Abstract
The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer > 1,500 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 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). 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. One-hundred and 15 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, 10 (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). In patients recently hospitalized 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. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860 .).
Keywords: SARS-CoV-2. COVID-19; interleukin 6; sarilumab; tocilizumab.
【저자키워드】 Tocilizumab, sarilumab, interleukin 6, SARS-CoV-2. COVID-19, 【초록키워드】 SARS-CoV-2, ARDS, Corticosteroids, Hospitalized, Open-label, randomization, mechanical ventilation, Tocilizumab, Pneumonia, outcomes, Randomized, comparison, early treatment, Patient, death, Efficacy and safety, systemic inflammation, single dose, acute respiratory distress, Invasive mechanical ventilation, Safe, IL-6 blockade, Standard of care, supplemental oxygen, Non-invasive, Primary outcome, HFNO, control group, Controlled clinical trial, hazard ratio, log-rank test, syndrome, Registered, participant, NIMV, FIVE, IMV, feature, added, hospitalized patient, receive, nasal oxygenation, subcutaneous dose, with COVID-19, 【제목키워드】 clinical, systemic, with COVID-19,