Efficacy of Tocilizumab in Patients Hospitalized with Covid-19

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

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.)