was high (r = 0.99). Correlation between MAFS scores and the Expanded Disability Status Scale was also strong (r = 0.85). Questionnaire items showed acceptable item-scale correlation (0.968-0.993). The Persian version of the MAFS appears to be a valid and reliable questionnaire. It is an appropriate short multidimensional instrument to assess fatigue in patients with multiple sclerosis in clinical practice and research. Implications for Rehabilitation The Persian version of Multidimensional Assessment of Fatigue is a valid and reliable instrument for the assessment and monitoring the fatigue in Persian-language patients with multiple sclerosis. It is very easy to administer and a time efficient scale in comparison to other instruments evaluating fatigue in patients with multiple sclerosis.

  4. The MS@Work study : a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis

    NARCIS (Netherlands)

    van der Hiele, Karin; van Gorp, Dennis A. M.; Heerings, Marco A. P.; van Lieshout, Irma; Jongen, Peter J.; Reneman, Michiel F.; van der Klink, Jac J. L.; Vosman, Frans; Middelkoop, Huub A. M.; Visser, Leo H.

    2015-01-01

    Background: Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading

  5. The MS@Work study : A 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis

    NARCIS (Netherlands)

    van der Hiele, K.; van Gorp, D.A.; Heerings, M.A.; van Lieshout, I.; Jongen, P.J.; Reneman, M.F.; van der Klink, J.J.L.; Vosman, F.; Middelkoop, H.A.; Visser, L.H.

    2015-01-01

    Background Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading

  6. An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability : a randomized controlled trial protocol

    NARCIS (Netherlands)

    Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Evers, Silvia; Duyverman, Lotte; Valkenburg-Vissers, Joyce; Cornelissen, Job; Bos, Michel; van Droffelaar, Maarten; Lemmens, Wim A.; Donders, Rogier; van der Zande, Anneke; Visser, Leo H.

    2016-01-01

    Background: In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found

  7. Improved self-efficacy in persons with relapsing remitting multiple sclerosis after an intensive social cognitive wellness program with participation of support partners: a 6-months observational study

    NARCIS (Netherlands)

    Jongen, P.J.H.; Ruimschotel, R.; Heerings, M.; Hussaarts, A.; Duyverman, L.; Zande, A. van der; Valkenburg-Vissers, J.; Wolper, H.; Droffelaar, M. van; Lemmens, W.A.J.G.; Donders, R.; Visser, L.H.

    2014-01-01

    BACKGROUND: For persons with multiple sclerosis (MS) it is important to preserve their autonomy, in spite of increasing disability. A major factor mediating autonomy is self-efficacy. According to the social cognitive theory stressors are crucial determinants of self-efficacy, as well as the

  8. An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol

    NARCIS (Netherlands)

    Jongen, P.J.; Heerings, M.; Ruimschotel, R.; Hussaarts, A.; Evers, S.; Duyverman, L.; Valkenburg-Vissers, J.; Cornelissen, J.; Bos, M.; Droffelaar, M. van; Lemmens, W.A.J.G.; Donders, R.; Zande, A. van der; Visser, L.H.

    2016-01-01

    BACKGROUND: In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found

  9. Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis

    DEFF Research Database (Denmark)

    Knudsen, S; Jennum, P J; Korsholm, K

    2008-01-01

    There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system...

  10. Muscle Fatigability During a Sustained Index Finger Abduction and Depression Scores Are Associated With Perceived Fatigue in Patients With Relapsing-Remitting Multiple Sclerosis

    NARCIS (Netherlands)

    Wolkorte, Ria; Heersema, Dorothea J.; Zijdewind, Inge

    Introduction. Fatigue is a common and debilitating symptom in patients with multiple sclerosis (MS). Self-reported levels of perceived fatigue are associated with both patient characteristics and clinical measures. Pilot analysis indicated that muscle fatigability combined with depression scores was

  11. Efficacy and Tolerability of Delayed-release Dimethyl Fumarate in Black, Hispanic, and Asian Patients with Relapsing-Remitting Multiple Sclerosis: Post Hoc Integrated Analysis of DEFINE and CONFIRM.

    Science.gov (United States)

    Fox, Robert J; Gold, Ralf; Phillips, J Theodore; Okwuokenye, Macaulay; Zhang, Annie; Marantz, Jing L

    2017-12-01

    Clinical course and treatment response may vary according to race/ethnicity in multiple sclerosis (MS) patients. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated significant efficacy and a favorable benefit-risk profile in relapsing-remitting MS (RRMS) patients in the 2-year phase III DEFINE/CONFIRM studies. In this post hoc analysis of integrated data from DEFINE/CONFIRM, we assessed clinical efficacy and safety/tolerability in black, Hispanic, and Asian patients treated with DMF 240 mg twice daily (approved dosage) or placebo. Eligible patients were 18-55 years of age with an Expanded Disability Status Scale score of 0-5.0. In the integrated intention-to-treat population, 769 and 771 patients were treated with DMF or placebo, respectively, of whom 10 and 19 were black, 31 and 23 were Hispanic, and 66 and 70 were Asian. In the black, Hispanic, and Asian subgroups, DMF was associated with lower annualized relapse rates at 2 years compared with placebo [rate ratio (95% confidence interval (CI)), 0.05 (0.00-1.07); 0.31 (0.10-0.95); and 0.64 (0.30-1.34), respectively]. The percentage of black, Hispanic, and Asian patients with 12-week confirmed disability progression was lower with DMF (43%, 8%, and 20%, respectively) compared with placebo [57%, 30%, and 25%, respectively; hazard ratio (95% CI), 0.53 (0.02-1.39); 0.17 (0.00-0.60); and 0.71 (0.32-1.58), respectively]. The safety/tolerability profile of DMF was generally consistent with that in the overall population of DEFINE/CONFIRM. The incidence of adverse events leading to treatment discontinuation in black, Hispanic, and Asian patients was 2/10, 2/31, and 3/66, respectively, with DMF, and 2/19, 1/23, and 8/70, respectively, with placebo. DMF may be an efficacious treatment with a favorable benefit-risk profile in black, Hispanic, and Asian patients with RRMS. Further clinical studies are needed to characterize differences in MS presentation and treatment outcomes across

  12. Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis.

    Science.gov (United States)

    Hernandez, Luis; Guo, Shien; Toro-Diaz, Hector; Carroll, Stuart; Syed Farooq, Syed Feisal

    2017-03-01

    Peginterferon beta-1a 125 mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland. A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year. Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44 mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20 mg. Results were most sensitive to variations in each DMT's efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators. Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either

  13. Improved self-efficacy in persons with relapsing remitting multiple sclerosis after an intensive social cognitive wellness program with participation of support partners: a 6-months observational study

    OpenAIRE

    Jongen, Peter Joseph; Ruimschotel, Rob; Heerings, Marco; Hussaarts, Astrid; Duyverman, Lotte; van der Zande, Anneke; Valkenburg-Vissers, Joyce; Wolper, Hanne; van Droffelaar, Maarten; Lemmens, Wim; Donders, Rogier; Visser, Leo H

    2014-01-01

    BACKGROUND: For persons with multiple sclerosis (MS) it is important to preserve their autonomy, in spite of increasing disability. A major factor mediating autonomy is self-efficacy. According to the social cognitive theory stressors are crucial determinants of self-efficacy, as well as the interaction with partners. METHODS: In an explorative observational study we assessed in 47 persons with MS (PwMS) the effect of an intense, multidisciplinary, 3-day, social cognitive wellness program wit...

  14. An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol

    OpenAIRE

    Jongen, P.J.; Heerings, M.; Ruimschotel, R.; Hussaarts, A.; Evers, S.; Duyverman, L.; Valkenburg-Vissers, J.; Cornelissen, J.; Bos, M.; Droffelaar, M. van; Lemmens, W.A.J.G.; Donders, R.; Van De Zande, A.; Visser, L. H.

    2016-01-01

    BACKGROUND: In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-relate...

  15. New and Emerging Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis: What is New and What is to Come

    Directory of Open Access Journals (Sweden)

    J. Nicholas

    2012-04-01

    Full Text Available The therapeutic landscape for multiple sclerosis (MS is rapidly changing. Currently, there are eight FDA approved disease modifying therapies for MS including: IFN-β-1a (Avonex, Rebif, IFN-β-1b (Betaseron, Extavia, glatiramer acetate (Copaxone, mitoxantrone (Novantrone, natalizumab (Tysabri, and fingolimod (Gilenya. This review will highlight the experience to date and key clinical trials of the newest FDA approved agents, natalizumab and fingolimod. It will also review available efficacy and safety data on several promising therapies under active investigation including four monoclonal antibody therapies: alemtuzumab, daclizumab, ocrelizumab and ofatumumab and three oral agents: BG12, laquinimod, and teriflunomide. To conclude, we will discuss where each of these new therapies may best fit into treatment algorithms.

  16. Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: study protocol for a cluster randomised controlled trial.

    Science.gov (United States)

    Rahn, Anne Christin; Köpke, Sascha; Kasper, Jürgen; Vettorazzi, Eik; Mühlhauser, Ingrid; Heesen, Christoph

    2015-03-21

    Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of evidence-based patient information and shared decision-making, has the potential to facilitate participation of individuals in the decision-making process. This cluster randomised controlled trial follows the assumption that decision coaching by trained nurses, using evidence-based patient information and preference elicitation, will facilitate informed choices and induce higher decision quality, as well as better decisional adherence. The decision coaching programme will be evaluated through an evaluator-blinded superiority cluster randomised controlled trial, including 300 patients with suspected or definite relapsing-remitting multiple sclerosis, facing an immunotherapy decision. The clusters are 12 multiple sclerosis outpatient clinics in Germany. Further, the trial will be accompanied by a mixed-methods process evaluation and a cost-effectiveness study. Nurses in the intervention group will be trained in shared decision-making, coaching, and evidence-based patient information principles. Patients who meet the inclusion criteria will receive decision coaching (intervention group) with up to three face-to-face coaching sessions with a trained nurse (decision coach) or counselling as usual (control group). Patients in both groups will be given access to an evidence-based online information tool. The primary outcome is 'informed choice' after six months, assessed with the multi-dimensional measure of informed choice including the sub-dimensions risk knowledge (questionnaire), attitude concerning immunotherapy (questionnaire), and immunotherapy uptake (telephone survey

  17. Patients with relapsing-remitting multiple sclerosis have normal Treg function when cells expressing IL-7 receptor α-chain are excluded from the analysis

    Science.gov (United States)

    Michel, Laure; Berthelot, Laureline; Pettré, Ségolène; Wiertlewski, Sandrine; Lefrère, Fabienne; Braudeau, Cécile; Brouard, Sophie; Soulillou, Jean-Paul; Laplaud, David-Axel

    2008-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease that results in demyelination in the central nervous system, and a defect in the regulatory function of CD4+CD25high T cells has been implicated in the pathogenesis of the disease. Here, we reanalyzed the function of this T cell subset in patients with MS, but we depleted cells expressing IL-7 receptor α-chain (CD127), a marker recently described as present on activated T cells but not Tregs. Similar to other studies, we observed a marked defect in the suppressive function of unseparated CD4+CD25high T cells isolated from MS patients. However, when CD127high cells were removed from the CD4+CD25high population, patient and control cells inhibited T cell proliferation and cytokine production equally. Likewise, when the CD25 gate used to sort the cells was stringent enough to eliminate CD127high cells, CD4+CD25high T cells from patients with MS and healthy individuals had similar regulatory function. Additional analysis indicated that the CD127high cells within the CD4+CD25high T cell population from patients with MS appeared more proliferative and secreted more IFN-γ and IL-2 than the same cells from healthy individuals. Taken together, we conclude that CD4+CD25highCD127low Tregs from MS patients and healthy individuals exhibit similar suppressive functions. The decreased inhibitory function of unfractioned CD4+CD25high cells previously observed might be due to abnormal activation of CD127high T cells in patients with MS. PMID:18769633

  18. Cognitive functioning and subjective quality of life in relapsing-remitting multiple sclerosis patients before and after percutaneous transluminal angioplasty: a preliminary report

    Directory of Open Access Journals (Sweden)

    De Pasquale C

    2014-06-01

    Full Text Available Concetta De Pasquale,1,2 Maria Luisa Pistorio,1 Massimiliano Veroux,2 Alessia Giaquinta,2 Pierfrancesco Veroux,2 Michele Fornaro11Department of Education Science, University of Catania, Catania, Italy; 2Vascular Surgery and Organ Transplant Unit, Department of Surgery Transplantation and Advanced Technologies, University Hospital of Catania, Catania, ItalyBackground: Multiple sclerosis (MS is a disease of the nervous system that has profound effects on everyday functioning and quality of life of not only the person who is diagnosed, but also her/his family and acquaintances. Despite this, the uncertainties of the actual etiological basis of MS make it difficult to reach a conclusive statement about the optimal therapeutic management of the disease, which may differ depending on the given case and phase of illness. This has led to an interest in potential novel therapeutic avenues, including percutaneous transluminal angioplasty (PTA. Yet, evidence in support of PTA in the management of MS is scarce and contradictory. The aim of the present study was to provide a preliminary assessment as to whether PTA may impact subjective quality of life and cognitive functioning in severe MS. Method: Ninety-five MS outpatients were followed-up for 24 months on a scheduled basis using the Milan Overall Dementia Assessment and the short-form 36-item scales, and were clinically evaluated by an appointed neurologist and psychiatrist. Results: At end point (month 24, only a minority of patients were still active in the study (n=33 or 34.74%. Among other measures, those who remained in the study until completion showed a significantly better Expanded Disability Status Scale and Milan Overall Dementia Assessment autonomy profile at study entrance compared to those patients who did not remain in the study until completion. Limitations were: a lack of any active control group; small sample size; Berkson’s bias; and selection by indication biases.Conclusion: Given

  19. Cost-effectiveness of different interferon beta products for relapsing-remitting and secondary progressive multiple sclerosis: Decision analysis based on long-term clinical data and switchable treatments.

    Science.gov (United States)

    Nikfar, Shekoufeh; Kebriaeezadeh, Abbas; Dinarvand, Rassoul; Abdollahi, Mohammad; Sahraian, Mohammad-Ali; Henry, David; Akbari Sari, Ali

    2013-06-22

    Multiple sclerosis (MS) is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000). Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF β) and their copied biopharmaceuticals (CBPs) and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs). A literature-based Markov model was developed to assess the cost-effectiveness of three INF βs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS) in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS). Disease progression transition probabilities for symptom management and INF β therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS). A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER) of cost/quality adjusted life year (QALY) for all available INF β products (brands, biosimilars and CBPs) were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model. ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($) respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913. The Markov pharmacoeconomics model determined that

  20. Iron deposition in the gray matter in patients with relapse-remitting multiple sclerosis: A longitudinal study using three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN)

    Energy Technology Data Exchange (ETDEWEB)

    Du, Silin, E-mail: 182389558@qq.com; Sah, Shambhu K., E-mail: mrsks2007@hotmail.com; Zeng, Chun, E-mail: zengchun19840305@163.com; Wang, Jingjie, E-mail: 345151097@qq.com; Liu, Yi, E-mail: 993537544@qq.com; Xiong, Hua, E-mail: rjdfxyh@163.com; Li, Yongmei, E-mail: lymzhang70@aliyun.com

    2015-07-15

    Purpose: To investigate the relationship between the iron content by magnetic resonance imaging (MRI) and clinic correlation in patients with relapse-remitting multiple sclerosis (RRMS) over a two-year period. Methods: Thirty RRMS patients and 30 healthy control subjects were examined twice, two years apart, by undergoing brain conventional MRI and three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN) sequences at 3.0 T. Quantitative differences in iron content in deep gray matter (GM) nuclei and precentral gyrus GM between patients and control subjects with repeated-measures the mean phase values (MPVs) for ESWAN-filtered phase images. Spearman's rank correlation coefficient analysis was used to evaluate correlations of the MPVs, both 2-year-difference and single-time measurements, to disease duration, expanded disability status scale (EDSS) and times of recurrence. Results: The RRMS patients had higher GM iron concentration than that of the healthy control subjects in both single-time measurements, but only the substantia nigra (SN), and the precentral gyrus GM (PGM) showed a significant statistical difference (p < 0.05). Using the paired samples t test, we found that there were significant differences in two-year-difference measurements of the MPVs in the putamen (PUT), the globus pallidus (GP), the head of the caudate nucleus (HCN), the thalamus (THA), SN, the red nucleus (RN), the dentate nucleus (DN) and PGM, especially in SN (t = 2.92, p = 0.007) in RRMS patients. The MPVs of the PUT, GP, HCN, THA, SN, RN, DN and PGM for the subgroup with RRMS patients in times of recurrence less than twice were similar to the healthy controls. There was no significant difference in all regions of interests (ROIs). However, there were significant differences in all ROIs except THA and GP for the other subgroup with RRMS patients in times of recurrence more than and equal to twice. Spearman's rank correlation coefficient analysis showed there were

  1. Cost-Effectiveness of Different Interferon Beta Products for Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: Decision Analysis Based on Long-Term Clinical Data and Switchable Treatments

    Directory of Open Access Journals (Sweden)

    Shekoufeh Nikfar

    2013-06-01

    Full Text Available Multiple sclerosis (MS is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000. Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF β and their copied biopharmaceuticals (CBPs and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs.Methods:A literature-based Markov model was developed to assess the cost-effectiveness of three INF βs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS. Disease progression transition probabilities for symptom management and INF β therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS. A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER of cost/quality adjusted life year (QALY for all available INF β products (brands, biosimilars and CBPs were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model.Results:ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($ respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913.Conclusions:The Markov

  2. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  3. 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

  4. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    Science.gov (United States)

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. © 2015 S. Karger AG, Basel.

  5. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS

    Science.gov (United States)

    Hutton, George J.; Racke, Michael K.; Popat, Uday; Devine, Steven M.; Steinmiller, Kaitlyn C.; Griffith, Linda M.; Muraro, Paolo A.; Openshaw, Harry; Sayre, Peter H.; Stuve, Olaf; Arnold, Douglas L.; Wener, Mark H.; Georges, George E.; Wundes, Annette; Kraft, George H.; Bowen, James D.

    2017-01-01

    Objective: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT). Methods: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0–5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE). Results: Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12–72). EFS was 69.2% (90% confidence interval [CI] 50.2–82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%–97.2%), 86.9% (90% CI 69.5%–94.7%), and 86.3% (90% CI 68.1%–94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of −0.5 (interquartile range −1.5 to 0.0; p = 0.001) among participants who survived and completed the study. Conclusion: HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years. ClinicalTrials.gov identifier: NCT00288626. Classification of evidence: This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT. PMID:28148635

  6. Memory B cells from a subset of treatment-naïve relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-γ production in response to myelin basic protein and myelin oligodendrocyte glycoprotein.

    Science.gov (United States)

    Harp, Christopher T; Ireland, Sara; Davis, Laurie S; Remington, Gina; Cassidy, Bonnie; Cravens, Petra D; Stuve, Olaf; Lovett-Racke, Amy E; Eagar, Todd N; Greenberg, Benjamin M; Racke, Michael K; Cowell, Lindsay G; Karandikar, Nitin J; Frohman, Elliot M; Monson, Nancy L

    2010-10-01

    Recent evidence suggests that B- and T-cell interactions may be paramount in relapsing-remitting MS (RRMS) disease pathogenesis. We hypothesized that memory B-cell pools from RRMS patients may specifically harbor a subset of potent neuro-APC that support neuro-Ag reactive T-cell proliferation and cytokine secretion. To test this hypothesis, we compared CD80 and HLA-DR expression, IL-10 and lymphotoxin-α secretion, neuro-Ag binding capacity, and neuro-Ag presentation by memory B cells from RRMS patients to naïve B cells from RRMS patients and to memory and naïve B cells from healthy donors (HD). We identified memory B cells from some RRMS patients that elicited CD4(+) T-cell proliferation and IFN-γ secretion in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Notwithstanding the fact that the phenotypic parameters that promote efficient Ag presentation were observed to be similar between RRMS and HD memory B cells, a corresponding capability to elicit CD4(+) T-cell proliferation in response to myelin basic protein and myelin oligodendrocyte glycoprotein was not observed in HD memory B cells. Our results demonstrate for the first time that the memory B-cell pool in RRMS harbors neuro-Ag specific B cells that can activate T cells.

  7. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

    DEFF Research Database (Denmark)

    Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

    2012-01-01

    The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

  8. Trichurs suis ova theraphy in relapsing multiple sclerosis is safe but without signals of beneficial effect

    DEFF Research Database (Denmark)

    Voldsgaard, A.; Bager, P.; Garde, E.

    2015-01-01

    BACKGROUND: An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. OBJECTIVE: To evaluate the safety and efficacy on MRI activity of treatment with ...... not change. CONCLUSIONS: In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect.......BACKGROUND: An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. OBJECTIVE: To evaluate the safety and efficacy on MRI activity of treatment...... with TSO in relapsing MS. METHODS: The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24-55) years, disease duration 9 (4-34) years, Expanded Disability Status...

  9. MRI findings in a remitting-relapsing case of Bickerstaff encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Mondejar, R.R. [Diagnostic Radiology Department, HGU Morales Meseguer, Murcia (Spain); Santos, J.M.G. [Diagnostic Radiology Department, HGU Morales Meseguer, Murcia (Spain); Section of Neuroradiology, HGU Morales Meseguer, Murcia (Spain); Villalba, E.F. [Section of Neurology, HGU Morales Meseguer, Murcia (Spain)

    2002-05-01

    A case of remitting-relapsing Bickerstaff encephalitis is reported. The article focuses on its imaging findings and their significance when a clinical differentiation between Bickerstaff encephalitis and Miller-Fisher syndrome is attempted. Signs and symptoms may occasionally overlap. However, because Miller-Fisher syndrome is related to the peripheral nervous system and Bickerstaff encephalitis is a central disease, the recognition of brain stem hypointense lesions on T1-weighted images, which are hyperintense on T2-weighted sequences, could be a reliable tool when the clinical diagnosis is unclear. (orig.)

  10. Monthly ambient sunlight, infections and relapse rates in multiple sclerosis.

    Science.gov (United States)

    Tremlett, Helen; van der Mei, Ingrid A F; Pittas, Fotini; Blizzard, Leigh; Paley, Glenys; Mesaros, Desiree; Woodbaker, Richard; Nunez, Manuel; Dwyer, Terence; Taylor, Bruce V; Ponsonby, Anne-Louise

    2008-01-01

    Monthly variation in multiple sclerosis (MS) relapses has been found. The relationship between seasonal environmental factors, infections, serum vitamin D [25(OH)D] and MS relapses is undetermined. We prospectively followed a population-based cohort of relapsing-remitting (RR) MS patients in Southern Tasmania for a mean 2.3 years (January 2002-April 2005). Associations between monthly ambient environmental factors, estimated serum 25(OH)D, upper respiratory tract (URT) infections and relapse rates were examined using weighted Pearson's correlation and linear regression. Of 199 definite MS patients, 142 had RRMS. The lowest relapse rate of 0.5 per 1,000 days (95% CI: 0.2-1.3) occurred in February (mid-late summer) versus the March-January RR of 1.1 per 1,000 days (95% CI: 0.9-1.3; p = 0.018, weighted regression). Monthly relapse rates correlated with: (1) prior erythemal ultraviolet radiation (EUV): lagged 1.5 months, r = -0.32, p = 0.046; (2) URT infection rate: no lag, r = 0.39, p = 0.014; (3) 25(OH)D: no lag, r = -0.31, p = 0.057. The association between URT infections and relapses was reduced after adjustment for monthly EUV. Relapse rates were inversely associated with EUV and serum 25(OH)D levels and positively associated with URT infections. The demonstrated lag between EUV but not 25(OH)D and relapse rates is consistent with a role for EUV-generated 25(OH)D in the alteration of relapse rates. Future work on the association between URT infections and relapses should be considered in the context of ultraviolet radiation and vitamin D. Copyright 2008 S. Karger AG, Basel.

  11. Depressed patients' perceptions of facial emotions in depressed and remitted states are associated with relapse - A longitudinal study

    NARCIS (Netherlands)

    Bouhuys, AL; Geerts, E; Gordijn, MCM

    1999-01-01

    Within the framework of interpersonal and cognitive theories of depression, we investigated whether the perception of facial emotions was associated with subsequent relapse into depression. The 23 inpatients with major depression who remitted (65 admitted patients) were studied at admission (TO), at

  12. Progression of relapsing-remitting demyelinating disease does not require increased TCR affinity or epitope spread.

    Science.gov (United States)

    Kersh, Anna E; Edwards, Lindsay J; Evavold, Brian D

    2014-11-01

    In this study, we investigate the basis of T cell recognition of myelin that governs the progression from acute symptoms into disease remission, relapse, and chronic progression in a secondary progressive model of demyelinating disease. Until now, the frequency and affinity of myelin-reactive CD4 T cells that elicit relapsing-remitting disease have not been quantified. The micropipette adhesion frequency assay was used to obtain a sensitive and physiologically relevant two-dimensional measurement of frequency and TCR affinity for myelin, as the inherent low affinity does not allow the use of specific peptide:MHC-II tetramers for this purpose. We found the highest affinity and frequency of polyclonal myelin oligodendrocyte glycoprotein-reactive cells infiltrate the CNS during acute disease, whereas affinities during remission, relapse, and chronic disease are not significantly different from each other. Frequency analysis revealed that the vast majority of CNS-infiltrating CD4 T cells are myelin oligodendrocyte glycoprotein reactive at all time points, demonstrating epitope spread is not a predominant factor for disease progression. Furthermore, time points at which mice were symptomatic were characterized by an infiltration of Th17 cells in the CNS, whereas symptom remission showed an enrichment of cells producing IFN-γ. Also, the ratio of regulatory T cells to Foxp3(-) CD4 T cells was significantly higher in the CNS at remission than during acute disease. The results of this study indicate that a high frequency of T cells specific for a single myelin Ag, rather than increased TCR affinity or epitope spread, governs the transition from acute symptoms through remission, relapse, and chronic disease states. Copyright © 2014 by The American Association of Immunologists, Inc.

  13. Comparison of efficacy and safety of oral agents for the treatment of relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Guarnera C

    2017-07-01

    Full Text Available Cristina Guarnera, Placido Bramanti, Emanuela Mazzon IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy Abstract: In the therapeutic scenario of disease-modifying therapies for relapsing–remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing–remitting multiple sclerosis, are reviewed in this work. Results of Phase III clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate – a superior efficacy compared to placebo. Fingolimod 0.5 mg consistently reduced clinical relapses and brain volume loss. In all Phase III studies, teriflunomide 14 mg dose showed a reduction in the risk of disability accumulation. Regarding safety profile, fingolimod had more safety issues than the other two agents. For this reason, it should be strictly monitored for risks of infections, cancers, and certain transitory effects such as irregular cardiac function, decreased lymphocyte count, and a higher level of liver enzymes. Adverse effects of teriflunomide are well characterized and can be considered manageable. The main risks marked with dimethyl fumarate were flushing and gastrointestinal events. Keywords: oral agents, comparison, efficacy, safety, relapsing-remitting multiple sclerosis

  14. Neural response to catecholamine depletion in remitted bulimia nervosa: Relation to depression and relapse.

    Science.gov (United States)

    Mueller, Stefanie Verena; Mihov, Yoan; Federspiel, Andrea; Wiest, Roland; Hasler, Gregor

    2017-07-01

    Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has involved the behavioral and neural responses to experimental catecholamine depletion. The purpose of this study was to examine the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its relationship to relapse. In a randomized, double-blind and crossover study design, catecholamine depletion was achieved by using the oral administration of alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up telephone interview, bulimic relapse was assessed. Following AMPT, rBN participants revealed an increased vigor reduction and CBF decreases in the pallidum and posterior midcingulate cortex (pMCC) relative to HC participants showing no CBF changes in these regions. These results indicated that the pallidum and the pMCC are the functional neural correlates of the dysregulated catecholamine system in bulimia nervosa. Bulimic relapse was associated with increased depressive symptoms and CBF reduction in the hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced increased CBF in this region predicted staying in remission. These findings demonstrated the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Investigating associations between cortisol and cognitive reactivity to sad mood provocation and the prediction of relapse in remitted major depression.

    Science.gov (United States)

    Chopra, K K; Segal, Z V; Buis, T; Kennedy, S H; Levitan, R D

    2008-12-01

    In remitted depressed patients, an increase in dysfunctional thoughts following a sad mood induction can predict relapse over 18 months. The current analysis examined whether salivary cortisol levels could also predict relapse in these same individuals. 99 subjects with major depression were first treated to full remission using either antidepressant medication or cognitive behavioural therapy. While in the remitted state, subjects were exposed to sad music to trigger dysfunctional thoughts. In a subset of 55 subjects, salivary cortisol levels taken before and after the mood challenge were also obtained. Unexpectedly, cortisol levels tended to decrease rather than increase following the mood challenge, suggesting that anticipation of the mood challenge was more stressful than the challenge itself. We thus used pre-challenge cortisol levels as the main grouping variable. Based on Kaplan-Meier survival curves, among subjects with low pre-challenge cortisol levels, those with a history of three or more prior episodes had significantly higher rates of relapse than did subjects with two or less prior episodes. In subjects with high pre-challenge cortisol levels, there was no significant difference in rates of relapse based on the number of prior episodes. In depressed patients with few prior episodes, assessing risk of relapse and thus establishing the duration for treatment can be a difficult clinical problem. Pending replication, the current results suggest that high anticipatory cortisol levels may have utility in predicting relapse even in patients with few prior episodes. Copyright © 2008 Elsevier B.V. All rights reserved.

  16. Intraventricularly Injected Olig2-NSCs Attenuate Established Relapsing-Remitting EAE in Mice

    NARCIS (Netherlands)

    Sher, Falak; Amor, Sandra; Gerritsen, Wouter; Baker, David; Jackson, Samuel L.; Boddeke, Erik; Copray, Sjef

    2012-01-01

    In multiple sclerosis (MS), a chronic inflammatory relapsing demyelinating disease, failure to control or repair damage leads to progressive neurological dysfunction and neurodegeneration. Implantation of neural stem cells (NSCs) has been shown to promote repair and functional recovery in the acute

  17. New rapid, accurate T2 quantification detects pathology in normal-appearing brain regions of relapsing-remitting MS patients.

    Science.gov (United States)

    Shepherd, Timothy M; Kirov, Ivan I; Charlson, Erik; Bruno, Mary; Babb, James; Sodickson, Daniel K; Ben-Eliezer, Noam

    2017-01-01

    Quantitative T2 mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2 changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38). The EMC algorithm uses Bloch simulations to model T2 decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings. T2 values were extracted from normal-appearing white and gray matter brain regions using both expert manual regions-of-interest and user-independent FreeSurfer segmentation. Compared to conventional exponential T2 modeling, EMC fitting provided more accurate estimations of T2 with less variance across scans, MRI systems, and healthy individuals. Thalamic T2 was increased 8.5% in RRMS subjects (p brain regions of RRMS patients. These presumably capture both axon and myelin changes from inflammation and neurodegeneration. Further, T2 variations between different brain regions of healthy controls may correlate with distinct nervous tissue environments that differ from one another at a mesoscopic length-scale.

  18. Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial

    NARCIS (Netherlands)

    Mikol, D.D.; Barkhof, F.; Chang, P.; Coyle, P.K.; Jeffery, D.R.; Schwid, S.R.; Stubinski, B.; Uitdehaag, B.M.J.

    2008-01-01

    Background: Interferon beta-1a and glatiramer acetate are commonly prescribed for relapsing-remitting multiple sclerosis (RRMS), but no published randomised trials have directly compared these two drugs. Our aim in the REGARD (REbif vs Glatiramer Acetate in Relapsing MS Disease) study was to compare

  19. A new small molecule for treating inflammation and chorioretinal neovascularization in relapsing-remitting and chronic experimental autoimmune uveitis.

    Science.gov (United States)

    Diedrichs-Möhring, Maria; Leban, Johann; Strobl, Stefan; Obermayr, Franz; Wildner, Gerhild

    2014-12-16

    We investigated the effect of PP-001, a new small molecule inhibitor of dihydro-orotate dehydrogenase in two experimental rat experimental autoimmune uveitis (EAU) models: a spontaneously relapsing-remitting model and a monophasic/chronic disease model that results in late chorioretinal neovascularization. Both of the diseases are induced by immunization with autoantigen peptides. Prevention was tested using daily oral applications of PP-001 after immunization with the retinal S-antigen peptide PDSAg (for induction of monophasic uveitis and neovascularization) or the interphotoreceptor retinoid-binding protein peptide R14 (for induction of spontaneously relapsing-remitting EAU). Treatment to inhibit relapses and neovascularization was tested using PP-001 daily after the first attack of R14-induced or after onset of PDSAg-induced EAU. Uveitis was graded clinically and histologically. The effect of PP-001 on cytokine secretion and proliferation was evaluated using rat T-cell lines. Preventive feeding of PP-001 abrogated both types of EAU. Starting treatment after the resolution of the first attack led to a significant reduction of the number and intensity of relapses in R14-induced EAU. PP-001-treatment initiated after onset or after peak of PDSAg-induced EAU significantly reduced neovascularization (as determined by histology). Proliferation of antigen-specific T-cell lines and secretion of IFN-γ, IL-17, IL-10, IP-10, and VEGF were efficiently suppressed by PP-001. We investigated a new dihydroorotate dehydrogenase inhibitor as treatment for primary and recurrent disease in relapsing-remitting and chronic rat models of experimental autoimmune uveitis. The small molecule compound PP-001 suppressed proliferation and cytokine secretion of autoreactive T cells (i.e., IFN-g, IL-17, and VEGF) and chorioretinal neovascularization in chronic EAU. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  20. Pathological Assessment of Brain White Matter in Relapsing-Remitting MS Patients using Quantitative Magnetization Transfer Imaging

    Directory of Open Access Journals (Sweden)

    Khodarahm Pahlevan

    2011-09-01

    Full Text Available Introduction: Multiple sclerosis (MS is characterized by lesions in the white matter (WM of the central nervous system. Magnetic resonance imaging is the most specific and sensitive method for diagnosis of multiple sclerosis. However, the ability of conventional MRI to show histopathologic heterogeneity of MS lesions is insufficient. Quantitative magnetization transfer imaging (qMTI is a relatively new method to investigate pathologic processes of the brain tissue occurring in MS patients. Material and Methods: Voxel-based analyses allow regional comparisons between groups to be made for the whole brain in a single analysis. This is done by coregistering data from all individual subjects to a reference brain, generally referred to as the "standard space", and then comparing them on a voxel-by-voxel basis. This study aimed to analyze whole-brain quantitative T1 maps, not to find global changes or changes in selected regions, but specifically to investigate the spatial distribution throughout the brain of T1 increases in MS WM with respect to control WM. In this study, 11 healthy controls, 10 relapsing-remitting (RR MS patients and 13 CIS patients were studied using MT-MRI imaging. MT parameters, including magnetization transfer ratio (MTR, magnetization transfer rate between free protons and restricted macromolecular protons, Ksat and longitudinal relaxation times (with and without MT saturation pulse, T1sat and T1free values were evaluated. Results: The results showed that, at a group level, there is widespread involvement of WM throughout the brain in CIS MS and especially in RRMS, where a significant T1 increase was found in 15.58% of WM voxels (normals < RR. Discussion and Conclusion: This study demonstrates that WM in large parts of the brain is susceptible to disease processes in RR and CIS MS

  1. A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing’s syndrome

    Directory of Open Access Journals (Sweden)

    M J Trott

    2016-05-01

    Full Text Available We present a case of a young female patient with a rare cause of relapsing and remitting Cushing’s syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing’s syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms ‘relapsing and remitting’ in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing’s syndrome with thymic neuroendocrine tumours (NETs, although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking.

  2. Intractable and highly active relapsing multiple sclerosis - role of alemtuzumab.

    Science.gov (United States)

    Dubey, Divyanshu; Cano, Christopher A; Stuve, Olaf

    2015-01-01

    Alemtuzumab is a humanized recombinant monoclonal antibody that was recently approved by the US Food and Drug Administration and the European Medicines Agency for the management of relapsing forms of multiple sclerosis (MS). It has been utilized for the management of chronic lymphocytic leukemia, bone marrow and renal transplantation, or graft versus host disease. Because of its immunomodulatory properties, it was brought into clinical development in MS. One Phase II (CAMMS223) and two Phase III clinical trials (CARE-MSI and -II) have evaluated the safety and efficacy of alemtuzumab in patients with relapsing-remitting MS. Even though its efficacy profile and long-lasting effect have attracted much interest among physicians and patients, it has significant potential adverse effects that may limit its use to patients with active disease. Here, we review the history of drug development of alemtuzumab. Furthermore, we outline the postulated mechanisms of action, clinical evidence, and safety of alemtuzumab for its use as a disease-modifying agent in active and highly active MS.

  3. Teriflunomide in relapsing multiple sclerosis: therapeutic utility

    OpenAIRE

    Freedman, Mark S

    2013-01-01

    Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent...

  4. Randomized trial of oral teriflunomide for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    O'Connor, Paul; Wolinsky, Jerry S; Confavreux, Christian

    2011-01-01

    Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis.......Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis....

  5. Comparison of efficacy and safety of oral agents for the treatment of relapsing–remitting multiple sclerosis

    Science.gov (United States)

    Guarnera, Cristina; Bramanti, Placido; Mazzon, Emanuela

    2017-01-01

    In the therapeutic scenario of disease-modifying therapies for relapsing–remitting multiple sclerosis, the introduction of oral agents, starting in 2010 with fingolimod, has been a huge step forward in therapeutic options due to the easier administration route. Three oral drugs fingolimod, teriflunomide, and dimethyl fumarate, which are clinically approved for the treatment of relapsing–remitting multiple sclerosis, are reviewed in this work. Results of Phase III clinical trials and their extension studies showed that the three oral agents significantly reduced the annualized relapse rate – a superior efficacy compared to placebo. Fingolimod 0.5 mg consistently reduced clinical relapses and brain volume loss. In all Phase III studies, teriflunomide 14 mg dose showed a reduction in the risk of disability accumulation. Regarding safety profile, fingolimod had more safety issues than the other two agents. For this reason, it should be strictly monitored for risks of infections, cancers, and certain transitory effects such as irregular cardiac function, decreased lymphocyte count, and a higher level of liver enzymes. Adverse effects of teriflunomide are well characterized and can be considered manageable. The main risks marked with dimethyl fumarate were flushing and gastrointestinal events. PMID:28814828

  6. Teriflunomide in relapsing multiple sclerosis: therapeutic utility.

    Science.gov (United States)

    Freedman, Mark S

    2013-09-01

    Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent benefits on both clinical and magnetic resonance imaging outcomes. In long-term studies, teriflunomide treatment was associated with low rates of relapse and disability progression for up to 8 years. The safety profile of teriflunomide has been well characterized, with adverse events generally mild to moderate in nature and infrequently leading to permanent treatment discontinuation. The evidence reviewed here indicates that teriflunomide is an effective addition to the current DMTs used to treat RMS.

  7. Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Damiano Paolicelli

    2009-07-01

    Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

  8. Risk of relapse phenotype recurrence in multiple sclerosis.

    Science.gov (United States)

    Kalincik, Tomas; Buzzard, Katherine; Jokubaitis, Vilija; Trojano, Maria; Duquette, Pierre; Izquierdo, Guillermo; Girard, Marc; Lugaresi, Alessandra; Grammond, Pierre; Grand'Maison, Francois; Oreja-Guevara, Celia; Boz, Cavit; Hupperts, Raymond; Petersen, Thor; Giuliani, Giorgio; Iuliano, Gerardo; Lechner-Scott, Jeannette; Barnett, Michael; Bergamaschi, Roberto; Van Pesch, Vincent; Amato, Maria Pia; van Munster, Erik; Fernandez-Bolanos, Ricardo; Verheul, Freek; Fiol, Marcela; Cristiano, Edgardo; Slee, Mark; Rio, Maria Edite; Spitaleri, Daniele; Alroughani, Raed; Gray, Orla; Saladino, Maria Laura; Flechter, Sholmo; Herbert, Joseph; Cabrera-Gomez, Jose Antonio; Vella, Norbert; Paine, Mark; Shaw, Cameron; Moore, Fraser; Vucic, Steve; Savino, Aldo; Singhal, Bhim; Petkovska-Boskova, Tatjana; Parratt, John; Sirbu, Carmen-Adella; Rozsa, Csilla; Liew, Danny; Butzkueven, Helmut

    2014-10-01

    The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype. Information about relapses was collected using MSBase, an international observational registry. Associations between relapse phenotypes and history of similar relapses or patient characteristics were tested with multivariable logistic regression models. Tendency of relapse phenotypes to recur sequentially was assessed with principal component analysis. Among 14,969 eligible patients (89,949 patient-years), 49,279 phenotypically characterised relapses were recorded. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were more frequent in early or non-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women presented more often with sensory or visual symptoms. Men were more prone to pyramidal, brainstem and cerebellar relapses. Importantly, relapse phenotype was predicted by the phenotypes of previous relapses. (OR = 1.8-5, p = 10(-14)). Sensory, visual and brainstem relapses showed better recovery than other relapse phenotypes. Relapse severity increased and the ability to recover decreased with age or more advanced disease. Relapse phenotype was associated with demographic and clinical characteristics, with phenotypic recurrence significantly more common than expected by chance. © The Author(s), 2014.

  9. A Case of Relapsing-Remitting Neuroborreliosis Challenges in the Differential Diagnosis of Recurrent Myelitis

    Directory of Open Access Journals (Sweden)

    P. Albrecht

    2012-03-01

    Full Text Available We report the case of a 31-year-old woman with 4 episodes of myelitis with pleocytosis, a positive Borrelia burgdorferi serology with positive antibody indices, and full recovery each time after antibiotic and steroid treatment, suggesting neuroborreliosis. We nevertheless believe that recurrent neuroborreliosis is improbable based on the levels of the chemokine CXCL13 in cerebrospinal fluid and favor the diagnosis of post-infectious autoimmune-mediated transverse myelitis possibly triggered by an initial neuroborreliosis as the cause of the relapses observed in our patient. We demonstrate the diagnostic steps and procedures which were important in the differential diagnosis of this unusual and challenging case.

  10. Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect.

    Science.gov (United States)

    Voldsgaard, A; Bager, P; Garde, E; Åkeson, P; Leffers, A M; Madsen, C G; Kapel, C; Roepstorff, A; Thamsborg, S M; Melbye, M; Siebner, H; Søndergaard, H B; Sellebjerg, F; Sørensen, P Soelberg

    2015-11-01

    An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. To evaluate the safety and efficacy on MRI activity of treatment with TSO in relapsing MS. The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24-55) years, disease duration 9 (4-34) years, Expanded Disability Status Scale score 2.5 (1-5.0), and number of relapses within the last two years 3 (2-5). Four patients received no disease modifying therapy, while six patients received IFN-β. After an observational period of 8 weeks, patients received 2500 ova from the helminth Trichuris suis orally every second week for 12 weeks. Patients were followed with serial magnetic resonance imaging, neurological examinations, laboratory safety tests and expression of immunological biomarker genes. Treatment with Trichuris suis orally was well-tolerated apart from some gastrointestinal symptoms. Magnetic resonance imaging revealed 6 new or enlarged T2 lesions in the run-in period, 7 lesions in the early period and 21 lesions in the late treatment period. Two patients suffered a relapse before treatment and two during treatment. Eight patients developed eosinophilia. The expression of cytokines and transcription factors did not change. In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect. © The Author(s), 2015.

  11. A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.

    Science.gov (United States)

    O'Connor, P W; Li, D; Freedman, M S; Bar-Or, A; Rice, G P A; Confavreux, C; Paty, D W; Stewart, J A; Scheyer, R

    2006-03-28

    Teriflunomide, a dihydro-orotate dehydrogenase inhibitor, has immunomodulatory effects, including the ability to suppress experimental allergic encephalomyelitis. In this randomized, double-blind, placebo-controlled Phase II study, the authors examined the safety and efficacy of oral teriflunomide in multiple sclerosis (MS) with relapses. Patients (n = 179) with relapsing-remitting MS (n = 157) or secondary progressive MS with relapses (n = 22) were randomized to receive placebo, teriflunomide 7 mg/day, or teriflunomide 14 mg/day for 36 weeks. MRI brain scans were performed every 6 weeks. The primary endpoint was the number of combined unique active lesions per MRI scan. Secondary endpoints included MRI-defined disease burden, relapse frequency, and disability increase. The median number of combined unique active lesions per scan was 0.5, 0.2, and 0.3 in the placebo, teriflunomide 7 mg/day (p teriflunomide 14 mg/day (p Teriflunomide-treated patients also had significantly fewer T1 enhancing lesions per scan, new or enlarging T2 lesions per scan, and new T2 lesions. Patients receiving teriflunomide 14 mg/day had significantly reduced T2 disease burden. Teriflunomide treatment resulted in trends toward a lower annualized relapse rate and fewer relapsing patients (14 mg/day only) vs placebo. Significantly fewer patients receiving teriflunomide 14 mg/day vs placebo demonstrated disability increase. Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups. Oral teriflunomide was effective in reducing MRI lesions and was well tolerated in patients with relapsing multiple sclerosis.

  12. Impact of multiple sclerosis relapse: The NARCOMS participant perspective.

    Science.gov (United States)

    Nickerson, Molly; Cofield, Stacey S; Tyry, Tuula; Salter, Amber R; Cutter, Gary R; Marrie, Ruth Ann

    2015-05-01

    Acute relapses continue to be a significant aspect of multiple sclerosis (MS) on both the epidemiologic level and the individual patient level. Past work demonstrates residual disability from relapses as well as high patient-reported rates of ineffective relapse treatment. To better characterize the impact of MS relapses on the patient, a relapse-specific survey was administered through the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry to 1000 registry participants who had reported at least one relapse in the past 12 months. Thirty percent of respondents confirmed lack of relapse treatment efficacy at one month and at three months. Relapses also impacted socioeconomic measures; for individuals still going to school or working, more than half missed days and their average loss of school or work was 12.7 days. An impact on household tasks was reported by 68% of respondents. A healthcare facility such as a hospital, emergency room or urgent care center was utilized by 20.4% of respondents. The most common relapse symptoms were fatigue, weakness of the lower extremity, sensory symptoms, problems walking, and weakness of the upper extremity. Of the respondents who reported receiving corticosteroid treatment (53.3%), over half reported an adverse event. However, this was not a significant factor in dictating whether or not respondents would seek a different treatment on their next relapse, although 31% would choose a different treatment for their next relapse. Relapses continue to be an impactful experience that requires continued clinical attention. Improved follow-up from relapses and relapse treatment might be beneficial. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  14. Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells

    Directory of Open Access Journals (Sweden)

    Or-Bach Rotem

    2009-07-01

    Full Text Available Abstract Background The ability to predict the spatial frequency of relapses in multiple sclerosis (MS would enable physicians to decide when to intervene more aggressively and to plan clinical trials more accurately. Methods In the current study our objective was to determine if subsets of genes can predict the time to the next acute relapse in patients with MS. Data-mining and predictive modeling tools were utilized to analyze a gene-expression dataset of 94 non-treated patients; 62 patients with definite MS and 32 patients with clinically isolated syndrome (CIS. The dataset included the expression levels of 10,594 genes and annotated sequences corresponding to 22,215 gene-transcripts that appear in the microarray. Results We designed a two stage predictor. The first stage predictor was based on the expression level of 10 genes, and predicted the time to next relapse with a resolution of 500 days (error rate 0.079, p Conclusion We conclude that gene expression analysis is a valuable tool that can be used in clinical practice to predict future MS disease activity. Similar approach can be also useful for dealing with other autoimmune diseases that characterized by relapsing-remitting nature.

  15. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Alireza Boloori

    Full Text Available Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM. Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT.To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications.We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1 immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid, (2 demographic and medical-related risk factors, and (3 inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1 a time-dependent model to analyze the recurrent cases of hyperglycemia and (2 a time-independent model to analyze the first incidence of hyperglycemia.Age (P = 0.018, HDL cholesterol (P = 0.010, and the average trough level of tacrolimus (P<0.0001 are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001, non-White race (P = 0.002, BMI (P = 0.002, HDL cholesterol (P = 0.003, uric acid (P = 0.012, and using steroid (P = 0.007 are the significant risk factors for the recurrent cases of hyperglycemia.This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.

  16. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients

    Science.gov (United States)

    Boloori, Alireza; Saghafian, Soroush; Chakkera, Harini A.; Cook, Curtiss B.

    2015-01-01

    Background Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT). Objective To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications). Methods We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia. Results Age (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (Phyperglycemia, while age (Phyperglycemia. Discussion This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature. PMID:26551468

  17. [Dimethyl fumarate (tecfidera) is the first line treatment choice in patients with remitting multiple sclerosis].

    Science.gov (United States)

    Shmidt, T E

    2017-01-01

    Dimethyl fumarate (DMF) is a new oral option for disease-modifying therapy (DMT) in patients with remitting multiple sclerosis as a first line treatment. The results of international randomized studies comparing DMF with placebo and other DMTs are presented. DMF is a DMT with promised efficacy and favorable safety profile that could be a treatment option for patients with suboptimal response for other first line DMTs and used as initial therapy for treatment-naive patients with unfavorable prognostic factors.

  18. Increased multiple sclerosis relapses related to lower prevalence of pain

    Directory of Open Access Journals (Sweden)

    José Vinícius Martins da Silva

    2015-07-01

    Full Text Available Objective The study aims to investigate the presence of pain amongst multiple sclerosis (MS patients. Method One hundred MS patients responded to questionnaires evaluating neuropathic and nociceptive pain, depression and anxiety. Statistical analysis was performed using the Mann–Whitney U, Chi-Square and two-tailed Fisher’s exact tests and multivariate logistic regression. Results Women had a statistically higher prevalence of pain (p = 0.037, and chances of having pain after the age of 50 reduced. Women with pain had a statistically significant lower number of relapses (p = 0.003, restricting analysis to those patients with more than one relapse. After the second relapse, each relapse reduced the chance of having pain by 46%. Presence of pain was independent of Expanded Disability Status Scale (EDSS anxiety, and depression. Conclusion Our findings suggest a strong inverse association between relapses and pain indicating a possible protective role of focal inflammation in the control of pain.

  19. 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

  20. Disease relapses in multiple sclerosis can be influenced by air pollution and climate seasonal conditions

    Directory of Open Access Journals (Sweden)

    Vojinović Slobodan

    2015-01-01

    Full Text Available Background/Aim. Environmental factors may influence the disease activity in patients with relapsing-remitting multiple sclerosis (MS. The aim of this study was to evaluate the influence of air pollution and seasonal climate factors of any on number of relapses in MS patients during a consecutive 5 years of observation. Methods. We retrospectively analyzed data of MS patients from the town of Niš, hospitalized at the Clinic of Neurology, Clinical Center Niš, Serbia, from 2005 to 2009. Climate data: mean daily sun shining; mean monthly sun shining, mean whole daily cloudiness, daily cloudiness at 7 a.m, 2 p.m. and 9 p.m. and air pollution expressed by NSR (New Source Review were obtained from the Meteorology Observatory Niš. Results. During a 5-year of observation there were 260 relapses in 101 MS patients. The number of relapses showed a significantly negative correlation with the number of days with NSR < 2 (ρ = -0.31; p < 0.01 and a positive correlation with the mean whole daily cloudiness (p < 0.05, mean daily cloudiness at 7 a.m. (p < 0.05 and 2 p.m. (p < 0.01. We found a significantly positive correlation (p < 0.05 between the reduced number of relapses during the period of high vitamin D season, i.e. July-October. There was a statistically significant increase (p < 0.01 of the number of relapses during spring (ґ = 6.53; SD = 3.98 compared to the other three seasons. The joint presence of lower number of days with NSR < 2 during low vitamin D season (January-April correlated with a statistically significant increase of the number of relapses in MS patients (F = 5.06, p < 0.01. Conclusion. The obtained results confirmed the influence of air pollution and climate seasonal conditions on disease relapses in MS patients based on a long-term observation. Lower numbers of days with low air pollution during the periods with low vitamin D (January-April, especially with increased cloudiness at 2 p.m, induce a higher risk of MS relapses in

  1. Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Slobodan M Jankovic

    2010-03-01

    Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

  2. New management algorithms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg

    2014-01-01

    complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis...

  3. Genetic variation in PBMC-produced IFN-γ and TNF-α associations with relapse in multiple sclerosis.

    Science.gov (United States)

    Zhou, Yuan; Taylor, Bruce; van der Mei, Ingrid; Stewart, Niall; Charlesworth, Jac; Blizzard, Leigh; Ponsonby, Anne-Louise; Dwyer, Terence; Pittas, Fotini; Simpson, Steve

    2015-02-15

    Alterations in peripheral blood mononuclear cell (PBMC) cytokine production have been found in multiple sclerosis (MS) compared to healthy controls. We have previously found that stimulated PBMC-produced TNF-α and IFN-γ modulated MS relapse risk, such that raised TNF-α was protective, while raised IFN-γ increased relapse risk. To assess whether SNPs within genes for relevant cytokines and their receptors modulate the associations of TNF-α and IFN-γ with relapse, thus providing additional information about these cytokine effects and the roles of these genes in MS. Prospective cohort of 91 participants with relapsing-remitting MS and cytokine and genotype data. SNPs (N=361) within a window of 10 kb around each cytokine/cytokine receptor gene (N=84) were selected for analysis. Predictors of PBMC cytokines were evaluated by multilevel mixed-effects linear regression. Predictors of relapse were evaluated by Cox proportional hazards regression. Bonferroni correction was used to adjust for multiple testing; thus p<1.39 × 10(-4) was defined as significant. Individuals of GG genotype of rs3218295 (within the gene IL2RB) demonstrated a significant protective effect of TNF-α on relapse while those of GA/AA genotype showed a significant positive association (pinteraction=5.04 × 10(-5)). Carriers of CC genotype of rs522807 (3' region of TNFRSF1B) and the AA genotype of rs25879 (5' region of IL3) showed a strong association between IFN-γ and increased relapse risk (pinteraction=8.21 × 10(-5) and 1.70 × 10(-5), respectively). Our results show novel modulation of TNF-α and IFN-γ associations with relapse by SNPs in major cytokines. These findings suggest the potential for these genes and/or their products as potential therapeutic targets in MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Modifiable factors influencing relapses and disability in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, M. B.; Nagels, G.; Bissay, V.; De Keyser, J.

    A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and

  5. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis.

    OpenAIRE

    Cohen, Jeffrey A; Barkhof, Frederik; Comi, Giancarlo; Hartung, Hans-Peter; Khatri, Bhupendra O; Montalban, Xavier; Pelletier, Jean; Capra, Ruggero; Gallo, Paolo; Izquierdo, Guillermo; Tiel-Wilck, Klaus; de Vera, Ana; Jin, James; Stites, Tracy; Wu, Stacy

    2010-01-01

    This trial showed the superior efficacy of oral fingolimod with respect to relapse rates and MRI outcomes in patients with multiple sclerosis, as compared with intramuscular interferon beta-1a. Longer studies are needed to assess the safety and efficacy of treatment beyond 1 year. (ClinicalTrials.gov number, NCT00340834.)

  6. Evolving concepts in the treatment of relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Comi, Giancarlo; Radaelli, Marta; Soelberg Sørensen, Per

    2017-01-01

    In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical...

  7. Novel modulating effects of PKC family genes on the relationship between serum vitamin D and relapse in multiple sclerosis.

    Science.gov (United States)

    Lin, Rui; Taylor, Bruce V; Simpson, Steve; Charlesworth, Jac; Ponsonby, Anne-Louise; Pittas, Fotini; Dwyer, Terence; van der Mei, Ingrid A F

    2014-04-01

    The interplay between genes and environmental factors on multiple sclerosis (MS) clinical course has been little studied. We conducted a prospective cohort study of 141 participants with relapsing-remitting MS (RRMS) and genotype data followed from 2002 to 2005 and examined genes in the vitamin D metabolism and vitamin D receptor (VDR)/retinoid X receptor (RXR) transcription factor formation pathway. Gene-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis. Genetic predictors of 25-hydroxyvitamin D (25(OH)D) were evaluated by multilevel mixed-effects linear regression. Significance threshold was adjusted by Bonferroni correction for the number of genes evaluated. The relationship between 25(OH)D and hazard of relapse was significantly different for different alleles of two intronic single nucleotide polymorphisms (SNPs) (rs908742 in PRKCZ and rs3783785 in PRKCH) in the protein kinase C (PKC) family genes (p(interaction)=0.001, p(adj)=0.021, respectively). Two other intronic SNPs (rs1993116 in CYP2R1and rs7404928 in PRKCB) were significantly associated with lower levels of 25(OH)D (p(interaction)=0.001, p(adj)=0.021, respectively). A cumulative effect of multiple 'risk' genotypes on 25(OH)D levels and hazard of relapse was observed for the significant SNPs (p(trend)=7.12×10(-6) for 25(OH)D levels, p(trend)=8.86×10(-6) for hazard of relapse). Our data support the hypothesis that gene-vitamin D interactions may influence MS clinical course and that the PKC family genes may play a role in the pathogenesis of MS relapse through modulating the association between 25(OH)D and relapse.

  8. Relapse of Multiple Myeloma Presenting as Lower Lip Numbness

    Directory of Open Access Journals (Sweden)

    Yusra M. Al-Riyami

    2016-11-01

    Full Text Available Multiple myeloma (MM is an uncommon malignancy characterised by the proliferation of clonal plasma cells. There are few published reports describing the extramedullary presentation of MM manifesting primarily in the head and neck region. In addition, the occurrence of an isolated relapse of MM in these sites is exceedingly rare. We report a 56-year-old female who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2010 with sudden-onset numbness of the lower lip. She had a history of MM in remission following chemotherapy and a bone marrow transplant. Clinical and radiographic examinations were indicative of a possible relapse of MM, which was subsequently confirmed by bone marrow aspiration and histopathological evaluation. This unique case highlights the unusual site of relapse of a haematolymphoid malignancy.

  9. Dimethyl fumarate for treating relapsing multiple sclerosis.

    Science.gov (United States)

    Sheremata, William; Brown, Andrew D; Rammohan, Kottil W

    2015-01-01

    Outcomes of two large double-blind placebo-controlled studies of oral dimethyl fumarate (DMF) in multiple sclerosis (MS) provided the basis for its marketing approval as Tecfidera® by the US FDA in early 2013 and the European Medicines Agency in February 2014. The safety of DMF is complemented by experience in the use of an oral mixture of fumaric acid esters, including DMF for psoriasis (Fumaderm®; DMF and monoethyl fumarate [DMF-MEF]) licensed in Germany in 1994. This article reviews the pivotal trials leading to the approval of DMF for MS and the pharmacological literature related to the extensive use of oral fumaric acid esters for psoriasis over the last quarter century. Anecdotal reports of serious adverse reactions to DMF-MEF are also reviewed in this report. DMF is generally safe and well tolerated. Flushing and gastrointestinal side effects are relatively common for the approved DMF dose but are ordinarily mild and self-limited. No increase in malignancies has been reported despite theoretical concerns. Although progressive multifocal encephalopathy has been reported anecdotally in 5 of > 196,000 patient-years of experience with fumaric acid esters, none of the 65,000 DMF MS patients treated in the first year has been affected. Appendix to the abstract: Subsequent to the acceptance of this article for publication, the manufacturer has notified physicians of the death of one patient from PML complicating use of DMF in the DEFINE study extension (ENDORSE). This does not alter the expert opinion rendered regarding the safety of DMF. We await the outcomes and recommendations from the ongoing investigation into this case.

  10. RGC-32 as a potential biomarker of relapse and response to treatment with glatiramer acetate in multiple sclerosis.

    Science.gov (United States)

    Kruszewski, Adam M; Rao, Gautam; Tatomir, Alexandru; Hewes, Daniel; Tegla, Cosmin A; Cudrici, Cornelia D; Nguyen, Vingh; Royal, Walter; Bever, Christopher T; Rus, Violeta; Rus, Horea

    2015-12-01

    Currently there is critical need for the identification of reliable biomarkers to help guide clinical management of multiple sclerosis (MS) patients. We investigated the combined roles of Response Gene to Complement 32 (RGC-32), FasL, CDC2, AKT, and IL-21 as possible biomarkers of relapse and response to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2 years, a cohort of 15 GA-treated RRMS patients was clinically monitored and peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, 6, and 12 months. Target gene mRNA expression was measured in patients' isolated PBMCs by real-time qRT-PCR. Compared to stable MS patients, those with acute relapses exhibited decreased expression of RGC-32 (p32 (p32, 88% for FasL, and 75% for IL-21. The probability of accurately detecting response to GA was 85% for RGC-32, 90% for FasL, and 85% for IL-21. Our data suggest that RGC-32, FasL, and IL-21 could serve as potential biomarkers for the detection of MS relapse and response to GA therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Tratamento do Mieloma Múltiplo recidivado Relapsed Multiple Myeloma treatment

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    Vania T. M. Hungria

    2007-03-01

    Full Text Available O mieloma múltiplo ainda é uma doença incurável. Apesar das novas estratégias de tratamento, a maioria dos pacientes recidiva. O padrão da recidiva é muito heterogêneo, podendo se apresentar com comportamento indolente ou agressivo. O tratamento da doença recidivada depende de vários fatores: do tratamento realizado como primeira linha, se transplante autólogo de medula óssea ou não, da resposta e sua duração, se a recidiva ocorreu com ou sem tratamento de manutenção, do performance status do paciente e da reserva medular. Se a recidiva ocorrer após seis meses do término do tratamento, o mesmo esquema quimioterápico inicial pode ser instituído. O transplante autólogo de medula óssea pode ser proposto como consolidação em recidivas quimiossensíveis ou como tratamento de resgate, se as células-tronco periféricas tiverem sido coletadas anteriormente. A talidomida tem sido utilizada em pacientes com mieloma múltiplo recidivado após quimioterapia convencional ou após o transplante autólogo da medula óssea. A talidomida sozinha pode induzir respostas objetivas em pelo menos 1/3 dos pacientes que já receberam muitos tratamentos; e quando combinada com quimioterapia, as respostas objetivas ocorrem em aproximadamente 2/3 dos pacientes. O bortezomibe está indicado em pacientes recidivados, sozinho ou associado a dexametasona e a outras drogas, com taxas de resposta de 43% a 76%. O melhor tratamento do paciente com mieloma múltiplo recidivado deve ser individualizado, dependendo da idade, da função da medula óssea, da terapia inicial, do padrão e tempo para a recidiva.Multiple myeloma still remains an incurable disease. Despite the new treatment approaches, almost all patients face the risk of an eventual relapse. The pattern of relapse is very heterogeneous and can be indolent or more aggressive. The treatment of relapsed disease depends on a number of factors: duration of response, relapse on or off maintenance

  12. Intractable and highly active relapsing multiple sclerosis – role of alemtuzumab

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    Dubey D

    2015-09-01

    Full Text Available Divyanshu Dubey,1 Christopher A Cano,1 Olaf Stuve1–3 1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, 2Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA; 3Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Abstract: Alemtuzumab is a humanized recombinant monoclonal antibody that was recently approved by the US Food and Drug Administration and the European Medicines Agency for the management of relapsing forms of multiple sclerosis (MS. It has been utilized for the management of chronic lymphocytic leukemia, bone marrow and renal transplantation, or graft versus host disease. Because of its immunomodulatory properties, it was brought into clinical development in MS. One Phase II (CAMMS223 and two Phase III clinical trials (CARE-MSI and -II have evaluated the safety and efficacy of alemtuzumab in patients with relapsing–remitting MS. Even though its efficacy profile and long-lasting effect have attracted much interest among physicians and patients, it has significant potential adverse effects that may limit its use to patients with active disease. Here, we review the history of drug development of alemtuzumab. Furthermore, we outline the postulated mechanisms of action, clinical evidence, and safety of alemtuzumab for its use as a disease-modifying agent in active and highly active MS. Keywords: alemtuzumab, multiple sclerosis, monoclonal antibody, CD52, idiopathic thrombocytopenic purpura

  13. Randomized trial of oral teriflunomide for relapsing multiple sclerosis.

    Science.gov (United States)

    O'Connor, Paul; Wolinsky, Jerry S; Confavreux, Christian; Comi, Giancarlo; Kappos, Ludwig; Olsson, Tomas P; Benzerdjeb, Hadj; Truffinet, Philippe; Wang, Lin; Miller, Aaron; Freedman, Mark S

    2011-10-06

    Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis. We concluded a randomized trial involving 1088 patients with multiple sclerosis, 18 to 55 years of age, with a score of 0 to 5.5 on the Expanded Disability Status Scale and at least one relapse in the previous year or at least two relapses in the previous 2 years. Patients were randomly assigned (in a 1:1:1 ratio) to placebo, 7 mg of teriflunomide, or 14 mg of teriflunomide once daily for 108 weeks. The primary end point was the annualized relapse rate, and the key secondary end point was confirmed progression of disability for at least 12 weeks. Teriflunomide reduced the annualized relapse rate (0.54 for placebo vs. 0.37 for teriflunomide at either 7 or 14 mg), with relative risk reductions of 31.2% and 31.5%, respectively (Pteriflunomide at 7 mg (P=0.08), and 20.2% with teriflunomide at 14 mg (P=0.03). Both teriflunomide doses were superior to placebo on a range of end points measured by magnetic resonance imaging (MRI). Diarrhea, nausea, and hair thinning were more common with teriflunomide than with placebo. The incidence of elevated alanine aminotransferase levels (≥1 times the upper limit of the normal range) was higher with teriflunomide at 7 mg and 14 mg (54.0% and 57.3%, respectively) than with placebo (35.9%); the incidence of levels that were at least 3 times the upper limit of the normal range was similar in the lower- and higher-dose teriflunomide groups and the placebo group (6.3%, 6.7%, and 6.7%, respectively). Serious infections were reported in 1.6%, 2.5%, and 2.2% of patients in the three groups, respectively. No deaths occurred. Teriflunomide significantly reduced relapse rates, disability progression (at the higher dose), and MRI evidence of disease activity, as compared with placebo. (Funded by Sanofi-Aventis; TEMSO ClinicalTrials.gov number, NCT00134563.).

  14. Work productivity in relapsing multiple sclerosis: associations with disability, depression, fatigue, anxiety, cognition, and health-related quality of life.

    Science.gov (United States)

    Glanz, Bonnie I; Dégano, Irene R; Rintell, David J; Chitnis, Tanuja; Weiner, Howard L; Healy, Brian C

    2012-12-01

    To characterize work productivity in relapsing multiple sclerosis (MS) by using a work productivity scale and to identify associations between work productivity and disability, depression, fatigue, anxiety, cognition, and health-related quality of life. Three hundred seventy-seven subjects with a clinically isolated syndrome or relapsing remitting MS participated in the study. Subjects underwent neurological examinations and completed patient-reported outcome and cognitive measures. Subjects also completed the Work Productivity and Activity Impairment Questionnaire: General Health to quantify absenteeism (missing work because of health problems), presenteeism (impairment while working), overall work impairment, and daily activity impairment attributable to health problems. Univariate correlations and multivariate models were used to determine the associations between each work productivity variable and clinical, patient-reported outcome, and cognitive measures. Seventy-six percent of subjects were employed. Fourteen percent of working subjects reported absenteeism, and 47% reported presenteeism. The mean work time lost because of absenteeism was 4%, and the mean work time lost because of presenteeism was 12%. Absenteeism was not significantly associated with disease or patient-reported outcome measures. Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. No associations were observed between presenteeism and disease duration or cognitive function. Subjects with clinically isolated syndrome/relapsing remitting MS reported substantial work productivity losses due to presenteesim. Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life. It is possible that the early identification and treatment of fatigue and mental health symptoms may improve productivity while working and extend employment for individuals

  15. Second auto-SCT for treatment of relapsed multiple myeloma.

    Science.gov (United States)

    Gonsalves, W I; Gertz, M A; Lacy, M Q; Dispenzieri, A; Hayman, S R; Buadi, F K; Dingli, D; Hogan, W J; Kumar, S K

    2013-04-01

    High-dose therapy and auto-SCT remain integral in the initial treatment of multiple myeloma (MM), and are increasingly being applied for management of relapsed disease. We examined the outcomes in 98 patients undergoing salvage auto-SCT (auto-SCT2) for relapsed MM after receiving an initial transplant (auto-SCT1) between 1994 and 2009. The median age at auto-SCT2 was 60 years (range: 35-74). The median time between auto-SCT1 and auto-SCT2 was 46 months (range: 10-130). Treatment-related mortality was seen in 4%. The median PFS from auto-SCT2 was 10.3 (95% confidence interval (CI): 7-14) months and the median OS from auto-SCT2 was 33 months (95% CI: 28-51). In a multivariable analysis, shorter time to progression (TTP) after auto-SCT1, not achieving a CR after auto-SCT2, higher number of treatment regimens before auto-SCT2 and a higher plasma cell labeling index at auto-SCT2 predicted for shorter PFS. However, only a shorter TTP after auto-SCT1 predicted for a shorter OS post auto-SCT2. Hence, auto-SCT2 is an effective and feasible therapeutic option for MM patients relapsing after other treatments, especially in patients who had a TTP of at least 12 months after their auto-SCT1.

  16. Systemic lupus erythematosus prevalence in the UK: methodological issues when using the General Practice Research Database to estimate frequency of chronic relapsing-remitting disease.

    Science.gov (United States)

    Nightingale, A L; Farmer, R D T; de Vries, C S

    2007-02-01

    The purpose of this study was to calculate the prevalence of systemic lupus erythematosus (SLE) between 1992 and 1998 using the General Practice Research Database (GPRD) METHODS: We identified all individuals who had contributed at least 3 years of data to the GPRD and who had a diagnosis of SLE with supporting evidence of their diagnosis. We calculated the annual age- and sex-specific prevalence of SLE. Additionally, we stratified the prevalence by years of data contributed to the GRPD. In males the point estimate of the prevalence of SLE increased from 7.5/100,000 (CI(95) 6.3, 8.8) to 10.1/100,000 (CI(95) 7.8, 12.2) but this rise was not statistically significant. However, prevalence appeared to increase significantly amongst females from 42.6/100,000 (CI(95) 39.6, 45.6) in 1992 to 70.8/100,000 (CI(95) 65.1, 76.6) in 1998. This increase was mainly amongst women aged 50-79 and in those contributing more than 5 years of data and could not be explained by increasing incidence of SLE or decreasing mortality during the study period. We found an increasing prevalence of SLE that could not be explained by increasing incidence or decreasing mortality. This is almost certainly an artefact caused by the increased likelihood of detecting or confirming cases of chronic relapsing-remitting diseases with increasing time contributed to the GPRD.

  17. Teriflunomide: a review of its use in relapsing multiple sclerosis.

    Science.gov (United States)

    Garnock-Jones, Karly P

    2013-12-01

    Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data

  18. Teriflunomide for the treatment of relapsing–remitting multiple sclerosis: patient preference and adherence

    Science.gov (United States)

    Bayas, Antonios; Mäurer, Mathias

    2015-01-01

    Multiple sclerosis (MS), a chronic demyelinating neuroinflammatory disease of the central nervous system, is the most common neurological disorder leading to disability in young adulthood. In the last 2 decades, numerous treatments for relapsing–remitting MS have been approved with eleven treatment options available worldwide. One of the determinants in treatment selection is disease activity in the individual patient. However, patient preferences play an increasingly major role in treatment decision making. With teriflunomide, a reversible inhibitor of the enzyme dihydroorotate dehydrogenase, a new oral therapeutic option, given once daily, has been approved within the last 2 years by the regulatory agencies. The current review focuses on characteristics of the drug relevant for patients’ preferences in the treatment decision process in the light of the available medications. Perceiving and considering patients’ preferences will have an effect on treatment adherence, which is known to be often low in MS patients. Teriflunomide-related adherence issues will also be discussed regarding mode of application, dosing, and potential side effects. PMID:25709412

  19. Teriflunomide for the treatment of relapsing–remitting multiple sclerosis: patient preference and adherence

    Directory of Open Access Journals (Sweden)

    Bayas A

    2015-02-01

    Full Text Available Antonios Bayas,1 Mathias Mäurer2 1Department of Neurology, Klinikum Augsburg, Augsburg, Germany; 2Department of Neurology, Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany Abstract: Multiple sclerosis (MS, a chronic demyelinating neuroinflammatory disease of the central nervous system, is the most common neurological disorder leading to disability in young adulthood. In the last 2 decades, numerous treatments for relapsing–remitting MS have been approved with eleven treatment options available worldwide. One of the determinants in treatment selection is disease activity in the individual patient. However, patient preferences play an increasingly major role in treatment decision making. With teriflunomide, a reversible inhibitor of the enzyme dihydroorotate dehydrogenase, a new oral therapeutic option, given once daily, has been approved within the last 2 years by the regulatory agencies. The current review focuses on characteristics of the drug relevant for patients’ preferences in the treatment decision process in the light of the available medications. Perceiving and considering patients’ preferences will have an effect on treatment adherence, which is known to be often low in MS patients. Teriflunomide-related adherence issues will also be discussed regarding mode of application, dosing, and potential side effects. Keywords: disease modifying treatment, oral, first line, pharmacovigilance

  20. Natalizumab for the treatment of relapsing multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Richard A Rudick

    2008-06-01

    Full Text Available Richard A Rudick1, Michael A Panzara21Cleveland Clinic Foundation, Cleveland, OH, USA; 2Biogen Idec, Inc., Cambridge, MA, USAAbstract: Natalizumab is an α4-integrin antagonist approved as monotherapy for patients with relapsing multiple sclerosis (MS, based on demonstrated efficacy in the pivotal AFFIRM study (N = 942. Natalizumab monotherapy reduced risk of disability progression by 42%–54% and annualized relapse rate by 68% during a period of 2 years. Natalizumab was also associated with significant reductions in number of T2-hyperintense, gadolinium-enhancing, and T1-hypointense lesions and in volume of T2-hyperintense lesions (all p < 0.001 on magnetic resonance imaging. Furthermore, natalizumab-treated patients in AFFIRM experienced significant improvements from baseline in the physical and mental components of the Short Form-36 (p ≤ 0.01 and a 35% reduction in risk of clinically significant vision loss (p = 0.008 vs placebo. Natalizumab was well tolerated in phase 3 studies. Common adverse events were generally mild and included headache, fatigue, urinary tract infections, and arthralgia. Serious adverse events were similar between treatment groups. The incidence of serious hypersensitivity reactions associated with natalizumab was <1%. Progressive multifocal leukoencephalopathy was a rare complication of treatment, observed in 2 patients with MS who received natalizumab plus interferon β-1a. The robust clinical benefits of natalizumab, including benefits on patient-reported quality of life, make it an important addition to disease-modifying therapies available to patients with relapsing MS.Keywords: multiple sclerosis, natalizumab, α4-integrin antagonist

  1. Teriflunomide: a novel oral treatment for relapsing multiple sclerosis.

    Science.gov (United States)

    Sartori, Arianna; Carle, Dawn; Freedman, Mark S

    2014-05-01

    Multiple sclerosis is a disabling chronic inflammatory disease of the CNS. New emerging oral treatments can offer efficacy with higher levels of therapeutic adherence. Teriflunomide is one such oral agent that has recently been approved for the treatment of relapsing multiple sclerosis (RMS). The aim of this review is to describe the pharmacological profile of teriflunomide and review the vast clinical development program that paved the way for its approval, with emphasis on its safety and tolerability. Teriflunomide is a safe new oral medication for treating RMS. It is effective at reducing relapses, MRI activity and slowing disability progression. It is well tolerated, with mild and transitory side effects. Although teriflunomide is given a pregnancy category 'X' by the FDA and an effective contraception is needed, to date, there has been no evidence of teratogenicity in humans and a rapid washout procedure can lead to a virtually complete elimination. Its effectiveness appeared to be at least comparable to that of high-dose IFN-β-1a, and although direct comparisons with other orals are still lacking, its tolerability and encouraging safety data suggest that teriflunomide could be considered an ideal first-line medication for RMS.

  2. [PAD regimen for relapsed or refractory patients with multiple myeloma].

    Science.gov (United States)

    Zhang, Yong-Qing; Liang, Rong; Bai, Qing-Xian; Zhang, Tao; Yang, Lan; Wang, Yi-Wei; Wang, Wen-Qing; Gu, Hong-Tao; Shu, Mi-Mi; Zhu, Hua-Feng; Bai, Yan-Ni; Chen, Xie-Qun

    2009-04-01

    To investigate the efficacy and safety of PAD [bortezomib (PS-341), doxorubicin and dexamethasone] regimen for relapsed or refractory multiple myeloma (MM). Seventeen patients with relapsed or refractory MM received two to four 21-day cycles of PAD: an intravenous bolus of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11; doxorubicin 10 mg per day on days 1 to 4, and dexamethasone 40 mg on days 1-4. Response was evaluated according to International Myeloma Working Group Criteria (IMWG 2006), toxicity was graded according to NCI CTCAE (common terminology criteria for adverse events) v 3.0. After 2-4 courses of PAD, 14 patients (82.4%) response, including complete response (CR) in 4 (23.5%), very good partial response (VGPR) in 4 (23.5%), partial response (PR) in 6 (35.3%) and stable disease (SD) in 3 (17.6%). Median time to progression was 9.5 months. The median course to response was 1.6 (1-3). All of 5 patients with extramedullary plasmacytoma achieved at least PR after the first cycle therapy; the plasmacytoma disappeared after 1-2 cycles of PAD. The efficacy was independent of other prognostic factors such as beta2-MG. Adverse events included thrombocytopenia in 9 patients (52.9%), leukopenia in 4 (23.5%), peripheral neuropathy in 4 (23.5%), varicella herpes zoster in 3 (17.6%), fatigue in 6 (35.3%) and diarrhea in 2 (11.7%). All of these adverse reactions could be controlled with routine supportive treatment, only one patient died from respiratory failure during his fifth PAD cycle. PAD regimen should be considered as an appropriate treatment for relapsed or refractory MM, especially for MM with extramedullary plasmacytoma. Its efficacy is independent of traditional prognostic factors. The side effects are usually manageable.

  3. Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Markus Gschwind

    2016-01-01

    In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.

  4. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Confavreux, Christian; O'Connor, Paul; Comi, Giancarlo; Freedman, Mark S; Miller, Aaron E; Olsson, Tomas P; Wolinsky, Jerry S; Bagulho, Teresa; Delhay, Jean-Luc; Dukovic, Deborah; Truffinet, Philippe; Kappos, Ludwig

    2014-03-01

    Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing or relapsing-remitting multiple sclerosis. We aimed to provide further evidence for the safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis. This international, randomised, double-blind, placebo-controlled, phase 3 study enrolled adults aged 18-55 years with relapsing multiple sclerosis, one or more relapse in the previous 12 months or two or more in the previous 24 months but no relapse in the previous 30 days, and an Expanded Disability Status Scale (EDSS) score of 5.5 points or less. Patients were recruited from 189 sites in 26 countries and randomly assigned (1:1:1) to once-daily placebo, teriflunomide 7 mg, or teriflunomide 14 mg via an interactive voice recognition system. Treatment duration was variable, ending 48 weeks after the last patient was included. The primary endpoint was annualised relapse rate (number of relapses per patient-year) and the key secondary endpoint was time to sustained accumulation of disability (an EDSS score increase of at least 1 EDSS point sustained for a minimum of 12 weeks), both analysed in the modified intention-to-treat population (all patients who received at least one dose of assigned study medication). This study is registered with ClinicalTrials.gov, number NCT00751881. Between Sept 17, 2008, and Feb 17, 2011, 1169 patients were randomly assigned to a treatment group, of whom 388, 407, and 370 patients received at least one dose of placebo, teriflunomide 7 mg, or teriflunomide 14 mg, respectively. By the end of the study, the annualised relapse rate was higher in patients assigned to placebo (0.50 [95% CI 0.43-0.58]) than in those assigned to teriflunomide 14 mg (0.32 [0.27-0.38]; p=0.0001) or teriflunomide 7 mg (0.39 [0.33-0.46]; p=0.0183). Compared with placebo, teriflunomide 14 mg reduced the risk of sustained accumulation of disability (hazard ratio [HR] 0.68 [95% CI 0.47-1.00]; log-rank p=0

  5. Effect of dimethyl fumarate on gray and white matter pathology in subjects with relapsing multiple sclerosis: a longitudinal study.

    Science.gov (United States)

    Zivadinov, R; Hagemeier, J; Bergsland, N; Tavazzi, E; Weinstock-Guttman, B

    2018-03-01

    Dimethyl fumarate (DMF) is an oral treatment for relapsing-remitting multiple sclerosis (MS) with anti-inflammatory and possible neuroprotective properties. Its effect on white matter and gray matter pathology is still not fully understood. The aim of the study was to characterize the effect of DMF on normal-appearing white matter (NAWM) and thalamic pathology longitudinally. In this observational, longitudinal, 24-month magnetic resonance imaging study, 75 patients with relapsing-remitting MS treated with DMF and 40 age- and sex-matched healthy individuals were enrolled. Regional diffusion tensor imaging metrics and tract-based spatial statistics analyses were used to assess differences between groups. Mean diffusivity, axial diffusivity, radial diffusivity and fractional anisotropy were measured in the thalamus and NAWM. Baseline differences and changes over time were evaluated within and between study groups. At baseline, patients with MS showed significantly increased diffusivity and decreased fractional anisotropy in the thalamus (P < 0.001 for mean diffusivity, axial diffusivity and radial diffusivity) and NAWM (all P < 0.016) compared with healthy individuals. No significant within-group difference was found in diffusion tensor imaging measures over 24 months in either group. Healthy individuals showed a significantly greater rate of increased diffusivity parameters in the thalamus and NAWM compared with patients with MS, over 24 months (P < 0.05). The lack of changes in diffusion tensor imaging metrics in patients with MS over 24 months possibly indicates a neuroprotective role of DMF. These findings provide additional evidence of the beneficial effect of DMF on MS-related pathology. © 2018 EAN.

  6. Total cost comparison in relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Durie, Brian; Binder, Gary; Pashos, Chris; Khan, Zeba; Hussein, Mohamad; Borrello, Ivan

    2013-01-01

    Advances in survival in multiple myeloma have focused payer attention on the cost of care. An assessment was conducted to compare the costs of two recent treatments for relapsed/refractory multiple myeloma (rrMM), from the perspective of a US payer. An economic model estimated the total costs of care for two guideline-recommended therapies in rrMM patients: bortezomib (BORT) and lenalidomide plus dexamethasone (LEN/DEX). To evaluate total treatment costs, the costs associated with drug treatment, medical resource utilization, and adverse event (AE) management were determined for each regimen over a common 1-year period. Medical costs and grade 3/4 AE costs were based on rates from published literature, package inserts, and fee schedules (US dollars). To evaluate cost per outcome, assessments determined the monthly costs without disease progression based on pivotal clinical trials (APEX [BORT] and MM-009/MM-010 [LEN/DEX]). Univariate sensitivity analyses and alternative scenarios were also conducted. Drug costs for the treatments were very similar, differing by under $10 per day. Medical and AE management costs for BORT were higher by more than $40 per day. Treatment with BORT had annual excess total costs of >$17,000 compared with LEN/DEX. A cost advantage for LEN/DEX was maintained across a variety of sensitivity analyses. Total cost per month without progression was 11% lower with LEN/DEX. This analysis relied on separate studies having similar comparators, populations, and end-points. Actual treatment patterns and costs pre- and post-relapse may vary from the base scenario and sensitivities modeled. The 12-month time frame captures the preponderance of costs for a relapse line of therapy, yet may not reflect the entirety of costs. There is insufficient evidence to determine whether, or how, a difference in the lifetime costs of the two regimens would vary from the 1-year cost difference. While rrMM treatment with BORT and LEN/DEX had comparable drug costs, total

  7. Risk Knowledge in Relapsing Multiple Sclerosis (RIKNO 1.0--Development of an Outcome Instrument for Educational Interventions.

    Directory of Open Access Journals (Sweden)

    C Heesen

    Full Text Available Adequate risk knowledge of patients is a prerequisite for shared decision making but few attempts have been made to develop assessment tools. Multiple Sclerosis (MS is a chronic inflammatory disease of young adults with an increasing number of partially effective immunotherapies and therefore a paradigmatic disease to study patient involvement.Based on an item bank of MS risk knowledge items and patient feedback including perceived relevance we developed a risk knowledge questionnaire for relapsing remitting (RR MS (RIKNO 1.0 which was a primary outcome measure in a patient education trial (192 early RRMS patients.Fourteen of the RIKNO 1.0 multiple-choice items were selected based on patient perceived relevance and item difficulty indices, and five on expert opinion. Mean item difficulty was 0.58, ranging from 0.14 to 0.79. Mean RIKNO 1.0 score increased after the educational intervention from 10.6 to 12.4 (p = 0.0003. Selected items were particularly difficult (e.g. those on absolute risk reductions of having a second relapse and were answered correctly in only 30% of the patients, even after the intervention.Despite its high difficulty, RIKNO 1.0 is a responsive instrument to assess risk knowledge in RRMS patients participating in educational interventions.

  8. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... About the Society d Vision Strategic Plan Independent Review of Society's Research Programs d Careers d Leadership Board of Directors Senior Leadership Team Founder Sylvia Lawry d Cultural Values d Financials Annual Reports Sources of Support d News d ...

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    Full Text Available ... Disease T Cells d What Causes MS? Disproved Theories Viruses Clusters d Who Gets MS? Pediatric MS ... times as often as men; in PPMS, the number of women and men are approximately equal. RRMS ...

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    Full Text Available ... Become an MS Activist Take Action Current Advocacy Issues Advocacy Results Advocacy News d Raise Awareness d ... all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent ...

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    Full Text Available ... bowel and bladder problems, and problems with cognition (learning and memory or information processing). People with progressive ... Call 1-800-344-4867 or contact us online. Contact Us Contact Us Newly Diagnosed If you ...

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    Full Text Available ... which contain fewer inflammatory cells. In RRMS, women are affected two to three times as often as men; in PPMS, the number of women and men are approximately equal. RRMS is diagnosed earlier than the ...

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    Full Text Available ... Other Ways to Give Donate by Mail or Phone d About the Society d Vision Strategic Plan ... times as often as men; in PPMS, the number of women and men are approximately equal. RRMS ...

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  15. Understanding the positive benefit:risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical Development Program

    Directory of Open Access Journals (Sweden)

    Havrdova E

    2017-10-01

    Full Text Available Eva Havrdova,1 Jeffrey A Cohen,2 Dana Horakova,1 Ivana Kovarova,1 Eva Meluzinova3 1Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; 2Neurological Institute, Cleveland Clinic, Cleveland, OH, USA; 3Department of Neurology, Second Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic Abstract: The introduction of high-efficacy therapies for relapsing–remitting multiple sclerosis has driven re-evaluation of treatment goals and benefit:risk considerations in treatment choice. In the alemtuzumab Phase II and III clinical trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon beta-1a demonstrated significantly reduced annualized relapse rates and improved magnetic resonance imaging outcomes, and were significantly more likely to achieve no evidence of disease activity and reduction in brain volume loss. In two of the studies, alemtuzumab-treated patients had a significantly reduced risk of 6-month confirmed disease worsening, compared with subcutaneous interferon beta-1a. Benefits were maintained throughout 5 years, with a majority of patients receiving no alemtuzumab retreatment or other disease-modifying therapy. Trial results support alemtuzumab’s manageable, consistent safety profile in relapsing–remitting multiple sclerosis. Infusion-associated reactions, the most frequent adverse events (AEs, can be minimized by corticosteroid pretreatment, monitoring, and symptomatic management. Other AEs include infections and autoimmune events. Oral anti-herpes prophylaxis should be initiated on the first day of each alemtuzumab treatment course and continued according to local guidelines. Overall cancer risk was lower in the alemtuzumab clinical trials than in a reference population; however, continuing surveillance will determine if alemtuzumab may be associated with

  16. Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

    NARCIS (Netherlands)

    De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

    The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

  17. Assessing Relapse in Multiple Sclerosis Questionnaire: Results of a Pilot Study

    Directory of Open Access Journals (Sweden)

    Amy Perrin Ross

    2013-01-01

    Full Text Available There is need for a brief but comprehensive objective assessment tool to help clinicians evaluate relapse symptoms in patients with multiple sclerosis (MS and their impact on daily functioning, as well as response to treatment. The 2-part Assessing Relapse in Multiple Sclerosis (ARMS questionnaire was developed to achieve these aims. Part 1 consists of 7 questions that evaluate relapse symptoms, impact on activities of daily living (ADL, overall functioning, and response to treatment for previous relapses. Part 2 consists of 7 questions that evaluate treatment response in terms of symptom relief, functioning, and tolerability. The ARMS questionnaire has been evaluated in 103 patients with MS. The most commonly reported relapse symptoms were numbness/tingling (67%, fatigue (58%, and leg/foot weakness (55%. Over half of patients reported that ADL or overall functioning were affected very much (47% or severely (11% by relapses. Prescribed treatments for relapses included intravenous and/or oral corticosteroids (87% and adrenocorticotropic hormone (13%. Nearly half of patients reported that their symptoms were very much (33% or completely resolved (16% following treatment. The most commonly reported adverse events were sleep disturbance (45%, mood changes (33%, weight gain (29%, and increased appetite (26%. Systematic assessment of relapses and response to relapse treatment may help clinicians to optimize outcomes for MS patients.

  18. Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis Determinação dos níveis de ICAM-1 e TNFalfaR solúvel no líquido cefalorraqueano e soro numa população de pacientes brasileiros com esclerose múltipla forma surto-remissão

    Directory of Open Access Journals (Sweden)

    Soniza Vieira Alves-Leon

    2001-03-01

    Full Text Available Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS, a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF and serum levels of soluble intercellular adhesion molecule (ICAM-1 and TNFalphaR (60kD from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (pCitocinas e moléculas de adesão estão implicadas na patogênese da esclerose múltipla (EM, uma doença inflamatória crônica do sistema nervoso central. Neste estudo, nós determinamos os níveis solúveis da molécula de adesão intercelular (sICAM-1 e TNFalfaR (60kD no soro e líquido cefalorraqueano (LCR de 20 pacientes com EM clinicamente definida durante surto ou remissão. Os pacientes com EM apresentaram, em comparação com os grupos controle formados por indivíduos sadios e com hérnia de disco intervertebral submetidos a mielografia, níveis significativamente (p< 0.001 elevados de sICAM-1 e TNFalfaR tanto no soro como no LCR. Independente do estágio da doença, nenhuma diferença significativa foi encontrada entre os pacientes durante o surto (657±124.9 ng/ml ou na remissão (627±36.2 ng/ml. Um aumento consistente dos níveis de TNFalfaR no soro e LCR, apontam para a existência de processo inflamatório continuado no tecido cerebral dos pacientes com EM, a despeito da ausência de sinais clínicos de doença em atividade.

  19. Relapse of Multiple Myeloma Presenting as Extramedullary Plasmacytomas in Multiple Organs

    Directory of Open Access Journals (Sweden)

    Murat Köse

    2015-01-01

    Full Text Available Multiple myeloma is a neoplastic plasma cell disorder. It is characterized by collections of abnormal plasma cells accumulating in the bone marrow, where they interfere with the production of normal blood cells. It usually presents as a multisystemic involvement, whose symptoms and signs vary greatly. Some patients have slowly progressive disease while others have aggressive clinical behavior by extramedullary involvement. In addition to renal failure, anemia, hypercalcemia, lytic bone lesions, and immunodeficiency, it also affects multiple organ system, such as pancreas, adrenal glands, kidney, skin, lung, liver, spleen, lymph nodes, and bone. To raise awareness of the variable presentations of this disease, we report a 53-year-old male patient, with multiple myeloma in his first remission who relapsed with extramedullary plasmacytomas (EMPs involving multiple organs, such as pancreas, adrenal glands, kidney, skin, lung, liver, spleen, and lymph nodes.

  20. Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

    2015-01-01

    Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...

  1. Multiple-clone activation of hypnozoites is the leading cause of relapse in Plasmodium vivax infection.

    Directory of Open Access Journals (Sweden)

    Flávia Carolina F de Araujo

    Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.

  2. Comorbidity increases the risk of relapse in multiple sclerosis: A prospective study.

    Science.gov (United States)

    Kowalec, Kaarina; McKay, Kyla A; Patten, Scott B; Fisk, John D; Evans, Charity; Tremlett, Helen; Marrie, Ruth Ann

    2017-12-12

    To evaluate the association between comorbidity and relapse rate in individuals with multiple sclerosis (MS). We recruited individuals with prevalent relapsing-onset MS from 4 Canadian MS Clinics to participate in a 2-year prospective multicenter cohort study involving cross-sectional assessment of comorbidities and relapses. Comorbidities were recorded using questionnaires, and relapses were captured from medical records at each visit. The association between comorbidities at baseline and relapse rate over the subsequent 2-year follow-up period was examined using Poisson regression, adjusting for age, sex, disability, disease duration, and treatment status. Of 885 participants, 678 (76.6%) were women, averaging age 48.2 years at baseline. Anxiety (40.2%), depression (21.1%), hypertension (17.7%), migraine (18.1%), and hyperlipidemia (11.9%) were the most prevalent comorbidities. The frequency of participants experiencing relapses remained constant at 14.9% and 13.2% in years 1 and 2 post-baseline. After adjustment, participants reporting ≥3 baseline comorbidities (relative to none) had a higher relapse rate over the subsequent 2 years (adjusted rate ratio 1.45, 95% confidence interval [CI] 1.00-2.08). Migraine and hyperlipidemia were associated with increased relapse rate (adjusted rate ratio 1.38; 95% CI 1.01-1.89 and 1.67; 95% CI 1.07-2.61, respectively). Individuals with migraine, hyperlipidemia, or a high comorbidity burden (3 or more conditions) had an increased relapse rate over 2 years. These findings have potential implications for understanding the pathophysiology of MS relapses, and suggest that closer monitoring of individuals with specific or multiple comorbidities may be needed. Future research is needed to understand if the presence of comorbidity warrants a tailored approach to MS management. © 2017 American Academy of Neurology.

  3. Multiple Sclerosis

    OpenAIRE

    Gaby, Alan

    2013-01-01

    Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. M...

  4. Multiple sclerosis

    OpenAIRE

    Nicholas, Richard; Rashid, Waqar

    2012-01-01

    Multiple sclerosis is characterised by central nervous system lesions causing neurological dysfunction and other problems, such as fatigue, pain, depression, and anxiety. Early disease is usually relapsing and remitting, but most people develop secondary-progressive disease over time. No treatment has been shown to affect long-term outcome.Irreversible disability can occur, but life expectancy is generally not affected.

  5. NMR-Based Metabolomics Separates the Distinct Stages of Disease in a Chronic Relapsing Model of Multiple Sclerosis.

    Science.gov (United States)

    Dickens, Alex M; Larkin, James R; Davis, Benjamin G; Griffin, Julian L; Claridge, Timothy D W; Sibson, Nicola R; Anthony, Daniel C

    2015-09-01

    Relapsing experimental allergic encephalomyelitis (Cr-EAE) is commonly used to explore the pathogenesis and efficacy of new therapies for MS, but it is unclear whether the metabolome of Cr-EAE is comparable to human multiple sclerosis (MS). For MS, the diagnosis and staging can be achieved by metabolomics on blood using a combination of magnetic resonance spectroscopy and partial least squares discriminant analysis (PLS-DA). Here, we sought to discover whether this approach could be used to differentiate between sequential disease states in Cr-EAE and whether the same metabolites would be discriminatory. Urine and plasma samples were obtained at different time-points from a clinically relevant model of MS. Using PLS-DA modelling for the urine samples furnished some predictive models, but could not discriminate between all disease states. However, PLS-DA modelling of the plasma samples was able to distinguish between animals with clinically silent disease (day 10, 28) and animals with active disease (day 14, 38). We were also able to distinguish Cr-EAE mice from naive mice at all-time points and control mice, treated with complete Freund's adjuvant alone, at day 14 and 38. Key metabolites that underpin these models included fatty acids, glucose and taurine. Two of these metabolites, fatty acids and glucose, were also key metabolites in separating relapsing-remitting MS from secondary-progressive MS in the human study. These results demonstrate the sensitivity of this metabolomics approach for distinguishing between different disease states. Furthermore, some, but not all, of the changes in metabolites were conserved in humans and the mouse model, which could be useful for future drug development.

  6. Lenalidomide for the treatment of relapsed and refractory multiple myeloma

    Science.gov (United States)

    van de Donk, Niels WCJ; Görgün, Güllü; Groen, Richard WJ; Jakubikova, Jana; Mitsiades, Constantine S; Hideshima, Teru; Laubach, Jacob; Nijhof, Inger S; Raymakers, Reinier A; Lokhorst, Henk M; Richardson, Paul G; Anderson, Kenneth C

    2012-01-01

    Lenalidomide is an amino-substituted derivative of thalidomide with direct antiproliferative and cytotoxic effects on the myeloma tumor cell, as well as antiangiogenic activity and immunomodulatory effects. Together with the introduction of bortezomib and thalidomide, lenalidomide has significantly improved the survival of patients with relapsed and refractory myeloma. The most common adverse events associated with lenalidomide include fatigue, skin rash, thrombocytopenia, and neutropenia. In addition, when lenalidomide is combined with dexamethasone or other conventional cytotoxic agents, there is an increase in the incidence of venous thromboembolic events. There is now evidence that continued treatment with lenalidomide has a significant impact on survival by improving the depth and duration of response. This highlights the value of adverse event management and appropriate dose adjustments to prevent toxicity, and of allowing continued treatment until disease progression. In this review, we will discuss the different lenalidomide-based treatment regimens for patients with relapsed/refractory myeloma. This is accompanied by recommendations of how to manage and prevent adverse events associated with lenalidomide-based therapy. PMID:22956884

  7. A phase I trial of flavopiridol in relapsed multiple myeloma.

    Science.gov (United States)

    Hofmeister, Craig C; Poi, Ming; Bowers, Mindy A; Zhao, Weiqiang; Phelps, Mitch A; Benson, Don M; Kraut, Eric H; Farag, Sherif; Efebera, Yvonne A; Sexton, Jennifer; Lin, Thomas S; Grever, Michael; Byrd, John C

    2014-02-01

    Flavopiridol is primarily a cyclin-dependent kinase-9 inhibitor, and we performed a dose escalation trial to determine the maximum tolerated dose and safety and generate a pharmacokinetic (PK) profile. Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus and then continuous infusion weekly for 4 weeks in a 6-week cycle. Fifteen patients were treated at three dose levels (30 mg/m(2) bolus, 30 mg/m(2) CIV to 50 mg/m(2) bolus, and 50 mg/m(2) CIV). Cytopenias were significant, and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients and grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein >50 % that did not persist. PK properties were similar to prior publications, and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. Flavopiridol as a single agent given by bolus and then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723).

  8. Barkhof Magnetic Resonance Imaging Criteria Predict Early Relapse in Pediatric Multiple Sclerosis

    NARCIS (Netherlands)

    Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    We sought to identify clinical and radiologic features predicting early relapse after a diagnosis of multiple sclerosis in children. In this nationwide retrospective multicenter study in The Netherlands, we included 28 children with multiple sclerosis with onset before age 16 years. Magnetic

  9. Barkhof magnetic resonance imaging criteria predict early relapse in pediatric multiple sclerosis.

    NARCIS (Netherlands)

    Neuteboom, R.F.; Ketelslegers, I.A.; Boon, M.; Catsman-Berrevoets, C.E.; Hintzen, R.Q.

    2010-01-01

    We sought to identify clinical and radiologic features predicting early relapse after a diagnosis of multiple sclerosis in children. In this nationwide retrospective multicenter study in The Netherlands, we included 28 children with multiple sclerosis with onset before age 16 years. Magnetic

  10. Teriflunomide reduces relapses with sequelae and relapses leading to hospitalizations: results from the TOWER study.

    Science.gov (United States)

    Miller, Aaron E; Macdonell, Richard; Comi, Giancarlo; Freedman, Mark S; Kappos, Ludwig; Mäurer, Mathias; Olsson, Tomas P; Wolinsky, Jerry S; Bozzi, Sylvie; Dive-Pouletty, Catherine; O'Connor, Paul W

    2014-09-01

    Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing-remitting multiple sclerosis. This post hoc analysis of the Phase III TOWER study evaluated the effects of teriflunomide treatment on five severe relapse outcomes: relapses with sequelae defined by an increase in Expanded Disability Status Scale (EDSS)/functional system (FS) score (sequelae-EDSS/FS) 30 days post relapse; relapses with sequelae defined by the investigator (sequelae-investigator); relapses leading to hospitalization; relapses treated with intravenous corticosteroids; and intense relapses using the definition of Panitch et al. from the EVIDENCE study based on specified increases in EDSS for severe relapses. Adjusted annualized rates for the five severe relapse outcomes were derived using a Poisson model with robust error variance, with treatment, baseline EDSS strata and region as covariates. Compared with placebo, teriflunomide significantly reduced annualized rates of relapses with sequelae-EDSS/FS [14 mg, 36.6 % (p = 0.0021); 7 mg, 31.3 % (p = 0.0104)] and sequelae-investigator [14 mg only, 53.5 % (p = 0.0004)], relapses leading to hospitalization [14 mg only, 33.6 % (p = 0.0155)], relapses requiring intravenous corticosteroids [14 mg, 35.7 % (p = 0.0002); 7 mg, 21.5 % (p = 0.0337)], and intense relapses [14 mg only, 52.5 % (p = 0.0015)]. Patients treated with teriflunomide 14 mg spent significantly fewer nights in hospital for relapse (p = 0.009) and had lower annualized rates of all hospitalizations (p = 0.030). Taken together, the positive effects of teriflunomide on severe relapses indicate that teriflunomide may reduce relapse-related healthcare costs.

  11. A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis.

    Science.gov (United States)

    Freedman, M S; Wolinsky, J S; Truffinet, P; Comi, G; Kappos, L; Miller, A E; Olsson, T P; Benamor, M; Chambers, S; O'Connor, P W

    2015-01-01

    Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing-remitting MS. To evaluate the safety and tolerability of teriflunomide as add-on therapy to a stable dose of glatiramer acetate (GA) in patients with relapsing forms of MS (RMS). Phase II, randomized, double-blind, add-on, placebo-controlled study. The primary objective was to assess safety and tolerability; secondary objectives were to evaluate effects of treatment on disease activity assessed by MRI and relapse. Patients with RMS on GA (N = 123) were randomized 1:1:1 to receive teriflunomide 14 mg (n = 40), 7 mg (n = 42), or placebo (n = 41) for 24 weeks; 96 patients entered the 24-week extension, remaining on original treatment allocation. Teriflunomide was well tolerated over 48 weeks. The frequency of adverse events (AEs) was low across all groups; 5 (12.2%), 3 (7.1%), and 2 (5.0%) patients in the 14 mg, 7 mg, and placebo groups, respectively, discontinued treatment due to AEs. Teriflunomide reduced the number of T1-Gd lesions vs placebo (14 mg: 46.6% relative reduction, p = 0.1931; 7 mg: 64.0%: relative reduction, p = 0.0306). Teriflunomide added to stable-dose GA had acceptable safety and tolerability, and reduced some MRI markers of disease activity compared with GA alone. NCT00475865 (core study); NCT00811395 (extension).

  12. Impact of a switch to fingolimod on depressive symptoms in patients with relapsing multiple sclerosis: An analysis from the EPOC (Evaluate Patient OutComes) trial.

    Science.gov (United States)

    Hunter, Samuel F; Agius, Mark; Miller, Deborah M; Cutter, Gary; Barbato, Luigi; McCague, Kevin; Meng, Xiangyi; Agashivala, Neetu; Chin, Peter; Hollander, Eric

    2016-06-15

    Depression is common in patients with multiple sclerosis (MS), may confound evaluation of therapeutic effectiveness and may be impacted by MS-specific treatments. First, to assess the impact on depressive symptoms of a switch to fingolimod versus remaining on an injectable disease-modifying therapy (iDMT) in a post-hoc analysis of prospectively collected data from the EPOC study. Secondly, to investigate the underlying Beck Depression Inventory-II (BDI-II) factor structure in patients with MS, and estimate treatment differences using the resulting subscales. EPOC was a 6-month, open-label study assessing patient-reported outcomes after switch from iDMT to oral fingolimod 0.5mg versus remaining on iDMT in 1053 patients with relapsing-remitting MS. At end of study (EOS), a greater proportion of patients on fingolimod versus iDMT no longer had BDI-II scores indicating depression (p<0.001). Fewer mildly and moderately symptomatic patients developed severe depressive symptoms, and fewer severely symptomatic patients continued to have scores indicating severe depression at EOS on fingolimod versus iDMT (p=0.027, p=0.038, p=0.030, respectively). Two BDI-II subscales were identified and labelled Somatic and Affective; fingolimod demonstrated more reduction on both subscales at EOS versus iDMTs (p<0.0001 and p=0.0001, respectively). A switch to fingolimod versus remaining on/switching to another iDMT was associated with an improvement in depressive symptoms in patients with relapsing-remitting MS. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Country, Sex, EDSS Change and Therapy Choice Independently Predict Treatment Discontinuation in Multiple Sclerosis and Clinically Isolated Syndrome

    National Research Council Canada - National Science Library

    Meyniel, Claire; Spelman, Timothy; Jokubaitis, Vilija G; Trojano, Maria; Izquierdo, Guillermo; Grand'Maison, Francois; Oreja-Guevara, Celia; Boz, Cavit; Lugaresi, Alessana; Girard, Marc; Grammond, Pierre; Iuliano, Gerardo; Fiol, Marcela; Antonio Cabrera-Gomez, Jose; Fernandez-Bolanos, Ricardo; Giuliani, Giorgio; Lechner-Scott, Jeannette; Cristiano, Edgardo; Herbert, Joseph; Petkovska-Boskova, Tatjana; Bergamaschi, Roberto; Van Pesch, Vincent; Moore, Fraser; Vella, Norbert; Slee, Mark; Santiago, Vetere; Barnett, Michael; Havrdova, Eva; Young, Carolyn; Sirbu, Carmen-Adella; Tanner, Mary; Rutherford, Michelle; Hupperts, R; Butzkueven, Helmut

    2012-01-01

    ...) and early relapsing-remitting multiple sclerosis (RRMS). The MSBASIS Study, conducted by MSBase Study Group members, enrols patients seen from CIS onset, reporting baseline demographics, cerebral magnetic resonance imaging (MRI...

  14. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis.

    Science.gov (United States)

    James, Eleanor; Dobson, Ruth; Kuhle, Jens; Baker, David; Giovannoni, Gavin; Ramagopalan, Sreeram V

    2013-10-01

    Observational studies have shown an association between lower vitamin D levels and higher risk of relapse among people with multiple sclerosis (MS). This has raised interest in potential clinical benefits of vitamin D supplementation in the management of MS. The objectives were to examine the effect of vitamin D based interventions on the relative risk of relapse in MS. Any randomised controlled trial assessing the effect on the relative risk of relapse of any formulation or dose of vitamin D, in participants with MS, was eligible. The inverse variance with random effects model in Review Manager 5.1 was used to calculate the odds ratio of relapses in high dose vitamin D treated patients vs. controls. Five studies were published as of September 2012, yielding a total of 129 high-dose vitamin D-treated patients and 125 controls. We found no significant association between high-dose vitamin D treatment and risk of MS relapse (OR 0.98, 95% CI 0.45-2.16). In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. Further larger, more prolonged studies are merited.

  15. Fatal toxic epidermal necrolysis in a patient on teriflunomide treatment for relapsing multiple sclerosis.

    Science.gov (United States)

    Gerschenfeld, Gaspard; Servy, Amandine; Valeyrie-Allanore, Laurence; de Prost, Nicolas; Cecchini, Jérôme

    2015-10-01

    We report a case of toxic epidermal necrolysis in a 46-year-old woman on teriflunomide treatment. Such a severe adverse cutaneous drug reaction with this new therapy for relapsing forms of multiple sclerosis should be early recognized in order to ensure the rapid withdrawal of the drug. © The Author(s), 2015.

  16. Single agent lenalidomide activity in multiple myeloma relapse evidenced uniquely by CT/PET

    Directory of Open Access Journals (Sweden)

    Alessandro Gozzetti

    2012-06-01

    Full Text Available A71 year old female with multiple myeloma presented with back pain seven year after autologous stem cell transplant. Skeletal bone survey and magnetic resonance imaging did not show a relapse that was evidenced by CT/PET. Lenalidomide as single agent induced a complete disappearance of the lesions 6 months later at CT/PET

  17. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    Plesner, Torben; Arkenau, Hendrik-Tobias; Gimsing, Peter; Krejcik, Jakub; Lemech, Charlotte; Minnema, Monique C|info:eu-repo/dai/nl/171618149; Lassen, Ulrik; Laubach, Jacob P; Palumbo, Antonio; Lisby, Steen; Basse, Linda; Wang, Jianping; Sasser, A Kate; Guckert, Mary E; de Boer, Carla; Khokhar, Nushmia Z; Yeh, Howard; Clemens, Pamela L; Ahmadi, Tahamtan; Lokhorst, Henk M; Richardson, Paul G

    2016-01-01

    Daratumumab, a human CD38 IgG1κ monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose-escalation) evaluated 4 daratumumab doses plus lenalidomide

  18. Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting

    NARCIS (Netherlands)

    Waal, de Esther G.M.; Glaudemans, Andor W. J. M.; Schroder, Carolien P.; Vellenga, Edo; Slart, Riemer H. J. A.

    Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is

  19. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Polman, C.H.; O'Connor, P.W.; Havrdova, E.; Hutchinson, M.; Kappos, L.; Miller, D.H.; Phillips, J.T.; Lublin, F.D.; Giovannoni, G.; Wajgt, A.; Toal, M.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in patients with relapsing multiple sclerosis. METHODS: Of a total of 942 patients, 627 were randomly assigned to

  20. Advances in the treatment of relapsing–remitting multiple sclerosis – critical appraisal of fingolimod

    Directory of Open Access Journals (Sweden)

    Gasperini C

    2013-03-01

    Full Text Available Claudio Gasperini,1 Serena Ruggieri,2 Chiara Rosa Mancinelli,2 Carlo Pozzilli2 1Department of Neurosciences, S Camillo Forlanini Hospital, Rome, Italy; 2Department of Neurology and Psychiatry, Sapienza – University of Rome, Rome, Italy Abstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs for MS in Europe, and two second-line treatments. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side effects. Despite disease-modifying drugs being well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Therefore, the development of new therapeutic strategies is warranted. Several oral compounds are in late stages of development for treating MS. Fingolimod is an oral sphingosine-1-phosphate receptor modulator that has demonstrated superior efficacy compared with placebo and interferon β-1a in phase III studies. It has already been approved in the treatment of MS. This review focuses on advances in current and novel oral treatment approaches in MS. We summarily review the oral compounds in this study, focusing on the recent development, approval, and the clinical experience with fingolimod. Keywords: multiple sclerosis, oral compounds, fingolimod, sphingosine-1-phosphate, patient satisfaction, adherence

  1. The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease.

  2. Pharmacology and clinical efficacy of dimethyl fumarate (BG-12 for treatment of relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Ruggieri S

    2014-03-01

    Full Text Available Serena Ruggieri,1 Carla Tortorella,2 Claudio Gasperini31Department of Neurology and Psychiatry, Sapienza University of Rome “Sapienza”, Rome, Italy; 2Department of Basic Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy; 3Department of Neurosciences, S Camillo Forlanini Hospital, Rome, ItalyAbstract: The last two decades have seen the introduction of several therapies for multiple sclerosis (MS. These therapies are intended to work at different levels of the disease, typically targeting direct symptom management, brief corticosteroid administration for acute exacerbations, and the regular use of disease-modifying drugs. Nevertheless, in clinical practice, disease-modifying drugs or immunosuppressive treatments are frequently associated with suboptimal response in terms of efficacy and several side effects leading to poor patient adherence, so the proportion of relapsing–remitting MS patients not adequately responding to disease-modifying therapy have been reported to range from 7% to 49%. Natalizumab and fingolimod are the newest US Food and Drug Administration-approved agents that have been added to the MS treatment armamentarium, but their use is limited by a less known safety profile and recognized specific risk. Thus, there is an important need for new therapeutic strategies, especially those that may offer greater patient satisfaction and safer risk profile in order to optimize therapeutic outcomes. A number of potential therapies for MS are now in late-stage development. Effective, safe, and well-tolerated therapies may improve compliance and empower patients with a level of independence not presently possible. To meet these characteristics, most of these therapies are oral compounds. Herein, we review the pharmacology and efficacy of dimethyl fumarate (BG-12 to date and its role in the evolving marketplace.Keywords: disease-modifying drugs, nuclear factor erythroid-derived 2 (E2-related factor, Nrf2

  3. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

    Science.gov (United States)

    Cohan, Stanley

    2016-01-01

    Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

  4. Persistence of neutralizing antibodies after discontinuation of IFNbeta therapy in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Petersen, Bodil; Bendtzen, Klaus; Koch-Henriksen, Nils

    2006-01-01

    The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNbeta) after discontinuation of IFNbeta therapy.......The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNbeta) after discontinuation of IFNbeta therapy....

  5. Teriflunomide for the treatment of relapsing multiple sclerosis: a review of clinical data.

    Science.gov (United States)

    Brunetti, Luigi; Wagner, Mary L; Maroney, Megan; Ryan, Melody

    2013-09-01

    To review the pharmacology and clinical data for teriflunomide in relapsing multiple sclerosis (MS). A literature search from 1966 to May 2013 using PubMed/MEDLINE, Web of Science, International Pharmaceutical Abstracts, Academic Search Premiere, Science Citation Index, and the national clinical trials registry was performed using the terms teriflunomide, HMR1726, and A771726. All articles containing human clinical trial data and relevant pharmacologic information were reviewed. Phase 2 and phase 3 clinical trials for teriflunomide were evaluated. All peer-reviewed articles with clinically relevant information were reviewed. Priority for inclusion was placed on randomized controlled trials. Three phase 2 and three phase 3 clinical trials have evaluated teriflunomide as monotherapy or as adjunctive therapy in approximately 3000 patients with relapsing forms of MS. The phase 3 studies used annualized relapse rate, magnetic resonance imaging changes, and Expanded Disability Status Scale scores as outcome measures. One additional Phase 3 clinical study is ongoing. The annualized relapse rates and magnetic resonance imaging findings were improved compared to those with placebo and similar to or improved compared with those with subcutaneously administered interferon-β-1a 44 µg thrice weekly. Durability of response is supported by open-label extension studies. Common adverse events include increased liver function enzymes, alopecia, diarrhea, influenza, nausea, and paresthesias. Treatment discontinuation was not common and occurred in approximately 10% of patients in phase 3 studies. Teriflunomide is an effective and safe oral treatment option for relapsing MS. It can be used as monotherapy or added to an interferon or glatiramer acetate. It reduces the rate of relapse and may slow disease progression. The advantages of this drug are the convenience of oral administration and good tolerability. The disadvantage is the lack of long-term safety data and data about the

  6. Factors associated with onset, relapses or progression in multiple sclerosis: A systematic review.

    Science.gov (United States)

    McKay, Kyla A; Jahanfar, Shayesteh; Duggan, Tom; Tkachuk, Stacey; Tremlett, Helen

    2017-07-01

    Multiple sclerosis (MS) is a chronic disease of the central nervous system with an unidentified etiology. We systematically reviewed the literature on the possible risk factors associated with MS disease onset, relapses and progression from 1960 to 2012 by accessing six databases and including relevant systematic reviews, meta-analyses, case-control or cohort studies. The focus was on identifying modifiable risk factors. Fifteen systematic reviews and 169 original articles were quality assessed and integrated into a descriptive review. Best evidence, which included one or more prospective studies, suggested that lower exposure to sunlight and/or lower serum vitamin D levels were associated with an increased risk of developing MS onset and subsequent relapses, but a similar quality of evidence was lacking for disease progression. Prospective studies indicated that cigarette smoking may increase the risk of MS as well as accelerate disease progression, but whether smoking altered the risk of a relapse was largely unknown. Infections were implicated in both risk of developing MS and relapses, but data for progression were lacking. Specifically, exposure to the Epstein-Barr virus, particularly if this manifested as infectious mononucleosis during adolescence, was associated with increased MS risk. Upper respiratory tract infections were most commonly associated with an increase in relapses. Relapse rates typically dropped during pregnancy, but there was no strong evidence to suggest that pregnancy itself altered the risk of MS or affected long-term progression. Emerging research with the greatest potential to impact public health was the suggestion that obesity during adolescence may increase the risk of MS; if confirmed, this would be of major significance. Copyright © 2016. Published by Elsevier B.V.

  7. Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

    Science.gov (United States)

    Miller, Aaron E

    2015-10-01

    The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P teriflunomide significantly reduced annualized relapse rate (31% and 36% relative risk reduction compared with placebo, respectively; both P Teriflunomide treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. A case of lymphoma in a patient on teriflunomide treatment for relapsing multiple sclerosis.

    Science.gov (United States)

    Landais, Anne; Alhendi, Rabi; Gouverneur, Amandine; Teron-Aboud, Brigitte

    2017-10-01

    Teriflunomide is an oral therapy approved for relapsing forms of multiple sclerosis which has been shown to reduce relapse rate and disability progression. We report the case of a 54-year -old black woman with multiple sclerosis who developed follicular lymphoma after about 8 months of exposure to teriflunomide. Importantly, apart from age, the patient had none of the established risk factors for follicular lymphoma. Moreover, although this is the first published case of a lymphoma on teriflunomide, it is not the first confirmed case. Ten other cases have so far been reported to pharmacovigilance worldwide, and a further 82 with leflunomide. In conclusion, an association between teriflunomide and a higher risk of lymphoma cannot be ruled out. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

    Science.gov (United States)

    Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

    1991-09-01

    From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

  10. Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond

    Science.gov (United States)

    Chim, C S; Kumar, S K; Orlowski, R Z; Cook, G; Richardson, P G; Gertz, M A; Giralt, S; Mateos, M V; Leleu, X; Anderson, K C

    2018-01-01

    Despite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM. Daratumumab, targeting CD38, has multiple mechanisms of action including modulation of the immunosuppressive bone marrow micro-environment. In addition to the remarkable single agent activity in refractory MM, daratumumab produced deep responses and superior PFS in MM when combined with lenalidomide/dexamethasone, or bortezomib/dexamethasone. Other anti-CD38 antibodies, such as isatuximab and MOR202, are undergoing assessment. Elotuzumab, targeting SLAMF7, yielded superior response rates and PFS when combined with lenalidomide/dexamethasone. New combinations of these next generation novel agents and/or antibodies are undergoing clinical trials. Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone. Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. Pembrolizumab, an anti-PD1 check-point inhibitor, is being tested in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone. Chimeric antigen receptor-T cells targeting B-cell maturation antigen have yielded deep responses in RRMM. Finally, salvage autologous stem cell transplantation (ASCT) remains an important treatment in MM relapsing/progressing after a first ASCT. Herein, the clinical trial data of these agents are

  11. Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M. (University Coll. Hospital, London (United Kingdom)); Blackman, G. (Middlesex Hospital, London (United Kingdom))

    1993-01-01

    Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received [alpha]IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. [alpha]IFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance [alpha]IFN therapy could not be fully evaluated. (author).

  12. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis ......Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...

  13. Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis.

    Science.gov (United States)

    Lattanzi, Simona; Cagnetti, Claudia; Danni, Maura; Provinciali, Leandro; Silvestrini, Mauro

    2017-08-01

    Glucocorticoids are the standard of care for multiple sclerosis (MS) relapses, but the most desirable route of administration is still matter of debate. The aim of the study was to compare the efficacy and safety of oral versus intravenous steroids for treatment of acute relapses in patients with MS. Randomized or quasi-randomized, parallel group trials with direct comparison between oral and intravenous steroid treatment in MS patients with acute relapse were identified through a systematic literature search. Six trials were included involving 419 participants, 210 for oral, and 209 for intravenous groups, respectively. The weighted mean differences (WMDs) in the Kurtzke's Expanded Disability Status Scale (EDSS) score reduction between the oral and intravenous groups were 0.32 [(-0.09 to 0.73); p = 0.129] and 0.11 [(-0.12 to 0.33); p = 0.355] at 1 and 4 weeks after treatment, respectively. The risk ratios (RRs) for improvement by at least one EDSS point were 0.79 [(0.37-1.68); p = 0.539] at week 1 and 0.92 (0.76-1.12); p = 0.400] at week 4. There were no differences in the relapse rate and relapse freedom at 6 months between groups. The WMDs in the mean percentage reduction of Gadolinium-enhancing lesions between oral and intravenous arms were 0.14 (-0.02, 0.29); p = 0.083] and 0.04 (-0.19, 0.28); p = 0.705] at 1 and 4 weeks from treatment. Among the adverse events, insomnia was significantly associated with the oral route of steroid administration [RR 1.25 (1.07-1.46); p = 0.005]. In adult patients with acute MS relapse, there were no clear-cut differences in the efficacy and overall tolerability between oral and intravenous steroids.

  14. An exploration of the lived experiences of individuals with relapsed multiple myeloma.

    LENUS (Irish Health Repository)

    Maher, K

    2012-02-01

    The experience of living with relapsed Multiple Myeloma (myeloma) for eight patients accessing treatment within a haematology unit in a large London hospital is explored in this study. Myeloma is recognised as incurable and is sometimes described as an \\'incurable chronic disease\\' with a main treatment option of chemotherapy. Hermeneutic phenomenology was the methodology used in conducting the study and data were collected through open-ended, unstructured interviews. Findings suggest that living with relapsed myeloma in the context of a chronic illness causes an ever-shifting perspective between illness and wellness consequently maintaining a state of uncertainty. The patients in this study placed importance on the emotional aspect of their experience. Hope, intuitive knowing and a fighting spirit were expressed as required positive elements that enabled living with relapsed myeloma. These assisted in maintaining normality, coping with bad news and adjusting to the illness. Pervading through the themes was the need to control uncertainty. Having strong support from significant others provided something to live for and the necessary social support required to promote a new orientation to life.

  15. Oral treatment for multiple sclerosis

    NARCIS (Netherlands)

    Killestein, J.; Rudick, R.A.; Polman, C.H.

    2011-01-01

    Background: The armamentarium for the treatment of relapsing-remitting multiple sclerosis (RRMS) is increasing rapidly. Several oral treatments have shown benefit and will generate much interest because of the convenience of such administration. However, availability of convenient oral drugs will

  16. Psychiatric onset of multiple sclerosis.

    NARCIS (Netherlands)

    Jongen, P.J.H.

    2006-01-01

    We present a patient with psychotic disorder as onset of relapsing-remitting multiple sclerosis (MS). In this patient, a 26-year-old female, neurological examination revealed only minor abnormalities. As cranial CT scan was normal, her psychosis was diagnosed as psychogenic. Literature on

  17. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

  18. A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma.

    Science.gov (United States)

    Cook, Gordon; Zweegman, Sonja; Mateos, María-Victoria; Suzan, Florence; Moreau, Philippe

    2018-01-01

    Multiple classes of agent with distinct mechanisms of action are now available for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM), including immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors and monoclonal antibodies. Additionally, several different drugs may be available within each agent class, each with their own specific efficacy and safety profile. This expansion of the treatment landscape has dramatically improved outcomes for patients. However, as the treatment options for RRMM become more complex, choosing the class of agent or combination of agents to use in the relapsed setting becomes increasingly challenging. Furthermore, treatment options for specific patient populations such as the elderly, those with high-risk cytogenetic abnormalities and those with refractory disease are yet to be defined in the current treatment landscape. When choosing an appropriate treatment approach, physicians must consider multiple criteria including both patient-related and disease-related factors. The aim should be to provide patient-specific treatment in order to gain a clinical benefit while minimizing toxicity. This review provides an overview of the mechanism of action and efficacy and safety profiles of each class of agent and of treatment regimens that combine different classes of agent, with a special focus on treating specific patient populations. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in a Multicenter, Open-Label Study of Patients with Relapsing Forms of Multiple Sclerosis (MANAGE)

    Science.gov (United States)

    Fox, Edward J.; Vasquez, Alberto; Grainger, William; Ma, Tina S.; Walsh, John; Li, Jie; Zambrano, Javier

    2016-01-01

    Background: In phase 3 trials, delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) demonstrated efficacy in relapsing-remitting multiple sclerosis (MS). Gastrointestinal (GI) events were associated with DMF treatment. The single-arm, open-label MANAGE study examined the incidence, severity, duration, and management of GI events in adults with relapsing MS initiating DMF treatment in clinical practice in the United States shortly after marketing approval. Patients and Methods: Patients (N = 233) took DMF for up to 12 weeks and recorded information regarding GI events using an eDiary and numerical rating scales. Results: Overall, 54.1% of patients used symptomatic therapy and had GI symptoms. The incidence of GI events was highest in the first month of treatment. The duration of GI events varied by event type, and severity was generally mild to moderate. Decreased severity was seen in patients treated with antacids, bismuth subsalicylate, acid-secretion blockers, antidiarrheals, and antiemetics. Less than 10% of patients were using symptomatic therapy for GI events by week 12 of DMF treatment. A modest reduction in severe GI events was observed in patients who regularly took DMF with food compared with patients who did not. The incidence of GI-related events was comparable in patients with or without a history of GI abnormalities and in patients who did or did not use alcohol or tobacco. Conclusions: Gastrointestinal events associated with DMF are generally transient, mild to moderate in severity, and manageable. Symptomatic therapy and dosing with food may mitigate these events. PMID:26917993

  20. Role of oral teriflunomide in the management of multiple sclerosis.

    Science.gov (United States)

    Tanasescu, Radu; Evangelou, Nikos; Constantinescu, Cris S

    2013-01-01

    The landscape of the treatment of relapsing-remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing-remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing-remitting multiple sclerosis is discussed.

  1. Cyclophosphamide-based stem cell mobilization in relapsed multiple myeloma patients: A subgroup analysis from the phase III trial ReLApsE.

    Science.gov (United States)

    Baertsch, Marc-Andrea; Schlenzka, Jana; Lisenko, Katharina; Krzykalla, Julia; Becker, Natalia; Weisel, Katja; Noppeney, Richard; Martin, Hans; Lindemann, Hans W; Haenel, Mathias; Nogai, Axel; Scheid, Christof; Salwender, Hans; Fenk, Roland; Graeven, Ullrich; Reimer, Peter; Schmidt-Hieber, Martin; Goerner, Martin; Schmidt-Wolf, Ingo G H; Klein, Stefan; Ho, Anthony D; Goldschmidt, Hartmut; Wuchter, Patrick

    2017-07-01

    Analysis of the efficiency and toxicity of cyclophosphamide-based stem cell mobilization in patients with relapsed multiple myeloma (RMM). Peripheral blood stem cells (PBSCs) were mobilized with high dose cyclophosphamide (2 g/m2 daily on days 1 and 2) and G-CSF plus pre-emptive/rescue plerixafor in RMM patients (first to third relapse) treated within the ReLApsE trial of the German-Speaking Myeloma Multicenter Group (GMMG). Mobilization was initiated with high-dose cyclophosphamide (HD-CY) and G-CSF in 30 patients. Fifteen patients received additional pre-emptive/rescue administration of plerixafor. Stem cell collection was successful (≥2×106 CD34+ cells per kg bw) in 77% (23/30 patients). Patients with prior high-dose melphalan collected a significantly lower median total number of PBSCs than patients without prior high-dose melphalan (3.3×106 vs 17×106 CD34+ cells/kg bw). Toxicity of HD-CY was frequent with 12 serious adverse events (SAE) in 37% of patients (11/30 patients). Infections accounted for the majority of SAE reports. In two patients, SAEs were lethal (septic shock). These data proof feasibility of PBSC collection at relapse but emphasize the importance of collection and storage of additional PBSC transplants during first-line treatment when mobilization is more efficient and less toxic. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Primary progressive multiple sclerosis in the Polish population

    Directory of Open Access Journals (Sweden)

    Waldemar Brola

    2017-03-01

    Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

  3. A case of Multiple Unilateral Pulmonary arteriovenous Malformation Relapse: Efficacy of embolization treatment

    Directory of Open Access Journals (Sweden)

    Masiello Rossella

    2015-01-01

    Full Text Available Pulmonary arteriovenous Malformations (PAVMs are a rare vascular alteration characterized by abnormal communications between the pulmonary arteries and veins resulting in an extracardiac right-to-left (R-L shunt. The majority of PAVMs are associated with an autosomal dominant vascular disorder also known as Osler-Weber- Rendu Syndrome. PAVMs appearance can be both single and multiple. Clinical manifestations include hypoxemia, dyspnea cyanosis, hemoptysis and cerebrovascular ischemic events or abscesses. We report a case of an 18 year old female with severe respiratory failure caused by a relapse of multiple unilateral pulmonary arterovenous fistula. Symptoms at admission include dyspnea, cyanosis and clubbing. The patient underwent pulmonary angio-TC scan, brain CT and echocardiography. The thoracic angio-CT scan showed the presence of PAVMs of RUL and RLL; a marked increase of right bronchial artery caliber and its branches with an aneurismatic dilatation was also observed. The patient underwent percutaneous transcatheter embolization using Amplatzer Vascular Plug IV; a relevant clinical and functional improvement was subsequently recorded. Embolization is effective in the treatment of relapsing PAVMS.

  4. New patterns of relapse in multiple myeloma: a case of "light chain escape" in which FLC predicted relapse earlier than urine and serum immunofixation.

    Science.gov (United States)

    Caldini, Anna; Nozzoli, Chiara; Terreni, Alessandro; Staderini, Michela; Berardi, Margherita; Biagioli, Tiziana; Brogi, Marco; Bosi, Alberto

    2016-06-01

    Multiple myeloma (MM) is characterized, in about 80% of cases, by the production of monoclonal intact immunoglobulin and more than 95% of them have elevated concentrations of involved (i.e. of the same class of intact immunoglobulin) free light chain (FLC). The introduction of novel therapeutic strategies has changed the natural history of the disease, leading to new manifestations of relapse. Light chain escape (LCE) is a pattern of relapse in which the FLC increase is not accompanied by a concomitant raise of the original monoclonal component (MC). Here we present a case of a 55-year-old man with an IgG kappa MM stage III diagnosed in September 2007. At presentation an IgG kappa MC and urine Bence Jones protein (BJP) kappa were present. Bone marrow biopsy (BMB) showed the presence of 80% monotypic kappa plasma cells (PCs). The patient received bortezomib, thalidomide, dexamethasone before undergoing a double autologous stem cell transplantation (ASCT) in October 2008 and April 2009. In May 2011 he relapsed showing the same pattern of presentation and treatment with lenalidomide and dexamethasone was started. ln May 2013 serum and urine immunofixation and FLC became negative. In September 2014, an increase of kappa FLC was observed, while serum and urine immunofixations remained negative until January 2015, when urine immunofixation became positive. Eventually, in February 2015, serum immunofixation revealed the presence of a free kappa MC. After a new BMB showing 80% of monotypic kappa PCs, a LCE relapse was diagnosed and the patient started the treatment with bendamustine, bortezomib and dexamethasone. In the present case, the increase of kappa FLC has indicated relapse 4 and 5 months earlier than urine and serum IFE, respectively. Our observation confirms that it is advisable to routinely perform FLC or BJP during follow up of MM patients undergoing ASCT and/or treatment with biological drugs to ensure that LCE is not missed.

  5. Efficacy of lenalidomide, bortezomib, and prednisolone in patients with relapsed or refractory multiple myeloma

    Directory of Open Access Journals (Sweden)

    T. A. Мitinа

    2015-01-01

    Full Text Available 49 patients aged 28 to 81 years old (median age of 55 years old with relapsed or refractory multiple myeloma (MM were enrolled in the study. The relapse was diagnosed in 25 (51 % patients, the refractory disease was determined in 24 (49 % patients (including primary refractory disease in 14 (28.6 % patients. The prior therapy for all patients included bortezomib-based treatment in combination with thalidomide and autologus stem cell transplantation (8.1 %. Lenalidomide had not been used in the previous therapeutic regimens. All patients were given the original treatment regimen, which included lenalidomide, bortezomib, and prednisolone (RVP. The therapy was made up of seven induction cycles with each one lasting for 48 days. Length of courses was 14 days. After seven cycles of RVP therapy were over, such results were achieved: complete response (CR in 1 (2 % patient; very good partial response (VGPR in 4 (8 % patients; partial response (PR in 26 (53 % patients; minimal response (MR in 2 (4 % patients; stable disease (SD in 8 (16.3 % patients, and progressive disease (PD in 8 (16.3 % patients. The objective response rate, including CR+VGPR+PR, was obtained in 31 (63.1 % patients. The objective response rate, including MR, was seen in 33 (67.1 % patients. Hematological and non-hematological toxicities were moderate. Taking into account the above, the RVP therapeutic regimen has demonstrated its efficacy as a second-line therapy for MM, and its clinical use can solve the problem of relapsed/refractory to bortezomib-based regimens MM management.

  6. The participation of varicella zoster virus in relapses of multiple sclerosis.

    Science.gov (United States)

    Sotelo, Julio; Ordoñez, Graciela; Pineda, Benjamín; Flores, José

    2014-04-01

    Recent studies have documented the apparent participation of varicella zoster virus (VZV) in the etiopathogenesis of multiple sclerosis (MS). The present study aimed to corroborate the possible presence of VZV during exacerbations of MS. Fifty-three patients with definite MS were included; of them, 31 were studied during the first week of a clinical relapse, whereas 16 were studied during remission; 6 patients with progressive MS were also studied. Genes from 5 herpes viruses: varicella zoster, herpes simplex 1 and 2, Epstein-Barr and herpes 6 were studied by polymerase chain reaction in cerebrospinal fluid and in peripheral blood mononuclear cells (PBMC). As controls 21 patients with inflammatory or functional neurological disorders were included. DNA from varicella zoster virus was found in the CSF from all MS patients studied during relapse (100%) and in the PBMC from 28 of them (90%). However, VZV DNA was found in the CSF only in 5 MS patients studied during remission (31%) and in the PBMC from 3 of them (19%). VZV DNA was also found, but in lower amounts, in the CSF (83%) and PBMC (33%) from patients with progressive MS. In contrast, VZV was not found either in CSF or in PBMC from controls. Results from the other herpes viruses tested were similar in MS patients and in controls. Our results corroborate the conspicuous, but ephemeral presence of VZV during relapses of MS and support the idea of VZV involvement in the etiopathogenesis of MS. Recent epidemiological and molecular studies as well as reports of severe VZV infections triggered by specifically induced immunosuppression during therapy of MS give additional support to this potential association. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Teriflunomide added to interferon-β in relapsing multiple sclerosis: a randomized phase II trial.

    Science.gov (United States)

    Freedman, M S; Wolinsky, J S; Wamil, B; Confavreux, C; Comi, G; Kappos, L; Olsson, T P; Miller, A; Benzerdjeb, H; Li, H; Simonson, C; O'Connor, P W

    2012-06-05

    To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-β (IFNβ) in patients with relapsing forms of multiple sclerosis (RMS). A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate. Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p Teriflunomide as add-on therapy to IFNβ had acceptable safety and tolerability and reduced MRI disease activity compared with IFNβ alone. This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFNβ, is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.

  8. Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting.

    Science.gov (United States)

    de Waal, Esther G M; Glaudemans, Andor W J M; Schröder, Carolien P; Vellenga, Edo; Slart, Riemer H J A

    2017-02-01

    Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity. Modern imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography offer superior detection of myeloma bone disease and extramedullary manifestations. In particular, the properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells. In this review, an overview is provided of the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis. The available literature data for commonly used nuclear imaging tracers, the promising first results of new tracers, and our pilot work indicate that a number of these radiopharmaceutical applications can be used effectively for staging and response monitoring of relapsing MM patients. Moreover, some tracers can potentially be used for radio immunotherapy.

  9. Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting

    Energy Technology Data Exchange (ETDEWEB)

    Waal, Esther G.M. de; Vellenga, Edo [University of Groningen, University Medical Center Groningen, Department of Hematology, PO Box 30001, Groningen (Netherlands); Glaudemans, Andor W.J.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Schroeder, Carolien P. [University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen (Netherlands); Slart, Riemer H.J.A. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Twente, Department of Biomedical Photonic Imaging, Enschede (Netherlands)

    2017-02-15

    Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity. Modern imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography offer superior detection of myeloma bone disease and extramedullary manifestations. In particular, the properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells. In this review, an overview is provided of the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis. The available literature data for commonly used nuclear imaging tracers, the promising first results of new tracers, and our pilot work indicate that a number of these radiopharmaceutical applications can be used effectively for staging and response monitoring of relapsing MM patients. Moreover, some tracers can potentially be used for radio immunotherapy. (orig.)

  10. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations

    Directory of Open Access Journals (Sweden)

    Aurelio Lopez

    2015-01-01

    Full Text Available We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients and more aggressive forms of disease (32 patients were the most common patterns of relapse. After second-line therapy, 75 (51.7% patients achieved at partial response and 16 (11% complete response (CR. Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037, in patients achieving CR (28.3 vs. 14.8 months; P=0.04, and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007.

  11. Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis.

    Science.gov (United States)

    Chataway, Jeremy; Martin, Keith; Barrell, Kevin; Sharrack, Basil; Stolt, Pelle; Wraith, David C

    2018-02-21

    To assess safety, tolerability, and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis using different treatment protocols to induce tolerance. Two open-label trials in adult participants with relapsing multiple sclerosis were conducted. Study 1 was a multicenter, phase 1b safety evaluation comparing intradermal (i.d.) (cohort 1) with subcutaneous (cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800-μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a phase 2a, multicenter, single-arm trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 μg i.d. on day 1 to 200 μg on day 15 and 800 μg on day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety endpoints included treatment-emergent adverse events and injection-site reactions. In study 1, there was a significant decrease in new/persisting T1 gadolinium-enhanced (GdE) lesions in cohort 1 from baseline to week 16, returning to baseline values at week 48. In study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post treatment. Further trials of ATX-MS-1467 are warranted. This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions. © 2018 American Academy of Neurology.

  12. Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal.

    Science.gov (United States)

    Serafini, Barbara; Scorsi, Eleonora; Rosicarelli, Barbara; Rigau, Valérie; Thouvenot, Eric; Aloisi, Francesca

    2017-06-15

    Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal is a potentially life-threatening event. To verify whether highly destructive inflammation after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient who died during a fulminating MS relapse following natalizumab withdrawal. Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white matter lesions; the highest frequency of EBV lytically infected cells and granzyme B+ CD8+ T cells was observed in actively demyelinating lesions. These results may encourage switching to B-cell depleting therapy after natalizumab discontinuation. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A

    2010-01-01

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI......) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving...... natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277...

  14. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom's macroglobulinemia

    DEFF Research Database (Denmark)

    Chen, Christine; Siegel, David; Gutierrez, Martin

    2018-01-01

    Novel therapies are needed for patients with relapsed or refractory multiple myeloma (MM). We conducted a multicenter, phase 1 study in advanced hematological malignancies to assess the safety, efficacy and recommended phase 2 dose (RP2D) of oral selinexor, a selective inhibitor of the nuclear...... export protein XPO1. In the dose-escalation phase, 25 patients with heavily pretreated MM (22) or Waldenstrom's macroglobulinemia (3) were administered selinexor (3-60 mg/m2) in 8 or 10 doses per 28-day cycle. In the dose-expansion phase, 59 patients with MM received selinexor at 45 or 60 mg/m2 with 20...... with all responses of ≥PR occurring in the 45 mg/m2 selinexor plus 20mg dexamethasone twice weekly cohort (ORR=50%). Furthermore, 46% of all patients showed a reduction in MM markers from baseline. Based on these findings, we conclude that selinexor in combination with dexamethasone is active in heavily...

  15. Phase II study of the c-MET inhibitor tivantinib (ARQ 197) in patients with relapsed or relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Baljevic, Muhamed; Zaman, Shadia; Baladandayuthapani, Veerabhadran; Lin, Yan Heather; de Partovi, Claudia Morales; Berkova, Zuzana; Amini, Behrang; Thomas, Sheeba K; Shah, Jatin J; Weber, Donna M; Fu, Min; Cleeland, Charles S; Wang, Xin Shelley; Stellrecht, Christine M; Davis, Richard E; Gandhi, Varsha; Orlowski, Robert Z

    2017-06-01

    The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression. Primary objectives were to determine the overall response rate and the toxicities of tivantinib in this patient population. Sixteen patients were enrolled in a two-stage design. Notable grade 3 and 4 hematological adverse events were limited to neutropenia in five and four patients, respectively. Nonhematological adverse events of grade 3 or higher included hypertension (in four patients); syncope, infection, and pain (two each); and fatigue, cough, and pulmonary embolism (one each). Four of 11 evaluable patients (36%) had stable disease as their best response, while the remainder showed disease progression. Overall, tivantinib as a single agent did not show promise for unselected relapsed/refractory myeloma patients. However, the ability to achieve stable disease does suggest that combination regimens incorporating targeted inhibitors in patients with c-MET pathway activation could be of interest.

  16. Relapse rates in patients with multiple sclerosis switching from interferon to fingolimod or glatiramer acetate: a US claims database study.

    Directory of Open Access Journals (Sweden)

    Niklas Bergvall

    Full Text Available BACKGROUND: Approximately one-third of patients with multiple sclerosis (MS are unresponsive to, or intolerant of, interferon (IFN therapy, prompting a switch to other disease-modifying therapies. Clinical outcomes of switching therapy are unknown. This retrospective study assessed differences in relapse rates among patients with MS switching from IFN to fingolimod or glatiramer acetate (GA in a real-world setting. METHODS: US administrative claims data from the PharMetrics Plus™ database were used to identify patients with MS who switched from IFN to fingolimod or GA between October 1, 2010 and March 31, 2012. Patients were matched 1∶1 using propensity scores within strata (number of pre-index relapses on demographic (e.g. age and gender and disease (e.g. timing of pre-index relapse, comorbidities and symptoms characteristics. A claims-based algorithm was used to identify relapses while patients were persistent with therapy over 360 days post-switch. Differences in both the probability of experiencing a relapse and the annualized relapse rate (ARR while persistent with therapy were assessed. RESULTS: The matched sample population contained 264 patients (n = 132 in each cohort. Before switching, 33.3% of patients in both cohorts had experienced at least one relapse. During the post-index persistence period, the proportion of patients with at least one relapse was lower in the fingolimod cohort (12.9% than in the GA cohort (25.0%, and ARRs were lower with fingolimod (0.19 than with GA (0.51. Patients treated with fingolimod had a 59% lower probability of relapse (odds ratio, 0.41; 95% confidence interval [CI], 0.21-0.80; p = 0.0091 and 62% fewer relapses per year (rate ratio, 0.38; 95% CI, 0.21-0.68; p = 0.0013 compared with those treated with GA. CONCLUSIONS: In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

  17. Effectiveness and Safety of Dimethyl Fumarate Treatment in Relapsing Multiple Sclerosis Patients: Real-World Evidence.

    Science.gov (United States)

    Alroughani, Raed; Ahmed, Samar Farouk; Behbehani, Raed; Al-Hashel, Jasem

    2017-12-01

    Dimethyl fumarate (DMF) has been recently approved as a disease-modifying therapy for the treatment of multiple sclerosis (MS). Post-marketing studies are important to confirm what was established in clinical trials. To evaluate effectiveness and safety of DMF and to measure the occurrence of lymphopenia in a cohort of MS patients in a clinical setting. Using the national MS registry, we prospectively assessed relapsing MS patients who had been prescribed DMF for at least 6 months. Primary outcome measure was the proportion of relapse-free patients at last follow-up visit. Secondary outcome measures were the mean change in expanded disability status scale (EDSS) and the proportion of patients with radiological activity (gadolinium-enhancing or new T2 lesions) at the last follow-up visit. Absolute lymphocyte count (ALC) was assessed at baseline (within 6 months prior to DMF initiation) and at one or more times during DMF treatment 3 months post-initiation. Of 134 patients identified, 119 were eligible and included in the analysis. Women represented 59.7% of the studied cohort. Mean age and mean disease duration were 33.5 ± 11.1 and 8.3 ± 7 years, respectively. A total of 75.6% of the patients received prior disease-modifying therapies. Mean duration of DMF exposure was 20.5 ± 9.5 months. The proportion of relapse-free patients increased significantly from 51.2% to 89.9% (p < 0.0001), while the mean EDSS score decreased from 2.8 ± 1.8 at baseline to 2.3 ± 1.7 (p < 0.058) at last follow-up visit. The proportion of patients with MRI activity decreased significantly from 61.1% to 15.1% (p < 0.0001). The mean ALCs decreased from 2170 to 1430 cells/μl (34% decrease). Lymphopenia was seen in 13 (10.9%) patients, of whom 3 (2.5%) patients had grade 3 lymphopenia necessitating discontinuation of DMF. Although no serious adverse events were reported, 19.3% of patients discontinued DMF. In clinical practice, DMF appeared to be effective in reducing

  18. Perforin Expression by CD4+ Regulatory T Cells Increases at Multiple Sclerosis Relapse: Sex Differences

    Directory of Open Access Journals (Sweden)

    Silvia Sánchez-Ramón

    2012-06-01

    Full Text Available Multiple sclerosis (MS represents the leading cause of neurological deficit among young adults, affecting women more frequently than men. In MS, the extent of central nervous system lesions is determined by the net balance between self-reactive and regulatory T-cells at any given time, among other factors, as well as by the effect of inflammatory response. Here, we studied both CD4+ and CD8+ TReg in parallel in blood and CSF during MS relapse. A recruitment of both regulatory CD4+ and CD8+ T cells (TReg within the cerebrospinal fluid (CSF takes place during MS relapse. Not previously described, the presence of CD4+ TReg in CSF was higher in women than in men, which could account for the sexual dimorphism in the incidence of MS. A direct correlation between plasma oestradiol (E2 and IL-2 levels was observed, in line with a putative circuit of E2 and perforin expression by CD4+ TReg playing a role in MS. Also, serum IFN-alpha was higher in females, with direct correlation with serum E2 levels. This is the first study to analyze perforin expression by CD4+ TReg in MS, which was greatly enhanced in CSF, what points out a relevant role of this molecule in the suppressive effects of the CD4+ TReg in MS, and contributes to the understanding of MS pathophysiology.

  19. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

    DEFF Research Database (Denmark)

    Kumar, S K; Lee, J H; Lahuerta, J J

    2012-01-01

    Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with...

  20. Effects of fluoxetine on disease activity in relapsing multiple sclerosis : a double-blind, placebo-controlled, exploratory study

    NARCIS (Netherlands)

    Mostert, J. P.; Admiraal-Behloul, F.; Hoogduin, J. M.; Luyendijk, J.; Heersema, D. J.; van Buchem, M. A.; De Keyser, J.

    Background: Suppressing the antigen-presenting capacity of glial cells could represent a novel way of reducing inflammatory activity in multiple sclerosis (MS). Aims: To evaluate the effects of fluoxetine on new lesion formation in patients with relapsing MS. Methods: In a double-blind,