Pharmacological and Clinical Heterogeneity of Anti-Amyloid Monoclonal Antibodies in Early Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Trials
Abstract
Background: Anti-amyloid monoclonal antibodies represent the first disease-modifying therapeutic strategy targeting amyloid-β pathology in early Alzheimer's disease (AD). Although several agents have demonstrated the ability to reduce cerebral amyloid burden, their clinical efficacy and safety remain subjects of substantial scientific and regulatory debate. This study aimed to synthesize randomized evidence evaluating the benefit-risk profile of anti-amyloid monoclonal antibodies in biomarker-confirmed early AD. Methods: A systematic review and classical pairwise meta-analysis of randomized controlled trials (RCTs) was conducted following the PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for phase III placebo-controlled trials evaluating lecanemab, donanemab, aducanumab, and gantenerumab in patients with mild cognitive impairment due to AD or mild AD dementia with biomarker confirmation of amyloid pathology. The primary outcome was change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at the longest available follow-up. Safety outcomes included amyloid-related imaging abnormalities with edema or effusion (ARIA-E), amyloid-related imaging abnormalities with hemorrhage (ARIA-H), serious adverse events, and treatment discontinuation. Random-effects meta-analyses were performed. Results: Six randomized comparisons derived from four phase III trials involving 7695 participants met the…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,695 participants or records.
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