Uptake and safety profile of anti-amyloid immunotherapies in routine clinical practice

BACKGROUND: Anti-amyloid immunotherapies are approved by the United States Food and Drug Administration for the treatment of Alzheimer's disease; however, the adoption and safety profile of these medications in routine clinical practice have not been described. OBJECTIVE: To describe the adoption and safety profile of anti-amyloid immunotherapies in routine clinical practice. METHODS: This was a retrospective observational cohort study using target trial emulation methods. The data source was nationwide electronic health record data from Epic Cosmos. The primary exposure was the first prescription of anti-amyloid immunotherapy versus the active comparator of oral dementia therapy (acetylcholinesterase inhibitor (AChEI) or memantine, selected to minimize bias by baseline health status and disease severity). The primary end point was time to first nontraumatic intracranial hemorrhage (ICH). Propensity score overlap weighting was used to balance baseline demographic and clinical characteristics across treatment groups. RESULTS: Between July 1, 2023 and January 1, 2025, 2616 patients (median age 74.8 years [IQR 69.8-78.8]; 53.9% female) were prescribed anti-amyloid immunotherapy (with or without AChEI/memantine), and 1,065,192 patients (median age 79.98 [IQR 73.6-85.6], 57.9% female) were prescribed AChEI/memantine alone. In total, 401 patients prescribed anti-amyloid immunotherapy and 274,470 patients prescribed AChEI/memantine were assessed for safety endpoints. Compared with AChEI/memantine, the analysis did not detect a statistically significant association between prescription of anti-amyloid immunotherapy and ICH (owHR 0.73 [95% CI 0.10-5.12]). CONCLUSIONS: The study did not detect a statistically significant association between prescription of anti-amyloid immunotherapy and ICH. The small treated cohort and low event count yielded imprecise estimates; these findings do not confirm safety and cannot exclude a clinically important increase in risk.