Placebo-controlled trial of rituximab in IgM- anti MAG neuropathy

ABSTRACT

Objective: To determine whether rituximab 375 mg/m2

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/m2 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 6 2.7 in the rituximab group, and 1.0 6 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 5 0.027), the self-evaluation scale (p 5 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.

(Fonts: Neurology 80; 24: June 2013)