巴西葡萄牙圣保罗慈善医院Viviane C Veiga团队研究了托珠单抗对严重或危重Covid-19患者15天临床转归的影响。2021年1月20日，该研究发表在《英国医学杂志》上。

为了确定托珠单抗能否改善严重或危重Covid-19患者的临床预后，2020年5月8日至7月17日，研究组在巴西的9家医院进行了一项随机开放试验。招募了129例接受补充氧气或机械通气，且至少有两种血清生物标志物（C反应蛋白、D二聚体、乳酸脱氢酶或铁蛋白）水平异常的covid-19确诊成人患者，其中65例接受托珠单抗联合标准治疗，64例仅接受标准治疗。主要结局为第15天用七级序贯量表测量的临床状况，作为死亡或机械通气的综合分析。

129名患者的平均年龄为57岁，68%为男性，所有患者均完成了随访。托珠单抗组的所有患者和标准治疗组的2例患者均接受了托珠单抗治疗。托珠单抗组中有18例患者（28%）在第15天时接受机械通气或死亡，标准护理组中有13例（20%），比值比为1.54。

托珠单抗组中有11例（17%）患者在15天时死亡，显著高于标准治疗组的2例（3%），比值比为6.42。在67例接受托珠单抗治疗的患者中，有29例（43%）出现不良事件；而在62例未接受托珠单抗治疗的患者中，有21例（34%）出现不良事件。

研究结果表明，对于重度或危重covid-19患者，采用托珠单抗联合标准治疗，在15天临床预后方面并不优于单独标准治疗，甚至有可能增加死亡率。

附：英文原文

Title: Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial

Author: Viviane C Veiga, Joo A G G Prats, Danielle L C Farias, Regis G Rosa, Leticia K Dourado, Fernando G Zampieri, Flávia R Machado, Renato D Lopes, Otavio Berwanger, Luciano C P Azevedo, álvaro Avezum, Thiago C Lisboa, Salomón S O Rojas, Juliana C Coelho, Rodrigo T Leite, Júlio C Carvalho, Luis E C Andrade, Alex F Sandes, Maria C T Pinto, Claudio G Castro, Sueli V Santos, Thiago M L de Almeida, André N Costa, Otávio C E Gebara, Flávio G Rezende de Freitas, Eduardo S Pacheco, David J B Machado, Josiane Martin, Fábio G Conceio, Suellen R R Siqueira, Lucas P Damiani, Luciana M Ishihara, Daniel Schneider, Denise de Souza, Alexandre B Cavalcanti, Phillip Scheinberg

Issue&Volume: 2021/01/20

Abstract:

Objective To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19).

Design Randomised, open label trial.

Setting Nine hospitals in Brazil, 8 May to 17 July 2020.

Participants Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group.

Interventions Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64).

Main outcome measure The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met.

Results A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab.

Conclusions In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality.

DOI: 10.1136/bmj.n84

Source: https://www.bmj.com/content/372/bmj.n84