journal articles
LOWER BASELINE AMYLOID BETA BURDEN IS ASSOCIATED WITH GREATER PERCENT OF AMYLOID BETA POSITRON EMISSION TOMOGRAPHY REDUCTION AND BETTER CLINICAL OUTCOMES IN THE ADUCANUMAB PHASE 3 TRIALS ENGAGE AND EMERGE IN EARLY ALZHEIMER\'S DISEASE
Jackson Burton, Holly M. Brothers, R. Matthew Hutchison, Jennifer Murphy, Tao Sun, Gersham Dent, Gioacchino Curiale, Ken Kowalski
BACKGROUND: Aducanumab is a human immunoglobulin G1 anti-amyloid beta antibody for early-stage Alzheimer’s disease. After the discontinuation of the aducanumab clinical program and market withdrawal, the Phase 3 data were further assessed to characterize the relationship between baseline amyloid beta load, degree of amyloid beta removal, and subsequent clinical outcomes to provide context for future research.
OBJECTIVES: This analysis leveraged modelling techniques to impute missing amyloid beta positron emission tomography values and better understand the relationship between baseline amyloid beta positron emission tomography status, amyloid beta positron emission tomography reduction, and clinical outcomes in the aducanumab Phase 3 ENGAGE and EMERGE (NCT02477800/NCT02484547) studies.
DESIGN: Exploratory data analysis.
SETTING: A previously developed model which characterized the relationship between aducanumab exposure and amyloid beta positron emission tomography standard uptake value ratio was updated to impute centiloid values for participants not enrolled in the amyloid beta positron emission tomography substudy. Additional clinically-relevant variables were also summarized.
PARTICIPANTS: 1876 participants with baseline amyloid beta positron emission tomography and clinical endpoints in a pooled ENGAGE/EMERGE dataset at week 78.
INTERVENTION: Aducanumab.
MEASUREMENTS: Amyloid burden measured by centiloids and clinical endpoints.
RESULTS: In older participants whose baseline amyloid beta burden is lower than the average trial population, exposure to aducanumab provides greater clinical benefit across cognitive and functional endpoints.
CONCLUSIONS: The relationship between baseline amyloid beta load and treatment benefit in a large population after exposure to an amyloid beta–directed antibody provides insight into which subpopulations are likely to benefit from this class of treatment.
CITATION:
Jackson Burton ; Holly M. Brothers ; R. Matthew Hutchison ; Jennifer Murphy ; Tao Sun ; Gersham Dent ; Gioacchino Curiale ; Ken Kowalski (2025): Lower baseline amyloid beta burden is associated with greater percent of amyloid beta positron emission tomography reduction and better clinical outcomes in the aducanumab Phase 3 trials ENGAGE and EMERGE in early Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100202