Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

Type Journal Article Author John H. Stone Author Matthew J. Frigault Author Naomi J. Serling-Boyd Author Ana D. Fernandes Author Liam Harvey Author Andrea S. Foulkes Author Nora K. Horick Author Brian C. Healy Author Ruta Shah Author Ana Maria Bensaci Author Ann E. Woolley Author Sarah Nikiforow Author Nina Lin Author Manish Sagar Author Harry Schrager Author David S. Huckins Author Matthew Axelrod Author Michael D. Pincus Author Jorge Fleisher Author Chana A. Sacks Author Michael Dougan Author Crystal M. North Author Yuan-Di Halvorsen Author Tara K. Thurber Author Zeina Dagher Author Allison Scherer Author Rachel S. Wallwork Author Arthur Y. Kim Author Sara Schoenfeld Author Pritha Sen Author Tomas G. Neilan Author Cory A. Perugino Author Sebastian H. Unizony Author Deborah S. Collier Author Mark A. Matza Author Janeth M. Yinh Author Kathryn A. Bowman Author Eric Meyerowitz Author Amna Zafar Author Zsofia D. Drobni Author Marcy B. Bolster Author Minna Kohler Author Kristin M. D’Silva Author Jonathan Dau Author Megan M. Lockwood Author Caroline Cubbison Author Brittany N. Weber Author Michael K. Mansour URL https://www.nejm.org/doi/10.1056/NEJMoa2028836 Rights Copyright © 2020 Massachusetts Medical Society. All rights reserved. Publication New England Journal of Medicine Date 21/10/2020 Loc. in Archive world Extra Publisher: Massachusetts Medical Society DOI 10.1056/NEJMoa2028836 Library Catalog www.nejm.org Language en 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. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937. opens in new tab.)