阿杜那单抗3期研究中淀粉样蛋白清除后的纵向临床结局。
完整摘要 · 中文译文
引言：抗淀粉样蛋白抗体临床试验中，达到治疗相关淀粉样蛋白清除（TRAC）的参与者比例较高时，临床结局为阳性。我们评估了阿杜卡奴单抗3期项目，以确定双盲期内的TRAC是否同样与临床获益相关。 方法：我们汇总了ENGAGE和EMERGE（E/E）中接受阿杜卡奴单抗治疗、进入长期扩展研究≤134周（持续治疗人群）和/或在E/E终止后0.7至2.5年返回EMBARK再给药研究（治疗间隙人群）的淀粉样蛋白正电子发射断层扫描亚组参与者。临床结局按第78周TRAC状态分层。 结果：TRAC参与者在第78周、第134周和EMBARK基线时的临床衰退均少于非TRAC参与者。TRAC后，临床衰退呈异质性；约三分之二的TRAC参与者在临床痴呆评定量表盒子总和（Clinical Dementia Rating Sum of Boxes）上的年化衰退< 1分。 讨论：在这些探索性分析中，第78周TRAC状态与更好的临床结局相关。 临床试验注册：NCT02484547、NCT02477800、NCT04241068。
完整摘要 · 英文原文
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.