Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.
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DOI：
10.1056/nejmoa2100433
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发表时间：
2021-04-22
期刊：
影响因子：
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通讯作者：
Derde LPG
中科院分区：
文献类型：
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作者：
REMAP-CAP Investigators;Gordon AC;Mouncey PR;Al-Beidh F;Rowan KM;Nichol AD;Arabi YM;Annane D;Beane A;van Bentum-Puijk W;Berry LR;Bhimani Z;Bonten MJM;Bradbury CA;Brunkhorst FM;Buzgau A;Cheng AC;Detry MA;Duffy EJ;Estcourt LJ;Fitzgerald M;Goossens H;Haniffa R;Higgins AM;Hills TE;Horvat CM;Lamontagne F;Lawler PR;Leavis HL;Linstrum KM;Litton E;Lorenzi E;Marshall JC;Mayr FB;McAuley DF;McGlothlin A;McGuinness SP;McVerry BJ;Montgomery SK;Morpeth SC;Murthy S;Orr K;Parke RL;Parker JC;Patanwala AE;Pettilä V;Rademaker E;Santos MS;Saunders CT;Seymour CW;Shankar-Hari M;Sligl WI;Turgeon AF;Turner AM;van de Veerdonk FL;Zarychanski R;Green C;Lewis RJ;Angus DC;McArthur CJ;Berry S;Webb SA;Derde LPG
白细胞介素-6受体拮抗剂在2019冠状病毒病（Covid-19）重症患者中的疗效尚不清楚。我们在一项正在进行的国际、多因素、适应性平台试验中评估了托珠单抗和sar。在重症监护室（ICU）开始器官支持后24小时内，成年Covid-19患者被随机分配接受托珠单抗（8 mg/kg体重）、sar（400 mg）或标准治疗（对照）。主要结局是呼吸和心血管器官无支持天数，采用顺序量表，结合院内死亡（赋值为-1）和第21天无器官支持天数。本试验使用贝叶斯统计模型，预定义了优效性、有效性、等效性或无效性标准。比值比大于1表示生存率提高，无器官支持天数增加，或两者兼而有之。托珠单抗和sar均符合预定义的疗效标准。当时，353名患者被分配到tocilizumab组，48名患者分配到sar组，402名患者分配到对照组。托珠单抗组无器官支持天数的中位数为10（四分位数范围，-1至16），sar组为11（四分位数范围，0至16），对照组为0（四分位数范围，-1至15）。与对照组相比，托珠单抗和sar的中位校正累积比值比分别为1.64（95%可信区间，1.25 - 2.14）和1.76（95%可信区间，1.17 - 2.91），产生优于对照组的后验概率分别超过99.9%和99.5%。对90天生存期的分析显示，合并的白细胞介素-6受体拮抗剂组的生存率有所改善，与对照组相比的风险比为1.61（95%可信区间为1.25 - 2.08），优效性的后验概率超过99.9%。所有次要分析均支持这些白细胞介素-6受体拮抗剂的疗效。在ICU接受器官支持的新冠肺炎重症患者中，使用白细胞介素-6受体拮抗剂托珠单抗和sar治疗改善了包括生存率在内的结局。（REMAP-CAP ClinicalTrials.gov编号，NCT 02735707。）
The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support–free days, on an ordinal scale combining in-hospital death (assigned a value of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both. Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support–free days was 10 (interquartile range, −1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, −1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.)