Hatanaka Yuki, Mori-Yoshimura Madoka, Utsugisawa Kimiaki, Tsujino Akira, Fujita Nobuya, Yabe Ichiro, Igarashi Yuko, Motomura Masakatsu
Department of Neurology, Teikyo University Hospital, Japan.
Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Japan.
Intern Med. 2025 Jun 19. doi: 10.2169/internalmedicine.5363-25.
Objective To evaluate the efficacy and safety of amifampridine (3,4-diaminopyridine) phosphate in Japanese adults with Lambert-Eaton myasthenic syndrome (LEMS). Methods The LMS-005 study was an uncontrolled, single-blind (patient blinded), multicenter, one-year phase 3 clinical study. The administration of amifampridine phosphate was started at 15 mg/day, and the dose was increased every 3 to 4 days to determine the optimal dose for each patient. After 7 days of treatment with the optimal dose, efficacy was assessed by evaluating quantitative myasthenia gravis (QMG), subject global impression (SGI), and Clinical Global Impression-Improvement scale (CGI-I) scores. Patients Adult patients with LEMS were analyzed for safety (n=12, mean age±standard deviation [SD] of 61.1±14.6 years old) and efficacy (n=10, mean age±SD of 60.7±15.9 years old). Results In the efficacy population, the mean±SD (median [interquartile range]) QMG score was 13.2±3.1 (13.5 [11.0, 15.0]) at baseline and 8.0±2.7 (8.0 [6.0, 9.0]) at the end of the treatment period, with a mean±SD (median [interquartile range]) change of -5.2±2.8 (-5.5 [-7.0, -3.0]). All patients showed a decrease in the QMG score from baseline and experienced improvement in their LEMS symptoms. The SGI/CGI-I scores also improved. Efficacy was maintained until the end of the study. Five patients in the safety population experienced adverse drug reactions, the most common of which was dysesthesia (n=2). Conclusion This study revealed the long-term efficacy and tolerability of amifampridine phosphate in Japanese adults with LEMS.
目的 评估磷酸阿米芬啶（3,4 - 二氨基吡啶）对日本成年兰伯特 - 伊顿肌无力综合征（LEMS）患者的疗效和安全性。方法 LMS - 005研究是一项非对照、单盲（患者盲法）、多中心、为期一年的3期临床研究。磷酸阿米芬啶的给药起始剂量为15毫克/天，每3至4天增加剂量以确定每位患者的最佳剂量。在以最佳剂量治疗7天后，通过评估重症肌无力定量评分（QMG）、受试者整体印象（SGI）和临床总体印象改善量表（CGI - I）评分来评估疗效。患者 对成年LEMS患者进行安全性分析（n = 12，平均年龄±标准差[SD]为61.1±14.6岁）和疗效分析（n = 10，平均年龄±SD为60.7±15.9岁）。结果 在疗效分析人群中，治疗期开始时QMG评分的平均值±SD（中位数[四分位间距]）为13.2±3.1（13.5[11.0, 15.0]），治疗期末为8.0±2.7（8.0[6.0, 9.0]），平均±SD（中位数[四分位间距]）变化为-5.2±2.8（-5.5[-7.0, -3.0]）。所有患者的QMG评分均较基线下降，且LEMS症状有所改善。SGI/CGI - I评分也有所改善。疗效持续至研究结束。安全性分析人群中有5名患者出现药物不良反应，最常见的是感觉异常（n = 2）。结论 本研究揭示了磷酸阿米芬啶对日本成年LEMS患者的长期疗效和耐受性。
