Program in Clinical and Translational Neuromuscular Research, Division of Neuromuscular Medicine, Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.
Department of Neurology, Hospital for Special Surgery, New York, New York.
JAMA Neurol. 2017 Jan 1;74(1):60-66. doi: 10.1001/jamaneurol.2016.4190.
Myasthenia gravis (MG), an autoimmune disorder of neuromuscular transmission, is treated by an array of immunotherapeutics, many of which are nonspecific. Even with current therapies, a subset of patients has medically refractory MG. The benefits of B-cell-targeted therapy with rituximab have been observed in MG; however, the duration of these benefits after treatment is unclear.
To evaluate the durability of response to rituximab in the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG.
DESIGN, SETTING AND PARTICIPANTS: This retrospective case series study included 16 patients with AChR+ MG referred to an MG clinic from January 1, 2007, to December 31, 2015. The patients were treated with rituximab and followed up for 18 to 84 months after treatment.
Assessment of long-term clinical response, durability of response and/or relapse rate, AChR autoantibody levels, adverse effects, and inflammatory markers.
In the 16 patients (6 men and 10 women; median age, 42 [range, 18-69] years), clinical improvement was observed in parallel with complete withdrawal or reduction of other immunotherapies, with all patients achieving complete stable remission, pharmacologic remission, or minimal manifestations based on the Myasthenia Gravis Foundation of America postintervention status criteria. Nine patients (56%) had a relapse during a mean follow-up of 36 (range, 24-47) months. Seven patients (44%) remained relapse free with a mean follow-up of 47 (range, 18-81) months since the last rituximab treatment. All values were normalized to a pretreatment anti-AChR antibody level of 100% and the mean levels after each rituximab cycle were calculated. A 33% decrease was seen after cycle 1 of rituximab treatment (100% vs 67%; P = .004); 20% after cycle 2 (compared with cycle 1) (67% vs 47%; P = .008); and 17% after cycle 3 (compared with cycle 2) (47% vs 30%; P = .02). However, the serum cytokine levels measured were found to be unchanged.
Rituximab therapy appears to be an effective option in patients with refractory AChR+ MG, who were observed to have a durable response after treatment. Identification of markers of disease relapse and sustained remission are critical next steps in the development of pathophysiology-relevant, evidence-based practice parameters for rituximab in the treatment of MG.
重症肌无力（MG）是一种神经肌肉传递的自身免疫性疾病，采用多种免疫疗法进行治疗，其中许多是非特异性的。即使采用目前的治疗方法，仍有一部分患者的 MG 具有医学难治性。利妥昔单抗对 B 细胞靶向治疗的益处已在 MG 中得到观察；然而，尚不清楚这些益处治疗后的持续时间。
评估利妥昔单抗治疗乙酰胆碱受体自身抗体阳性（AChR+）全身性 MG 的反应持久性。
设计、地点和参与者：这项回顾性病例系列研究纳入了 2007 年 1 月 1 日至 2015 年 12 月 31 日期间因 MG 就诊于一家 MG 诊所的 16 例 AChR+MG 患者。这些患者接受了利妥昔单抗治疗，并在治疗后随访 18 至 84 个月。
评估长期临床反应、反应持久性和/或复发率、AChR 自身抗体水平、不良反应和炎症标志物。
在这 16 例患者（6 名男性和 10 名女性；中位年龄 42 岁[范围 18-69 岁]）中，临床改善与完全停用或减少其他免疫疗法同时发生，所有患者均根据美国重症肌无力基金会干预后状态标准达到完全稳定缓解、药物缓解或最小表现。9 例患者（56%）在平均 36 个月（范围 24-47 个月）的随访期间出现复发。7 例患者（44%）在最后一次利妥昔单抗治疗后平均 47 个月（范围 18-81 个月）内无复发。所有值均归一化为预处理抗 AChR 抗体水平的 100%，并计算每个利妥昔单抗周期后的平均水平。利妥昔单抗治疗第 1 周期后观察到 33%的下降（100%比 67%；P = .004）；第 2 周期（与第 1 周期相比）下降 20%（67%比 47%；P = .008）；第 3 周期（与第 2 周期相比）下降 17%（47%比 30%；P = .02）。然而，所测量的血清细胞因子水平没有变化。
利妥昔单抗治疗似乎是一种有效的选择，可用于治疗难治性 AChR+MG 患者，这些患者在治疗后观察到持久的反应。确定疾病复发和持续缓解的标志物是制定与重症肌无力病理生理学相关的、基于证据的利妥昔单抗治疗实践参数的关键下一步。
