Early Use of Sarilumab in Patients Hospitalised with COVID-19 Pneumonia and Features of Systemic Inflammation.

Abstract

In this phase II, open-label, randomized, controlled clinical trial of 115 patients hospitalized with COVID-19 and systemic inflammation, early use of sarilumab was associated with a low risk of acute respiratory distress syndrome requiring high-flow devices or mechanical ventilation. Objective: To investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalised adults with COVID-19. Methods: Phase II, open-label, randomized, controlled clinical trial of hospitalised patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or D-dimer > 1500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (Sarilumab-200) or SOC plus a single subcutaneous dose of sarilumab 400 mg (Sarilumab-400). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. Results: One-hundred and fifteen participants (control group, n = 39; Sarilumab-200, n = 37; Sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, ten (27%) in Sarilumab-200 and five (13%) in Sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of Sarilumab-400 vs control group: 0.41 [0.14-1.18]; p=0.09). Seven (6%) patients died: three in the control group and four in Sarilumab-200. There were no deaths in Sarilumab-400 (p = 0.079, log-rank test for comparisons with the control group). Conclusion: In patients recently hospitalised with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes.