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.

Abstract

BACKGROUND:

Our objective was to determine whether anti-interleukin (IL)-6 receptors improve outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. We report on two cohort-embedded, investigator-initiated, multicentre, open-label, Bayesian randomised controlled clinical trials.

METHODS:

Patients were randomly assigned to receive either usual care (UC) or UC+tocilizumab (TCZ) 8 mg·kg-1 (TOCI-2 trial) or UC or UC+sarilumab (SARI) 200 mg (SARI-2 trial), both intravenously on day 1 and, if clinically indicated, on day 3.

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 noninvasive ventilation (NIV) or mechanical ventilation (MV) and were alive with TCZ or UC were similar (47% versus 42%; median posterior hazard ratio (HR) 1.19, 90% credible interval (CrI) 0.71-2.04), 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 or MV and were alive with SARI or UC were similar (38% versus 33%; median posterior HR 1.05, 90% CrI 0.55-2.07), with a posterior probability of HR >1 of 54.9%. Overall, the risk of death up to day 90 was: UC+TCZ 24% versus UC 30% (HR 0.67, 95% CI 0.30-1.49) and UC+SARI 29% versus UC 39% (HR 0.74, 95% CI 0.35-1.58). 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 or MV by day 14.

• Authors: Olivier Hermine, Xavier Mariette, Raphael Porcher, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Philippe Ravaud, CORIMUNO-19 Collaborative Group
• Journal: The European respiratory journal (Eur Respir J) Vol. 60 Issue 2 (08 2022) ISSN: 1399-3003 [Electronic] England
• PMID: 35115337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright ©The authors 2022.

Chemical References

• Receptors, Interleukin-6

Topics

• Adult
• Bayes Theorem
• COVID-19
• Critical Illness
• Humans
• Randomized Controlled Trials as Topic
• Receptors, Interleukin-6
• Respiration, Artificial
• SARS-CoV-2
• Treatment Outcome