Takei Koji, Takahashi Fumihiro, Liu Shawn, Tsuda Kikumi, Palumbo Joseph
a Mitsubishi Tanabe Pharma Development America, Inc , Jersey City , NJ , USA , and.
b Mitsubishi Tanabe Pharma Corporation , Chuo-ku , Tokyo , Japan.
Amyotroph Lateral Scler Frontotemporal Degener. 2017 Oct;18(sup1):49-54. doi: 10.1080/21678421.2017.1361443.
Post-hoc analyses of the ALS Functional Rating Scale-Revised (ALSFRS-R) score data, the primary endpoint in the 24-week double-blind placebo-controlled study of edaravone (MCI186-19, NCT01492686), were performed to confirm statistical robustness of the result. The previously reported original analysis had used a last observation carried forward (LOCF) method and also excluded patients with fewer than three completed treatment cycles. The post-hoc sensitivity analyses used different statistical methods as follows: 1) including all patients regardless of treatment cycles received (ALL LOCF); 2) a mixed model for repeated measurements (MMRM) analysis; and 3) the Combined Assessment of Function and Survival (CAFS) endpoint. Findings were consistent with the original primary analysis in showing superiority of edaravone over placebo. We also investigated the distribution of change in ALSFRS-R total score across all patients in the study as well as which ALSFRS-R items and domains may have contributed to the overall efficacy findings. The distribution of changes in ALSFRS-R total score from baseline to the end of cycle 6 (ALL LOCF) shifted in favour of edaravone compared to placebo. Edaravone was descriptively favoured for each ALSFRS-R item and each of the four ALSFRS-R domains at the end of cycle 6 (ALL LOCF), suggesting a generalised effect of edaravone in slowing functional decline across all anatomical regions. The effect of edaravone appeared to be similar in patients with bulbar onset and limb onset. Together, these observations would be consistent with its putative neuroprotective effects against the development of oxidative damage unspecific to anatomical regions.
对依达拉奉（MCI186-19，NCT01492686）进行的为期24周的双盲安慰剂对照研究的主要终点——肌萎缩侧索硬化功能评定量表修订版（ALSFRS-R）评分数据进行事后分析，以确认结果的统计稳健性。先前报告的原始分析使用了末次观察值结转（LOCF）方法，并且还排除了治疗周期少于三个的患者。事后敏感性分析使用了以下不同的统计方法：1）纳入所有患者，无论其接受的治疗周期数（全部LOCF）；2）重复测量混合模型（MMRM）分析；3）功能与生存综合评估（CAFS）终点。研究结果与原始主要分析一致，表明依达拉奉优于安慰剂。我们还研究了研究中所有患者的ALSFRS-R总分变化分布情况，以及哪些ALSFRS-R项目和领域可能对总体疗效结果有贡献。与安慰剂相比，从基线到第6周期末（全部LOCF），ALSFRS-R总分变化分布有利于依达拉奉。在第6周期末（全部LOCF），依达拉奉在每个ALSFRS-R项目和四个ALSFRS-R领域中的每一个方面在描述上都更具优势，这表明依达拉奉在减缓所有解剖区域的功能衰退方面具有普遍作用。依达拉奉在延髓起病和肢体起病的患者中的作用似乎相似。总之，这些观察结果与其对非特定解剖区域氧化损伤发展的假定神经保护作用一致。
