Shieh Perry, Sharma Khema, Kohrman Bruce, Oh Shin J
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
University of Miami Miller School of Medicine, Miami, FL.
J Clin Neuromuscul Dis. 2019 Mar;20(3):111-119. doi: 10.1097/CND.0000000000000239.
To assess tolerability and efficacy of amifampridine phosphate versus placebo for symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS).
This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in 26 adults with LEMS compared efficacy of amifampridine phosphate versus placebo over a 4-day period. The primary endpoints were quantitative myasthenia gravis score (QMG) and subject global impression, and the secondary endpoint was Clinical Global Impression-Improvement. The exploratory endpoints were 3TUG (timed up and go) test and QMG limb domain score. All participants had been receiving amifampridine phosphate (30-80 mg/d divided into 3 or 4 doses daily) in an expanded access protocol and had been titrated to the optimal dose and frequency for at least 1 week before randomization into the current study. After completion of assessments after 4 days of double-blind treatment, patients had the option to return to open-label amifampridine phosphate. The efficacy endpoints were mean changes from baseline in the various evaluation parameters.
Amifampridine phosphate (n = 13) demonstrated significant benefit in QMG and subject global impression compared with placebo (n = 13) at 4 days. Other measures of efficacy, including Clinical Global Impression-Improvement, 3TUG, and QMG limb domain score also improved. The most common "adverse events" in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as expected from withdrawal of amifampridine phosphate, whereas only back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in amifampridine phosphate group.
This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in adults with LEMS provided class I evidence of efficacy of amifampridine phosphate as symptomatic treatment in LEMS.
评估磷酸阿米芬啶与安慰剂对兰伯特-伊顿肌无力综合征（LEMS）进行症状性治疗的耐受性和疗效。
这项3期随机、双盲、安慰剂对照撤药试验纳入了26例成年LEMS患者，比较了磷酸阿米芬啶与安慰剂在4天内的疗效。主要终点为重症肌无力定量评分（QMG）和受试者整体印象，次要终点为临床总体印象改善情况。探索性终点为30秒起立行走（3TUG）试验和QMG肢体域评分。所有参与者在一项扩大准入方案中接受磷酸阿米芬啶（30 - 80mg/天，分3或4次服用），并在随机分组进入本研究前至少1周已滴定至最佳剂量和频率。双盲治疗4天后完成评估后，患者可选择恢复接受开放标签的磷酸阿米芬啶治疗。疗效终点为各评估参数相对于基线的平均变化。
在4天时，与安慰剂组（n = 13）相比，磷酸阿米芬啶组（n = 13）在QMG和受试者整体印象方面显示出显著益处。其他疗效指标，包括临床总体印象改善情况、3TUG试验和QMG肢体域评分也有所改善。安慰剂组最常见的“不良事件”是肌无力（n = 5）和疲劳（n = 4），这是停用磷酸阿米芬啶后预期出现的情况，而磷酸阿米芬啶组仅报告了背痛（n = 1）、肢体疼痛（n = 1）和头痛（n = 1）。
这项针对成年LEMS患者的3期随机、双盲、安慰剂对照撤药试验提供了I类证据，证明磷酸阿米芬啶作为LEMS的症状性治疗有效。
