使用PRO-ACT数据作为历史安慰剂对照，分析依达拉奉口服混悬液治疗的肌萎缩侧索硬化症患者的长期功能和生存率。

Analysis of Long-Term Function and Survival of Edaravone Oral Suspension-Treated Patients With Amyotrophic Lateral Sclerosis Using PRO-ACT Data as Historical Placebo Controls.

作者信息

Takahashi Fumihiro, Genge Angela, Hirai Manabu, Selness Daniel, Todorovic Vesna, Wamil Art, Sasson Nissim, Apple Stephen, Ushirogawa Yoshiteru

机构信息

Mitsubishi Tanabe Pharma America, Inc., Jersey City, New Jersey, USA.

Montreal Neurological Institute and Hospital, Montreal, Canada.

出版信息

Muscle Nerve. 2025 Oct;72(4):586-596. doi: 10.1002/mus.28462. Epub 2025 Jul 1.

DOI:10.1002/mus.28462

PMID:40590340

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12435165/

Abstract

INTRODUCTION/AIMS: On/Off dosing of intravenous (IV) edaravone and edaravone oral suspension was US Food and Drug Administration (FDA)-approved for Amyotrophic Lateral Sclerosis (ALS) treatment. Placebo-controlled trials showed that IV edaravone slows the rate of physical functional decline in patients with ALS. Here, the impact of edaravone oral suspension on function and survival was assessed.

METHODS

Edaravone oral suspension was investigated in clinical trials MT-1186-A01/A02/A03/A04. Patients from Studies MT-1186-A02/A04 (prespecified analysis) and Studies MT-1186-A01/A02/A03/A04 (post hoc analysis) were propensity score matched 1:1 on 10 baseline variables with historical Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) placebo patients (not receiving active investigational treatment in their trials) to assess the impact of edaravone oral suspension on function and survival.

RESULTS

In the prespecified analysis, 78 edaravone oral suspension-treated patients from Studies MT-1186-A02/A04 demonstrated a survival benefit versus 78 matched PRO-ACT placebo patients (p = 0.005). Baseline risk-adjusted hazard ratio showed an 84% decreased risk of death in edaravone oral suspension versus PRO-ACT placebo patients (p = 0.005). ALS Functional Rating Scale-Revised (ALSFRS-R) total score change from baseline at Week 48 was -8.4 points for edaravone oral suspension versus -14.1 points for PRO-ACT placebo patients (p < 0.001). In the post hoc analysis, patients from Studies MT-1186-A01/A02/A03/A04 (n = 210) propensity score matched to PRO-ACT placebo patients (n = 210) showed statistically significantly longer time to death and smaller ALSFRS-R change from baseline at Week 48; restricted mean survival time showed a 7.3-month improvement (p < 0.001).

DISCUSSION

This suggests edaravone oral suspension significantly increases survival time and decreases physical functional decline versus PRO-ACT placebo patients.

摘要

引言/目的：静脉注射依达拉奉和依达拉奉口服混悬液的间歇性给药已获得美国食品药品监督管理局（FDA）批准用于治疗肌萎缩侧索硬化症（ALS）。安慰剂对照试验表明，静脉注射依达拉奉可减缓ALS患者身体功能下降的速度。在此，评估了依达拉奉口服混悬液对功能和生存的影响。

方法

在临床试验MT - 1186 - A01/A02/A03/A04中对依达拉奉口服混悬液进行了研究。来自研究MT - 1186 - A02/A04（预设分析）和研究MT - 1186 - A01/A02/A03/A04（事后分析）的患者，在10个基线变量上与历史汇总资源开放获取ALS临床试验（PRO - ACT）安慰剂患者（在其试验中未接受活性研究性治疗）进行1:1倾向得分匹配，以评估依达拉奉口服混悬液对功能和生存的影响。

结果

在预设分析中，来自研究MT - 1186 - A02/A04的78例接受依达拉奉口服混悬液治疗的患者与78例匹配的PRO - ACT安慰剂患者相比显示出生存获益（p = 0.005）。基线风险调整后的风险比显示，与PRO - ACT安慰剂患者相比，依达拉奉口服混悬液治疗患者的死亡风险降低了84%（p = 0.005）。在第48周时，依达拉奉口服混悬液组的ALS功能评定量表修订版（ALSFRS - R）总分较基线变化为 - 8.4分，而PRO - ACT安慰剂组为 - 14.1分（p < 0.001）。在事后分析中，来自研究MT - 1186 - A01/A02/A03/A04（n = 210）且倾向得分与PRO - ACT安慰剂患者（n = 210）匹配的患者显示，至死亡时间在统计学上显著更长，且在第48周时ALSFRS - R较基线的变化更小；受限平均生存时间显示改善了7.3个月（p < 0.001）。