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N Engl J Med
. 2020 Oct 21.
doi: 10.1056/NEJMoa2028836. Online ahead of print.
Efficacy of Tocilizumab in Patients Hospitalized with Covid-19
John H Stone 1 , Matthew J Frigault 1 , Naomi J Serling-Boyd 1 , Ana D Fernandes 1 , Liam Harvey 1 , Andrea S Foulkes 1 , Nora K Horick 1 , Brian C Healy 1 , Ruta Shah 1 , Ana Maria Bensaci 1 , Ann E Woolley 1 , Sarah Nikiforow 1 , Nina Lin 1 , Manish Sagar 1 , Harry Schrager 1 , David S Huckins 1 , Matthew Axelrod 1 , Michael D Pincus 1 , Jorge Fleisher 1 , Chana A Sacks 1 , Michael Dougan 1 , Crystal M North 1 , Yuan-Di Halvorsen 1 , Tara K Thurber 1 , Zeina Dagher 1 , Allison Scherer 1 , Rachel S Wallwork 1 , Arthur Y Kim 1 , Sara Schoenfeld 1 , Pritha Sen 1 , Tomas G Neilan 1 , Cory A Perugino 1 , Sebastian H Unizony 1 , Deborah S Collier 1 , Mark A Matza 1 , Janeth M Yinh 1 , Kathryn A Bowman 1 , Eric Meyerowitz 1 , Amna Zafar 1 , Zsofia D Drobni 1 , Marcy B Bolster 1 , Minna Kohler 1 , Kristin M D'Silva 1 , Jonathan Dau 1 , Megan M Lockwood 1 , Caroline Cubbinson 1 , Brittany N Weber 1 , Michael K Mansour 1 , BACC Bay Tocilizumab Trial Investigators
Affiliations
- PMID: 33085857
- DOI: 10.1056/NEJMoa2028836
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.).