Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review

PLoS One. 2013 Jul 2;8(7):e66308. doi: 10.1371/journal.pone.0066308. Print 2013.

Abstract

Background: Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS.

Objectives: To evaluate the efficacy and safety of rituximab for MS treatment.

Data collection: Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies.

Main results: Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events. AUTHOR’S CONCLUSION: Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Central Nervous System / drug effects*
  • Central Nervous System / immunology
  • Central Nervous System / pathology
  • Clinical Trials as Topic
  • Databases, Bibliographic
  • Humans
  • Immunologic Factors / therapeutic use*
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Immunologic Factors
  • Rituximab

Grant support

Dr. Castillo-Trivino received a Rio Hortega grant from the Spanish Society of Neurology and the Carlos III Institute of Health and a Du Pré grant from the Multiple Sclerosis International Federation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.