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.

IF 3.1 3区医学 Q2 CLINICAL NEUROLOGY

Muscle & Nerve Pub Date : 2025-10-01 Epub Date: 2025-07-01 DOI:10.1002/mus.28462

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

{"title":"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.","authors":"Fumihiro Takahashi, Angela Genge, Manabu Hirai, Daniel Selness, Vesna Todorovic, Art Wamil, Nissim Sasson, Stephen Apple, Yoshiteru Ushirogawa","doi":"10.1002/mus.28462","DOIUrl":null,"url":null,"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.","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"586-596"},"PeriodicalIF":3.1000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435165/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Muscle & Nerve","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mus.28462","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

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肌萎缩性侧索硬化症患者的长期功能和生存

简介/目的：静脉（IV）依达拉奉和依达拉奉口服混悬液的开/关给药是美国食品和药物管理局（FDA）批准用于肌萎缩性侧索硬化症（ALS）治疗的。安慰剂对照试验表明，静脉注射依达拉奉可以减缓ALS患者身体功能下降的速度。本研究评估依达拉奉口服混悬液对功能和生存的影响。方法：在MT-1186-A01/A02/A03/A04临床试验中对依达拉奉口服混悬液进行研究。研究MT-1186-A02/A04（预先分析）和MT-1186-A01/A02/A03/A04（事后分析）的患者在10个基线变量上与历史合并资源开放获取ALS临床试验（PRO-ACT）安慰剂患者（在其试验中未接受积极的研究性治疗）进行1:1的倾向评分匹配，以评估依达拉奉口服悬停剂对功能和生存的影响。结果：在预先指定的分析中，研究MT-1186-A02/A04中78名依达拉奉口服混悬液治疗的患者与78名匹配的PRO-ACT安慰剂患者相比显示出生存获益（p = 0.005）。基线风险校正风险比显示，依达拉奉口服混悬液与PRO-ACT安慰剂患者相比，死亡风险降低84% （p = 0.005）。在第48周，依达拉奉口服混悬液患者的ALS功能评分（ALSFRS-R）从基线开始的总评分变化为-8.4分，而PRO-ACT安慰剂患者为-14.1分(p)。讨论：这表明与PRO-ACT安慰剂患者相比，依达拉奉口服混悬液显着增加了生存时间，减少了身体功能下降。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Muscle & Nerve 医学-临床神经学

CiteScore

6.40

自引率

5.90%

发文量

287

审稿时长

3-6 weeks

期刊介绍： Muscle & Nerve is an international and interdisciplinary publication of original contributions, in both health and disease, concerning studies of the muscle, the neuromuscular junction, the peripheral motor, sensory and autonomic neurons, and the central nervous system where the behavior of the peripheral nervous system is clarified. Appearing monthly, Muscle & Nerve publishes clinical studies and clinically relevant research reports in the fields of anatomy, biochemistry, cell biology, electrophysiology and electrodiagnosis, epidemiology, genetics, immunology, pathology, pharmacology, physiology, toxicology, and virology. The Journal welcomes articles and reports on basic clinical electrophysiology and electrodiagnosis. We expedite some papers dealing with timely topics to keep up with the fast-moving pace of science, based on the referees'' recommendation.