Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.
Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.
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DOI：
10.1056/nejmoa2030340
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发表时间：
2021-01-07
期刊：
影响因子：
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通讯作者：
Mohan SV
中科院分区：
文献类型：
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作者：
Salama C;Han J;Yau L;Reiss WG;Kramer B;Neidhart JD;Criner GJ;Kaplan-Lewis E;Baden R;Pandit L;Cameron ML;Garcia-Diaz J;Chávez V;Mekebeb-Reuter M;Lima de Menezes F;Shah R;González-Lara MF;Assman B;Freedman J;Mohan SV
2019冠状病毒病（Covid-19）肺炎通常与过度炎症有关。尽管Covid-19在服务不足和种族和少数民族人群中的发病率不成比例，但抗白细胞介素-6受体抗体tocilizumab在这些人群中因Covid-19肺炎住院的患者中的安全性和有效性尚不清楚。我们随机分配（以2:1的比例）未接受机械通气的Covid-19肺炎住院患者接受标准治疗加1或2剂tocilizumab（每公斤体重静脉注射8毫克）或安慰剂。地点选择的重点是纳入高风险和少数民族人口的地点。主要结局为机械通气或第28天死亡。共有389名患者接受了随机分组，修改后的意向治疗人群包括249名托珠单抗组患者和128名安慰剂组患者；56.0%为西班牙裔或拉丁裔，14.9%为黑人，12.7%为美洲印第安人或阿拉斯加原住民，12.7%为非西班牙裔白人，3.7%为其他或未知种族或族裔。tocilizumab组接受机械通气或在第28天死亡的患者的累积百分比为12.0%(95%可信区间[CI]， 8.5至16.9)，安慰剂组为19.3% (95% CI， 13.3至27.4)（机械通气或死亡的风险比为0.56;95% CI， 0.33至0.97；log-rank检验P=0.04）。在事件发生时间分析中评估的临床失败倾向于托珠单抗而不是安慰剂（风险比，0.55;95% CI， 0.33至0.93）。tocilizumab组中10.4%的患者和安慰剂组中8.6%的患者在第28天因任何原因死亡（加权差，2.0个百分点；95% CI, -5.2至7.8）。在安全人群中，tocilizumab组250例患者中有38例（15.2%）发生严重不良事件，安慰剂组127例患者中有25例（19.7%）发生严重不良事件。在未接受机械通气的住院Covid-19肺炎患者中，托珠单抗降低了进展为机械通气或死亡的复合结局的可能性，但没有提高生存率。没有发现新的安全信号。（由Genentech资助；EMPACTA ClinicalTrials.gov编号：NCT04372186。）
Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti–interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P=0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, –5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.)