Placebo-controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy

Neurology. 2013 Jun 11;80(24):2217-25. doi: 10.1212/WNL.0b013e318296e92b. Epub 2013 May 10.

Abstract

Objective: To determine whether rituximab 375 mg/m(2) was efficacious in patients with immunoglobulin M (IgM) anti-myelin-associated glycoprotein antibody demyelinating neuropathy (IgM anti-MAG demyelinating neuropathy).

Methods: Fifty-four patients with IgM anti-MAG demyelinating neuropathy were enrolled in this randomized, double-blind, placebo-controlled trial. The inclusion criteria were inflammatory neuropathy cause and treatment (INCAT) sensory score (ISS) ≥4 and visual analog pain scale >4 or ataxia score ≥2. The primary outcome was mean change in ISS at 12 months.

Results: Twenty-six patients were randomized to a group receiving 4 weekly infusions of 375 mg/m(2) rituximab, and 28 patients to placebo. Intention-to-treat analysis, with imputation of missing ISS values by the last observation carried forward method, showed a lack of mean change in ISS at 12 months, 1.0 ± 2.7 in the rituximab group, and 1.0 ± 2.8 in the placebo group. However, changes were observed, in per protocol analysis at 12 months, for the number of patients with an improvement of at least 2 points in the INCAT disability scale (p = 0.027), the self-evaluation scale (p = 0.016), and 2 subscores of the Short Form-36 questionnaire.

Conclusions: Although primary outcome measures provide no evidence to support the use of rituximab in IgM anti-MAG demyelinating neuropathy, there were improvements in several secondary outcomes in per protocol analysis.

Level of evidence: This study provides Class I evidence that rituximab is ineffective in improving ISS in patients with IgM anti-MAG demyelinating neuropathy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Demyelinating Diseases / drug therapy*
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / pathology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin M / biosynthesis*
  • Male
  • Middle Aged
  • Myelin-Associated Glycoprotein / immunology*
  • Polyneuropathies / drug therapy
  • Polyneuropathies / immunology
  • Polyneuropathies / pathology
  • Rituximab
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Immunoglobulin M
  • Myelin-Associated Glycoprotein
  • Rituximab