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Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.
Gordon, Anthony C; Mouncey, Paul R; Al-Beidh, Farah; Rowan, Kathryn M; Nichol, Alistair D; Arabi, Yaseen M; Annane, Djillali; Beane, Abi; van Bentum-Puijk, Wilma; Berry, Lindsay R; Bhimani, Zahra; Bonten, Marc J M; Bradbury, Charlotte A; Brunkhorst, Frank M; Buzgau, Adrian; Cheng, Allen C; Detry, Michelle A; Duffy, Eamon J; Estcourt, Lise J; Fitzgerald, Mark; Goossens, Herman; Haniffa, Rashan; Higgins, Alisa M; Hills, Thomas E; Horvat, Christopher M; Lamontagne, Francois; Lawler, Patrick R; Leavis, Helen L; Linstrum, Kelsey M; Litton, Edward; Lorenzi, Elizabeth; Marshall, John C; Mayr, Florian B; McAuley, Daniel F; McGlothlin, Anna; McGuinness, Shay P; McVerry, Bryan J; Montgomery, Stephanie K; Morpeth, Susan C; Murthy, Srinivas; Orr, Katrina; Parke, Rachael L; Parker, Jane C; Patanwala, Asad E; Pettilä, Ville; Rademaker, Emma; Santos, Marlene S; Saunders, Christina T; Seymour, Christopher W; Shankar-Hari, Manu.
  • Gordon AC; 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 Foundatio
  • Mouncey PR; 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 Foundatio
  • Al-Beidh F; 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 Foundatio
  • Rowan KM; 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 Foundatio
  • Nichol AD; 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 Foundatio
  • Arabi YM; 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 Foundatio
  • Annane D; 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 Foundatio
  • Beane A; 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 Foundatio
  • van Bentum-Puijk W; 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 Foundatio
  • Berry LR; 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 Foundatio
  • Bhimani Z; 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 Foundatio
  • Bonten MJM; 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 Foundatio
  • Bradbury CA; 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 Foundatio
  • Brunkhorst FM; 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 Foundatio
  • Buzgau A; 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 Foundatio
  • Cheng AC; 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 Foundatio
  • Detry MA; 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 Foundatio
  • Duffy EJ; 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 Foundatio
  • Estcourt LJ; 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 Foundatio
  • Fitzgerald M; 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 Foundatio
  • Goossens H; 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 Foundatio
  • Haniffa R; 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 Foundatio
  • Higgins AM; 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 Foundatio
  • Hills TE; 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 Foundatio
  • Horvat CM; 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 Foundatio
  • Lamontagne F; 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 Foundatio
  • Lawler PR; 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 Foundatio
  • Leavis HL; 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 Foundatio
  • Linstrum KM; 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 Foundatio
  • Litton E; 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 Foundatio
  • Lorenzi E; 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 Foundatio
  • Marshall JC; 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 Foundatio
  • Mayr FB; 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 Foundatio
  • McAuley DF; 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 Foundatio
  • McGlothlin A; 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 Foundatio
  • McGuinness SP; 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 Foundatio
  • McVerry BJ; 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 Foundatio
  • Montgomery SK; 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 Foundatio
  • Morpeth SC; 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 Foundatio
  • Murthy S; 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 Foundatio
  • Orr K; 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 Foundatio
  • Parke RL; 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 Foundatio
  • Parker JC; 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 Foundatio
  • Patanwala AE; 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 Foundatio
  • Pettilä V; 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 Foundatio
  • Rademaker E; 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 Foundatio
  • Santos MS; 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 Foundatio
  • Saunders CT; 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 Foundatio
  • Seymour CW; 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 Foundatio
  • Shankar-Hari M; 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 Foundatio
N Engl J Med ; 384(16): 1491-1502, 2021 04 22.
Article in English | MEDLINE | ID: covidwho-1101727
ABSTRACT

BACKGROUND:

The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

METHODS:

We 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.

RESULTS:

Both 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.

CONCLUSIONS:

In 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.).
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Interleukin-6 / Antibodies, Monoclonal, Humanized / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: N Engl J Med Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Interleukin-6 / Antibodies, Monoclonal, Humanized / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: N Engl J Med Year: 2021 Document Type: Article