Longitudinal clinical outcomes after amyloid clearance in aducanumab phase 3 studies

Why clinicians should know about it

• Picked for Neurology (clinical) (paper of the day, 9 October 2026): Phase III RCT, practice-changing for adjuvant therapy

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.

Abstract as published, via PubMed.