Role of Ocrelizumab in the Treatment of Multiple Sclerosis

Smew, Aziza Tawfik (2020-02-18)

MS is an autoimmune response against components of the myelin sheath characterized by episodes of disease activity in separated time that produce white matter lesions in separated space1 . It's the most common demyelinating disorder, include prevalence of approximately 1 per 1000 individuals in Europe and United States1 . The disease may present at any age, but onset in childhood or after age 50 is rare, females are affected twice as often as males1 . The most common clinical course is the relapsing-remitting (RR) phenotype, while a minority of patients have an immediate progression of disability, referred to as the primary progressive (PP) phenotype accounts for 10% to 15% of the overall subject's with MS

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Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system, in which B-cells play an important role in its pathogenesis. However, Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody that can diminish the targeted B-cells through antibody-dependent cell mediated cytotoxicity. It's the only MS drug that has been approved by the US Food and Drug Administration (FDA) for patients with relapsing–remitting MS (RRMS) and primary progressive MS (PPMS). Phase II clinical trials studies OCR role on MRI and clinical features in patients with RRMS, while Phase III clinical trials have confirmed the results of previous Phase II studies. However, OPERA I and II clinical trials, which were performed on subjects with RRMS, has shown a reduction in the risk of disability progression, the annualized relapse rate, enhancing lesions measured using brain magnetic resonance and the number of enlarging/new T2 lesions. The ORATORIO trial performed in patients with PPMS, showed that OCR can decrease disability progression, enhance the performance on the timed 25-foot walk, and reduce the number of new/enlarging T2 lesions. This report is aimed to study the role of B-cell in the pathophysiology of MS, OCR mechanism of action and its efficacy in patient with RRMS and PPMS.

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