抗β淀粉样蛋白免疫治疗III期临床试验中淀粉样蛋白相关影像学异常的发生率：一项最新的荟萃分析

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Neurology Pub Date : 2025-04-22 Epub Date: 2025-03-19 DOI:10.1212/WNL.0000000000213483

So Yeong Jeong, Chong Hyun Suh, Jae-Sung Lim, Woo Hyun Shim, Hwon Heo, Yangsean Choi, Ho Sung Kim, Sang Joon Kim, Jae-Hong Lee

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引用次数: 0

摘要

背景和目的：淀粉样蛋白相关成像异常（ARIA）是抗淀粉样蛋白-β (Aβ)免疫治疗中关键的安全性考虑因素。ARIA可分为2种类型：以水肿和积液为特征的ARIA （ARIA- e）或微出血和浅表性铁沉着（ARIA- h）。在本研究中，我们评估了抗a β免疫治疗的3期随机对照试验（rct）中ARIA的发生率，并比较了不同药物和APOE ε4携带者的发生率。方法：检索PubMed和Embase数据库，检索2024年5月23日及之前发表的抗a β免疫治疗的3期rct。纳入标准是抗β免疫疗法治疗阿尔茨海默病（AD）或轻度AD痴呆引起的轻度认知障碍的3期试验，具有ARIA-E/H的足够数据。按不同药物及APOE ε4携带者情况计算ARIA合并发病率，并进行亚组分析。进行排除异常值的敏感性分析。根据APOE ε4携带者的状态计算ARIA-E的合并优势比（OR）。结果：从8项符合条件的研究中确定了9个3期RCT队列，分析了6,315例患者的数据。在敏感性分析中，ARIA-E的合并发病率为9.5% (95% CI 2.8% ~ 27.3%)，调整后的合并发病率为25.5% （95% CI 20.4% ~ 31.8%）。症状性ARIA-E的总发生率为6.7% (95% CI 3.5%-12.5%)，重度ARIA-E的总发生率为3.5% （95% CI 13.8%-8.4%）。ARIA-H的总发病率为17.8% (95% CI 11.0%-27.5%)，浅表性铁沉着的发病率为9.3% （95% CI 6.1%-13.9%）。分离ARIA-H的合并发病率为8.7% （95% CI 7.6%-10.1%）。亚组分析显示，APOE ε4纯合子携带者发生ARIA-E的几率显著高于非携带者（OR 5.6, 95% CI 3.8 ~ 8.2, p < 0.001）。杂合APOE ε4携带者发生ARIA-E的几率显著高于非携带者（OR 1.9, 95% CI 1.5 ~ 2.4, p < 0.001）。讨论：尽管受到小样本量和队列水平数据的限制，我们的荟萃分析显示，在最近的抗a β免疫治疗的3期随机对照试验中，ARIA-E的调整合并发病率为25.5%，ARIA-H的合并发病率为17.8%。纯合子APOE ε4携带者发生ARIA-E的风险比非携带者高5.6倍。

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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Incidence of Amyloid-Related Imaging Abnormalities in Phase III Clinical Trials of Anti-Amyloid-β Immunotherapy: An Updated Meta-Analysis.

Background and objectives: Amyloid-related imaging abnormalities (ARIA) are key safety considerations in anti-amyloid-β (Aβ) immunotherapy. ARIA can be categorized into 2 types: ARIA characterized by edema and effusion (ARIA-E) or microhemorrhages and superficial siderosis (ARIA-H). In this study, we assessed the incidence of ARIA in phase 3 randomized controlled trials (RCTs) of anti-Aβ immunotherapy and compared the incidence among different agents and APOE ε4 carrier status.

Methods: PubMed and Embase databases were searched for phase 3 RCTs of anti-Aβ immunotherapy published on or before May 23, 2024. The inclusion criteria were phase 3 trials of anti-Aβ immunotherapy for mild cognitive impairment due to Alzheimer disease (AD) or mild AD dementia, with sufficient data on ARIA-E/H. The pooled incidences of ARIA and subgroup analyses according to various agents and APOE ε4 carrier status were calculated. A sensitivity analysis excluding outliers was performed. The pooled odds ratio (OR) of ARIA-E according to the APOE ε4 carrier status was also calculated.

Results: Nine phase 3 RCT cohorts from 8 eligible studies were identified, analyzing data from 6,315 patients. The pooled incidence of ARIA-E was 9.5% (95% CI 2.8%-27.3%), and the adjusted pooled incidence of ARIA-E was 25.5% (95% CI 20.4%-31.8%) in the sensitivity analysis. The pooled incidence of symptomatic ARIA-E was 6.7% (95% CI 3.5%-12.5%) and that of severe ARIA-E was 3.5% (95% CI 13.8%-8.4%). The pooled incidence of ARIA-H was 17.8% (95% CI 11.0%-27.5%), with the incidence of superficial siderosis was 9.3% (95% CI 6.1%-13.9%). The pooled incidence of isolated ARIA-H was 8.7% (95% CI 7.6%-10.1%). Subgroup analysis showed that homozygous APOE ε4 carriers had significantly higher odds of developing ARIA-E (OR 5.6, 95% CI 3.8-8.2, p < 0.001) than noncarriers. Heterozygous APOE ε4 carriers also had significantly higher odds of developing ARIA-E (OR 1.9, 95% CI 1.5-2.4, p < 0.001) than noncarriers.

Discussion: Although limited by small sample size and cohort-level data, our meta-analysis shows the adjusted pooled incidence of ARIA-E was 25.5% and the pooled incidence of ARIA-H was 17.8% in the recent phase 3 RCTs of anti-Aβ immunotherapy. Homozygous APOE ε4 carriers have a 5.6-fold higher risk of developing ARIA-E than noncarriers.

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来源期刊

Neurology 医学-临床神经学

CiteScore

12.20

自引率

4.00%

发文量

1973

审稿时长

2-3 weeks

期刊介绍： Neurology, the official journal of the American Academy of Neurology, aspires to be the premier peer-reviewed journal for clinical neurology research. Its mission is to publish exceptional peer-reviewed original research articles, editorials, and reviews to improve patient care, education, clinical research, and professionalism in neurology. As the leading clinical neurology journal worldwide, Neurology targets physicians specializing in nervous system diseases and conditions. It aims to advance the field by presenting new basic and clinical research that influences neurological practice. The journal is a leading source of cutting-edge, peer-reviewed information for the neurology community worldwide. Editorial content includes Research, Clinical/Scientific Notes, Views, Historical Neurology, NeuroImages, Humanities, Letters, and position papers from the American Academy of Neurology. The online version is considered the definitive version, encompassing all available content. Neurology is indexed in prestigious databases such as MEDLINE/PubMed, Embase, Scopus, Biological Abstracts®, PsycINFO®, Current Contents®, Web of Science®, CrossRef, and Google Scholar.