Genome-Wide Association Studies of ARIA From the Aducanumab Phase 3 ENGAGE and EMERGE Studies
Stephanie Loomis, Ryan Miller, Carmen Castrillo‐Viguera, Kimberly Umans, Wenting Cheng, John O’Gorman, Richard A. Hughes, Samantha Budd Haeberlein, Christopher D. Whelan
Abstract
BACKGROUND AND OBJECTIVES: influence risk of ARIA in aducanumab-treated patients. METHODS: We performed genome-wide association studies (GWAS) of ARIA in participants in the ENGAGE and EMERGE trials. Participants had mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease dementia and were amyloid-positive on PET scans. All participants underwent regular MRI monitoring to detect and diagnose ARIA. RESULTS: did not appear to modulate symptomatic status. No other genome-wide significant associations were found. DISCUSSION: is the strongest genetic risk factor of ARIA incidence, with implications for patient management and risk-benefit treatment decisions. TRIAL REGISTRATION INFORMATION: Both trials (ENGAGE [221AD301]: NCT02477800 and EMERGE [221AD302]: NCT02484547) were registered in June 2015 at clinicaltrials.gov and enrolled patients from August 2015 to July 2018.