A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis
A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis
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DOI：
10.1080/21678421.2017.1363780
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发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
Yoshino, Hiide
中科院分区：
文献类型：
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作者：
Abe, Koji;Itoyarna, Yasuto;Yoshino, Hiide
我们的第一期III期研究未能证明依达拉奉与安慰剂相比对肌萎缩侧索硬化症(ALS)的疗效。在这里，我们进行了特定后亚组分析，以确定依达拉奉可能显示疗效的亚组。我们集中讨论了两个新定义的子群：EESP和dpEESP2y。EESP定义为治疗前ALSFRS-R评分中强迫肺活量百分比=80%，且所有项目得分均为2分的疗效预期亚群。DpEESP2y被定义为EESP中疗效更好的亚群，根据El Ecorial修订的Airlie House诊断标准，诊断为‘确定的’或‘可能的’ALS，并在两年内发病。研究后分析的主要终点是24周治疗期间ALSFRS-R评分的变化。治疗期间ALSFRS-R评分+/-标准差的最小二乘平均变化的组间差异在全分析组为0.65±0.78(p=0.4108)，在EESP组为2.201.03(p=0.0360)，在dpEESP2y组为3.01+/-1.33(p=0.0270)。依达拉奉在dpEESP2y亚组中显示出疗效。有必要对符合dpEESP2y标准的患者进行进一步的临床研究。
Our first phase III study failed to demonstrate efficacy of edaravone for amyotrophic lateral sclerosis (ALS) compared to placebo. Here, we performed post-hoc subgroup analysis to identify a subgroup in which edaravone might be expected to show efficacy. We focussed on two newly defined subgroups, EESP and dpEESP2y. The EESP was defined as the efficacy expected subpopulation with % forced vital capacity of >= 80%, and >= 2 points for all item scores in the revised ALS functional rating scale (ALSFRS-R) score before treatment. The dpEESP2y was defined as the greater-efficacy-expected subpopulation within EESP having a diagnosis of 'definite' or 'probable' ALS according to the El Escorial revised Airlie House diagnostic criteria and onset of disease within two years. The primary endpoint of the post-hoc analysis was the change in the ALSFRS-R score during the 24-week treatment period. The intergroup differences of the least-squares mean change in the ALSFRS-R score +/- standard error during treatment were 0.65+ 0.78 (p = 0.4108) in the full analysis set, 2.20 1.03 (p= 0.0360) in the EESP, and 3.01 +/- 1.33 (p 0.0270) in the dpEESP2y. Edaravone exhibited efficacy in the dpEESP2y subgroup. A further clinical study in patients meeting dpEESP2y criteria is warranted.