{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T15:15:10Z","timestamp":1793459710012,"version":"4.5.0"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To characterize ARIA in participants treated with donanemab.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcomes were the frequency, radiographic severity, seriousness, symptoms, timing relative to donanemab treatment, and risk factors for ARIA.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Across 3030 total participants (placebo-controlled trials: 999 placebo participants, 984 donanemab participants; open-label addendum: 1047 donanemab participants), mean (SD) age was approximately 73.7 (6.0) years and 1684 participants (55.6%) were female. Frequencies of ARIA\u2013edema\/effusions (ARIA-E) and ARIA\u2013microhemorrhages and hemosiderin deposition (ARIA-H) were higher with donanemab (24.4% and 31.3% in placebo-controlled trials, respectively; 19.8% and 27.2% in open-label addendum, respectively) than with placebo (1.9% and 13.0%, respectively). ARIA-E was mostly mild or moderate in severity. Serious ARIA-E was reported in 1.5% and symptomatic ARIA-E in 5.8% of donanemab-treated participants in the placebo-controlled trials. Symptoms most frequently reported with ARIA-E were headache and confusional state. In 58.3% of donanemab-treated participants with ARIA-E, the first event occurred by the third infusion (approximately month 3). Risk analysis demonstrated independent associations between ARIA-E and 6 baseline variables, including increased risk with\n APOE<\/jats:italic>\n \u03b54 allele number, greater number of microhemorrhages, presence of cortical superficial siderosis, higher amyloid plaque, and elevated mean arterial pressure, and decreased risk with antihypertensive use.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n ARIA is an adverse event associated with donanemab treatment that requires safety monitoring. Individual ARIA risk can be assessed by\n APOE<\/jats:italic>\n \u03b54 status and baseline imaging findings.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registrations<\/jats:title>\n \n ClinicalTrials.gov Identifiers:\n NCT03367403<\/jats:ext-link>\n and\n NCT04437511<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.0065","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T11:01:29Z","timestamp":1741604489000},"page":"461","source":"Crossref","is-referenced-by-count":197,"title":["Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease"],"prefix":"10.1001","volume":"82","author":[{"given":"Jennifer A.","family":"Zimmer","sequence":"first","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Ardayfio","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, 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Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Biffi","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Svaldi","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Salloway","sequence":"additional","affiliation":[{"name":"Butler Hospital, Providence, Rhode Island"},{"name":"Department of Neurology and Department of Psychiatry, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa 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