Bayesian meta‐analysis of phase 3 results of aducanumab, lecanemab, donanemab, and high‐dose gantenerumab in prodromal and mild Alzheimer's disease

Abstract

Abstract INTRODUCTION Phase 3 trials using the anti‐amyloid antibodies aducanumab, lecanemab, donanemab, and high‐dose gantenerumab in prodromal and mild Alzheimer's disease dementia were heterogeneous in respect to statistical significance of effects. However, heterogeneity of results has not yet directly be quantified. METHODS We used Bayesian random effects meta‐analysis to quantify evidence for or against a treatment effect, and assessed the size of the effect and its heterogeneity. Data were extracted from published studies where available and Web based data reports, assuming a Gaussian data generation process. RESULTS We found moderate evidence in favor of a treatment effect (Bayes factor = 13.2). The effect was moderate to small with −0.33 (95% credible interval −0.54 to −0.10) points on the Clinical Dementia Rating – Sum of Boxes (CDR‐SB) scale. The heterogeneity parameter was low to moderate with 0.21 (0.04 to 0.45) CDR‐SB points. DISCUSSION Heterogeneity across studies was moderate despite some trials reaching statistical significance, while others did not. This suggests that the negative aducanumab and gantenerumab trials are in full agreement with the expected effect sizes.

Keywords

• amyloid lowering treatment
• Bayes factor
• effect size estimate
• heterogeneity
• prodromal Alzheimer's disease
• treatment effect