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

Abstract

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.

• Authors: Marinos C Dalakas, Goran Rakocevic, Mohammad Salajegheh, James M Dambrosia, Angelika F Hahn, Raghavan Raju, Beverly McElroy
• Journal: Annals of neurology (Ann Neurol) Vol. 65 Issue 3 Pg. 286-93 (Mar 2009) ISSN: 1531-8249 [Electronic] United States
• PMID: 19334068 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• B-Lymphocytes (drug effects)
• Demyelinating Diseases (complications, 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, immunology)
• Rituximab
• Seveso Accidental Release
• T-Lymphocytes (drug effects)
• Treatment Outcome