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Multiple Sclerosis and rituximab

Sareh Shahmohammadi, Mohammad Ali Sahraian, Abootorab Shahmohammadi, Rozita Doosti, Ali Zare-Mirzaie, Abdorreza Naser Moghadasi
Multiple sclerosis (MS) is one of the most important demyelinating diseases that affects the central nervous system. Its treatment often involves a long-term disease modifying therapy. According to some studies, the prevalence of autoimmune disorders, such as autoimmune hepatitis (AIH) and ulcerative colitis (UC) is higher in MS patients than in the normal population. There are also few studies that have reported the onset of UC after rituximab therapy. The present study presents a report of a 31-years old female patient suffering from aggressive multiple sclerosis, which developed into autoimmune hepatitis during the MS therapy...
March 1, 2018: Multiple Sclerosis and related Disorders
R Rahmanzadeh, M S Weber, W Brück, S Navardi, M A Sahraian
For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and the disease was always regarded as a T cell-mediated disorder. Recent evidence shows that there is an antigen-driven B-cell response in the central nervous system of patients with MS, and memory B cells/plasma cells are detectable in MS lesions. The striking efficacy of B cell-depleting therapies in reducing the inflammatory activity of the disease highlights that B cells may play more pathogenetic roles than expected. B cells express several unique characteristic markers on their surface, for example, CD19, CD20 molecules, that provide selective targets for monoclonal antibodies...
March 7, 2018: Acta Neurologica Scandinavica
Fredrik Piehl, Jan Hillert
No abstract text is available yet for this article.
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Bruce Ac Cree
No abstract text is available yet for this article.
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Mitchell T Wallin
No abstract text is available yet for this article.
February 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Philippe Cabre, M Mejdoubi, S Jeannin, H Merle, Y Plumelle, G Cavillon, D Smadja, R Marignier
OBJECTIVE: Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the central nervous system. It affects young subjects and has a poor prognosis both on a functional and vital level. Therefore, it is imperative to reduce the frequency of relapses. The purpose of this study was to evaluate the clinical and neuroradiological effectiveness of rituximab (RTX) on active forms of NMO. METHODS: We conducted a 2-year open prospective multicenter study that included 32 patients treated with RTX at a dose of 375 mg/m2 /week for 1 month...
February 17, 2018: Journal of Neurology
Khalaf Kridin, Shira Zelber-Sagi, Doron Comaneshter, Arnon D Cohen
Importance: The association between pemphigus and neurologic diseases was not evaluated systematically in the past. In a recent uncontrolled cross-sectional study, Parkinson disease was found to be significantly associated with pemphigus; in the same study, epilepsy had a nonsignificant association with pemphigus. Several case reports have suggested that pemphigus coexists with multiple sclerosis and dementia. Objective: To estimate the association between pemphigus and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple sclerosis), using one of the largest cohorts of patients with pemphigus...
February 16, 2018: JAMA Dermatology
Elisabeth Maillart, Anaïs Lippi, Catherine Lubetzki, Céline Louapre, Caroline Papeix
BACKGROUND: We report a dramatic clinical and radiological worsening within two months after rituximab initiation in a patient with NeuroMyelitis Optica/Multiple Sclerosis (NMO/MS) overlap syndrome. METHODS: Case study. RESULTS: A 45-year-old Caucasian woman with NMO/MS overlap syndrome experienced a severe myelitis nine weeks after first rituximab infusion, with extensive new gadolinium-enhanced spinal cord lesions. CONCLUSION: This case report illustrates the limits of MS and NMO-Spectrum Disorder classification and challenges the criteria of therapeutic failure within the 6 months after rituximab initiation...
February 6, 2018: Multiple Sclerosis and related Disorders
Irene Eriksson, Joris Komen, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used). METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017...
February 10, 2018: European Journal of Clinical Pharmacology
Pierre de Flon, Lars Söderström, Katarina Laurell, Ann Dring, Peter Sundström, Martin Gunnarsson, Anders Svenningsson
OBJECTIVE: To investigate changes in the cerebrospinal fluid (CSF) immunological profile after treatment switch from first-line injectables to rituximab in patients with relapsing-remitting MS (RRMS), and to compare the profile in MS patients with healthy controls (HC). METHOD: Cerebrospinal fluid from 70 patients with clinically stable RRMS and 55 HC was analysed by a multiplex electrochemiluminescence method for a broad panel of cytokines and immunoactive substances before, and over a two-year period after, treatment switch to rituximab...
2018: PloS One
Brett Alldredge, Allison Jordan, Jaime Imitola, Michael K Racke
OBJECTIVES: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. B cells play an important pathogenic role in MS. Rituximab (RTX), a B-cell depleting drug, has been used to treat MS and neuromyelitis optica (NMO). Patient characteristics, safety, and efficacy measures are reviewed to ascertain the therapeutic benefit and safety of RTX in a real-world setting with long-term follow-up. METHODS: This is a retrospective chart review of patients who received RTX at The Ohio State University's MS clinic from January 2005 to October 2016...
January 31, 2018: Clinical Neuropharmacology
Yael Hacohen, Yu Yi Wong, Christian Lechner, Maciej Jurynczyk, Sukhvir Wright, Bahadir Konuskan, Judith Kalser, Anne Lise Poulat, Helene Maurey, Esther Ganelin-Cohen, Evangeline Wassmer, Chery Hemingway, Rob Forsyth, Eva Maria Hennes, M Isabel Leite, Olga Ciccarelli, Banu Anlar, Rogier Hintzen, Romain Marignier, Jacqueline Palace, Matthias Baumann, Kevin Rostásy, Rinze Neuteboom, Kumaran Deiva, Ming Lim
Importance: Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are consistently identified in a range of demyelinating disorders in adults and children. Current therapeutic strategies are largely center specific, and no treatments have been formally evaluated. Objective: To examine the clinical phenotypes, treatment responses, and outcomes of children with relapsing MOG-Ab-associated disease. Design, Setting, and Participants: This study prospectively collected demographic, clinical, and radiologic data from 102 patients from 8 countries of the EU Paediatric Demyelinating Disease Consortium from January 1, 2014, through December 31, 2016...
January 5, 2018: JAMA Neurology
L Midaglia, L Mora, P Mulero, J Sastre-Garriga, X Montalban
INTRODUCTION: There is increasing evidence that B cells and humoral immunity play key roles in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, an anti-CD20 monoclonal antibody, has been shown to be effective in controlling the disease and has recently been aproved by the Food and Drug Administration for the treatment of primary progressive and relapsing MS. While awaiting its marketing authorization, the use of rituximab, with a similar mechanism of action, has expanded widely in the area of demyelinating diseases...
January 1, 2018: Revista de Neurologia
Georgia McCaughan, Jennifer Massey, Ian Sutton, Jennifer Curnow
Alemtuzumab is a highly efficacious therapy used in the treatment of multiple sclerosis (MS), but uncoupling of T and B cell repopulation during immune reconstitution associates with an increasing range of secondary B cell-mediated autoimmune complications. A 34-year-old woman developed Graves' disease 11 months following an initial course of alemtuzumab treatment for MS. Nine months following the second treatment with alemtuzumab, the patient presented with spontaneous intramuscular and subcutaneous haemorrhage due to development of an inhibitory autoantibody to coagulation factor VIII...
December 5, 2017: BMJ Case Reports
Fanny Huynh Du, Elizabeth A Mills, Yang Mao-Draayer
The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine-human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab...
November 16, 2017: Auto- Immunity Highlights
Jagannadha Avasarala
Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies...
2017: Drug Target Insights
Pedro Sánchez, Virginia Meca-Lallana, Antonio Barbosa, Rafael Manzanares, Itziar Palmí, José Vivancos
BACKGROUND AND OBJECTIVE: Tumefactive demyelinating lesions (TDLs) are large inflammatory lesions that can mimic tumors or other space-occupying lesions. Differential diagnosis and management of these lesions remain challenging for neurologists. We aim to review the clinico-radiological features of patients with TDLs, as well as their management. METHODS: We performed a retrospective review of cases of TDLs treated in our center from January 2010 to February 2017...
October 15, 2017: Journal of the Neurological Sciences
Marco Allinovi, Calogero Lino Cirami, Leonardo Caroti, Giulia Antognoli, Silvia Farsetti, Maria Pia Amato, Enrico Eugenio Minetti
BACKGROUND: Interferon-beta (IFN-beta) is one of the most widely prescribed medications for relapsing-remitting multiple sclerosis (RRMS). IFN-related thrombotic microangiopathy (TMA) is a rare but severe complication, with a fulminant clinical onset and a possibly life-threatening outcome that may occur years after a well-tolerated treatment with IFN. Most patients evolve rapidly to advanced chronic kidney disease and eventually to renal failure. METHODS: We performed a retrospective analysis of TMA cases diagnosed and managed in our Nephrology Department from 2010 to 2015, and performed a literature review of IFN-beta-induced TMA...
October 2017: Clinical Kidney Journal
Jeffrey R Atkinson, Cornelia C Bergmann
B cell subsets with phenotypes characteristic of naive, non-isotype-switched, memory (Bmem ) cells and antibody-secreting cells (ASC) accumulate in various models of central nervous system (CNS) inflammation, including viral encephalomyelitis. During neurotropic coronavirus JHMV infection, infiltration of protective ASC occurs after T cell-mediated viral control and is preceded by accumulation of non-isotype-switched IgD+ and IgM+ B cells. However, the contribution of peripheral activation events in cervical lymph nodes (CLN) to driving humoral immune responses in the infected CNS is poorly defined...
December 1, 2017: Journal of Virology
Arya Dadgar, Anna Grankvist, Lennart Wernbro, Christine Wennerås
Fever of unknown origin in a multiple sclerosis patient on immunomodulatory therapy was due to neoehrlichiosis The emerging tick-borne bacterium Candidatus Neoehrlichia mikurensis is the etiologic agent of neoehrlichiosis, a febrile illness that may be accompanied by vascular complications. Severe cases of neoehrlichiosis have been described in patients with hematologic malignancies and systemic rheumatic diseases. We present the first case of neoehrlichiosis in a patient with multiple sclerosis undergoing rituximab therapy...
September 18, 2017: Läkartidningen
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