Title : Real-world safety of lecanemab and donanemab in Alzheimer's disease: A single-center retrospective cohort study
Abstract:
Background: Anti-amyloid monoclonal antibodies, including lecanemab and donanemab, represent an emerging disease-modifying treatment approach for early Alzheimer’s disease. However, treatment is associated with amyloid-related imaging abnormalities (ARIA), including ARIA with edema (ARIA-E) and hemorrhage (ARIA-H), with APOE ε4 carrier status recognized as an important potential risk factor. This study evaluated real-world adverse events, specifically ARIA associated with lecanemab and donanemab and explored the relationship between APOE ε4 status and ARIA.
Methods: We conducted a single-center retrospective cohort study of patients with confirmed Alzheimer’s disease treated with lecanemab or donanemab. Electronic health records were reviewed for demographics, Alzheimer’s diagnostic testing, APOE genotype, baseline Mini-Mental State Examination (MMSE) score, imaging findings, ARIA, and other documented adverse events. ARIA rates were compared using Fisher’s exact tests.
Results: Seventy-six patients were included: 26 received lecanemab and 50 received donanemab. Mean age was 72 and 76 years, and mean baseline MMSE was 26 and 24, respectively. ARIA occurred in 5/26 (19.2%) lecanemab-treated patients compared with 3/50 (6.0%) donanemab-treated patients (p=0.114). Four lecanemab-associated cases were ARIA-E and one was ARIA-H; all three donanemab-associated cases were ARIA-E. Among patients with documented APOE status, ARIA occurred exclusively in APOE ε4 carriers. In the lecanemab cohort, ARIA occurred in 4/17 (23.5%) carriers versus 0/9 noncarriers (p=0.263); in the donanemab cohort, ARIA occurred in 3/24 (12.5%) carriers versus 0/26 noncarriers (p=0.103). Other adverse events occurred in 6/26 (23%) and 11/50 (22%) of lecanemab- and donanemab-treated patients, respectively with headache and flu-like symptoms among the most documented complaints.
Conclusion: In this real-world cohort, both lecanemab and donanemab demonstrated safety profiles generally consistent with those reported in clinical trials, with no major treatment-related complications observed. ARIA was numerically more frequent with lecanemab than donanemab, although the difference was not statistically significant. Notably, the observed incidence of ARIA with donanemab was lower than rates reported in clinical trials, supporting its tolerability in routine clinical practice. Among patients with documented genotypes, ARIA occurred exclusively in APOE ε4 carriers, reinforcing the importance of APOE status in risk assessment and treatment monitoring. These findings support the real-world use of anti-amyloid therapies with appropriate patient selection and surveillance; however, larger multicenter studies are needed to confirm comparative ARIA risk and further characterize the influence of APOE genotype.
