Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies

Mult Scler. 2018 Aug;24(9):1224-1233. doi: 10.1177/1352458517720044. Epub 2017 Aug 1.


Background: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown.

Objective: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients.

Methods: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house-validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records.

Results: ADAs were detected in 37% of relapsing-remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive.

Conclusion: Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.

Keywords: Antidrug antibodies; B-cell depletion; MAb; anti-CD20; immunogenicity; multiple sclerosis; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Anti-Idiotypic / blood*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunologic Factors / immunology*
  • Immunologic Factors / therapeutic use
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology*
  • Rituximab / immunology*
  • Rituximab / therapeutic use


  • Antibodies, Anti-Idiotypic
  • Immunologic Factors
  • Rituximab