1. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
- Author
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Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., Derde, L.P.G., Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), REMAP-CAP Investigators, Pour la France: Bruno Megarbane, Inserm U1144, European Project: 602386,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,CREDITS4HEALTH(2013), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), NIHR, National Institute for Health Research, Gordon, Anthony C [0000-0002-0419-547X], Mouncey, Paul R [0000-0002-8510-8517], Beane, Abi [0000-0001-7046-1580], Bradbury, Charlotte A [0000-0001-5248-8165], Detry, Michelle A [0000-0002-2794-1439], Duffy, Eamon J [0000-0002-4515-5116], Estcourt, Lise J [0000-0003-4309-9162], Haniffa, Rashan [0000-0002-8288-449X], Higgins, Alisa M [0000-0001-8295-7559], Hills, Thomas E [0000-0003-0322-5822], Horvat, Christopher M [0000-0002-1593-2252], Lawler, Patrick R [0000-0001-5155-5071], Litton, Edward [0000-0002-5125-6829], Mayr, Florian B [0000-0002-2298-9011], McVerry, Bryan J [0000-0002-1175-4874], Patanwala, Asad E [0000-0003-3999-4703], Saunders, Christina T [0000-0003-4325-9568], Shankar-Hari, Manu [0000-0002-5338-2538], Angus, Derek C [0000-0002-7026-5181], Derde, Lennie PG [0000-0002-3577-5629], Apollo - University of Cambridge Repository, Investigators, REMAP-CAP, HAL UVSQ, Équipe, Credits-based, people-centric approach for the adoption of healthy life-styles and balanced Mediterranean diet in the frame of social participation and innovation for health promotion. - CREDITS4HEALTH - - EC:FP7:HEALTH2013-09-01 - 2016-08-31 - 602386 - VALID, and Platform foR European Preparedness Against (Re-)emerging Epidemics - PREPARE - - EC:FP7:HEALTH2014-02-01 - 2019-01-31 - 602525 - VALID
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Male ,[SDV]Life Sciences [q-bio] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,030204 cardiovascular system & hematology ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,Interquartile range ,middle aged ,Credible interval ,Odds Ratio ,odds ratio ,030212 general & internal medicine ,Hospital Mortality ,humans ,11 Medical and Health Sciences ,adult ,Hazard ratio ,Covid19 ,General Medicine ,Middle Aged ,Intensive care unit ,3. Good health ,[SDV] Life Sciences [q-bio] ,aged ,Intensive Care Units ,Antibodies, Monoclonal, Humanized/adverse effects ,COVID-19/complications ,Original Article ,Female ,Adult ,medicine.medical_specialty ,Critical Care ,Critical Illness ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Tocilizumab ,male ,Internal medicine ,General & Internal Medicine ,medicine ,Humans ,Aged ,hospital mortality ,business.industry ,SARS-CoV-2 ,COVID-19 ,Odds ratio ,Receptors, Interleukin-6 ,Respiration, Artificial ,COVID-19 Drug Treatment ,Coronavirus ,Sarilumab ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,chemistry ,Receptors, Interleukin-6/antagonists & inhibitors ,REMAP-CAP Investigators ,interleukin-6 receptor antagonists ,coronavirus disease ,business - Abstract
BACKGROUNDThe efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.METHODSWe evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support–free days, on an ordinal scale combining in-hospital death (assigned a value of −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both.RESULTSBoth tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support–free days was 10 (interquartile range, −1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, −1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists.CONCLUSIONSIn critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707. opens in new tab.)
- Published
- 2021
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