Cummings Jeffrey, Cohen Sharon, Murphy Jennifer, Brothers Holly M, Nejati Mina, Forrestal Fiona, de Moor Carl, O'Gorman John, Harrison John, Jaeger Judith, Mummery Catherine Jane, Porsteinsson Anton P, Potashman Michele, Tian Ying, Yang Lili, He Ping, Haeberlein Samantha Budd
University of Las Vegas, UNLV, Las Vegas, NV, USA.
Toronto Memory Program, Toronto, ON, Canada.
Alzheimers Dement. 2025 Jun;21(6):e70224. doi: 10.1002/alz.70224.
In EMERGE (NCT02484547), participants receiving aducanumab had significantly less progression versus placebo on all prespecified clinical endpoints at week 78. Here, we explicate the clinical meaningfulness of these treatment effects by analyzing item-level data and the persistence of treatment benefit.
Participants with early Alzheimer's disease (AD) were stratified by apolipoprotein E (APOE) ε4 status and randomized (1:1:1) to receive low- or high-dose aducanumab, or placebo. Prespecified principal component analyses (PCAs) per the Statistical Analysis Plan were followed by post hoc examination of individual domains/items across all five clinical endpoints. Progression analysis assessed reduction in clinical decline.
High-dose aducanumab demonstrated clinically meaningful slowing of progression across clinical endpoints measuring cognition, daily function, and behavioral symptoms. Delay of progression over 18 months was consistent across measures; treatment effects increased over time.
Across multiple analyses aducanumab slowed cognitive decline, prolonged functional independence, and attenuated behavioral symptoms in participants with early AD. These outcomes comprise the elements of a clinically meaningful response to treatment.
Endpoints in EMERGE assessed different aspects of cognition, daily function, and behavioral symptoms. Treatment benefits were observed across subdomains on all five clinical endpoints. Aducanumab meaningfully slowed disease progression in participants with early AD.
在EMERGE（NCT02484547）研究中，在第78周时，接受阿杜卡单抗治疗的参与者在所有预先设定的临床终点上与接受安慰剂治疗的参与者相比，病情进展显著减缓。在此，我们通过分析项目层面的数据和治疗益处的持续性来阐明这些治疗效果的临床意义。
患有早期阿尔茨海默病（AD）的参与者按载脂蛋白E（APOE）ε4状态分层，并随机（1:1:1）接受低剂量或高剂量阿杜卡单抗或安慰剂治疗。按照统计分析计划进行预先设定的主成分分析（PCA），随后对所有五个临床终点的各个领域/项目进行事后检查。进展分析评估临床衰退的减少情况。
高剂量阿杜卡单抗在测量认知、日常功能和行为症状的临床终点上显示出具有临床意义的进展减缓。在各项测量中，超过18个月的进展延迟是一致的；治疗效果随时间增加。
在多项分析中，阿杜卡单抗减缓了早期AD参与者的认知衰退，延长了功能独立性，并减轻了行为症状。这些结果构成了对治疗具有临床意义反应的要素。
EMERGE研究中的终点评估了认知、日常功能和行为症状的不同方面。在所有五个临床终点的各个子领域均观察到治疗益处。阿杜卡单抗显著减缓了早期AD参与者的疾病进展。
