三种抗β淀粉样蛋白药物对阿尔茨海默病患者临床、生物标志物、神经影像学结局和安全性指标的影响：系统评价和 II/III 期临床试验的荟萃分析。
Effects of three kinds of anti-amyloid-β drugs on clinical, biomarker, neuroimaging outcomes and safety indexes: A systematic review and meta-analysis of phase II/III clinical trials in Alzheimer's disease.
机构信息
Neurological Rehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
Neurological Rehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
出版信息
Ageing Res Rev. 2023 Jul;88:101959. doi: 10.1016/j.arr.2023.101959. Epub 2023 May 20.
OBJECTIVE
To investigate the effects of the three kinds of anti-amyloid-β (Aβ) drugs on cognitive and other functions, fluid and neuroimaging biomarkers, and safety on patients with Alzheimer's disease (AD), and rank the three kinds of anti-Aβ drugs.
METHODS
We searched Medline, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and AlzForum from inception to January 21, 2023 to include randomized controlled clinical trials. Random effects meta-analyses were performed.
RESULTS
Forty-one clinical trials (20929 participants, 9167 male) were included. Anti-Aβ drugs had significant but relatively low efficacy in preventing cognitive decline (ADAS-Cog SMD -0.07, 95% CI: -0.10 to -0.03, p < 0.001; CDR-SOB -0.05, -0.09 to -0.01, p = 0.017). Instrumental variable meta-analysis and trial sequential analysis confirmed the reliability of the pooled estimation. Beneficial effects were also observed by assessing other cognitive and activity of daily living scales and biomarkers, with acceptable safety of anti-Aβ drugs. Meta-regression demonstrated significant association between higher baseline mini-mental statement examination scores (MMSE) and better cognitive protective effects on cognitive function (ADAS-Cog β: -0.02, -0.05 to 0.00, p = 0.017) and clearance of pathological productions of anti-Aβ drugs. Network meta-analysis ranked the passive immunotherapy drugs to have the best cognitive efficacy, followed by active immunotherapy and small molecule drugs.
CONCLUSION
Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety. Patients with higher baseline MMSE scores benefit more from anti-Aβ drugs. Passive immunotherapy anti-Aβ drugs show relatively better efficacy than active immunotherapy and small molecule anti-Aβ drugs.
目的
探讨三种抗淀粉样β（Aβ）药物对阿尔茨海默病（AD）患者认知及其他功能、体液及神经影像学标志物的影响，并对三种抗 Aβ 药物进行排序。
方法
我们检索了 Medline、Embase、Cochrane 中央对照试验注册库、ClinicalTrials.gov 和 AlzForum，从建库到 2023 年 1 月 21 日，纳入随机对照临床试验。采用随机效应荟萃分析。
结果
共纳入 41 项临床试验（20929 名参与者，9167 名男性）。抗 Aβ 药物在预防认知衰退方面具有显著但相对较低的疗效（ADAS-Cog SMD -0.07，95%CI：-0.10 至 -0.03，p<0.001；CDR-SOB -0.05，-0.09 至 -0.01，p=0.017）。基于工具变量的荟萃分析和试验序贯分析证实了汇总估计的可靠性。通过评估其他认知和日常生活活动量表和生物标志物，也观察到了有益的效果，且抗 Aβ 药物具有可接受的安全性。元回归表明，较高的基线简易精神状态检查评分（MMSE）与认知功能的更好的认知保护作用相关（ADAS-Cog β：-0.02，-0.05 至 0.00，p=0.017），并与抗 Aβ 药物清除病理性产物有关。网络荟萃分析将被动免疫疗法药物的认知疗效排在首位，其次是主动免疫疗法和小分子药物。
结论
抗 Aβ 药物在预防认知衰退方面的疗效相对较低，且具有可接受的安全性，降低病理性产物。基线 MMSE 评分较高的患者从抗 Aβ 药物中获益更多。与主动免疫疗法和小分子抗 Aβ 药物相比，被动免疫疗法抗 Aβ 药物显示出相对更好的疗效。
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