美国基因泰克公司Shalini V. Mohan团队研究了托珠单抗治疗Covid-19肺炎住院患者的疗效。2020年12月17日，该研究发表在《新英格兰医学杂志》上。

Covid-19肺炎通常与过度炎症相关。尽管在医疗服务不足的人群和少数族裔人群中Covid-19的发病率不成比例，但尚不清楚抗白介素6受体抗体托珠单抗治疗Covid-19肺炎住院患者的安全性和有效性。

研究组共招募了389例少数族裔高危Covid-19住院患者，未接受机械通气，将其按2：1随机分配，在常规治疗的基础上，249例接受托珠单抗治疗，128例接受安慰剂治疗。主要结局是第28天出现机械通气或死亡。

参与者中西班牙裔或拉丁美洲裔占56.0％，黑人占14.9％，美洲印第安人或阿拉斯加原住民占12.7％，非西班牙裔白人占12.7％，其他或未知族裔占3.7％。托珠单抗组第28天接受机械通气或死亡患者的累计百分比为12.0%，显著低于安慰剂组（19.3%）。

在事件分析评估中托珠单抗的临床失败率显著低于安慰剂。托珠单抗组第28天的全因死亡率为10.4％，安慰剂组为8.6％。托珠单抗组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％）。

总之，在未接受机械通气的住院Covid-19肺炎患者中，托珠单抗降低了机械通气或死亡的综合风险，但并未提高生存率，未发生新的安全事件。

附：英文原文

Title: Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia

Author: Carlos Salama, M.D.,, Jian Han, Ph.D.,, Linda Yau, Ph.D.,, William G. Reiss, Pharm.D.,, Benjamin Kramer, M.D.,, Jeffrey D. Neidhart, M.D.,, Gerard J. Criner, M.D.,, Emma Kaplan-Lewis, M.D.,, Rachel Baden, M.D.,, Lavannya Pandit, M.D.,, Miriam L. Cameron, M.D.,, Julia Garcia-Diaz, M.D.,, Victoria Chávez, M.D.,, Martha Mekebeb-Reuter, M.D.,, Ferdinando Lima de Menezes, M.D.,, Reena Shah, F.R.C.P.,, Maria F. González-Lara, M.D.,, Beverly Assman, M.S.,, Jamie Freedman, M.D., Ph.D.,, and Shalini V. Mohan, M.D.

Issue&Volume: 2020-12-17

Abstract:

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

DOI: 10.1056/NEJMoa2030340

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2030340