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

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Human Psychopharmacology: Clinical and Experimental Pub Date : 2025-09-15 DOI:10.1002/hup.70017

Yun Wei, Hualing Li

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引用次数: 0

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

Anti-Aβ mAbs offer modest clinical benefits, and pose some serious complications, necessitating a cautious approach to their prescription.

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淀粉样蛋白定向单克隆抗体治疗阿尔茨海默病的疗效和安全性：III期随机对照试验的系统评价和荟萃分析

阿尔茨海默病（AD）是世界范围内导致死亡的主要原因。淀粉样蛋白（Aβ）定向单克隆抗体（mab）是治疗AD的新方法之一。本系统综述和荟萃分析旨在评估这类药物的疗效和安全性。方法检索截至2025年1月30日的Scopus、Web of Science、PubMed和Cochrane图书馆的文献，重点检索评估抗β单抗的III期随机对照试验（rct）。结果共纳入12项随机对照试验，共24组。抗β单抗显著降低了临床痴呆评分-盒和（CDR-SB）评分（平均差值（MD）： - 0.16, 95%可信区间（CI）（- 0.29, - 0.04））、阿尔茨海默病评估量表-认知亚量表（ADAS-Cog）评分（MD: - 0.87, 95% CI(- 1.13, - 0.60)）和淀粉样正电子发射断层扫描（PET）标准化摄取值比（SUVR）（MD: - 0.11, 95% CI(- 0.19, - 0.02)）。他们还显著提高了最小精神状态检查（MMSE）评分（MD: 0.31, 95% CI(0.15, 0.46)）和阿尔茨海默病日常生活活动合作研究（ADCS-ADL）评分（MD: 1.21, 95% CI(0.89, 1.53)）。然而，它们与并发症的显著增加相关，包括淀粉样蛋白相关影像学异常-水肿/积液（ARIA-E）（优势比（OR）： 10.20, 95% CI (7.17, 14.50)）， aria -含血黄素沉着或微出血（ARIA-H）（OR: 1.75, 95% CI（1.22, 2.50)）和任何不良事件（OR: 1.22, 95% CI (1.08, 1.38), I2: 48.59%））。亚组分析显示，在AD的早期/临床前阶段进行治疗导致CDR-SB和ADAS-Cog评分以及淀粉样蛋白负担的更大降低。结论抗β单抗的临床疗效有限，但存在一些严重的并发症，需要谨慎用药。

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

Human Psychopharmacology: Clinical and Experimental 医学-精神病学

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Human Psychopharmacology: Clinical and Experimental provides a forum for the evaluation of clinical and experimental research on both new and established psychotropic medicines. Experimental studies of other centrally active drugs, including herbal products, in clinical, social and psychological contexts, as well as clinical/scientific papers on drugs of abuse and drug dependency will also be considered. While the primary purpose of the Journal is to publish the results of clinical research, the results of animal studies relevant to human psychopharmacology are welcome. The following topics are of special interest to the editors and readers of the Journal: -All aspects of clinical psychopharmacology- Efficacy and safety studies of novel and standard psychotropic drugs- Studies of the adverse effects of psychotropic drugs- Effects of psychotropic drugs on normal physiological processes- Geriatric and paediatric psychopharmacology- Ethical and psychosocial aspects of drug use and misuse- Psychopharmacological aspects of sleep and chronobiology- Neuroimaging and psychoactive drugs- Phytopharmacology and psychoactive substances- Drug treatment of neurological disorders- Mechanisms of action of psychotropic drugs- Ethnopsychopharmacology- Pharmacogenetic aspects of mental illness and drug response- Psychometrics: psychopharmacological methods and experimental design