Clinical Perspectives on the Molecular and Pharmacological Attributes of Anti-CD20 Therapies for Multiple Sclerosis

CNS Drugs. 2021 Sep;35(9):985-997. doi: 10.1007/s40263-021-00843-8. Epub 2021 Aug 9.

Abstract

Anti-CD20 therapies have demonstrated considerable efficacy in the treatment of relapsing multiple sclerosis, constituting a high-efficacy treatment approach for reducing relapse risk and mitigating disability progression. These therapies have been shown to strongly deplete circulating B cells and small subsets of CD3+ CD4 and CD8 T cells that express low levels of CD20. While the clinical profiles of the various anti-CD20 monoclonal antibodies used in treating multiple sclerosis are well-described in the literature, greater understanding of the implications of their distinct molecular and pharmacological attributes is needed. In this review, we focus on four anti-CD20 monoclonal antibodies-rituximab, ocrelizumab, ofatumumab, and ublituximab-that are currently used, approved, or in late-stage clinical development for the treatment of multiple sclerosis. We provide clinical perspectives on the potential implications of differences in molecular structures, target epitopes, dosing regimens, mechanisms and impact on B-cell depletion and reconstitution, immunogenicity, administration-related reactions, and infection risks.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antigens, CD20 / immunology*
  • Antigens, CD20 / metabolism
  • B-Lymphocytes, Regulatory / drug effects
  • B-Lymphocytes, Regulatory / immunology
  • Humans
  • Immunologic Factors / administration & dosage*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Rituximab / administration & dosage

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • Immunologic Factors
  • Rituximab
  • ocrelizumab
  • ofatumumab
  • ublituximab