In this review, we provide a brief overview about anti-CD20 B cell-based therapies in MS, in the perspective of their influence on the future management of the disease, and of their possible positioning in a new wider therapeutic scenario.
Areas covered: In this review, the authors discuss the rationale of the depletion of B cells in RRMS and PPMS across recent studies on the role of B cells in the pathogenesis of MS; previous clinical trials with treatments targeting B cells; the mechanism of action of ocrelizumab - a second generation anti-CD20 mAb - and recent phase III clinical trials with ocrelizumab in RRMS and PPMS.
In the present study, we summarized several applications of anti-CD20 antibodies in various immune related disorders including B-CLL (B-cell chronic lymphocytic leukemia), rheumatoid arthritis (RA), multiple sclerosis (MS) and melanoma.
The recent interest in the key role of B cells in MS has been evoked by the profound anti-inflammatory effects of rituximab, a chimeric monoclonal antibody (mAb) targeting the B cell surface marker CD20, observed in relapsing-remitting MS.
B cell depletion through anti-CD20 monoclonal antibody utilization and other immunomodulatory therapies have been promising in reducing episodes of relapse and slowing progression, further strengthening the concept that B cells and antibodies are significant players in formation of brain lesions in MS.
Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS).
A real-world study from Wales suggests that early initiation of highly effective therapy may provide more benefit that an escalation approach in relapsing MS. A study from the MSBase dataset found evidence that early treatment with highly effective therapies decreased the risk of developing secondary progressive MS. Ocrelizumab is highly efficacious in relapsing MS and in a group of patients with primary progressive MS. Another CD20 directed mAb, ofatumumab, is in phase 3.
An increased proportion of myelin-specific CD8<sup>+</sup> T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8<sup>+</sup> T cells.
These data represent an important contribution to the understanding of the nature of CD20+ T cells and strongly suggests a role of CD20+ T cells in the pathogenesis of multiple sclerosis.
In this manuscript, we review mechanisms of action, efficacy, safety, and tolerance of anti-CD20 therapies for MS, including rituximab, ocrelizumab, and ofatumumab.
These data suggest that loss of B cells as antigen presenting cells is a major mechanism of action for the beneficial effects of CD20 antibody therapy in MS.
While it was long held that T cells were the primary mediators of multiple sclerosis (MS) pathogenesis, the beneficial effects observed in response to treatment with Rituximab (RTX), a monoclonal antibody (mAb) targeting CD20, shed light on a key contributor to MS that had been previously underappreciated: B cells.
A role for B cells in autoimmune diseases is now clearly established both in mouse models and humans by successful treatment of multiple sclerosis and rheumatoid arthritis with anti-CD20 monoclonal antibodies that eliminate B cells.
Last, we summarize remaining unanswered questions regarding the proper role of anti-CD20 therapy in MS, its limitations, and the future landscape of B-cell-based approaches to treatment.Ann Neurol 2018;83:13-26.
Ocrelizumab, a humanized monoclonal anti-CD20 antibody, has shown pronounced effects in reduction of disease activity in multiple sclerosis (MS) patients and has recently been approved for the treatment of patients with relapsing MS (RMS) and primary progressive MS (PPMS).