A systematic review of the efficacy and safety of anti-amyloid beta monoclonal antibodies in treatment of Alzheimer’s disease

Alzheimer’s disease can cause dementia through brain matter degradation. This study investigates the monoclonal antibody usage for AD treatment, following PRISMA 2020 guidelines, and aims to discern the monoclonal antibody that offers the optimal balance of efficacy and safety for individuals with AD. A systematic search was conducted across databases such as PubMed, Cochrane Library, and clinical trial registries for randomized controlled trials. The quality of studies was assessed using the Cochrane risk of bias 2 tool. Cognitive function and daily activities were evaluated using MMSE, ADAS-Cog, and CDR-SB test data. According to CDR-SB measurements, lecanemab showed effectiveness in reducing brain amyloid and cognitive decline, with a change from baseline of 1.21. Aducanumab resulted in a decrease of −0.39 (−22%). Bapineuzumab showed no significant benefit, with scores of 2.4 (2.8). Gantenerumab, scoring 1.69 (1.37, 2.01), reduces amyloid, particularly in early Alzheimer’s stages. Crenezumab was ineffective, with a score of 3.61. The findings provide various perspectives. Lecanemab showed the most promise in brain amyloid reduction and decelerating cognitive decline compared to the other therapies. Further research is needed, highlighting the necessity of AD therapeutic research to alter AD’s trajectory and provide reliable treatment. www.crd.york.ac.uk/prospero identifier is CRD42024504358 This study investigates the safety and efficacy of treating Alzheimer’s disease (AD) with monoclonal antibodies. In order to determine which antibody could be most helpful, we looked over a number of trials. Several antibodies, such as lecanemab, solanezumab, aducanumab, bapineuzumab, gantenerumab, and crenezumab, were the subject of the study. According to our research, lecanemab is particularly effective at lowering brain amyloid plaques and delaying cognitive deterioration, two major problems associated with Alzheimer’s disease. Other antibodies, such as solanezumab and bapineuzumab, had little to no beneficial effects, making their benefits less evident. The contradictory results of aducanumab indicate that further research is necessary to ascertain its actual efficacy. When administered at the earliest stages of Alzheimer’s disease or when used at a higher dose, crenezumab may be beneficial. Even though lecanemab seems promising, research in this field is still in its infancy. To validate these results and get further insight into the potential applications of these medicines in the management of Alzheimer’s disease, additional research is required. In summary, this study emphasizes the necessity of ongoing research to discover trustworthy treatments for AD patients.

阿尔茨海默病（Alzheimer’s disease, AD）可通过脑物质退化引发痴呆。本研究遵循PRISMA 2020声明指南，探讨单克隆抗体（monoclonal antibody）用于阿尔茨海默病治疗的相关情况，旨在明确可在疗效与安全性间实现最优平衡的阿尔茨海默病治疗用单克隆抗体。研究通过PubMed、考克兰图书馆（Cochrane Library）及临床试验注册库等数据库开展系统检索，纳入随机对照试验（randomized controlled trial, RCT）；采用考克兰偏倚风险2工具（Cochrane risk of bias 2 tool）评估研究质量；以简易精神状态检查表（Mini-Mental State Examination, MMSE）、阿尔茨海默病评估量表-认知子量表（Alzheimer’s Disease Assessment Scale-Cognitive Subscale, ADAS-Cog）及临床痴呆评定量表-总得分（Clinical Dementia Rating Scale-Sum of Boxes, CDR-SB）的相关数据评估认知功能与日常活动能力。基于CDR-SB检测结果，仑卡奈单抗（lecanemab）可有效减少脑淀粉样蛋白沉积并延缓认知衰退，较基线变化值为1.21；阿杜卡玛单抗（aducanumab）可使指标降低-0.39（降幅22%）；巴匹珠单抗（bapineuzumab）未显示显著获益，相关评分为2.4（2.8）；甘特奈单抗（gantenerumab）评分达1.69（95%置信区间1.37, 2.01），可减少淀粉样蛋白沉积，尤其在阿尔茨海默病早期阶段；克瑞奈单抗（crenezumab）未显示有效性，评分为3.61。本研究结果提供了多维度视角。相较于其他治疗手段，仑卡奈单抗在减少脑淀粉样蛋白沉积、延缓认知衰退方面展现出最大潜力。目前仍需开展进一步研究，凸显了阿尔茨海默病治疗研究对于改变疾病进程、提供可靠治疗方案的必要性。本研究的PROSPERO注册标识符为CRD42024504358，注册网址为www.crd.york.ac.uk/prospero。本研究旨在调查单克隆抗体治疗阿尔茨海默病的安全性与有效性，为此回顾了多项临床试验，纳入的抗体包括仑卡奈单抗（lecanemab）、索拉珠单抗（solanezumab）、阿杜卡玛单抗（aducanumab）、巴匹珠单抗（bapineuzumab）、甘特奈单抗（gantenerumab）及克瑞奈单抗（crenezumab）。研究结果显示，仑卡奈单抗可有效降低脑淀粉样斑块沉积并延缓认知衰退，这正是阿尔茨海默病的两大核心问题。索拉珠单抗与巴匹珠单抗仅展现出微弱甚至无获益，其临床获益尚不明确。阿杜卡玛单抗的研究结果存在矛盾，仍需进一步研究以明确其真实疗效。克瑞奈单抗在阿尔茨海默病最早期阶段或采用高剂量给药时，或可产生临床获益。尽管仑卡奈单抗展现出良好的应用前景，但该领域的研究仍处于起步阶段。目前仍需开展更多研究以验证本研究结果，并深入阐明上述药物在阿尔茨海默病管理中的潜在应用价值。总而言之，本研究强调了持续开展研究以探索阿尔茨海默病可靠治疗方案的必要性。