China
Africa
Explore chapters and articles related to this topic
Inflammatory Disorders of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Ocrelizumab is an anti-CD20 monoclonal antibody that blocks B cells and their activity. It is delivered by two infusions 2 weeks apart, followed 6 months later by a third, and reduces RR by 70%. It appears relatively safe, though carries a short-term risk of infections.
Central nervous system viral infections complicating immunosuppression
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Rituximab, an anti-CD20 monoclonal antibody, profoundly depletes B lymphocytes and has been used for an increasing number of neurologic and oncologic indications. Use of Rituximab has been associated with numerous opportunistic infections (Table 24.4) as well as increased severity of usually relatively benign pathogens such as enteroviral infection [39]. CMV reactivation has been reported as has the development of primary CNS lymphoma (PCNSL) [40]. Ocrelizumab, whose mode of action is similar to that of rituximab, thus far has not been associated with any increased risk of PML, though a few cases of disseminated VZV have been reported.
Organ-specific autoimmune diseases
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, George C. Tsokos
Recently, several new pharmacological agents have been found to be useful in the treatment of MS. Teriflunomide, a pyrimidine synthesis inhibitor, has been found in phase III trials to be equivalent to IFNβ. Dimethyl fumarate has a comparable clinical effect that correlates inversely with lymphocyte counts and has been approved by the U.S. Food and Drug Administration (FDA). Fingolimod, a sphingosine-1-phosphate-1 receptor antagonist, inhibits the egression of lymphocytes from lymph nodes to the bloodstream. It has been shown to have a good clinical effect and has also been approved by the FDA. Natalizumab is a humanized monoclonal antibody that recognizes the adhesion molecule α4 integrin and blocks its interaction with the vascular cell adhesion molecule 1. Natalizumab has great clinical efficacy. A downside is there is a substantial risk for the development of progressive multifocal leukoencephalopathy caused by activation of the JC virus. Other monoclonal antibodies shown to be clinically valuable and used to treat MS are the B cell–depleting antibodies (rituximab and ocrelizumab).
B cell depletion in the treatment of multiple sclerosis
Published in Expert Opinion on Biological Therapy, 2019
Kjell-Morten Myhr, Øivind Torkildsen, Andreas Lossius, Lars Bø, Trygve Holmøy
Ocrelizumab, an anti-CD20 monoclonal antibody, was recently approved for the treatment of MS by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Results from randomized clinical trials (RCTs) have proven high efficacy, and the drug seems to be well tolerated in relapsing MS [15], but studies of the long-term evaluation of adverse effects related to infections and cancer risks need to be performed. Although the effect on disability progression is limited, the drug is also the first approved therapy for the treatment of primary progressive MS [16]. Other anti-CD20 monoclonal antibodies, including rituximab and ofatumumab have shown similar effects in phase II trials [17–20], and there is an increasing experience from off label use of rituximab [21–28] in MS as well in neuromyelitis optica spectrum disorders [29].
Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review
Published in Expert Opinion on Drug Safety, 2020
Huah Shin Ng, Constanza Luzon Rosenbult, Helen Tremlett
Several new drugs representing new therapeutic agents have been approved for the treatment of MS in the recent years. One such example is ocrelizumab, approved by the United States Food and Drug Administration (FDA) in 2017 and was also the first drug indicated to treat both relapsing-remitting and primary progressive MS [7]. Its efficacy and safety had been demonstrated in short-term clinical trials conducted over 2–3 years [8–10]. However, there remains considerable uncertainty about the potential risks of infections, as well as longer term outcomes such as malignancy in relation to ocrelizumab use [11]. This review aimed to provide a comprehensive summary and qualitative synthesis of reported adverse events (AEs) for ocrelizumab, using a systematic approach.
Glial cells as therapeutic targets in progressive multiple sclerosis
Published in Expert Review of Neurotherapeutics, 2019
Brandon Wilbanks, LJ Maher, Moses Rodriguez
Ocrelizumab is the lone therapy approved in the United States for primary progressive MS. This drug is a humanized monoclonal anti-CD20 antibody targeting B lymphocytes. Like the similar anti-CD20 antibody rituximab, it downregulates immune response by removing B cells from the periphery. The mechanism of B cell depletion has not been described, but it likely involves some combination of three factors: 1) pore formation in cell membranes leading to lysis, 2) antibody-mediated targeting of B cells by macrophages, natural killer cells, and T cells, and 3) apoptosis following CD20 cross-linking. It is thought that ocrelizumab may be more effective for MS than rituximab due to its decreased complement-dependent cytotoxic effects [59].