CD20 monoclonal antibodies for the treatment of multiple sclerosis: up-to-date

Featuring demyelination and axonal degeneration, multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system representing a prominent cause of disability in young adults. The recently established therapeutic targeting of B cells in MS patients using CD20 monoclonal antibodies (CD20-mAbs) not only profoundly suppresses inflammatory disease activity but also materializes as the first treatment approach against disability accumulation in a subset of patients with primary progressive MS.

We will review current concepts regarding the immunopathology of B cells as well as results of clinical trials with CD20-mAbs in MS, from the murine-human chimeras rituximab and ublituximab to their increasingly humanized counterparts ocrelizumab and ofatumumab. We conducted a literature search using PubMed, clinicaltrials.gov, and clinicaltrialsregister.eu. We will focus on studies emphasizing the effectiveness of these mAbs in reducing MS disease activity and progression, long-term safety, optimal dosage and maintenance regimens. Lastly, we will turn to outstanding questions regarding anti-CD20 therapy in MS.

CD20-mAbs could become first-line drugs in selected patients with highly active MS and already constitute an option for PPMS. Future studies could evaluate whether administration regimens currently in use can be optimized, while registry data could shed light on risk versus benefits on the long run, considering immunosenescence and a potentially increased risk of malignancies and infections in an aging population.