Efficacy, safety, and ARIA risk of anti–β-amyloid antibodies in early Alzheimer’s disease: a systematic review, meta-analysis, and meta-regression

Alzheimer’s disease (AD) is the most prevalent cause of dementia and has been closely linked to βSupplemental data for this article can be accessed online at ht tps://doi.org/-amyloid accumulation. However, the efficacy and safety of anti–β-amyloid monoclonal antibodies remain debated. We systematically searched PubMed, Embase, and Cochrane databases for RCTs comparing anti–β-amyloid monoclonal antibodies with placebo in early-stage AD. Eligible trials enrolled participants with biomarker-supported AD and reported global, cognitive, or safety outcomes, including the CDR-SB, ADAS-Cog 13/14, ARIA, and brain volumetric measures. Six RCTs including 7837 participants were analyzed. Mean age ranged from 69.8 to 75.4 years, and 57.4% were APOE ε4 carriers. Anti–β-amyloid therapy was associated with small differences in global and cognitive outcomes, best described as a modest slowing of decline on the CDR-SB and ADAS-Cog scales. Treatment was associated with increased risks of ARIA-E (RR, 9.40; 95% CI, 6.98–12.66) and ARIA-H (RR, 2.40; 95% CI, 2.08–2.78), as well as greater ventricular enlargement and hippocampal atrophy. In early AD, anti–β-amyloid monoclonal antibodies are associated with modest slowing of decline accompanied by increased ARIA risk and unfavorable structural brain changes, limiting clinical applicability. www.crd.york.ac.uk/prospero identifier is CRD420251071393.