A secondary analysis of the TRAILBLAZER-ALZ and TRAILBLAZER-ALZ 2 clinical trials found that amyloid-related imaging abnormalities (ARIA) were more frequent in participants receiving donanemab for early symptomatic Alzheimer disease than in those receiving placebo. 

The study analyzed data from 3,030 participants aged 60 to 85 years, with a mean age of approximately 73.7 years, including 1,684 (55.6%) females. Patients were randomized 1:1 to donanemab or placebo.

In the pooled placebo-controlled trials, ARIA-E occurred in 24.4% and ARIA-H in 31.3% of donanemab-treated participants, compared to 1.9% and 13% in the placebo group. In an open-label extension, ARIA-E and ARIA-H were observed in 19.8% and 27.2% of participants, respectively.

"ARIA is an adverse event associated with donanemab treatment that requires safety monitoring,” reported Jennifer Zimmer, MD and colleagues in JAMA Neurology.

The researchers identified six independent baseline risk factors for ARIA-E: presence of the apolipoprotein E (APOE) ε4 allele, higher amyloid plaque burden, greater number of microhemorrhages, cortical superficial siderosis, elevated mean arterial pressure, and absence of antihypertensive medication use. Among donanemab-treated participants, ARIA-E occurred in 42.1% of APOE ε4 homozygotes, 21.5% of heterozygotes, and 11% of noncarriers. Most ARIA-E cases were mild or moderate in severity, with 96% resolving based on MRI findings over a median of 58 days.

In 58.3% of donanemab-treated participants with ARIA-E, the first event occurred by the third infusion, underscoring the importance of early monitoring. To enhance safety, a 4-week MRI scan was added to the TRAILBLAZER-ALZ 2 protocol, which reduced the risk of symptomatic ARIA-E by 36.3%. Serious ARIA-E was reported in 1.5% of donanemab-treated participants. Symptoms such as headache and confusion were the most frequently reported.

Researcher disclosures are available in the published study.