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

Ann Neurol. 2009 Mar;65(3):286-93. doi: 10.1002/ana.21577.


Objective: Report a double-blind, placebo-controlled study of rituximab in patients with anti-MAG demyelinating polyneuropathy (A-MAG-DP).

Methods: Twenty-six patients were randomized to four weekly infusions of 375 mg/m(2) rituximab or placebo. Sample size was calculated to detect changes of > or = 1 Inflammatory Neuropathy Course and Treatment (INCAT) leg disability scores at month 8. IgM levels, anti-MAG titers, B cells, antigen-presenting cells, and immunoregulatory T cells were monitored every 2 months.

Results: Thirteen A-MAG-DP patients were randomized to rituximab and 13 to placebo. Randomization was balanced for age, electrophysiology, disease duration, disability scores, and baseline B cells. After 8 months, by intention to treat, 4 of 13 rituximab-treated patients improved by > or = 1 INCAT score compared with 0 of 13 patients taking placebo (p = 0.096). Excluding one rituximab-randomized patient who had normal INCAT score at entry, and thus could not improve, the results were significant (p = 0.036). The time to 10m walk was significantly reduced in the rituximab group (p = 0.042) (intention to treat). Clinically, walking improved in 7 of 13 rituximab-treated patients. At month 8, IgM was reduced by 34% and anti-MAG titers by 50%. CD25+CD4+Foxp3+ regulatory cells significantly increased by month 8. The most improved patients were those with high anti-MAG titers and most severe sensory deficits at baseline.

Interpretation: Rituximab is the first drug that improves some patients with A-MAG-DP in a controlled study. The benefit may be exerted by reducing the putative pathogenic antibodies or by inducing immunoregulatory T cells. The results warrant confirmation with a larger trial.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • B-Lymphocytes / drug effects
  • Demyelinating Diseases / complications
  • Demyelinating Diseases / immunology*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin M / blood*
  • Immunologic Factors / therapeutic use*
  • Male
  • Middle Aged
  • Myelin-Associated Glycoprotein / immunology*
  • Polyneuropathies / complications
  • Polyneuropathies / immunology*
  • Rituximab
  • Seveso Accidental Release
  • T-Lymphocytes / drug effects
  • Treatment Outcome


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