Efficacy and safety of aducanumab, lecanemab, and donanemab in Alzheimer's disease: A meta-analysis of randomized controlled trials.

BackgroundAnti-amyloid monoclonal antibodies offer a treatment strategy for early Alzheimer's disease, but their modest efficacy must be weighed against important safety concerns.ObjectiveTo evaluate the efficacy and safety of aducanumab, lecanemab, and donanemab in randomized placebo-controlled trials.MethodsPubMed, 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 APOE ε4-stratified ARIA-E. Random-effects meta-analyses were performed.ResultsSeven 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 APOE ε4-stratified ARIA-E data, APOE ε4 carriers had higher ARIA-E risk than non-carriers (29.3% versus 13.8%; RR 2.10, 95% CI 1.67 to 2.64). Brain-volume loss, ventricular enlargement, and treatment-related deaths were narratively identified but not pooled.ConclusionsAducanumab, 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.