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Multiple Sclerosis and rituximab

Dennis Bourdette
No abstract text is available yet for this article.
October 19, 2016: Neurology
Jonatan Salzer, Rasmus Svenningsson, Peter Alping, Lenka Novakova, Anna Björck, Katharina Fink, Protik Islam-Jakobsson, Clas Malmeström, Markus Axelsson, Mattias Vågberg, Peter Sundström, Jan Lycke, Fredrik Piehl, Anders Svenningsson
OBJECTIVE: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS)...
October 19, 2016: Neurology
Marisa P McGinley, Brandon P Moss, Jeffrey A Cohen
Monoclonal antibodies are a potent therapeutic approach for relapsing-remitting multiple sclerosis. This group of medications comprises diverse mechanisms of action resulting in both shared and unique adverse effects. Areas covered: The major trials and safety profiles of natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab are discussed. While each drug has a unique safety profile, one of the potential safety concerns for all of these drugs is infection, including for some progressive multifocal leukoencephalopathy...
October 19, 2016: Expert Opinion on Drug Safety
Irene Del Pilar Moreno Torres, Antonio García-Merino
INTRODUCTION: The therapeutic utility of the anti-CD20 monoclonal antibodies (mAbs) is currently being evaluated in multiple sclerosis (MS) in line with the better understanding of the role of B lymphocytes in MS pathogenesis. AREA COVERED: We conducted a literature search using Medline/Pub Med database of basic research and available controlled trials about anti-CD20 mAbs in MS. Additionally, ongoing studies were identified in the database. B cells exert multiple inflammatory and regulatory functions playing an important role in MS pathogenesis as is demonstrated by the production of autoantibodies, infiltration of B cells in MS lesions and the formation of ectopic B cell follicle-like structures in meninges, among others...
October 10, 2016: Expert Review of Neurotherapeutics
Jasna Jancic, Blazo Nikolic, Nikola Ivancevic, Vesna Djuric, Ivan Zaletel, Dejan Stevanovic, Sasa Peric, John N van den Anker, Janko Samardzic
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment...
September 17, 2016: Neurology and Therapy
Joakim Bergman, Ann Dring, Henrik Zetterberg, Kaj Blennow, Niklas Norgren, Jonathan Gilthorpe, Tommy Bergenheim, Anders Svenningsson
OBJECTIVE: In an ongoing, open-label, phase 1b study on the intrathecal administration of rituximab for progressive multiple sclerosis, an intraventricular catheter was inserted for drug delivery. The objective of this study was to characterize the limited white matter axonal injury evoked by catheter insertion by analyzing a panel of markers for tissue damage in CSF and serum. METHODS: Lumbar CSF and serum were collected before catheter insertion and at regular intervals during the follow-up period of 1 year...
October 2016: Neurology® Neuroimmunology & Neuroinflammation
Ulrike W Kaunzner, Gaurav Kumar, Gulce Askin, Susan A Gauthier, Nancy N Nealon, Timothy Vartanian, Jai S Perumal
OBJECTIVE: Identify aggressive onset multiple sclerosis (AOMS) and describe its clinical course. METHODS: AOMS patients were identified from a multiple sclerosis (MS) database based on a set of criteria. The subsequent clinical course of AOMS patients was then reviewed with the goal of potentially identifying the best approaches to manage these patients. RESULTS: Fifty-eight of 783 (7.4%) patients in the MS database met the criteria for AOMS, and 43 patients who had complete data for the duration of their follow-up were included in the subsequent analysis...
2016: Neuropsychiatric Disease and Treatment
Jonathan Rubio Tabares, Pablo Felipe Amaya Gonzalez
Neuromyelitis optica (NMO) or Devic's disease is an autoimmune inflammatory demyelinating condition affecting the central nervous system (CNS). It was initially believed to be a variant of multiple sclerosis (MS). However, the discovery of NMO-IgG anti-AQP4 antibodies marked an objective distinction between these conditions. Treatment of acute attacks is generally based on pulsed steroids, followed by long-term immunosuppression with azathioprine, oral steroids, and rituximab as first-line therapies. Plasma exchange therapy is indicated for steroid-resistant relapses...
September 2016: Clinical Neurology and Neurosurgery
Elisabeth Schuh, Kerstin Berer, Matthias Mulazzani, Katharina Feil, Ingrid Meinl, Harald Lahm, Markus Krane, Rüdiger Lange, Kristina Pfannes, Marion Subklewe, Robert Gürkov, Monika Bradl, Reinhard Hohlfeld, Tania Kümpfel, Edgar Meinl, Markus Krumbholz
Monoclonal Abs against CD20 reduce the number of relapses in multiple sclerosis (MS); commonly this effect is solely attributed to depletion of B cells. Recently, however, a subset of CD3(+)CD20(+) T cells has been described that is also targeted by the anti-CD20 mAb rituximab. Because the existence of cells coexpressing CD3 and CD20 is controversial and features of this subpopulation are poorly understood, we studied this issue in detail. In this study, we confirm that 3-5% of circulating human T cells display CD20 on their surface and transcribe both CD3 and CD20...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
M Diebold, L Kappos, T Derfuss
BACKGROUND: The treatment of autoimmune disorders of the nervous system is based on interventions for the underlying immune phenomena. OBJECTIVE: To summarize concepts of cell depletion and myeloablation studied in the context of neuroimmunological disorders. METHOD: Evaluation of the available literature on multiple sclerosis as the most widely studied neuroimmunological entity. RESULTS: Three concepts have been introduced: classical immunosuppressants, such as azathioprine, mitoxantrone and cyclophosphamide exert general lymphopenic effects and thereby moderately decrease disease activity...
August 2016: Der Nervenarzt
Staley A Brod
BACKGROUND: Blocking CD20 can inhibit autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). OBJECTIVE: We examined whether an antibody against CD20, rituximab (RTX) (Rituxan®), used clinically in oncology, MS and RA would have similar anti-inflammatory effects in EAE after oral administration. DESIGN/METHODS: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or RTX during ongoing disease...
September 2016: Cytokine
Pierre de Flon, Martin Gunnarsson, Katarina Laurell, Lars Söderström, Richard Birgander, Thomas Lindqvist, Wolfgang Krauss, Ann Dring, Joakim Bergman, Peter Sundström, Anders Svenningsson
OBJECTIVE: To describe the effects of switching treatment from ongoing first-line injectable therapies to rituximab on inflammatory activity measured by MRI and levels of CSF neurofilament light chain (CSF-NFL) in a cohort of patients with clinically stable relapsing-remitting multiple sclerosis (RRMS). METHOD: Seventy-five patients with clinically stable RRMS treated with the first-line injectables interferon-β (IFN-β) and glatiramer acetate (GA) at 3 Swedish centers were switched to rituximab in this open-label phase II multicenter study...
July 12, 2016: Neurology
Marta Simone, Tanuja Chitnis
Pediatric multiple sclerosis (PedMS) is a rare disease with a more severe prognosis compared to adult-onset MS. It remains a challenging condition to treat because of the highly inflammatory nature of the disease, the prominent cognitive issues, and the limited knowledge about the efficacy and safety of current available disease-modifying therapies. Over the past decade, there has been a dramatic increase in the number of drugs licensed for adult-onset MS and several of them, although not tested in PedMS, are currently being used off-label in this population...
August 2016: Current Treatment Options in Neurology
Maria Dubos, Kim Ly, Clothilde Martel, Anne Laure Fauchais
Calcinosis, the deposition of calcified material in soft tissues, is frequently seen in systemic sclerosis and dermatomyositis. Treatment options are limited, with disappointing results. Some recent case reports suggest that rituximab may be an attractive therapeutic option. In case 1, a 54-year-old woman who presented with rheumatoid arthritis in association with scleromyositis was treated with rituximab for rheumatoid arthritis. Despite this, she developed multiple progressive calcinosis, necessitating extracorporeal shock wave lithotripsy to limit calcinosis extension and pain...
2016: BMJ Case Reports
Mark D Kvarta, Deva Sharma, Rudolph J Castellani, Robert E Morales, Stephen G Reich, Amy S Kimball, Robert K Shin
BACKGROUND: Primary central nervous system lymphoma (PCNSL) may rarely be preceded by "sentinel demyelination," a pathologic entity characterized by histologically confirmed demyelinating inflammatory brain lesions that mimic multiple sclerosis (MS) or acute disseminated encephalomyelitis (ADEM). Interpreting the overlapping radiologic and clinical characteristics associated with each of these conditions-contrast-enhancing demyelination of white matter and relapsing and remitting steroid-responsive symptoms respectively-can be a significant diagnostic challenge...
2016: BMC Neurology
Stacy Ellen Hatcher, Emmanuelle Waubant, Bardia Nourbakhsh, Elizabeth Crabtree-Hartman, Jennifer S Graves
IMPORTANCE: The appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety and protection against relapse. The cases presented herein highlight that rebound events after ceasing fingolimod treatment may happen even with short washout periods (4 weeks) and may perpetuate despite steroid treatment or the immediate use of fast-acting immune therapies, such as rituximab. OBJECTIVE: To describe rebound syndrome in patients with multiple sclerosis (MS) after cessation of fingolimod treatment...
July 1, 2016: JAMA Neurology
Nicolas Collongues, Jérôme de Seze
Neuromyelitis optica spectrum disorders (NMOSDs) is a new concept which includes classical neuromyelitis optica (NMO) and partial forms of NMO such as recurrent optic neuritis with positive aquaporin-4 antibodies (AQP4) or brainstem symptoms (intractable hiccups or vomiting). This disease is clearly distinguished from multiple sclerosis (MS) and the therapeutic approach is clearly different. Rituximab is actually considered to be one of the most efficient treatments of NMOSD, even if class I studies are clearly lacking...
May 2016: Therapeutic Advances in Neurological Disorders
Barry A Singer
Improved disease control is critical for enhancing the lives of those living with multiple sclerosis. With specific immunologic targets, monoclonal antibody (mAb) treatments are highly effective options for relapsing forms of multiple sclerosis. The mechanism, efficacy, and current safety profiles are detailed for the two mAb therapies, natalizumab and alemtuzumab, with regulatory approval in multiple countries. Daclizumab, which targets the interleukin-2 receptor, and ocrelizumab, which depletes B cells, have convincing phase 3 clinical trial data and may very well provide new options in the near future...
April 2016: Seminars in Neurology
Patrice H Lalive
No abstract text is available yet for this article.
March 2, 2016: Revue Médicale Suisse
Albane Joly-Battaglini, Clara Hammarström, Branislava Stankovic, Henrik Aamodt, Johan Stjärne, Odd Terje Brustugun, Åslaug Helland, Inger Øynebråten, Alexandre Corthay
Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated...
2016: F1000Research
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