JMIR Publications

ABSTRACT

Background:

The risk/benefit profile and clinical relevance of anti-amyloid antibodies in Alzheimer’s disease (AD) is uncertain, with no scientific basis for choosing one treatment over another.

Objective:

We developed AlzMeta.app 2.0 (https://alzmetaapp.shinyapps.io/ALZMETA_APP_2/), web application that allows everyone to evaluate these drugs by pair-wise, frequentist and Bayesian network meta-analyses of phase II and III trial-level data (30/09/2024).

Methods:

We followed PRISMA-NMA and GRADE guidelines for reporting and rating the certainty of evidence. Studies with < 20 sporadic AD patients and modified Jadad score < 3 were excluded. Relative risks and benefits are available with confidence, credible and prediction intervals for all outcomes.

Results:

For significant results, the interventions are ranked in frequentist and Bayesian framework, and their clinical relevance can be determined by absolute risks per 1,000 people and Number-Needed-to-Treat (NNT) for expected control responses. Among seven treatments tested in 21,236 patients (26 studies with low risk of bias or with some concerns), Donanemab was the best-ranked on cognitive and functional measures, almost 2x more effective than Aducanumab and Lecanemab, and significantly more beneficial (p < 0.05) than other treatments on Clinical Dementia Rating Sum-of-Boxes (NNT = 10; 95% CI: 8; 16). Caution is required regarding cerebral edema and microbleeding, due to clinically relevant risks of edema for Donanemab (NNT = 8; 95% CI: 5; 16), Aducanumab (NNT = 10; 95% CI: 6; 17), and Lecanemab (NNT = 14; 95% CI: 7; 31).

Conclusions:

AlzMeta.app 2.0 allows predictions of absolute risks and benefits of treatments based on clinical trial results, different prior choices, and assumptions of baseline risks of decline and adverse events. Our results show that Donanemab is more effective, yet with safety profile similar to Aducanumab and Lecanemab.