John H Stone, et al.

Background: The efficacy of interleukin-6 receptor blockade in hospitalized patients with c oronavirus 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.).