Takei Koji, Tsuda Kikumi, Takahashi Fumihiro, Palumbo Joseph
a Mitsubishi Tanabe Pharma Development America , Jersey City , NJ , USA and.
b Mitsubishi Tanabe Pharma Corporation , Tokyo , Japan.
Amyotroph Lateral Scler Frontotemporal Degener. 2017 Oct;18(sup1):64-70. doi: 10.1080/21678421.2017.1365372.
Study MCI186-19 investigated the safety and efficacy of edaravone in the treatment of ALS. The 24-week, double-blind period was followed by a 24-week, open-label, active extension period. Patients originally receiving edaravone continued edaravone (E-E group, n = 65), and patients originally receiving placebo switched to edaravone (P-E group, n = 58). Because no statistical tests had been prospectively planned in the open-label period, we performed post-hoc analyses to assist in the interpretation of efficacy data. A mixed model for repeated measures (MMRM) and the Combined Assessment of Function and Survival (CAFS) were assessed. Additionally, slopes of time-dependent change between baseline in cycle 1 and the end of cycle 6 (24 weeks double-blind) and between the end of cycle 6 and end of cycle 12 (24 weeks open-label) were calculated using a random coefficient model including all available data during each period. At week 48, the MMRM analysis showed significantly less decline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score in the E-E group than in the P-E group (least-squares mean change from baseline ± standard error, 4.17 ± 1.40, p = 0.0037), meaning that the differences in the ALSFRS-R total score during the 24-week double-blind period were maintained in patients receiving edaravone for an additional 24 weeks. The CAFS endpoint (p = 0.0089) supported this finding. The slope analysis during the double-blind period showed a significant difference between the treatment groups, while there was no significant difference between the groups during the active extension period. These analyses suggest a potential benefit of early and continued edaravone treatment over delayed edaravone treatment.
研究MCI186 - 19调查了依达拉奉治疗肌萎缩侧索硬化症（ALS）的安全性和有效性。24周的双盲期之后是24周的开放标签、活性药物延长期。最初接受依达拉奉治疗的患者继续使用依达拉奉（E - E组，n = 65），而最初接受安慰剂治疗的患者改用依达拉奉（P - E组，n = 58）。由于在开放标签期未预先计划进行统计检验，我们进行了事后分析以辅助解释疗效数据。评估了重复测量混合模型（MMRM）和功能与生存综合评估（CAFS）。此外，使用随机系数模型计算了第1周期基线至第6周期末（24周双盲期）以及第6周期末至第12周期末（24周开放标签期）的时间依赖性变化斜率，该模型纳入了每个时期的所有可用数据。在第48周时，MMRM分析显示E - E组的ALS功能评定量表修订版（ALSFRS - R）总分下降幅度明显小于P - E组（从基线的最小二乘均值变化±标准误差，4.17 ± 1.40，p = 0.0037），这意味着在24周双盲期内ALSFRS - R总分的差异在接受依达拉奉额外治疗24周的患者中得以维持。CAFS终点（p = 0.0089）支持了这一发现。双盲期的斜率分析显示治疗组之间存在显著差异，而在活性药物延长期两组之间无显著差异。这些分析表明早期和持续使用依达拉奉治疗相较于延迟使用依达拉奉治疗可能具有益处。
