Efficacy and safety of anti-amyloid antibodies in early Alzheimer’s disease

a systematic review of Lecanemab and Donanemab

Abstract

Alzheimer’s disease has historically been treated with symptomatic drugs, without consistent modification of its biological course. The recent approval of anti-amyloid monoclonal antibodies has changed this landscape, especially for patients with mild cognitive impairment or mild dementia associated with amyloid pathology. This systematic review without meta-analysis assessed evidence on the efficacy and safety of lecanemab and donanemab in early Alzheimer’s disease. Randomized, double-blind, placebo-controlled clinical trials evaluating these drugs in biomarker-confirmed Alzheimer’s disease were included. The synthesis followed PRISMA 2020 and SWiM recommendations, grouping findings by drug, trial phase, cognitive-functional outcomes, biomarkers, and adverse events. Four clinical trials met eligibility criteria. Lecanemab and donanemab reduced amyloid burden and slowed cognitive-functional decline in phase 3 studies, although the absolute magnitude of benefit was moderate. The main adverse events were amyloid-related imaging abnormalities, infusion-related reactions, and rare hemorrhagic events, with higher risk among ApoE ε4 carriers. The findings suggest a real but limited therapeutic advance, restricted to carefully selected patients and dependent on biomarker confirmation, serial magnetic resonance imaging, and healthcare infrastructure able to recognize and manage treatment-related adverse events.