University of Missouri Health Care, Columbia, MO, USA.
J Neuromuscul Dis. 2020;7(3):269-277. doi: 10.3233/JND-190464.
The role of the complement cascade in acetylcholine receptor antibody-negative (AChR-) myasthenia gravis (MG) is unclear.
To assess the efficacy and tolerability of eculizumab (terminal complement inhibitor) in patients with AChR-MG.
Retrospective chart review of data from six patients treated for 12 months with eculizumab for treatment-refractory, AChR-(by radioimmunoassay) generalized MG (gMG). The eculizumab dose was 900 mg/week for 4 weeks then 1200 mg every 2 weeks. Outcome measures were Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores, number of exacerbations, and qualitative physical assessments based on selected items of the Quantitative Myasthenia Gravis evaluation (ptosis, double vision, eye closure, duration of ability to stretch out limbs).
All patients were female (mean age, 50.8 years). In the 12 months before eculizumab initiation, all measures were relatively stable. After its initiation, clinically meaningful reductions (≥2 points) in total MG-ADL scores were observed before or at 5 months and were maintained to Month 12 in all patients; mean (standard deviation [SD]) scores were 11.3 (0.9) and 5.0 (0.9), respectively. There was also a reduction in the mean (SD) number of exacerbations per patient, from 2.8 (1.2) to 0.3 (0.5) in the 12 months before and after eculizumab initiation, respectively. Physical assessment ratings were improved in all patients. Adverse events were reported in four patients, but all were mild and none were treatment-related.
This small retrospective analysis provides preliminary evidence for the efficacy of eculizumab in treatment-refractory gMG that was AChR-according to radioimmunoassay. Larger, more robust studies are warranted to evaluate this further.
补体级联在乙酰胆碱受体抗体阴性（AChR-）重症肌无力（MG）中的作用尚不清楚。
评估依库珠单抗（末端补体抑制剂）在 AChR-MG 患者中的疗效和耐受性。
对六名接受依库珠单抗治疗 12 个月的治疗抵抗性、AChR-（放射免疫测定）全身型 MG（gMG）患者的数据进行回顾性图表审查。依库珠单抗的剂量为 900mg/周，持续 4 周，然后每两周 1200mg。疗效评估指标包括重症肌无力日常生活活动量表（MG-ADL）评分、恶化次数以及根据定量重症肌无力评估的选择项目进行的定性体格评估（上睑下垂、复视、闭眼、四肢伸展能力持续时间）。
所有患者均为女性（平均年龄 50.8 岁）。在开始依库珠单抗治疗前的 12 个月中，所有指标均相对稳定。在开始依库珠单抗治疗后，所有患者在 5 个月之前或之时，MG-ADL 总分均有临床意义的降低（≥2 分），并在 12 个月时维持；平均（标准差 [SD]）评分分别为 11.3（0.9）和 5.0（0.9）。每位患者的恶化次数也有所减少，从依库珠单抗治疗前的每月 2.8（1.2）次减少至治疗后的每月 0.3（0.5）次。所有患者的体格评估评分均有所改善。四名患者报告了不良反应，但均为轻度，且均与治疗无关。
这项小型回顾性分析初步证明了依库珠单抗在放射性免疫测定为 AChR-的治疗抵抗性 gMG 中的疗效。需要更大、更稳健的研究来进一步评估。
