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Multiple Sclerosis and rituximab

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https://www.readbyqxmd.com/read/28799485/monoclonal-antibodies-a-review
#1
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
#2
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
#3
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
#4
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
#5
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 pathological feature of multiple sclerosis (MS), and are becoming an important therapeutic target for this condition. Currently, there is no approved technique to non-invasively 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 positron emission tomography (PET)...
July 7, 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28283109/classifying-pml-risk-with-disease-modifying-therapies
#13
REVIEW
Joseph R Berger
OBJECTIVE: To catalogue the risk of PML with the currently available disease modifying therapies (DMTs) for multiple sclerosis (MS). BACKGROUND: All DMTs perturb the immune system in some fashion. Natalizumab, a highly effective DMT, has been associated with a significant risk of PML. Fingolimod and dimethyl fumarate have also been unquestionably associated with a risk of PML in the MS population. Concerns about PML risk with other DMTs have arisen due to their mechanism of action and pharmacological parallel to other agents with known PML risk...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28161400/memory-b-cells-are-major-targets-for-effective-immunotherapy-in-relapsing-multiple-sclerosis
#14
REVIEW
David Baker, Monica Marta, Gareth Pryce, Gavin Giovannoni, Klaus Schmierer
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells...
February 2017: EBioMedicine
https://www.readbyqxmd.com/read/28078314/onset-of-secondary-progressive-ms-after-long-term-rituximab-therapy-a-case-report
#15
H-Christian von Büdingen, Antje Bischof, Erica L Eggers, Shengzhi Wang, Carolyn J Bevan, Bruce A C Cree, Roland G Henry, Stephen L Hauser
A patient with relapsing multiple sclerosis (RMS) was treated with a standard immunomodulatory therapy, but due to ongoing disease activity was switched to rituximab. Relapses ceased, but secondary progressive MS (SPMS) eventually appeared, associated with new focal spinal cord white matter lesions. Cerebrospinal fluid (CSF) showed persistent oligoclonal bands (OCB) and clonally related B cells in CSF and peripheral blood. The treatment escalation approach failed to prevent evolution to SPMS, raising the question of whether initiation of B-cell depleting therapy at the time of RMS diagnosis should be tested to more effectively address the immune pathology leading to SPMS...
January 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28060988/-neuromyelitis-optica-presenting-concomitantly-with-systemic-lupus-erythematosus-report-of-one-case
#16
Felipe Suárez H, Daniela Urrutia E, Felipe Canales P, Camila Gutiérrez O
Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system, which preferentially attacks the optic nerve and spinal cord. It is associated with antibodies against aquaporin 4. Morbidity and mortality are higher than in multiple sclerosis and its treatment focuses on immunosuppressive drugs. Immunomodulators are contraindicated. We report a previously healthy 35-year-old man, presenting with NMO concomitantly with systemic lupus erythematosus. His evolution was torpid with three outbreaks in the 10 months after the diagnosis, requiring a first-line therapy with methylprednisolone and cyclophosphamide and then a second-line therapy with rituximab...
September 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/28017256/treatment-of-neuromyelitis-optica-and-neuromyelitis-optica-spectrum-disorders-with-rituximab-using-a-maintenance-treatment-regimen-and-close-cd19-b-cell-monitoring-a-six-year-follow-up
#17
M E Evangelopoulos, E Andreadou, G Koutsis, V Koutoulidis, M Anagnostouli, P Katsika, D S Evangelopoulos, I Evdokimidis, C Kilidireas
Neuromyelitis optinca (NMO) represents a serious demyelinating disease of the central nervous system selectively attacking the spinal cord and optic nerve. Early differential diagnosis from multiple sclerosis is of vital importance, as NMO mandates immunosuppressive and not immunomodulatory treatment. Rituximab has been recently introduced as a treatment option for NMO. However, optimal surrogate measures and treatment intervals are still unclear. Five patients (females, mean age 54±10.21years) with NMO and NMO spectrum disorders (NMOSD) were evaluated with respect to disability and relapse rate...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28011145/a-functional-genomic-meta-analysis-of-clinical-trials-in-systemic-sclerosis-toward%C3%A2-precision-medicine-and-combination-therapy
#18
Jaclyn N Taroni, Viktor Martyanov, J Matthew Mahoney, Michael L Whitfield
Systemic sclerosis is an orphan, systemic autoimmune disease with no FDA-approved treatments. Its heterogeneity and rarity often result in underpowered clinical trials making the analysis and interpretation of associated molecular data challenging. We performed a meta-analysis of gene expression data from skin biopsies of patients with systemic sclerosis treated with five therapies: mycophenolate mofetil, rituximab, abatacept, nilotinib, and fresolimumab. A common clinical improvement criterion of -20% or -5 modified Rodnan skin score was applied to each study...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27919500/favorable-outcome-of-interferon-beta-associated-thrombotic-microangiopathy-following-treatment-with-corticosteroids-plasma-exchange-and-rituximab-a-case-report
#19
Lea M Gerischer, Eberhard Siebert, Oliver Janke, Gerhard Jan Jungehuelsing, Klemens Ruprecht
Thrombotic microangiopathy (TMA) is a rare but increasingly recognized complication of interferon-beta therapy, which can be associated with serious sequelae. We report on a 53-year-old woman with a longstanding history of relapsing-remitting multiple sclerosis, who developed TMA after 15 years of high-dose treatment with subcutaneous interferon-beta-1a. The patient presented with headaches, an epileptic seizure, confusion, and arterial hypertension. Laboratory findings included thrombocytopenia and hemolytic anemia...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27824545/targeted-therapy-in-systemic-sclerosis
#20
REVIEW
Murray Baron
Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma) has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc...
October 31, 2016: Rambam Maimonides Medical Journal
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