Influence of patient characteristics on efficacy and safety of anti-amyloid monoclonal antibodies in Alzheimer’s disease: A systematic review and meta-analysis

IF 15.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI:10.1016/j.arr.2025.102981

Grace H. Shim , Edward C.Y. Lau , Andrew L.H. Huynh , Christine Y. Lu , Edwin C.K. Tan

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引用次数: 0

Abstract

Background

Lecanemab and donanemab are the first anti-amyloid monoclonal antibodies (mAbs) clinically available as disease-modifying therapies for Alzheimer’s disease (AD). However, it remains unclear whether their treatment effects differ across demographic, clinical, or genetic subgroups.

Objective

This systematic review aimed to explore how patient characteristics modify the efficacy, safety and humanistic outcomes of anti-amyloid mAbs lecanemab and donanemab in patients with early AD.

Methods

A systematic search of MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library was conducted from database inception to July 30th, 2025, using a combination of keywords and Medical Subject Heading terms relating to lecanemab and donanemab. Meta-analyses were conducted for safety outcomes where sufficient data was available.

Results

Sixteen studies representing six randomised clinical trials (total N = 5633) were included. Both lecanemab and donanemab showed the greatest slowing of cognitive decline in White/Caucasian patients and apolipoprotein E4 (ApoE4) non-carriers. Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) and microhemorrhages (ARIA-H) were more prevalent in ApoE4 carriers. The risk of ARIA-E was 2.19 times higher (95 %CI:1.91–2.50) and ARIA-H was 3.45 times higher (95 %CI:1.35–8.72) in ApoE4 carriers versus non-carriers. Statistically significant improvements in health-related quality of life were observed with lecanemab in ApoE4 heterozygous participants and in those aged 65–74 years.

Conclusions

The efficacy and safety of anti-amyloid mAbs in AD may differ based on patients’ demographic and genetic factors. These findings highlight the potential for personalised treatment strategies and inform national drug policies. Further research is needed to evaluate long-term outcomes and address under-studied patient populations.

Summary

The efficacy and safety of lecanemab and donanemab varied across patient subgroups, including age, sex, race/ethnicity and genetic factors such as ApoE4 genotype status. The risk of ARIA was higher in ApoE4 carriers, particularly the homozygous.

查看原文本刊更多论文

阿尔茨海默病患者特征对抗淀粉样蛋白单克隆抗体疗效和安全性的影响：一项系统综述和荟萃分析

背景：lecanemab和donanemab是首批临床可用的抗淀粉样蛋白单克隆抗体（mab），可用于阿尔茨海默病（AD）的疾病改善治疗。然而，目前尚不清楚它们的治疗效果是否在人口统计学、临床或遗传亚群中有所不同。目的本系统综述旨在探讨患者特征如何改变抗淀粉样蛋白单克隆抗体lecanemab和donanemab治疗早期AD患者的疗效、安全性和人文预后。方法系统检索MEDLINE、Embase、Scopus、Web of Science、Cochrane Library数据库自建库至2025年7月30日，使用与lecanemab和donanemab相关的关键词和医学主题词组合进行检索。在有足够数据的情况下，对安全性结果进行荟萃分析。结果共纳入6项随机临床试验16项研究（总N = 5633）。lecanemab和donanemab在白人/高加索患者和载脂蛋白E4 （ApoE4）非携带者中显示出最大的认知衰退减缓。淀粉样蛋白相关影像学异常伴水肿/积液（ARIA-E）和微出血（ARIA-H）在ApoE4携带者中更为普遍。ApoE4携带者患ARIA-E的风险是非携带者的2.19倍（95 %CI:1.91 ~ 2.50）， ARIA-H的风险是非携带者的3.45倍（95 %CI:1.35 ~ 8.72）。在ApoE4杂合参与者和65-74岁的参与者中，使用lecanemab观察到与健康相关的生活质量有统计学意义的改善。结论抗淀粉样蛋白单抗治疗AD的疗效和安全性可能因患者的人口统计学和遗传因素而异。这些发现突出了个性化治疗策略的潜力，并为国家药物政策提供了信息。需要进一步的研究来评估长期结果并解决研究不足的患者群体。lecanemab和donanemab的疗效和安全性在不同的患者亚组中存在差异，包括年龄、性别、种族和遗传因素，如ApoE4基因型状态。ApoE4携带者发生ARIA的风险更高，特别是纯合子携带者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.