Hao Ying, Dong Mingrui, Sun Yingtong, Duan Xiaohui, Niu Wenquan
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Department of Neurology, China-Japan Friendship Hospital, Beijing, China.
Front Neurol. 2023 Mar 15;14:1147757. doi: 10.3389/fneur.2023.1147757. eCollection 2023.
Currently, no consensus has been reached on the therapeutic implications of monoclonal antibodies against amyloid-beta (Aβ) in Alzheimer's disease (AD). This study aimed to examine the effectiveness and safety of monoclonal antibodies against Aβ as a whole and also to determine the superiority of individual antibodies placebo in mild or moderate AD.
Literature retrieval, article selection, and data abstraction were performed independently and in duplicate. Cognition and function were appraised by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Effect sizes are expressed as standardized mean difference (SMD) with a 95% confidence interval (CI).
Twenty-nine articles involving 108 drug-specific trials and 21,383 participants were eligible for synthesis. Of the four assessment scales, only CDR-SB was significantly reduced after using monoclonal antibodies against Aβ relative to placebo (SMD: -0.12; 95% CI: -0.2 to -0.03; = 0.008). Egger's tests indicated a low likelihood of publication bias. At individual levels, bapineuzumab was associated with a significant increase in MMSE (SMD: 0.588; 95% CI: 0.226-0.95) and DAD (SMD: 0.919; 95% CI: 0.105-1.943), and a significant decrease in CDR-SB (SMD: -0.15; 95% CI: -0.282-0.018). Bapineuzumab can increase the significant risk of serious adverse events (OR: 1.281; 95% CI: 1.075-1.525).
Our findings indicate that monoclonal antibodies against Aβ can effectively improve instrumental activities of daily life in mild or moderate AD. In particular, bapineuzumab can improve cognition and function, as well as activities of daily life, and meanwhile, it triggers serious adverse events.
目前，针对阿尔茨海默病（AD）中抗淀粉样β蛋白（Aβ）单克隆抗体的治疗意义尚未达成共识。本研究旨在全面检验抗Aβ单克隆抗体的有效性和安全性，并确定其在轻度或中度AD中相对于安慰剂的个体抗体优势。
独立且重复地进行文献检索、文章筛选和数据提取。通过简易精神状态检查表（MMSE）、阿尔茨海默病评估量表认知分量表（ADAS-Cog）、痴呆症残疾评估量表（DAD）和临床痴呆评定量表盒式总和（CDR-SB）评估认知和功能。效应量以标准化平均差（SMD）及95%置信区间（CI）表示。
29篇文章涉及108项药物特异性试验和21383名参与者，符合综合分析要求。在四个评估量表中，相对于安慰剂，使用抗Aβ单克隆抗体后仅CDR-SB显著降低（SMD：-0.12；95%CI：-0.2至-0.03；P = 0.008）。Egger检验表明发表偏倚可能性较低。在个体水平上，巴匹克隆单抗与MMSE显著增加（SMD：0.588；95%CI：0.226 - 0.95）和DAD显著增加（SMD：0.919；95%CI：0.105 - 1.943）以及CDR-SB显著降低（SMD：-0.15；95%CI：-0.282至-0.018）相关。巴匹克隆单抗可增加严重不良事件的显著风险（OR：1.281；95%CI：1.075 - 1.525）。
我们的研究结果表明，抗Aβ单克隆抗体可有效改善轻度或中度AD患者的日常生活工具性活动。特别是，巴匹克隆单抗可改善认知、功能以及日常生活活动，同时引发严重不良事件。
