A randomized placebo-controlled trial of rituximab in IGM anti-myelin-associated glycoprotein antibody demyelinating neuropathy (rimag study).
Résumé
There is to date inadequate reliable evidence from most randomized controlled trials (RCT) in IgM anti-MAG demyelinating neuropathy (IgM-DN) torecommend any particular immunotherapy treatment (Lunn and Nobile-Orazio, Cochrane Database, 2006). In the only published placebo-controlled RCT with rituximab in IgM-DN, Dalakas et al . (2009) concluded to a small but significant difference between treated and untreated patients. We conducted a placebo-controlled trial of rituximab in patients with IgM-DN. All patients had demyelinating neuropathy according to the EFNS/PNS guideline criteria and significantly high anti-MAG titers in the same reference laboratory. In addition, the patients were included on INCAT sensoryscore (ISS) ≥ 4, and VAS pain score > 4 or ataxia score ≥ 2. The trial received approval from our ethical committee. Sample size was calculated to detect 20% improvement of ISS, as primary outcome measure, at 12 months. Secondary outcome measures were mainly INCAT score, ataxia score, 10 meters walking time, self-evaluation scale (SES) and immunological data. Fifty-four patients were randomized to receive either 4 weekly infusions of 375 mg/m 2 rituximab or placebo between March 2006 and November 2008. There were 38 M and 16 F, mean age was 66 ± 9.4 years; 26 patients received rituximab, and the 28 other patients received placebo. Six patients did not complete the trial and consequently were not eligible for the final analysis which concerned 48 patients: 21 with rituximab and 27 with placebo. Mean variation in ISS at 12 months did not disclose significant changein the rituximab group (1.3 ± 3) when compared to the placebo group (1 ±2.8) (p= 0.68). In addition, there was a slightly higher percentage of respondersby ISS ≥ 4 in the placebo group (22%), versus the rituximab group (20%). In conclusion, primary analysis on ISS consistently indicated that the patients in the rituximab group did not significantly improve when compared with those in the placebo group. However, the results of further analyses (number of patients improving by 20% on the INCAT score, SES) disclosed small but significant results in the rituximab group. Study supported by the French Ministry of Health (PHRC n ◦ 04049) and Roche France