4.7 Review

Anti-CD20 therapies for multiple sclerosis: current status and future perspectives

Journal

JOURNAL OF NEUROLOGY
Volume 269, Issue 3, Pages 1316-1334

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00415-021-10744-x

Keywords

Multiple sclerosis; Anti-CD20 therapy; Randomized clinical trials; Disease modifying therapy; B cells

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Multiple sclerosis is a chronic disease affecting the central nervous system, and recent advancements in immune pathophysiology have led to the identification of selective B-cell-depleting therapies like anti-CD20 monoclonal antibodies, which have shown strong efficacy and safety in treating MS. This has expanded the therapeutic options for both relapsing and progressive MS patients, highlighting the important role of B cells in the disease process.
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease affecting the central nervous system (CNS), often characterized by the accumulation of irreversible clinical disability over time. During last years, there has been a dramatic evolution in several key concepts of immune pathophysiology of MS and in the treatment of this disease. The demonstration of the strong efficacy and good safety profile of selective B-cell-depleting therapies (such as anti-CD20 monoclonal antibodies) has significantly expanded the therapeutic scenario for both relapsing and progressive MS patients with the identification of a new therapeutic target. The key role of B cells in triggering MS disease has been also pointed out, determining a shift from the traditional view of MS activity as largely being 'T-cell mediated' to the notion that MS-related pathological processes involve bi-directional interactions between several immune cell types, including B cells, both in the periphery and in the CNS. This review provides an updated overview of the involvement of B cells in the immune pathophysiology and pathology of MS. We summarize the rationale regarding the use of anti-CD20 therapies and the results of the main randomized controlled trials and observational studies investigating the efficacy and safety profile of rituximab, ocrelizumab, ofatumumab and ublituximab. Suggestions regarding vaccinations and management of MS patients during COVID-19 pandemic with anti-CD20 therapies are also discussed. Finally, therapies under investigation and future perspectives of anti-CD20 therapies are taken into consideration.

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