• REMAP-CAP Investigators, Anthony C Gordon, Paul R Mouncey, Farah Al-Beidh, Kathryn M Rowan, Alistair D Nichol, Yaseen M Arabi, Djillali Annane, Abi Beane, Wilma van Bentum-Puijk, Lindsay R Berry, Zahra Bhimani, BontenMarc J MMJMFrom Imperial College London (A.C.G., F.A.-B.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), Intensive Care National Audit and Research Centre (P.R.M., K.M.R.), University College London Hospital (R.H.), King's Col, Charlotte A Bradbury, Frank M Brunkhorst, Adrian Buzgau, Allen C Cheng, Michelle A Detry, Eamon J Duffy, Lise J Estcourt, Mark Fitzgerald, Herman Goossens, Rashan Haniffa, Alisa M Higgins, Thomas E Hills, Christopher M Horvat, Francois Lamontagne, Patrick R Lawler, Helen L Leavis, Kelsey M Linstrum, Edward Litton, Elizabeth Lorenzi, John C Marshall, Florian B Mayr, Daniel F McAuley, Anna McGlothlin, Shay P McGuinness, Bryan J McVerry, Stephanie K Montgomery, Susan C Morpeth, Srinivas Murthy, Katrina Orr, Rachael L Parke, Jane C Parker, Asad E Patanwala, Ville Pettilä, Emma Rademaker, Marlene S Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Wendy I Sligl, Alexis F Turgeon, Anne M Turner, Frank L van de Veerdonk, Ryan Zarychanski, Cameron Green, Roger J Lewis, Derek C Angus, Colin J McArthur, Scott Berry, Steve A Webb, and DerdeLennie P GLPG0000-0002-3577-5629From Imperial College London (A.C.G., F.A.-B.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), Intensive Care National Audit and Research Centre (P.R.M., K.M.R.), University College London Hospita.
• From Imperial College London (A.C.G., F.A.-B.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), Intensive Care National Audit and Research Centre (P.R.M., K.M.R.), University College London Hospital (R.H.), King's College London (M.S.-H.), and Guy's and St. Thomas' NHS Foundation Trust (M.S.-H.), London, University of Oxford (A. Beane) and NHS Blood and Transplant (L.J.E.), Oxford, and University of Bristol, Bristol (C.A.B.) - all in the United Kingdom; Monash University (A.D.N., A. Buzgau, A.C.C., A.M.H., S.P.M., J.C.P., C.G., S.A.W.) and Alfred Health (A.D.N., A.C.C.), Melbourne, VIC, Fiona Stanley Hospital (E. Litton, K.O.) and University of Western Australia (E. Litton), Perth, WA, University of Sydney and Royal Prince Alfred Hospital, Sydney (A.E.P.), and St. John of God Hospital, Subiaco, WA (S.A.W.) - all in Australia; University College Dublin, Dublin (A.D.N.); King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.M.A.); Hospital Raymond Poincaré (Assistance Publique-Hôpitaux de Paris) and Université Paris Saclay-Université de Versailles Saint-Quentin-en-Yvelines-INSERM, Garches, and Université de Versailles Saint-Quentin-en-Yvelines-Université Paris Saclay, Montigny-le-Bretonneux - all in France (D.A.); University Medical Center Utrecht, Utrecht (W.B.-P., M.J.M.B., H.L.L., E.R., L.P.G.D.), and Radboudumc, Nijmegen (F.L.V.) - both in the Netherlands; Berry Consultants, Austin, TX (L.R.B., M.A.D., M.F., E. Lorenzi, A.M., C.T.S., R.J.L., S.B.); St. Michael's Hospital Unity Health (Z.B., J.C.M., M.S.S.) and University Health Network and University of Toronto (P.R.L.), Toronto, Université de Sherbrooke, Sherbrooke, QC (F.L.), University of British Columbia, Vancouver (S.M.), University of Alberta, Edmonton (W.I.S.), Université Laval, Québec City (A.F.T.), and University of Manitoba, Winnipeg, MB (R.Z.) - all in Canada; Jena University Hospital, Jena, Germany (F.M.B.); Auckland City Hospital (E.J.D., T.E.H., S.P.M., R.L.P., C.J.M.), Middlemore Hospital (S.C.M.), and University of Auckland (R.L.P.), Auckland, and Medical Research Institute of New Zealand, Wellington (T.E.H., S.P.M., A.M.T.) - all in New Zealand; University of Antwerp, Wilrijk, Belgium (H.G.); University of Oxford, Bangkok, Thailand (R.H.); National Intensive Care Surveillance, Colombo, Sri Lanka (R.H.); UPMC Children's Hospital of Pittsburgh (C.M.H.) and University of Pittsburgh (K.M.L., F.B.M., B.J.M., S.K.M., C.W.S., D.C.A.), Pittsburgh; Queen's University Belfast and Royal Victoria Hospital, Belfast, Northern Ireland (D.F.M.); University of Helsinki and Helsinki University Hospital, Helsinki (V.P.); and Harbor-UCLA Medical Center, Torrance, CA (R.J.L.).
• N. Engl. J. Med. 2021 Apr 22; 384 (16): 149115021491-1502.

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.).Copyright © 2021 Massachusetts Medical Society.

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