What type of study is this?

This is a Meta-Analysis study (also classified as: Systematic Review, Phase 3).

September 16, 2025

The Efficacy and Safety of Amyloid Beta‐Directed Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta‐Analysis of Phase III Randomized Controlled Trials

Key Points

Anti-Aβ monoclonal antibodies significantly reduced CDR-SB and ADAS-Cog scores, indicating improved cognitive function.
A total of twelve randomized controlled trials were included, showing increased Mini-Mental State Examination scores with treatment.
However, treatment was associated with a significant rise in complications, particularly ARIA-E and ARIA-H events.
Subgroup analysis indicated better outcomes when treatment was initiated in early or preclinical stages of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a leading cause of mortality worldwide. One of the newer treatments for AD is amyloid beta (Aβ) directed monoclonal antibodies (mAbs). This systematic review and meta-analysis aimed to assess the efficacy and safety of this class of drugs. A comprehensive literature search was conducted across Scopus, Web of Science, PubMed, and the Cochrane Library until January 30, 2025, focusing on phase III randomized controlled trials (RCTs) evaluating anti-Aβ mAbs. Twelve RCTs with 24 arms were included. Anti-Aβ mAbs significantly reduced the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score (mean difference (MD): -0.16, 95% confidence interval (CI) (-0.29, -0.04)), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score (MD: -0.87, 95% CI (-1.13, -0.60)), and amyloid positron emission tomography (PET) standardized uptake value ratio (SUVR) (MD: -0.11, 95% CI (-0.19, -0.02)). They also significantly increased the Mini-Mental State Examination (MMSE) score (MD: 0.31, 95% CI (0.15, 0.46)) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score (MD: 1.21, 95% CI (0.89, 1.53)). However, they were associated with a significant increase in complications, including amyloid-related imaging abnormalities-edema/effusion (ARIA-E) (odds ratio (OR): 10.20, 95% CI (7.17, 14.50)), ARIA-hemosiderosis or microhemorrhage (ARIA-H) (OR: 1.75, 95% CI (1.22, 2.50)), and any adverse events (OR: 1.22, 95% CI (1.08, 1.38), I2: 48.59%)). The subgroup analysis showed that treatment administered in the early/preclinical stages of AD resulted in a greater reduction in CDR-SB and ADAS-Cog scores, as well as in amyloid burden. Anti-Aβ mAbs offer modest clinical benefits, and pose some serious complications, necessitating a cautious approach to their prescription.

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Cite This Study

Wei et al. (Mon,) studied this question.

synapsesocial.com/papers/68d44f8c31b076d99fa574aa https://doi.org/https://doi.org/10.1002/hup.70017

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