ABSTRACT
Background: Accumulating evidence points to an overactive immune response in Covid-19 disease and potential clinical benefit of the interleukin-6 inhibitor tocilizumab. We assessed the efficacy of early tocilizumab treatment for hospitalized patients in a randomized phase II study.Methods: Patients admitted to the general ward with proven Covid-19 and in need of supplemental oxygen were randomly assigned to receive standard of care with or without intravenous tocilizumab 8 mg/kg (maximal 800 mg). A second dose of tocilizumab was permitted if hypoxia persisted after 8 hrs. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α=0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days.Findings: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR)=0.62 (90% CI 0.39-0.98; p=0.086). 21% of patients were admitted to the ICU in each arm (p=0.89). The median stay in the ICU was 16 days (IQR 8-30) in the standard arm versus 9 days (IQR 5-16) in the tocilizumab arm (p=0.025). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p=0.042).Interpretation: Various studies have suggested a beneficial effect of tocilizumab in the treatment of COVID-19. This randomized phase II study, which met its primary endpoint, confirms these observations and demonstrates a clinically meaningful efficacy when given early in the disease course in hospitalized patients who need oxygen support, even when concomitantly treated with dexamethasone.Trial Registration: The trial was designed as a prospective randomized (1:1) open label phase II trial and was registered in the Netherlands Trial register (https://www.trialregister.nl/trial/8504).Funding Statement: Academic study, funded by participating hospitals. Roche supplied tocilizumab.Declaration of Interests: None to declare. Ethics Approval Statement: The trial was approved by the relevant medical ethical committee and was performed in accordance with Good Clinical Practice guidelines and the Helsinki Declaration.