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Placebo‐controlled trial of rituximab in IgM anti–myelin‐associated glycoprotein antibody demyelinating neuropathy
Author(s) -
Dalakas Marinos C.,
Rakocevic Goran,
Salajegheh Mohammad,
Dambrosia James M.,
Hahn Angelika F.,
Raju Raghavan,
McElroy Beverly
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21577
Subject(s) - rituximab , medicine , placebo , gastroenterology , randomized controlled trial , randomization , immunology , antibody , pathology , alternative medicine
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 375mg/m 2 rituximab or placebo. Sample size was calculated to detect changes of ≥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 ≥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. Ann Neurol 2009;65:286–293