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