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Objective  To evaluate whether the clinical benefit and relapse rates in anti‐muscle‐specific kinase (Mu SK ) myasthenia gravis ( MG ) differ depending on the protocol of rituximab followed.    Methods  This retrospective multicentre study in patients with Mu SK MG  compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan–Meier methods and survival analyses were undertaken using Cox proportional‐hazards models.    Results  Twenty‐five patients were included: 11 treated with protocol 4 + 2 (375 mg/m 2 /4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m 2 /4 weeks). Mean follow‐up was 5.0 years ( SD  3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 ( SD  1.5), 1.1 ( SD  0.4), and 2.5 ( SD  1.4) years, respectively. Based on Kaplan–Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log‐rank test  P  = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 ( HR  112.8, 95%  CI , 5.7–2250.4,  P  = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 ( HR  9.2, 95%  CI  0.9–91.8,  P  = 0.059).    Interpretation  This study provides class  IV  evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with Mu SK MG .

The impact of rituximab infusion protocol on the long‐term outcome in anti‐MuSK myasthenia gravis