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托珠单抗对COVID-19住院患者的疗效
Efficacy of Tocilizumab in Patients Hospitalized with Covid-19


John H. Stone ... 呼吸系统疾病 • 2020.12.10
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托珠单抗在COVID-19患者治疗中的作用

 

赵璇,张毅*

郑州大学第一附属医院肿瘤中心/生物治疗中心;河南省肿瘤免疫和生物治疗重点实验室

*通讯作者

 

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的新型冠状病毒肺炎,在全球范围内广泛传播,严重影响了人类健康和生活。随着确诊病例的不断增长,越来越多的研究表明细胞因子释放综合征(CRS)是重症COVID-19患者不良预后的重要特征,特别是血清白介素6(IL-6)在此过程中起到关键的作用1。病毒感染并活化单核细胞、巨噬细胞和树突状细胞,使其释放IL-6及其他炎症性细胞因子,IL-6通过JAK和STAT3信号通路介导了体内免疫细胞、内皮细胞等产生多重效应,促进CRS的发生2

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摘要


背景

白介素-6受体阻滞剂对未接受机械通气治疗的2019冠状病毒病(COVID-19)住院患者的疗效尚未明确。

 

方法

我们在有以下体征中的至少两项,并且处于高炎症状态的SARS-CoV-2感染患者中开展了一项随机、双盲、安慰剂对照试验:发热(体温>38℃)、肺浸润或者需要辅助供氧才能将氧饱和度保持在>92%。我们以2∶1的比例将患者随机分组,两组分别接受标准治疗+单剂托珠单抗(每千克体重8 mg)治疗或者标准治疗+安慰剂治疗。主要结局是插管或死亡(在至事件发生的时间分析中进行评估)。次要疗效结局是病情恶化以及基线时接受辅助供氧的患者停止辅助供氧(两项均在至事件发生的时间分析进行评估)。

 

结果

我们纳入了243例患者;141例(58%)为男性,102例(42%)为女性。中位年龄为59.8岁(范围,21.7~85.4),45%的患者为西班牙语裔或拉丁裔。与安慰剂组相比,托珠单抗组插管或死亡的风险比为0.83(95%置信区间[CI],0.38~1.81;P=0.64),病情恶化的风险比为1.11(95% CI,0.59~2.10;P=0.73)。14日时,托珠单抗组18.0%患者和安慰剂组14.9%患者的病情恶化。托珠单抗组和安慰剂组至停止辅助供氧的中位时间分别为5.0日(95% CI,3.8~7.6)和4.9日(95% CI,3.8~7.8)(P=0.69)。14日时,托珠单抗组24.6%的患者和安慰剂组21.2%的患者仍在接受辅助供氧。托珠单抗组发生的严重感染少于安慰剂组。

 

结论

托珠单抗未能有效避免中度COVID-19住院患者插管或死亡。但本试验不能排除托珠单抗有一些益处或害处,因为疗效比较中的置信区间较宽(由基因泰克资助,在ClinicalTrials.gov注册号为NCT04356937)。





作者信息

John H. Stone, M.D., M.P.H., Matthew J. Frigault, M.D., Naomi J. Serling-Boyd, M.D., Ana D. Fernandes, M.A., Liam Harvey, B.S., Andrea S. Foulkes, Ph.D., Nora K. Horick, M.S., Brian C. Healy, Ph.D., Ruta Shah, M.D., Ana Maria Bensaci, M.D., Ann E. Woolley, M.D., Sarah Nikiforow, M.D., Ph.D., Nina Lin, M.D., Manish Sagar, M.D., Harry Schrager, M.D., David S. Huckins, M.D., Matthew Axelrod, M.D., Michael D. Pincus, D.O., Jorge Fleisher, M.D., Chana A. Sacks, M.D., M.P.H., Michael Dougan, M.D., Ph.D., Crystal M. North, M.D., M.P.H., Yuan-Di Halvorsen, Ph.D., Tara K. Thurber, B.S., Zeina Dagher, Ph.D., Allison Scherer, Ph.D., Rachel S. Wallwork, M.D., Arthur Y. Kim, M.D., Sara Schoenfeld, M.D., Pritha Sen, M.D., Tomas G. Neilan, M.D., M.P.H., Cory A. Perugino, D.O., Sebastian H. Unizony, M.D., Deborah S. Collier, M.D., Mark A. Matza, M.D., Janeth M. Yinh, M.D., Kathryn A. Bowman, M.D., Eric Meyerowitz, M.D., Amna Zafar, M.D., Zsofia D. Drobni, M.D., Marcy B. Bolster, M.D., Minna Kohler, M.D., Kristin M. D’Silva, M.D., Jonathan Dau, M.D., Megan M. Lockwood, M.D., Caroline Cubbison, M.D., Brittany N. Weber, M.D., Ph.D., and Michael K. Mansour, M.D., Ph.D. for the BACC Bay Tocilizumab Trial Investigators*
From Massachusetts General Hospital (J.H.S., M.J.F., N.J.S.-B., A.D.F., L.H., A.S.F., N.K.H., B.C.H., C.A.S., M.D., C.M.N., Y.-D.H., T.K.T., Z.D., A.S., R.S.W., A.Y.K., S.S., P.S., T.G.N., C.A.P., S.H.U., D.S.C., M.A.M., J.M.Y., K.A.B., E.M., A.Z., Z.D.D., M.B.B., M.K., K.M.D., J.D., M.M.L., M.K.M.), Brigham and Women’s Hospital (A.E.W., S.N., B.N.W.), and Boston Medical Center (N.L., M.S.), Boston, North Shore Medical Center, Salem (R.S., A.M.B., C.C.), Newton–Wellesley Hospital, Newton (H.S., D.S.H.), Beth Israel Lahey Health, Burlington (M.A., M.D.P.), and St. Elizabeth’s Medical Center, Brighton (J.F.) — all in Massachusetts. Address reprint requests to Dr. Stone at the Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, 55 Fruit St., Boston, MA 02114, or at jhstone@mgh.harvard.edu. *A complete list of the BACC Bay Tocilizumab Trial investigators and members of the data and safety monitoring board is provided in the Supplementary Appendix, available at NEJM.org.

 

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