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

Twenty‐six patients were randomized to four weekly infusions of 375mg/m² 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.

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.

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