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Multiple Sclerosis and rituximab

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https://www.readbyqxmd.com/read/29143151/next-generation-anti-cd20-monoclonal-antibodies-in-autoimmune-disease-treatment
#1
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
https://www.readbyqxmd.com/read/29123374/anti-cd20-cell-therapies-in-multiple-sclerosis-a-fixed-dosing-schedule-for-ocrelizumab-is-overkill
#2
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
https://www.readbyqxmd.com/read/28991707/tumefactive-demyelinating-lesions-of-15-patients-clinico-radiological-features-management-and-review-of-the-literature
#3
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
https://www.readbyqxmd.com/read/28980667/thrombotic-microangiopathy-induced-by-interferon-beta-in-patients-with-multiple-sclerosis-three-cases-treated-with-eculizumab
#4
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
https://www.readbyqxmd.com/read/28931676/protective-humoral-immunity-in-the-central-nervous-system-requires-peripheral-cd19-dependent-germinal-center-formation-following-coronavirus-encephalomyelitis
#5
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
https://www.readbyqxmd.com/read/28926079/oklar-feber-hos-patient-med-ms-och-rituximab%C3%A2-behandling-var-neoehrlichios-ny-f%C3%A3-stingburen-infektion-som-%C3%A3-r-sv%C3%A3-r-att-diagnostisera
#6
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
https://www.readbyqxmd.com/read/28910968/efficiency-of-antibody-therapy-in-demyelinating-diseases
#7
Tetsuya Akaishi, Ichiro Nakashima
Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Food and Drug Administration...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28881516/-effectiveness-and-safety-of-rituximab-for-children-with-autoimmune-diseases-of-the-nervous-system
#8
Z Fu, X H Bao, Y Wu, J Zhou, Y H Zhang, Y Zhang, T Y Ji, Y Chen
Objective: To assess the effectiveness and safety of rituximab in Chinese children with autoimmune diseases of the nervous system. Method: An ambispective cohort study enrolled patients with refractory and(or) relapse autoimmune diseases of nervous system from June 2010 to June 2016 in Peking University First Hospital.These patients failed to respond to steroids and(or)intravenous immunoglobulin (IVIG) were treated with rituximab and seen for follow-up visits once every 3 months.The effectiveness was assessed by modified Rankin scale (mRs) and the annualized relapse rate...
September 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28799485/monoclonal-antibodies-a-review
#9
Surjit Singh, Nitish Kumar, Pradeep Dwiwedi, Jaykaran Charan, Rimplejeet Kaur, Preeti Sidhu, Vinay Kumar Chugh
Over the last three decades, monoclonal antibodies (MAbs) have made a striking transformation from scientific tools to powerful human therapeutics. Muromonab CD3 a murine MAb, was first FDA approved therapeutic MAb for prevention of kidney transplant rejection. Since its approval in 1986, there has been decline in the further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of low grade B cell lymphoma in 1997. With the approval by licensing authorities of chimeric, followed by humanized and then fully human monoclonal antibodies, rate of approval and monoclonal antibodies available in the market for the treatment of various diseases has increased dramatically...
August 9, 2017: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/28791286/autoimmune-thrombotic-thrombocytopenic-purpura-two-rare-cases-associated-with-juvenile-idiopathic-arthritis-and-multiple-sclerosis
#10
Despoina Dimopoulou, Athina Dimosiari, Eudokia Mandala, Theodoros Dimitroulas, Alaxandros Garyfallos
Secondary thrombotic microangiopathies are associated with several underlying conditions, with most of them being resolved after the treatment of background disease. Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy presenting with anemia, thrombocytopenia, and neurological deficits, occurring most often in various autoimmune diseases due to inhibition of ADAMTS13 by autoantibodies, as well as in pregnant women with or without an autoimmune substrate. In this article, we report two newly diagnosed TTP cases, who have not been published so far...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28762877/rituximab-in-multiple-sclerosis-frequency-and-clinical-relevance-of-anti-drug-antibodies
#11
Nicky Dunn, Alexander Juto, Malin Ryner, Ali Manouchehrinia, Luca Piccoli, Katharina Fink, Fredrik Piehl, Anna Fogdell-Hahn
BACKGROUND: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown. OBJECTIVE: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients. METHODS: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28695471/ocrelizumab-and-other-cd20-b-cell-depleting-therapies-in-multiple-sclerosis
#12
REVIEW
Jeffrey M Gelfand, Bruce A C Cree, Stephen L Hauser
Selective depletion of CD20(+) B cells by anti-CD20 monoclonal antibodies as monotherapy in multiple sclerosis (MS) profoundly suppresses acute inflammatory disease activity and signifies an important advance in the treatment of relapsing-remitting MS. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, is also the first proven therapy to lessen disability progression in primary progressive MS-a breakthrough for patients with a disease that had no proven therapy. Ocrelizumab is generally well tolerated, with the most common adverse events experienced being infusion reactions and infections...
July 10, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28687602/imaging-b-cells-in-a-mouse-model-of-multiple-sclerosis-using-64-cu-rituximab-pet
#13
Michelle L James, Aileen Hoehne, Aaron T Mayer, Kendra Lechtenberg, Monica Moreno, Gayatri Gowrishankar, Ohad Ilovich, Arutselvan Natarajan, Emily M Johnson, Joujou Nguyen, Lisa Quach, May Han, Marion Buckwalter, Sudeep Chandra, Sanjiv S Gambhir
B lymphocytes are a key pathologic feature of multiple sclerosis (MS) and are becoming an important therapeutic target for this condition. Currently, there is no approved technique to noninvasively visualize B cells in the central nervous system (CNS) to monitor MS disease progression and response to therapies. Here, we evaluated (64)Cu-rituximab, a radiolabeled antibody specifically targeting the human B cell marker CD20, for its ability to image B cells in a mouse model of MS using PET. Methods: To model CNS infiltration by B cells, experimental autoimmune encephalomyelitis (EAE) was induced in transgenic mice that express human CD20 on B cells...
November 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28649912/comparative-effectiveness-of-rituximab-relative-to-ifn-%C3%AE-or-glatiramer-acetate-in-relapsing-remitting-ms-from-the-swedish-ms-registry
#14
Tim Spelman, Thomas Frisell, Fredrik Piehl, Jan Hillert
OBJECTIVE: To compare treatment effectiveness and persistence in relapsing-remitting multiple sclerosis patients who initiated rituximab versus glatiramer acetate (GA) or interferon-beta (IFN-β). METHODS: A total of 461 patients from the Swedish MS registry in the rituximab arm were propensity score matched on a 1:2 basis with 922 patients from the IFN-β/GA comparator, between April 2005 and November 2015. Annualised relapse rate (ARR) was compared using the Poisson method...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28514773/a-feasibility-study-of-the-full-outpatient-conduction-of-hematopoietic-transplants-in-persons-with-multiple-sclerosis-employing-autologous-non-cryopreserved-peripheral-blood-stem-cells
#15
Guillermo J Ruiz-Argüelles, Andrés A León-Peña, Mónica León-González, Ana Karen Nuñez-Cortes, Juan Carlos Olivares-Gazca, Iván Murrieta-Alvarez, Jocelyn Vargas-Espinosa, Emilio Medina-Ceballos, Yahveth Cantero-Fortiz, Alejandro Ruiz-Argüelles, Manuel A Ruiz-Delgado, Rodrigo J Ruiz-Delgado, Guillermo Ruiz-Reyes, Manuel Priesca-Marín, Merari Starlight Torres-Priego, David Blumenkron-Marroquin, Guillermo J Ruiz-Delgado
BACKGROUND: With the goal of achieving immune system reset, autologous hematopoietic stem cell transplantations have been performed in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Two hundred and eighty-six consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSCs), on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217...
2017: Acta Haematologica
https://www.readbyqxmd.com/read/28450895/targeting-b-cells-in-relapsing-remitting-multiple-sclerosis-from-pathophysiology-to-optimal-clinical-management
#16
REVIEW
Stefan Bittner, Tobias Ruck, Heinz Wiendl, Oliver M Grauer, Sven G Meuth
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that is caused by an autoimmune response against central nervous system (CNS) structures. Traditionally considered a T-cell-mediated disorder, the contribution of B cells to the pathogenesis of MS has long been debated. Based on recent promising clinical results from CD20-depleting strategies by three therapeutic monoclonal antibodies in clinical phase II and III trials (rituximab, ocrelizumab and ofatumumab), targeting B cells in MS is currently attracting growing interest among basic researchers and clinicians...
January 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28443358/cerebral-rituximab-uptake-in-multiple-sclerosis-a-89-zr-immunopet-pilot-study
#17
Marloes Hj Hagens, Joep Killestein, Maqsood M Yaqub, Guus Ams van Dongen, Adriaan A Lammertsma, Frederik Barkhof, Bart Nm van Berckel
Previous studies have demonstrated that the chimeric monoclonal antibody rituximab significantly reduces clinical and radiological disease activity in relapsing-remitting multiple sclerosis as early as 4 weeks after the first administration. The exact mechanisms leading to this rapid effect have not yet been clarified. The aim of this positron emission tomography study was to assess central nervous system penetration as a possible explanation, using zirconium-89-labelled rituximab. No evidence was found for cerebral penetration of [(89)Zr]rituximab...
April 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28440858/treatment-with-disease-modifying-drugs-for-people-with-a-first-clinical-attack-suggestive-of-multiple-sclerosis
#18
REVIEW
Graziella Filippini, Cinzia Del Giovane, Marinella Clerico, Omid Beiki, Miriam Mattoscio, Federico Piazza, Sten Fredrikson, Irene Tramacere, Antonio Scalfari, Georgia Salanti
BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28325251/interferon-induced-thrombotic-microangiopathy-tma-analysis-and-concise-review
#19
REVIEW
Ajay Kundra, Jen Chin Wang
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28323224/progressive-multifocal-leukoencephalopathy-and-rheumatoid-arthritis-treatments
#20
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
December 2017: Joint, Bone, Spine: Revue du Rhumatisme
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