TY - JOUR
T1 - Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1)
T2 - An open-label randomised controlled trial
AU - Mariette, Xavier
AU - Hermine, Olivier
AU - Tharaux, Pierre Louis
AU - Resche-Rigon, Matthieu
AU - Porcher, Raphael
AU - Ravaud, Philippe
AU - Bureau, Serge
AU - Dougados, Maxime
AU - Tibi, Annick
AU - Azoulay, Elie
AU - Cadranel, Jacques
AU - Emmerich, Joseph
AU - Fartoukh, Muriel
AU - Guidet, Bertrand
AU - Humbert, Marc
AU - Lacombe, Karine
AU - Mahevas, Matthieu
AU - Pene, Frédéric
AU - Pourchet-Martinez, Valérie
AU - Schlemmer, Frédéric
AU - Yazdanpanah, Yazdan
AU - Baron, Gabriel
AU - Perrodeau, Elodie
AU - Vanhoye, Damien
AU - Kedzia, Cécile
AU - Demerville, Lauren
AU - Gysembergh-Houal, Anne
AU - Bourgoin, Alexandre
AU - Dalibey, Sarah
AU - Raked, Nabil
AU - Mameri, Lakhdar
AU - Alary, Stéphanie
AU - Hamiria, Samir
AU - Bariz, Thinhinane
AU - Semri, Hala
AU - Hai, Dhiaa Meriem
AU - Benafla, Moustafa
AU - Belloul, Mohamed
AU - Vauboin, Pernelle
AU - Flamand, Saskia
AU - Pacheco, Claire
AU - Walter-Petrich, Anouk
AU - Stan, Emilia
AU - Benarab, Souad
AU - Nyanou, Corine
AU - Montlahuc, Claire
AU - Biard, Lucie
AU - Charreteur, Robin
AU - Dupré, Celine
AU - Henry, Estelle
AU - The CORIMUNO-19 Collaborative group
N1 - Funding Information:
This trial was publicly funded by the Ministry of Health, Programme Hospitalier de Recherche Clinique (PHRC COVID-19–20–0151, PHRC COVID-19–20–0029), and Assistance Publique − Hôpitaux de Paris Foundation and Foundation for Medical Research. We are grateful to all patients who participated in the CORIMUNO-19 study, and their families. The authors also thank Prof Maxime Dougados who was in charge of the logistics, as well as the investigators who collaborated in this study and Universities of Paris, Paris-Saclay, Paris-Sorbonne, Paris-Nord Sorbonne, Paris-Est Créteil, Versailles-Saint Quentin and Strasbourg (medical students support), INSERM, and Reacting. Sanofi donated sarilumab as an unrestricted grant and had no role in the study design, no role in the collection, analysis, or interpretation of the data, and no role in the writing of the report.
Funding Information:
This trial was publicly funded by the Ministry of Health, Programme Hospitalier de Recherche Clinique (PHRC COVID-19?20?0151, PHRC COVID-19?20?0029), and Assistance Publique ? H?pitaux de Paris Foundation and Foundation for Medical Research. We are grateful to all patients who participated in the CORIMUNO-19 study, and their families. The authors also thank Prof Maxime Dougados who was in charge of the logistics, as well as the investigators who collaborated in this study and Universities of Paris, Paris-Saclay, Paris-Sorbonne, Paris-Nord Sorbonne, Paris-Est Cr?teil, Versailles-Saint Quentin and Strasbourg (medical students support), INSERM, and Reacting. Sanofi donated sarilumab as an unrestricted grant and had no role in the study design, no role in the collection, analysis, or interpretation of the data, and no role in the writing of the report.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/1
Y1 - 2022/1
N2 - Background: Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods: We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov, NCT04324073. Findings: 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation: Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival.
AB - Background: Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods: We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov, NCT04324073. Findings: 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation: Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival.
UR - http://www.scopus.com/inward/record.url?scp=85120442373&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/34812424
U2 - 10.1016/S2665-9913(21)00315-5
DO - 10.1016/S2665-9913(21)00315-5
M3 - Article
AN - SCOPUS:85120442373
SN - 2665-9913
VL - 4
SP - e24-e32
JO - The Lancet Rheumatology
JF - The Lancet Rheumatology
IS - 1
ER -