Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Suzhou Medical College of Soochow University, Suzhou, 215002, Jiangsu, China.
Eur J Med Res. 2023 Nov 28;28(1):544. doi: 10.1186/s40001-023-01512-w.
Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-β (anti-Aβ) monoclonal antibodies (mabs) for the treatment of AD.
PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included Aβ, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model.
Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-Aβ mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-Aβ mabs increased cerebrospinal fluid (CSF) Aβ1-42 (P = 0.002) and plasma Aβ42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-Aβ mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-Aβ mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001).
FDA-approved anti-Aβ mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.
阿尔茨海默病（AD）是一个全球性的公共卫生问题，难以治愈。已经开发出了旨在减缓疾病进展的药物，美国食品和药物管理局（FDA）于 2021 年 6 月 21 日加速批准了 aducanumab，于 2023 年 1 月 22 日加速批准了 lecanemab。我们进行了这项系统评价和荟萃分析，以评估 FDA 批准的抗淀粉样蛋白-β（抗-Aβ）单克隆抗体（mab）治疗 AD 的疗效和安全性。
系统检索了 PubMed、Embase 和 Cochrane Library 数据库，以确定截至 2023 年 5 月之前发表的相关研究。疗效结局包括 Aβ、神经影像学和生物标志物结局。安全性结局包括与水肿或渗出相关的淀粉样蛋白相关成像异常（ARIA-E）和伴有脑微出血、脑大血肿或脑表浅铁沉积的 ARIA（ARIA-H）。使用 Review Manager 5.4 软件评估数据。采用随机效应模型或固定效应模型分析和计算标准均数差（SMD）或比值比（OR）及其 95%置信区间（95%CI）。
共有 6 项随机对照试验（RCT）的 4471 名患者符合纳入标准，其中治疗组 2190 名，安慰剂组 2281 名。FDA 批准的抗-Aβ mab 在临床结局方面显示出统计学意义的改善，包括 CDR-SB（P=0.01）、ADCS-ADL-MCI（P=0.00003）、ADCOMS（P<0.00001）、ADAS-Cog（P<0.00001）。此外，FDA 批准的抗-Aβ mab 增加了脑脊液（CSF）中 Aβ1-42（P=0.002）和血浆 Aβ42/40 比值（P=0.0008）。它们还降低了 CSF P-Tau（P<0.00001）、CSF T-Tau（P<0.00001）和血浆 p-tau181（P<0.00001）。FDA 批准的抗-Aβ mab 在淀粉样蛋白正电子发射断层扫描标准化摄取值比（PET SUVr）方面显示出神经影像学变化（P<0.00001）。然而，与安慰剂相比，FDA 批准的抗-Aβ mab 发生 ARIA-E 的风险更高（P<0.00001）和 ARIA-H（P<0.0001）。
FDA 批准的抗-Aβ mab 可减缓 AD 患者的疾病进展，但副作用的发生概率增加。
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