Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial

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.

FIG 1

Disposition of patients in the trial.

FIG 2

Probability of developing the study outcomes in the first 28 days after randomization according to study groups in the modified intention-to-treat population (N = 115). (A) Clinical progression requiring high-flow nasal oxygen (HFNO) devices, non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV). (B) Need for IMV. (C) Overall mortality. (D) Clinical improvement. Clinical improvement was defined as a 2-point rise in a seven-category ordinal scale or hospital discharge, whichever occurred first.