Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.
Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.
复制标题
DOI：
10.1056/nejmoa2028700
复制
发表时间：
2021-04-22
期刊：
影响因子：
--
通讯作者：
Malhotra A
中科院分区：
文献类型：
--
作者：
Rosas IO;Bräu N;Waters M;Go RC;Hunter BD;Bhagani S;Skiest D;Aziz MS;Cooper N;Douglas IS;Savic S;Youngstein T;Del Sorbo L;Cubillo Gracian A;De La Zerda DJ;Ustianowski A;Bao M;Dimonaco S;Graham E;Matharu B;Spotswood H;Tsai L;Malhotra A
2019冠状病毒病（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tocilizumab（一种针对白细胞介素-6受体的单克隆抗体）治疗严重Covid-19肺炎患者的结果更好。需要随机、安慰剂对照试验的数据。在这项3期试验中，我们以2:1的比例随机分配因严重Covid-19肺炎住院的患者，接受单次静脉输注tocilizumab（剂量为每公斤体重8 mg）或安慰剂。大约四分之一的参与者在第一次剂量后8至24小时接受了第二剂量的tocilizumab或安慰剂。主要结局是第28天的临床状态，在修改意向治疗人群中按顺序量表从1（出院或准备出院）到7（死亡），其中包括所有接受过至少一剂tocilizumab或安慰剂的患者。在接受随机分组的452例患者中，438例（托珠单抗组294例，安慰剂组144例）被纳入初级和次级分析。第28天，托珠单抗组临床状态的中位数为1.0(95%可信区间[CI]， 1.0至1.0)，安慰剂组为2.0（非icu住院，无补充氧气）（95% CI， 1.0至4.0）（组间差异为- 1.0;95% CI, - 2.5至0；van Elteren检验P=0.31）。在安全人群中，tocilizumab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%）发生严重不良事件。托珠单抗组28天死亡率为19.7%，安慰剂组为19.4%(加权差0.3个百分点（95% CI, -7.6至8.2；名义P=0.94）。在这项涉及重症Covid-19肺炎住院患者的随机试验中，使用tocilizumab并没有显著改善临床状态或降低28天的死亡率。（由F. Hoffmann-La Roche和美国卫生与公众服务部资助；COVACTA ClinicalTrials.gov编号：NCT04320615。）
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. 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. 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). 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. (Funded by F. Hoffmann–La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.)