ABSTRACT INTRODUCTION Questions remain regarding safety and clinical relevance of anti-amyloid antibodies in Alzheimer's disease (AD), with no scientific basis for choosing between different therapies. METHODS Systematic review, frequentist and Bayesian network meta-analyses of phase III randomized placebo-controlled trials were performed to comparatively evaluate cognitive, functional and biomarker efficacy and safety of anti-amyloid antibodies in sporadic AD. Treatments were ranked with P- and SUCRA scores, with rank robustness measured by Cohen's kappa, and uncertainty in ranking probabilities estimated with Shannon's normalized entropy. RESULTS Based on data from 16,971 patients (16 studies), we found Donanemab the best-ranked antibody on cognitive measures. Lecanemab was the most effective at reducing amyloid burden. Caution is needed concerning brain edema and microbleeding, with clinically important risks for Donanemab, Aducanumab and Lecanemab. DISCUSSION Risk/benefit profile of anti-amyloid antibodies remains unfavorable. Patients in Donanemab study were stratified by tau load, with greater effects observed in low/medium tau population.

The authors have declared no competing interest.

This work was supported by grants PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033, and SBPLY/21/180501/000150 funded by JCCM/ERDF A way of making Europe, and 2022-GRIN-34354 grant by UCLM/ERDF intramural funding to LJ-D and JDN-L.

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