美国马萨诸塞州总医院John H. Stone团队研究了Tocilizumab治疗中症Covid-19住院患者的效果。2020年10月21日，该研究发表在《新英格兰医学杂志》上。

白细胞介素6受体阻滞剂治疗未接受机械通气的Covid-19住院患者的疗效尚不清楚。

研究组进行了一项随机、双盲、安慰剂对照试验，招募确诊为SARS-CoV-2感染、处于发炎状态，且至少有以下两种体征的患者：发烧（体温> 38 °C），肺部浸润；或需要补充氧气以维持血氧饱和度大于92％。将患者按2：1随机分组，分别接受标准治疗联合tocilizumab，或安慰剂治疗。

研究组共招募了243名患者，其中男性占58％，女性占42％。中位年龄为59.8岁，其中45％的患者为西班牙裔或拉丁裔。与安慰剂组相比，tocilizumab组插管或死亡的风险比为0.83，疾病恶化的风险比为1.11，差异均不显著。

在第14天，tocilizumab组中有18.0％的患者病情恶化，安慰剂组有14.9％。tocilizumab组停止供氧的中位时间为5.0天，安慰剂组为4.9天。第14天，tocilizumab组中有24.6％的患者仍在补充氧气，安慰剂组中有21.2％。Tocilizumab组患者的严重感染发生率显著低于安慰剂组。

总之，对于中症住院Covid-19患者，采用Tocilizumab治疗并不能有效预防插管或死亡。

附：英文原文

Title: Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

Author: John H. Stone, M.D., M.P.H.,, Matthew J. Frigault, M.D.,, Naomi J. Serling-Boyd, M.D.,, Ana D. Fernandes, M.A.,, Liam Harvey, B.S.,, Andrea S. Foulkes, Ph.D.,, Nora K. Horick, M.S.,, Brian C. Healy, Ph.D.,, Ruta Shah, M.D.,, Ana Maria Bensaci, M.D.,, Ann E. Woolley, M.D.,, Sarah Nikiforow, M.D., Ph.D.,, Nina Lin, M.D.,, Manish Sagar, M.D.,, Harry Schrager, M.D.,, David S. Huckins, M.D.,, Matthew Axelrod, M.D.,, Michael D. Pincus, D.O.,, Jorge Fleisher, M.D.,, Chana A. Sacks, M.D., M.P.H.,, Michael Dougan, M.D., Ph.D.,, Crystal M. North, M.D., M.P.H.,, Yuan-Di Halvorsen, Ph.D.,, Tara K. Thurber, B.S.,, Zeina Dagher, Ph.D.,, Allison Scherer, Ph.D.,, Rachel S. Wallwork, M.D.,, Arthur Y. Kim, M.D.,, Sara Schoenfeld, M.D.,, Pritha Sen, M.D.,, Tomas G. Neilan, M.D., M.P.H.,, Cory A. Perugino, D.O.,, Sebastian H. Unizony, M.D.,, Deborah S. Collier, M.D.,, Mark A. Matza, M.D.,, Janeth M. Yinh, M.D.,, Kathryn A. Bowman, M.D.,, Eric Meyerowitz, M.D.,, Amna Zafar, M.D.,, Zsofia D. Drobni, M.D.,, Marcy B. Bolster, M.D.,, Minna Kohler, M.D.,, Kristin M. D’Silva, M.D.,, Jonathan Dau, M.D.,, Megan M. Lockwood, M.D.,, Caroline Cubbinson, M.D.,, Brittany N. Weber, M.D., Ph.D.,, and Michael K. Mansour, M.D., Ph.D.

Issue&Volume: 2020-10-21

Abstract:

BACKGROUND

The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.

METHODS

We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses.

RESULTS

We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P=0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P=0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P=0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo.

CONCLUSIONS

Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide.

DOI: 10.1056/NEJMoa2028836

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2028836