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
Olivier Hermine, Xavier Mariette, Raphael Porcher, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Philippe Ravaud
doi:10.1183/13993003.02523-2021].
In two prospective randomised studies of COVID-19 patients in the ICU, anti-IL-6 receptor did not significantly increase early survival without mechanical ventilation. However, due to the small number of patients, no definitive conclusion could be drawn. https://bit.ly/
Secondary outcomes Overall survival (%) Estimate at day 14 90 (82-99) 79 (68-92) HR 0.37 (0.12-1. Author contributions: All authors made substantial contributions to the conception and design or acquisition, analysis or interpretation of the data, and the drafting or critical revision of the manuscript. All authors had full access to the data and take responsibility for the integrity of the work. Approval to submit the manuscript for publication was made by all authors. Conflict of interest: P-L. Tharaux has received honoraria for participation on advisory boards for Travere therapeutics. All other author disclose no potential conflicts of interest related to this work. Support statement: This trial was publicly funded (Ministry of Health, Programme Hospitalier de Recherche Clinique (PHRC COVID-19-20-0143, PHRC COVID-19-20-0029), Foundation for Medical Research (FRM), AP-HP Foundation and the Reacting programme). Funders had no access to the trial data and had no role in the design, conduct or reporting of the trial. Roche and Sanofi donated TCZ and SARI in unrestricted grants, respectively, and had no role in the trial design or conduct; the collection, management, analysis or interpretation of the data; or in the preparation, review of the manuscript or the approval of the manuscript for submission. Funding information for this article has been deposited with the Crossref Funder Registry.
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'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients were '
'randomly assigned to receive either usual care (UC) or UC+tocilizumab (TCZ) 8\u2005'
'mg·kg<jats:sup>−1</jats:sup> (TOCI-2 trial) or UC or UC+sarilumab (SARI) 200\u2005mg (SARI-2 '
'trial), both intravenously on day 1 and, if clinically indicated, on day '
'3.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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% '
'<jats:italic>versus</jats:italic> 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% <jats:italic>versus</jats:italic> 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% <jats:italic>versus</jats:italic> UC 30% (HR 0.67, '
'95% CI 0.30–1.49) and UC+SARI 29% <jats:italic>versus</jats:italic> UC 39% (HR 0.74, 95% CI '
'0.35–1.58). Both TCZ and SARI increased serious infectious '
'events.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>',
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