Effectiveness and safety of anti‐tau drugs for Alzheimer's disease: Systematic review and meta‐analysis

医学 荟萃分析 随机对照试验 子群分析 安慰剂 科克伦图书馆 不利影响 出版偏见 梅德林 临床试验 内科学 相对风险 置信区间 替代医学 病理 政治学 法学
作者
Xiaoyan Zheng,Yuyuan Tang,Qinghui Yang,Shuting Wang,Rouhao Chen,Chen-Yang Tao,Peiming Zhang,Baochao Fan,Jie Zhan,Chunzhi Tang,Liming Lu
出处
期刊:Journal of the American Geriatrics Society [Wiley]
卷期号:70 (11): 3281-3292 被引量:7
标识
DOI:10.1111/jgs.18025
摘要

Abstract Objective To assess the cognitive effectiveness and safety of tau‐targeting drugs for Alzheimer's disease ( AD ) Methods The MEDLINE , Embase, Cochrane Library, PsycINFO , ClinicalTrials.gov , and WHO International Clinical Trials Registry Platform databases were searched from inception to 22 November 2021. A systematic review and meta‐analysis of randomized controlled trials were performed Results Thirty‐four randomized controlled trials comprising 5549 participants, of which fifteen (51.7%) had a low risk of bias, were included. The meta‐analysis showed no differences in the cognitive subscale of the AD: Assessment Scale (ADAS‐Cog) between anti‐tau drugs and placebo (mean difference [MD]: −0.77, 95% CI: −1.64 to 0.10; minimal important difference 3.1–3.8 points, moderate certainty evidence). For ADAS‐Cog, the results subgroup analysis suggested a statistical effect of tau posttranslational modifications on drug inhibition (MD: −0.80, 95% CI: −1.43 to −0.17), which was not seen with tau aggregation inhibitors or immunotherapy (interaction p = 0.24). A total of 11.0%, 5.2%, and 4.8% of drugs inhibiting tau aggregation, immunotherapy, and drugs targeting posttranslational modifications, respectively, had a reduced risk of dropouts due to adverse events (AEs). Discussion Current evidence suggests that anti‐tau drugs are unlikely to have an important impact on slowing cognitive impairment. Although the subgroup analysis suggested that inhibition of tau posttranslational modifications is statistically effective and generally safer because of reduced dropouts due to AEs, the analysis has limited credibility. Additional large‐scale and well‐designed randomized and placebo‐controlled trials will be necessary to explore the benefit of a certain type of anti‐tau drug for AD .
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