New Insights into ARIA-E Risk from Donanemab Studies

In an effort to understand more about amyloid-related imaging abnormalities (ARIA) associated with anti-amyloid therapy, researchers analyzed pooled data from 3 studies involving donanemab (Eli Lilly and Company, Indianapolis, IN) therapy for individuals with early Alzheimer disease (AD):

• The phase 2 TRAILBLAZER-ALZ study (NCT03367403)
• The phase 3 TRAILBLAZER-ALZ2 study (NCT04437511)
• The open-label TRAILBLAZER-ALZ2 addendum

Although most cases of ARIA were transient and symptomatic, ARIA-E (cerebral edema) occurred in:

• 27.5% of participants in TRAILBLAZER-ALZ
• 24% of participants in TRAILBLAZER-ALZ2
• 19.8% of participants in the addendum

According to the researchers’ analysis, several baseline factors were strongly linked to an increased risk of developing ARIA-E, including:

• Greater amyloid burden
• High blood pressure
• Baseline microhemorrhages
• Cortical superficial siderosis
• APOE ε4/ε4 genotype

Taking antihypertensive medications was associated with a lower occurrence of ARIA-E.

The analysis included data from 2031 individuals treated with donanemab. Results were presented at the American Academy of Neurology (AAN) 2024 Annual Meeting.

According to John Sims, MD, Senior Medical Director, Eli Lilly and Company, “Baseline MRI scans can provide details about a number of factors important in Alzheimer disease. They can reveal signs of amyloid accumulation or burden in the brain, of course. If you see signs that amyloid is accumulating in the brain, amyloid is also building up in the blood vessel, making the blood vessel unhealthy as well. If you find evidence of microhemorrhages on baseline MRI scans, that person is at a higher risk of developing ARIA, although further studies are needed as well as replication of the results of this analysis.”