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

Elena Cortés-Vicente, Ricard Rojas-Garcia, Jordi Díaz-Manera, Luis Querol, Carlos Casasnovas, Antonio Guerrero-Sola, José Luis Muñoz-Blanco, José Eulalio Bárcena-Llona, Celedonio Márquez-Infante, Julio Pardo, Eva María Martínez-Fernández, Mercedes Usón, Pedro Oliva-Nacarino, Teresa Sevilla, Isabel Illa

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12 Citations (Scopus)

Abstract

© 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. Objective: To evaluate whether the clinical benefit and relapse rates in anti-muscle-specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. Methods: This retrospective multicentre study in patients with MuSK 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/m2/4 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/m2/4 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 MuSK MG.
Original languageEnglish
Pages (from-to)710-716
JournalAnnals of Clinical and Translational Neurology
Volume5
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

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