B-Cell Depletion Therapies in Multiple Sclerosis

Multiple sclerosis is an immune-mediated disorder in which both T and B lymphocytes contribute to central nervous system pathology. B-cell depletion therapies, targeting the CD20 molecule on pre-B and mature B cells, have transformed the treatment paradigm. Monoclonal antibodies against CD20 reduce inflammatory activity by limiting antigen presentation, pro-inflammatory cytokine secretion and the generation of pathogenic autoantibodies. Agents such as rituximab, ocrelizumab, ofatumumab and ublituximab have demonstrated robust effects on relapse rate, lesion formation on magnetic resonance imaging and disability progression—particularly in relapsing forms of the disease. The therapeutic impact extends to primary progressive multiple sclerosis, where slowing of disability accrual has been observed. Safety considerations include infusion reactions, hypogammaglobulinaemia and risk of infections; these risks are mitigated by patient selection, immunoglobulin monitoring and tailored dosing intervals guided by peripheral B-cell repopulation. Emerging strategies seek to improve central nervous system penetration through receptor-mediated transport technologies. Overall, B-cell depletion therapies are now a cornerstone of multiple sclerosis management, offering precise immunomodulation and a favourable benefit–risk profile.

Research from Nature Portfolio

No recent Nature Portfolio content available.

B-Cell Depletion Therapies in Multiple Sclerosis publication trend

The graph below shows the total number of articles in b-cell depletion therapies in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

B cell: A type of white blood cell that contributes to immune responses by producing antibodies and presenting antigens.

CD20: A surface molecule expressed on B cells that serves as the target for certain depletion therapies.

Monoclonal antibody: A laboratory-made protein designed to bind specifically to a target molecule, such as CD20.

No evidence of disease activity (NEDA): A composite clinical measure indicating absence of relapses, disability progression and new MRI lesions.

Hypogammaglobulinaemia: A reduction in immunoglobulin levels in the blood that can result from prolonged B-cell depletion.

References

1. Preclinical B cell depletion and safety profile of a brain‐shuttled crystallizable fragment‐silenced CD20 antibody. Clinical and Translational Medicine (2025).
2. Assessing Sustained B-Cell Depletion and Disease Activity in a French Multiple Sclerosis Cohort Treated by Long-Term IV Anti-CD20 Antibody Therapy. Neurotherapeutics (2023).
3. Peripheral CD19+ B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders. Journal of Neurology (2018).
4. Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic. Frontiers in Immunology (2023).
5. Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic. Neurotherapeutics (2022).