JAMA Neurol

Study evaluates donanemab's role in amyloid-related imaging abnormalities in early Alzheimer's

March 13, 2025

Rigorous safety monitoring is essential in patients treated with donanemab. Consider assessing individual amyloid-related imaging abnormality (ARIA) risk based on APOE ε4 status and baseline imaging and informing patients about potential risks and symptoms of ARIA.

Study design: This analysis used data from the placebo-controlled portions of the TRAILBLAZER-ALZ and ALZ 2 randomized trials, as well as an open-label addendum. Participants aged 60 to 85 years with early symptomatic Alzheimer disease and elevated amyloid levels were randomized to receive either donanemab or placebo, with donanemab administered every 4 weeks for up to 72 weeks.

Results: Among 3,030 participants, ARIA-edema/effusions (ARIA-E) and ARIA-microhemorrhages (ARIA-H) were significantly more frequent in the donanemab groups compared with placebo. ARIA-E was mostly mild or moderate, with serious cases in 1.5% and symptomatic cases in 5.8% of donanemab-treated participants. Headache and confusional state were common symptoms. Risk factors for ARIA-E included APOE ε4 allele number, microhemorrhages, cortical superficial siderosis, amyloid plaque levels, and mean arterial pressure, while antihypertensive use was associated with decreased risk.

Source:

Zimmer JA, et al. (2025, March 10). JAMA Neurol. Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials. https://pubmed.ncbi.nlm.nih.gov/40063015/