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.