Lipka Alexander F, Vrinten Charlotte, van Zwet Erik W, Schimmel Kirsten J M, Cornel Martina C, Kuijpers Marja R, Hekster Yechiel A, Weinreich Stephanie S, Verschuuren Jan J G M
Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Clinical Genetics and EMGO Institute for Health and Care Research, section Community Genetics & Public Health Genomics, VU University Medical Center, Amsterdam, The Netherlands; Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, United Kingdom.
Neuromuscul Disord. 2017 Mar;27(3):259-265. doi: 10.1016/j.nmd.2016.11.009. Epub 2016 Nov 18.
We studied the effect and safety of ephedrine as add-on treatment for patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG), who do not sufficiently respond to standard treatment. Four patients with AChR MG were included in a placebo-controlled, double-blind, and randomised, multiple crossover series of n-of-1 trials. Each n-of-1 trial consisted of 3 cycles, in which two 5-day intervention periods were followed by 2 days washout. In each cycle, ephedrine 50 mg daily in 2 doses was compared with placebo in the alternate treatment period. Primary outcome was a change in QMG score. Add-on treatment with ephedrine compared with placebo improved QMG score by 1.0 point (95% confidence interval 0.21-1.79), which was significant for the group of trial patients as well as for the population treatment effect. Ephedrine also showed a significant trial average treatment effect for all secondary outcomes, improving MG Composite by 2.7, MG-ADL by 1.0 and VAS score for muscle strength by 1.1. Adverse events were mild and included palpitations, tremor and restlessness. Although all ECGs were normal, ephedrine prolonged the corrected QT interval. Ephedrine as add-on treatment for myasthenia gravis resulted in a small but consistent reduction of symptoms and weakness in patients with moderate disease severity.
我们研究了麻黄碱作为附加治疗对乙酰胆碱受体抗体阳性重症肌无力（AChR MG）患者的疗效和安全性，这些患者对标准治疗反应欠佳。4例AChR MG患者被纳入一项安慰剂对照、双盲、随机、多次交叉的n-of-1系列试验。每个n-of-1试验包括3个周期，每个周期有两个为期5天的干预期，之后是2天的洗脱期。在每个周期中，在交替治疗期将每日2次服用共50 mg麻黄碱与安慰剂进行比较。主要结局是QMG评分的变化。与安慰剂相比，麻黄碱附加治疗使QMG评分提高了1.0分（95%置信区间0.21 - 1.79），这对试验患者组以及总体治疗效果均具有显著性。麻黄碱对所有次要结局也显示出显著的试验平均治疗效果，使MG综合评分提高2.7分、MG-ADL评分提高1.0分、肌肉力量视觉模拟评分提高1.1分。不良事件较轻，包括心悸、震颤和烦躁不安。虽然所有心电图均正常，但麻黄碱延长了校正QT间期。麻黄碱作为重症肌无力的附加治疗可使中度病情严重程度的患者症状和肌无力出现小幅但持续的减轻。
