Severe amyloid-related imaging abnormalities associated with aducanumab: a case series from the EMBARK study

Amyloid-related imaging abnormalities (ARIA) on magnetic resonance imaging during treatment with amyloid beta–directed antibodies are well documented; however, detailed accounts of severe clinical presentations, although rare in occurrence, have not yet been well-described. We briefly describe 4 cases of radiographically severe and clinically serious ARIA. This case series presents the radiographic and clinical manifestations of severe ARIA events after aducanumab treatment from the EMBARK study. EMBARK (ClinicalTrials.gov identifier NCT04241068) was an open-label, multicenter, longitudinal, single-arm, Phase 3b study. EMBARK enrolled 1696 participants with Alzheimer’s disease who were previously enrolled in aducanumab trials (PRIME, EMERGE, ENGAGE, or EVOLVE). Participants received a monthly 10 mg/kg dose of aducanumab after an aducanumab treatment gap period imposed by the discontinuation of the aducanumab studies. The clinical history, management, and imaging findings of 4 selected severe and/or serious case reports of ARIAs in participants treated with aducanumab are presented. All of the participants carried the apolipoprotein E ( ApoE) ε4 allele (3 were homozygous ApoE ε4 carriers). Possible risk factors were explored, and the clinical courses were delineated. These 4 cases were chosen to highlight key lessons on the monitoring and management of ARIAs. Observations from these select severe cases improve our understanding of the risk factors, symptoms, and management of ARIAs.