英国帝国理工学院圣玛丽医院Anthony C. Gordon团队研究了白细胞介素-6受体拮抗剂治疗Covid-19危重患者的疗效。2021年2月25日，《新英格兰医学杂志》发表了该成果。

白细胞介素-6受体拮抗剂治疗Covid-19危重患者的疗效尚不清楚。

研究组在一个正在进行的国际性、多因素、适应性平台试验中评估了托珠单抗和萨瑞鲁单抗。在重症监护室（ICU）开始器官支持后24小时内，患有Covid-19的成年患者被随机分配接受托珠单抗、萨瑞鲁单抗或标准治疗（对照组）。主要结局是无呼吸和心血管器官支持的天数，依序量表结合住院死亡（赋值为-1）和第21天无器官支持的天数。

托珠单抗和萨瑞鲁单抗均符合预先确定的疗效标准。其中托珠单抗组有353名患者、萨瑞鲁单抗组有48名、对照组有402名。托珠单抗组中位无器官支持天数为10天，萨瑞鲁单抗组为11天，对照组为0天。

与对照组相比，托珠单抗组和萨瑞鲁单抗组的中位校正累积优势比分别为1.64和1.76，后验优势概率分别大于99.9%和99.5%。对90天存活率的分析显示，与对照组相比，联合使用白介素-6受体拮抗剂组的存活率提高，风险比为1.61，后验优势概率大于99.9%。所有二次分析均支持这些白细胞介素-6受体拮抗剂的疗效。

研究结果表明，对于在ICU接受器官支持的Covid-19危重患者，白介素-6受体拮抗剂托珠单抗和萨瑞鲁单抗的治疗显著改善了包括生存率在内的预后。

附：英文原文

Title: Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author: The REMAP-CAP Investigators

Issue&Volume: 2021-02-25

Abstract:

BACKGROUND

The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

DOI: 10.1056/NEJMoa2100433

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2100433