QUESTION: To determine whether anti-IL-6 Receptors improve outcomes of critically ill patients with COVID-19 pneumonia. PATIENTS AND METHODS: Two cohort-embedded, investigator-initiated, multicenter, open-label, Bayesian randomised controlled clinical trials. Patients were randomly assigned to receive either usual care (UC) or UC+Tocilizumab (TCZ) 8 mg/kg (TOCI-2 trial), or UC or UC+ Sarilumab (SARI) 200 mg (SARI-2 trial), both intravenously on day 1 (D1) and on D3 if clinically indicated. RESULTS: Between 31 March and 20 April 2020, 97 patients were randomised in the TOCI-2 trial, to receive UC (n=46) or UC+TCZ (n=51). At day 14, numbers of patients who did not need NIV, MV and alive with TCZ or UC were similar (47% versus 42%, median posterior hazard ratio [HR] 1.19, 90% CrI, 0.71 to 2.04), with a posterior probability of HR>1 of 71.4%. Between 27 March and 4 April 2020, 91 patients were randomised in the SARI-2 trial, to receive UC (n=41) or UC+SARI (n=50). At day 14, numbers of patients who did not need NIV, MV and alive with SARI or UC were similar (38% versus 33%, median posterior hazard ratio [HR] 1.05, 90% CrI, 0.55 to 2.07), with a posterior probability of HR>1 of 54.9%. Overall, the risk of death up to day 90 was: UC+TCZ versus UC (24% versus 30%, HR 0.67 [0.30 to 1.49]); UC+SARI versus UC (29% versus 39%, (HR 0.74 ([0.35 to 1.58]). Both TCZ and SARI increased serious infectious events. CONCLUSION: In critically ill patients with COVID-19, anti-IL-6 Receptors did not significantly increase the number of patients alive without any NIV, MV by D14. TRIAL REGISTRATION: ClinicalTrials.gov numbers: (NCT04331808 and NCT04324073)
Effect of Interleukin-6 Receptor Antagonists in Critically Ill Adult Patients with COVID-19 Pneumonia: two Randomised Controlled Trials of the CORIMUNO-19 Collaborative Group