Cai Wenting, Zhang Hui, Wu Yan, Yao Yao, Zhang Jinping
Department of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Front Aging Neurosci. 2025 Jan 29;16:1465871. doi: 10.3389/fnagi.2024.1465871. eCollection 2024.
The aim of this study was to compare the efficacy and safety of anti-tau protein monoclonal antibodies for Alzheimer's disease (AD). Tau protein aggregation, a key pathological feature of AD, is closely associated with neurodegeneration and cognitive decline. Targeting tau protein has emerged as a promising therapeutic strategy. By investigating the effects of monoclonal antibodies on cognitive function, disease progression, and overall quality of life in patients with AD, which can provide valuable insights into their potential as a therapeutic option for this devastating neurodegenerative disorder.
The randomized controlled trials (RCTs) investigating the efficacy of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in Alzheimer's disease (AD) were systematically searched across PubMed, Embase, Web of Science and Cochrane Library, up to May 2024. The control group included placebo. The efficacy indicators were change in the Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL) from baseline until the time of efficacy observation. Statistical analysis was conducted using Stata 14 and RevMan 5.4. The purpose of data processing, including generating network evidence plots, surface under the cumulative ranking curve (SUCRA) ranking, league plots, and funnel plots, is to visually summarize and evaluate the relative effectiveness and safety and potential publication bias of multiple interventions. Mean differences (MD) and 95% confidence interval (95%CI) as effect sizes to analyze continuous variables.
This study encompassed six RCTs involving 2,193 patients. Semorinemab were more effective than placebo in MMSE and ADAS-Cog scores (MDs ranging between 0.52 and 3.21; MDs ranging between 0.17 and 3.30). Placebo showed relatively good efficacy according to SUCRA ranking on change in CDR-SB and ADCS-ADL scores (75.7 and 79.5%). Tilavonemab and Semorinemab exhibited efficacy similar to that of a placebo in the analysis of the two indicators. Tilavonemab showed a lower incidence of AE, SAE, fall, and urinary tract infections than placebo, and the differences were statistically significant. Most safety analysis results showed no statistical difference.
The results indicated that anti-tau protein monoclonal antibodies, such as Semorinemab and Tilavonemab, showed promise in terms of efficacy and safety for managing AD. Further studies are needed to confirm these findings, assess long-term effects, and refine treatment protocols.
https://www.crd.york.ac.uk/prospero/#myprospero, CRD42024583388.
本研究旨在比较抗tau蛋白单克隆抗体治疗阿尔茨海默病（AD）的疗效和安全性。Tau蛋白聚集是AD的关键病理特征，与神经退行性变和认知功能下降密切相关。靶向tau蛋白已成为一种有前景的治疗策略。通过研究单克隆抗体对AD患者认知功能、疾病进展和总体生活质量的影响，可为其作为这种毁灭性神经退行性疾病的治疗选择的潜力提供有价值的见解。
截至2024年5月，在PubMed、Embase、Web of Science和Cochrane图书馆系统检索了研究戈苏瑞单抗、塞莫瑞单抗、替拉维单抗和扎戈替单抗治疗阿尔茨海默病（AD）疗效的随机对照试验（RCT）。对照组包括安慰剂。疗效指标为简易精神状态检查表（MMSE）、临床痴呆评定量表框和（CDR-SB）、阿尔茨海默病评估量表-认知部分（ADAS-Cog）、阿尔茨海默病协作研究-日常生活活动量表（ADCS-ADL）从基线到疗效观察时的变化。使用Stata 14和RevMan 5.4进行统计分析。数据处理的目的，包括生成网状证据图、累积排序曲线下面积（SUCRA）排序、联赛图和漏斗图，是直观地总结和评估多种干预措施的相对有效性、安全性和潜在的发表偏倚。采用平均差（MD）和95%置信区间（95%CI）作为效应量来分析连续变量。
本研究纳入了6项RCT，涉及2193例患者。塞莫瑞单抗在MMSE和ADAS-Cog评分方面比安慰剂更有效（MD范围在0.52至3.21之间；MD范围在0.17至3.30之间）。根据SUCRA对CDR-SB和ADCS-ADL评分变化的排序，安慰剂显示出相对较好的疗效（分别为75.7%和79.5%）。在对这两个指标的分析中，替拉维单抗和塞莫瑞单抗显示出与安慰剂相似的疗效。替拉维单抗的不良事件、严重不良事件、跌倒和尿路感染的发生率低于安慰剂，差异具有统计学意义。大多数安全性分析结果无统计学差异。
结果表明，塞莫瑞单抗和替拉维单抗等抗tau蛋白单克隆抗体在治疗AD的疗效和安全性方面显示出前景。需要进一步研究来证实这些发现，评估长期效果，并完善治疗方案。
https://www.crd.york.ac.uk/prospero/#myprospero，CRD42024583388。
