託珠單抗治療Covid-19肺炎住院患者療效分析
作者：
小柯機器人發布時間：2020/12/22 21:49:42
美國基因泰克公司Shalini V. Mohan團隊研究了託珠單抗治療Covid-19肺炎住院患者的療效。2020年12月17日，該研究發表在《新英格蘭醫學雜誌》上。
Covid-19肺炎通常與過度炎症相關。儘管在醫療服務不足的人群和少數族裔人群中Covid-19的發病率不成比例，但尚不清楚抗白介素6受體抗體託珠單抗治療Covid-19肺炎住院患者的安全性和有效性。
研究組共招募了389例少數族裔高危Covid-19住院患者，未接受機械通氣，將其按2：1隨機分配，在常規治療的基礎上，249例接受託珠單抗治療，128例接受安慰劑治療。主要結局是第28天出現機械通氣或死亡。
參與者中西班牙裔或拉丁美洲裔佔56.0％，黑人佔14.9％，美洲印第安人或阿拉斯加原住民佔12.7％，非西班牙裔白人佔12.7％，其他或未知族裔佔3.7％。託珠單抗組第28天接受機械通氣或死亡患者的累計百分比為12.0%，顯著低於安慰劑組（19.3%）。
在事件分析評估中託珠單抗的臨床失敗率顯著低於安慰劑。託珠單抗組第28天的全因死亡率為10.4％，安慰劑組為8.6％。託珠單抗組250例患者中有38例（15.2％）發生嚴重不良事件，安慰劑組127例患者中有25例（19.7％）。
總之，在未接受機械通氣的住院Covid-19肺炎患者中，託珠單抗降低了機械通氣或死亡的綜合風險，但並未提高生存率，未發生新的安全事件。
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