Cortés-Vicente Elena, Rojas-Garcia Ricard, Díaz-Manera Jordi, Querol Luis, Casasnovas Carlos, Guerrero-Sola Antonio, Muñoz-Blanco José Luis, Bárcena-Llona José Eulalio, Márquez-Infante Celedonio, Pardo Julio, Martínez-Fernández Eva María, Usón Mercedes, Oliva-Nacarino Pedro, Sevilla Teresa, Illa Isabel
Neuromuscular Diseases Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.
Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain.
Ann Clin Transl Neurol. 2018 Apr 14;5(6):710-716. doi: 10.1002/acn3.564. eCollection 2018 Jun.
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.
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.
Twenty-five patients were included: 11 treated with protocol 4 + 2 (375 mg/m/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/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 = 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, = 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, = 0.059).
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.
评估抗肌肉特异性激酶（MuSK）型重症肌无力（MG）患者的临床获益和复发率是否因所采用的利妥昔单抗治疗方案而异。
这项针对MuSK MG患者的回顾性多中心研究，比较了三种利妥昔单抗治疗方案在临床状态、复发情况、治疗变化及不良反应方面的差异。主要有效性终点为需要再次输注利妥昔单抗的临床复发。采用Kaplan-Meier方法估计生存曲线，并使用Cox比例风险模型进行生存分析。
共纳入25例患者：11例采用4 + 2方案治疗（375 mg/m²/4周，然后每月1次，共2个月），5例采用1 + 1方案治疗（2周内分两次给予1 g剂量），9例采用4方案治疗（375 mg/m²/4周）。平均随访时间为5.0年（标准差3.3年）。复发率分别为18.2%、80%和33.3%，复发的平均时间分别为3.5年（标准差1.5年）、1.1年（标准差0.4年）和2.5年（标准差1.4年）。根据Kaplan-Meier估计，采用4 + 2方案治疗的患者复发次数更少且复发时间更晚，与采用其他两种方案治疗的患者相比差异有统计学意义（对数秩检验P = 0.0001）。采用1 + 1方案治疗的患者比采用4 + 2方案治疗的患者复发风险更高（风险比112.8，95%置信区间5.7 - 2250.4，P = 0.002）。采用4方案治疗的患者比采用4 + 2方案治疗的患者复发风险有升高趋势（风险比9.2，95%置信区间0.9 - 91.8，P = 0.059）。
本研究提供了IV级证据，表明在MuSK MG患者中，与1 + 1方案和4方案相比，4 + 2利妥昔单抗方案具有更低的临床复发率且疗效更持久。
