Longitudinal clinical outcomes after amyloid clearance in aducanumab phase 3 studies

IF 12.8 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2026-10-01 DOI:10.1002/alz.71758

Menglan Pang,Holly M. Brothers,John O'Gorman,Jennifer Murphy,Yuval Zabar,Tyler Lasky,Changyu Shen,Ivana Rubino,David Knopman

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Abstract

Abstract INTRODUCTION Anti‐amyloid antibody clinical trials with a high proportion of participants reaching treatment‐related amyloid clearance (TRAC) had positive clinical outcomes. We evaluated the aducanumab phase 3 program to determine whether TRAC during the double‐blind period was likewise associated with clinical benefit. METHODS We pooled ENGAGE and EMERGE (E/E) aducanumab‐treated participants in the amyloid positron emission tomography substudy who continued into the long‐term extension ≤ 134 weeks (continuously treated population) and/or returned to the EMBARK redosing study 0.7 to 2.5 years after termination of E/E (treatment gap population). Clinical outcomes were stratified by week 78 TRAC status. RESULTS TRAC participants had less clinical decline at week 78, week 134, and EMBARK baseline than non‐TRAC participants. Post‐TRAC, clinical decline was heterogeneous; approximately two thirds of TRAC participants had annualized decline of < 1 point on Clinical Dementia Rating Sum of Boxes. DISCUSSION In these exploratory analyses, week 78 TRAC status was associated with better clinical outcomes. CLINICAL TRIAL REGISTRATION NCT02484547, NCT02477800, NCT04241068

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aducanumab 3期研究中淀粉样蛋白清除后的纵向临床结果

抗淀粉样蛋白抗体临床试验中，高比例达到治疗相关淀粉样蛋白清除（TRAC）的参与者具有积极的临床结果。我们评估了aducanumab的3期项目，以确定双盲期间的TRAC是否同样与临床获益相关。方法：在淀粉样蛋白正电子发射断层扫描亚研究中，我们汇集了ENGAGE和EMERGE (E/E) aducanumab治疗的参与者，这些参与者持续到长期延长≤134周（持续治疗人群）和/或在E/E（治疗间隙人群）终止后0.7至2.5年返回到EMBARK再给药研究。临床结果按第78周TRAC状态分层。结果TRAC参与者在第78周、134周和EMBARK基线时的临床衰退比非TRAC参与者要少。TRAC后，临床衰退是异质性的；大约三分之二的TRAC参与者在临床痴呆评分框总和上的年化下降了1分。在这些探索性分析中，第78周TRAC状态与更好的临床结果相关。临床试验注册编号nct02484547、nct02477800、nct04241068

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.