Janus激酶抑制剂用于COVID-19患者的疗效和安全性：一项动态系统评价和荟萃分析
The Efficacy and Safety of Janus Kinase Inhibitors for Patients With COVID-19: A Living Systematic Review and Meta-Analysis.
作者信息
Zhang Xueyang, Shang Lianhan, Fan Guohui, Gu Xiaoying, Xu Jiuyang, Wang Yeming, Huang Lixue, Cao Bin
机构信息
School of Medicine, Tsinghua University, Beijing, China.
Beijing University of Chinese Medicine, Beijing, China.
出版信息
Front Med (Lausanne). 2022 Jan 27;8:800492. doi: 10.3389/fmed.2021.800492. eCollection 2021.
BACKGROUND
Cytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19.
METHODS
Databases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR).
RESULTS
Of 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis ( = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51-0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41-0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42-0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49-0.78) with no increase in the risk of adverse events.
CONCLUSION
Baricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.
背景
在重症2019冠状病毒病（COVID-19）患者中观察到的细胞因子风暴会导致临床预后不良和死亡率增加。 Janus激酶（JAKs）是细胞因子风暴中的重要介质。因此，我们对研究JAK抑制剂治疗COVID-19患者的疗效和安全性的文献进行了一项实时系统评价和荟萃分析。
方法
检索截至2021年12月1日的数据库，查找比较JAK抑制剂治疗与COVID-19患者同期对照的干预性和观察性研究。通过合并风险比（RR）评估疗效和安全性结果。
结果
在检索到的3170条记录中，15项研究符合纳入标准，13项研究纳入荟萃分析（n = 3977）。基于三项随机对照试验（RCT）的数据，巴瑞替尼治疗可显著降低COVID-19住院患者第28天的死亡率（RR = 0.64，95%CI 0.51-0.80），且不增加不良事件的发生率。在亚组分析中，基线时需要补充氧气（RR = 0.62，95%CI 0.41-0.95）或高流量氧气/无创通气（RR = 0.59，95%CI 0.42-0.85）的患者获益最大。对所有符合条件的JAK抑制剂（巴瑞替尼、鲁索替尼、托法替布和奈祖利替尼）研究的汇总分析显示，死亡率显著降低（RR = 0.62，95%CI 0.49-0.78），不良事件风险未增加。
结论
巴瑞替尼可能降低COVID-19住院成年患者的死亡率，尤其是基线时需要补充氧气或高流量氧气/无创通气的患者。其他JAK抑制剂，如鲁索替尼、托法替布和奈祖利替尼的疗效和安全性有待更多证据。
系统评价注册
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414，标识符：CRD42021261414 。
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