Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab

Abstract

Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS.

Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates

“…These DMTs can also be classified broadly according to their pharmacological mechanisms of action. For example, dimethyl fumarate, teriflunomide, fingolimod, natalizumab, and the anti-CD20 agents ocrelizumab and ofatumumab [14] (the latter is newly approved for the management of RRMS in the USA) are continuously administered immunosuppressants. Interferons and glatiramer acetate are administered continuously and act via complex mechanisms that do not require a generalised suppression of the immune system [15][16][17].…”

Rituximab in Multiple Sclerosis: Are We Ready for Regulatory Approval?

“…There are three major mAbs targeting CD20+ B-cells, rituximab, ocrelizumab, and ofatumumab. The mechanisms of apoptotic B-cell depletion include antibody-dependent cell-mediated phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) ( 28 , 31 ). Recent studies have shown also a depleting action on CD20+ T cells, which are shown to be present in MS patients, suggesting an alternative contributing mechanism ( 38 ).…”

Breast Carcinoma After Ocrelizumab Therapy in Multiple Sclerosis Patients: A Case Series and Literature Review

“…Common adverse reactions associated with ocrelizumab are mostly related to increased infections including skin infections and upper respiratory infections; however, malignancy particularly of the breast has been reported earlier in the clinical trials. 16 - 18 …”