美国贝勒医学院Ivan O. Rosas团队研究了托珠单抗治疗严重Covid-19肺炎住院患者的疗效。2021年2月25日，《新英格兰医学杂志》发表了该成果。

Covid-19与免疫失调和过度炎症有关，包括白细胞介素-6水平升高。在病例报告和回顾性观察队列研究中，使用托珠单抗（一种抗白细胞介素-6受体的单克隆抗体）治疗严重Covid-19肺炎患者取得了较好的疗效。数据来自随机、安慰剂对照试验。

在这项临床3期试验中，研究组招募患有严重Covid-19肺炎的住院患者，将其按2：1的比例随机分组，分别进行单次静脉输注托珠单抗或安慰剂治疗。两组中大约四分之一的受试者在第一次给药后8到24小时接受了第二次给药。主要结局是改良意向治疗人群在第28天的临床状态，按序号从1（出院或准备出院）到7（死亡）不等。

在452名接受随机分组的患者中，共有438名被纳入主要和次要分析，其中托珠单抗组294名，安慰剂组144名。在第28天，托珠单抗组依序量表的临床状态中位数为1.0，安慰剂组为2.0（无需补充氧气的非ICU住院治疗），组间差异显著。

在安全人群中，托珠单抗组295例患者中有103例（34.9%）发生严重不良事件，安慰剂组143例患者中有55例（38.5%）。托珠单抗组第28天的死亡率为19.7%，安慰剂组为19.4%，差异不显著。

研究结果表明，对于严重Covid-19肺炎住院患者，使用托珠单抗治疗，与安慰剂相比，在28天时并没有显著改善临床状况或降低死亡率。

附：英文原文

Title: Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia

Author: Ivan O. Rosas, M.D.,, Norbert Bru, M.D.,, Michael Waters, M.D.,, Ronaldo C. Go, M.D.,, Bradley D. Hunter, M.D.,, Sanjay Bhagani, M.D.,, Daniel Skiest, M.D.,, Mariam S. Aziz, M.D.,, Nichola Cooper, M.D.,, Ivor S. Douglas, M.D.,, Sinisa Savic, Ph.D.,, Taryn Youngstein, M.D.,, Lorenzo Del Sorbo, M.D.,, Antonio Cubillo Gracian, M.D.,, David J. De La Zerda, M.D.,, Andrew Ustianowski, Ph.D.,, Min Bao, M.D.,, Sophie Dimonaco, M.Sc.,, Emily Graham, Ph.D.,, Balpreet Matharu, M.D.,, Helen Spotswood, Ph.D.,, Larry Tsai, M.D.,, and Atul Malhotra, M.D.

Issue&Volume: 2021-02-25

Abstract:

BACKGROUND

Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS

In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo.

RESULTS

Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, 1.0; 95% CI, 2.5 to 0; P=0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, –7.6 to 8.2; nominal P=0.94).

CONCLUSIONS

In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days.

DOI: 10.1056/NEJMoa2028700

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2028700