Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Neurology, Akron Children's Hospital, Akron, Ohio.
Pediatr Neurol. 2024 Jul;156:198-207. doi: 10.1016/j.pediatrneurol.2024.04.020. Epub 2024 Apr 26.
This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG).
Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded.
Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab.
Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.
本研究评估了末端补体 C5 抑制剂依库珠单抗在青少年全身性重症肌无力（gMG）中的疗效和安全性。
12 至 17 岁的难治性抗乙酰胆碱受体（AChR）抗体阳性 gMG 青少年接受依库珠单抗（每周诱导[1 至 2 剂 600mg 或 4 剂 900mg]，随后每两周维持剂量[300 至 1200mg]，最多 26 周）治疗，这是一项 3 期、开放标签、多中心研究（NCT03759366）。从基线到第 26 周的定量重症肌无力（QMG）总评分（主要终点）和次要终点的变化包括重症肌无力日常生活活动（MG-ADL）总评分、重症肌无力综合评分、重症肌无力基金会干预后状态、欧洲五维健康量表（青年）和神经生活质量儿科疲劳问卷评分，以及药代动力学、药效学和安全性。
共纳入 11 名青少年（平均年龄 ± 标准差 14.8 ± 1.8 岁）；10 名完成了主要评估期。从基线到第 26 周的最小二乘均数变化为 QMG 总评分下降 5.8（标准误差 [SE] 1.2；P=0.0004），MG-ADL 总评分下降 2.3（SE 0.6；P=0.0017）。总体而言，主要和所有次要疗效终点分析从首次评估开始就具有统计学意义，并持续存在。所有患者的完全末端补体抑制均持续至第 26 周。治疗出现的不良事件均为轻度/中度，主要与依库珠单抗无关。
依库珠单抗可有效减轻疾病负担，且在难治性抗 AChR 抗体阳性 gMG 青少年中耐受性良好。
