Efficacy and safety of aducanumab, lecanemab, and donanemab in Alzheimer's disease: A meta-analysis of randomized controlled trials
Muaz Ali, Haroon Shabbir, Maheen Shaharyar, Sindu Mukesh, Adriana Rodriguez, Mansour Afshani, Deepak Kalra, Ahmed KorieshBackground
Anti-amyloid monoclonal antibodies offer a treatment strategy for early Alzheimer's disease, but their modest efficacy must be weighed against important safety concerns.
Objective
To evaluate the efficacy and safety of aducanumab, lecanemab, and donanemab in randomized placebo-controlled trials.
Methods
PubMed, Cochrane, and ClinicalTrials.gov were searched through February 2026 for randomized placebo-controlled trials evaluating aducanumab, lecanemab, or donanemab in early symptomatic Alzheimer's disease. Outcomes included Clinical Dementia Rating–Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), Mini-Mental State Examination (MMSE), amyloid-related imaging abnormalities–edema/effusion (ARIA-E), amyloid-related imaging abnormalities–hemosiderin deposition (ARIA-H), and
Results
Seven trials were included. Treatment favored intervention for ADAS-Cog (SMD −0.15, 95% CI −0.21 to −0.10), CDR-SB (MD −0.41, 95% CI −0.63 to −0.18), and MMSE (MD 0.44, 95% CI 0.03 to 0.86), although effects were small. Treatment increased ARIA-E (23.9% versus 1.9%; RR 11.65, 95% CI 9.06 to 14.99) and ARIA-H (16.8% versus 6.8%; RR 2.45, 95% CI 1.94 to 3.09). Among treated participants with
Conclusions
Aducanumab, lecanemab, and donanemab showed statistically significant but small slowing of decline that may not reach patient-perceptible clinical meaningfulness. Increased ARIA risk and additional safety signals support cautious selection, imaging surveillance, and individualized risk-benefit discussions.