Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease

Amyloid-related imaging abnormalities (ARIA) are the major adverse event associated with amyloid-targeting immunotherapy. Identifying clinical features and individual risk factors for ARIA could facilitate effective prediction and prevention strategies.

To characterize ARIA in participants treated with donanemab. Design, Setting, and Participants: These prespecified and post hoc exploratory analyses use data from the placebo-controlled portions of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials, conducted from December 2017 to December 2020 and from June 2020 to April 2023, respectively. Additional analyses are included from a stand-alone open-label addendum conducted from August 2021 through August 2023. Participants in the placebo-controlled trials and the open-label addendum aged 60 to 85 years with early symptomatic Alzheimer disease and elevated amyloid levels were included. The placebo-controlled trials, but not the addendum, had tau inclusion criteria. Interventions: Placebo-controlled trial participants were randomized 1:1 to receive placebo or donanemab, and all open-label participants received donanemab. Donanemab was administered every 4 weeks for up to 72 weeks. Main Outcomes and Measures: The primary outcomes were the frequency, radiographic severity, seriousness, symptoms, timing relative to donanemab treatment, and risk factors for ARIA.