托珠单抗
医学
阿纳基纳
内科学
荟萃分析
回顾性队列研究
疾病
作者
Fasihul Khan,Iain Stewart,Laura Fabbri,Samuel Moss,Karen A. Robinson,Alan R Smyth,Gisli Jenkins
出处
期刊:Thorax
[BMJ]
日期:2021-02-12
卷期号:76 (9): 907-919
被引量:115
标识
DOI:10.1136/thoraxjnl-2020-215266
摘要
Background There is accumulating evidence for an overly activated immune response in severe COVID-19, with several studies exploring the therapeutic role of immunomodulation. Through systematic review and meta-analysis, we assess the effectiveness of specific interleukin inhibitors for the treatment of COVID-19. Methods Electronic databases were searched on 7 January 2021 to identify studies of immunomodulatory agents (anakinra, sarilumab, siltuximab and tocilizumab) for the treatment of COVID-19. The primary outcomes were severity on an Ordinal Scale measured at day 15 from intervention and days to hospital discharge. Key secondary endpoints included overall mortality. Results 71 studies totalling 22 058 patients were included, 6 were randomised trials. Most studies explored outcomes in patients who received tocilizumab (60/71). In prospective studies, tocilizumab was associated with improved unadjusted survival (risk ratio 0.83, 95% CI 0.72 to 0.96, I 2 =0.0%), but conclusive benefit was not demonstrated for other outcomes. In retrospective studies, tocilizumab was associated with less severe outcomes on an Ordinal Scale (generalised OR 1.34, 95% CI 1.10 to 1.64, I 2 =98%) and adjusted mortality risk (HR 0.52, 95% CI 0.41 to 0.66, I 2 =76.6%). The mean difference in duration of hospitalisation was 0.36 days (95% CI −0.07 to 0.80, I 2 =93.8%). There was substantial heterogeneity in retrospective studies, and estimates should be interpreted cautiously. Other immunomodulatory agents showed similar effects to tocilizumab, but insufficient data precluded meta-analysis by agent. Conclusion Tocilizumab was associated with a lower relative risk of mortality in prospective studies, but effects were inconclusive for other outcomes. Current evidence for the efficacy of anakinra, siltuximab or sarilumab in COVID-19 is insufficient, with further studies urgently needed for conclusive findings. PROSPERO registration number CRD42020176375.
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