Comparisons of efficacy and safety of immunotherapies for Alzheimer's disease treatment: A network meta-analysis of randomised controlled trials

Background: Alzheimer's disease (AD) remains a major challenge due to limited effective therapies. Moreover, direct comparisons between newly developed and symptomatic drugs are lacking. This network meta-analysis aimed to compare the efficacy and safety of immunotherapies for AD. Methods: A systematic search of PubMed, Embase, the Cochrane Library and ClinicalTrials.gov was conducted for randomised controlled trials (RCTs) up to 29 June 2024. Eligible studies included adults with AD receiving immunotherapy versus placebo or symptomatic treatment. Results: Fifty-nine RCTs were included. Donanemab and lecanemab ranked among the most effective treatments for improving cognitive function (Clinical Dementia Rating Scale – Sum of Boxes P-scores: 0.88 and 0.77) and daily activities (Alzheimer's Disease Cooperative Study – Activities of Daily Living P-scores: 0.85 and 0.90), based on network meta-analysis findings. Conclusions: Anti-Aβ monoclonal antibodies, particularly donanemab and lecanemab, demonstrated superior efficacy over other immunotherapies in slowing cognitive deterioration, supporting their role in AD management. PROSPERO registration number: CRD42023461680.