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 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