Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

Abdullah Abdullah; Mohammad Ahmad; David Alderdice; John Alexander; Peter D.G. Alexander; Syed Ali; Kerry Allen; Julie Anderson; Samantha Anderson; Wendy Anderson; Mark Baker; Richard Barlow; Clare Brady; Andrew Brown; Duncan Browne; Amy Burns; Mark Campbell; Sharon Carr; Emma Chambers; Katie Chapman; Patricia Clark; Emma Collins; David Comer; David Cooper; Victoria Craig; Nicola Cunningham; David Curran; Simon Davies; Elizabeth Dawson; Conor Doherty; Eilish Donnelly; Ronan Donnelly; Damian Downey; Maire Drain; Jennifer Evans; John Evans; Jenny Ferguson; Stephen Fowler; William Gallagher; Chris Gordon; Rebecca Gosling; David Grant; David Green; Sandra Griffiths; Mohammed Hameed; Thomas Harrison; Dominic Hart; Emma Heron; Richard Hewitt; Stephen Hughes; Ahmed Ibrahim; Amanda Jackson; Gillian Johnson; Mark Johnson; Janet Johnston; Amy Jones; Louise Jones; Samantha Jones; Sophie Jones; Tim Jones; Breffni Keegan; David Kelly; Dominic Kelly; Emma Kelly; Martin Kelly; Michael Kelly; Stephen Kelly; A. Kerr; Waleed Khan; Deborah J. Kinnear; Satish Kumar; Simon Lee; Dermot Linden; Edward Malone; Andrew Marshall; Paul McCourt; John McDermott; Fred McElwaine; Lorcan McGarvey; Clodagh McGettigan; Brendan McGrath; Stephen McMahon; Terence McManus; Helen McNally; Jonathan Millar; Aoife Molloy; David A.J. Moore; Laura Moore; Patrick Morgan; Paul Morris; Clare Murray; Lisa Murray; Tracey Murray; Quang Nguyen; Fiona North; Anne M. Nugent; Ciaran O'Gorman; Sarah Orr; Robert Patterson; James Quinn; Martin Regan; A. Rehman; Andrew Reid; Jennifer Reid; Matthew Rice; Jane Ritchie; Emma Robinson; Matthew Robinson; John Rogers; Stephen Rowan; Kathryn Ryan; M. Saad; Anne Scott; Stephen Scott; Syed Shah; Christopher Shaw; Richard Simms; Thomas Simpson; Kathryn Simpson; Brendan Sloan; Catherine Smith; Christopher Smith; Oliver Smith; Rachel Smith; Richard Smith; Sally Smith; Stephanie Smith; Susan Smith; John Smith; Shiva Sreenivasan; Andrew Stevenson; Christopher Stewart; Wei Teen Tan; Julie Taylor; Samantha Taylor; Victoria Taylor; Catherine Thompson; Laura Thompson; Luke Thompson; Marianne Tinkler; Elizabeth Walsh; James Walters; Michael Walton; Ran Wang; Christopher Ward; Hannah Ward; Nicola Ward; Thomas Ward; J. G.R. Watson; Robert Watson; Deborah Webster; Ian Webster; Christopher White; Jonathan White; Gina Williams; James Williams; John Williams; Mark Williams; Robin Williams; James D. Williamson; Alison Wilson; Anna Wilson; David Wilson; Mark Wilson; Jing Zhang; Xiaobei Zhao; RECOVERY Collaborative Group

doi:10.1016/S0140-6736(22)01109-6

Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

Abdullah Abdullah, Mohammad Ahmad, David Alderdice, John Alexander, Peter D.G. Alexander, Syed Ali, Kerry Allen, Julie Anderson, Samantha Anderson, Wendy Anderson, Mark Baker, Richard Barlow, Clare Brady, Andrew Brown, Duncan Browne, Amy Burns, Mark Campbell, Sharon Carr, Emma Chambers, Katie ChapmanPatricia Clark, Emma Collins, David Comer, David Cooper, Victoria Craig, Nicola Cunningham, David Curran, Simon Davies, Elizabeth Dawson, Conor Doherty, Eilish Donnelly, Ronan Donnelly, Damian Downey, Maire Drain, Jennifer Evans, John Evans, Jenny Ferguson, Stephen Fowler, William Gallagher, Chris Gordon, Rebecca Gosling, David Grant, David Green, Sandra Griffiths, Mohammed Hameed, Thomas Harrison, Dominic Hart, Emma Heron, Richard Hewitt, Stephen Hughes, Ahmed Ibrahim, Amanda Jackson, Gillian Johnson, Mark Johnson, Janet Johnston, Amy Jones, Louise Jones, Samantha Jones, Sophie Jones, Tim Jones, Breffni Keegan, David Kelly, Dominic Kelly, Emma Kelly, Martin Kelly, Michael Kelly, Stephen Kelly, A. Kerr, Waleed Khan, Deborah J. Kinnear, Satish Kumar, Simon Lee, Dermot Linden, Edward Malone, Andrew Marshall, Paul McCourt, John McDermott, Fred McElwaine, Lorcan McGarvey, Clodagh McGettigan, Brendan McGrath, Stephen McMahon, Terence McManus, Helen McNally, Jonathan Millar, Aoife Molloy, David A.J. Moore, Laura Moore, Patrick Morgan, Paul Morris, Clare Murray, Lisa Murray, Tracey Murray, Quang Nguyen, Fiona North, Anne M. Nugent, Ciaran O'Gorman, Sarah Orr, Robert Patterson, James Quinn, Martin Regan, A. Rehman, Andrew Reid, Jennifer Reid, Matthew Rice, Jane Ritchie, Emma Robinson, Matthew Robinson, John Rogers, Stephen Rowan, Kathryn Ryan, M. Saad, Anne Scott, Stephen Scott, Syed Shah, Christopher Shaw, Richard Simms, Thomas Simpson, Kathryn Simpson, Brendan Sloan, Catherine Smith, Christopher Smith, Oliver Smith, Rachel Smith, Richard Smith, Sally Smith, Stephanie Smith, Susan Smith, John Smith, Shiva Sreenivasan, Andrew Stevenson, Christopher Stewart, Wei Teen Tan, Julie Taylor, Samantha Taylor, Victoria Taylor, Catherine Thompson, Laura Thompson, Luke Thompson, Marianne Tinkler, Elizabeth Walsh, James Walters, Michael Walton, Ran Wang, Christopher Ward, Hannah Ward, Nicola Ward, Thomas Ward, J. G.R. Watson, Robert Watson, Deborah Webster, Ian Webster, Christopher White, Jonathan White, Gina Williams, James Williams, John Williams, Mark Williams, Robin Williams, James D. Williamson, Alison Wilson, Anna Wilson, David Wilson, Mark Wilson, Jing Zhang, Xiaobei Zhao, RECOVERY Collaborative Group

Research output: Contribution to journal › Article › peer-review

194 Citations (Scopus)

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Abstract

Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.

Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.

Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.

Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth.

Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Original language	English
Pages (from-to)	359-368
Number of pages	10
Journal	The Lancet
Volume	400
Issue number	10349
DOIs	https://doi.org/10.1016/S0140-6736(22)01109-6
Publication status	Published - 30 Jul 2022

Bibliographical note

Funding Information:
Above all, we thank the thousands of patients who participated in this trial. We also thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056), the Wellcome Trust (grant reference 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. Baricitinib was provided from routine NHS stock. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Funding Information:
Above all, we thank the thousands of patients who participated in this trial. We also thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056), the Wellcome Trust (grant reference 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. Baricitinib was provided from routine NHS stock. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

ASJC Scopus subject areas

General Medicine

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Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis
Copyright 2023 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
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Cite this

Abdullah, A., Ahmad, M., Alderdice, D., Alexander, J., Alexander, P. D. G., Ali, S., Allen, K., Anderson, J., Anderson, S., Anderson, W., Baker, M., Barlow, R., Brady, C., Brown, A., Browne, D., Burns, A., Campbell, M., Carr, S., Chambers, E., ... RECOVERY Collaborative Group (2022). Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. The Lancet, 400(10349), 359-368. https://doi.org/10.1016/S0140-6736(22)01109-6

@article{6fb6a24fe7f3456e842e88fa6985c574,

title = "Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis",

abstract = "Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",

author = "Abdullah Abdullah and Mohammad Ahmad and David Alderdice and John Alexander and Alexander, {Peter D.G.} and Syed Ali and Kerry Allen and Julie Anderson and Samantha Anderson and Wendy Anderson and Mark Baker and Richard Barlow and Clare Brady and Andrew Brown and Duncan Browne and Amy Burns and Mark Campbell and Sharon Carr and Emma Chambers and Katie Chapman and Patricia Clark and Emma Collins and David Comer and David Cooper and Victoria Craig and Nicola Cunningham and David Curran and Simon Davies and Elizabeth Dawson and Conor Doherty and Eilish Donnelly and Ronan Donnelly and Damian Downey and Maire Drain and Jennifer Evans and John Evans and Jenny Ferguson and Stephen Fowler and William Gallagher and Chris Gordon and Rebecca Gosling and David Grant and David Green and Sandra Griffiths and Mohammed Hameed and Thomas Harrison and Dominic Hart and Emma Heron and Richard Hewitt and Stephen Hughes and Ahmed Ibrahim and Amanda Jackson and Gillian Johnson and Mark Johnson and Janet Johnston and Amy Jones and Louise Jones and Samantha Jones and Sophie Jones and Tim Jones and Breffni Keegan and David Kelly and Dominic Kelly and Emma Kelly and Martin Kelly and Michael Kelly and Stephen Kelly and A. Kerr and Waleed Khan and Kinnear, {Deborah J.} and Satish Kumar and Simon Lee and Dermot Linden and Edward Malone and Andrew Marshall and Paul McCourt and John McDermott and Fred McElwaine and Lorcan McGarvey and Clodagh McGettigan and Brendan McGrath and Stephen McMahon and Terence McManus and Helen McNally and Jonathan Millar and Aoife Molloy and Moore, {David A.J.} and Laura Moore and Patrick Morgan and Paul Morris and Clare Murray and Lisa Murray and Tracey Murray and Quang Nguyen and Fiona North and Nugent, {Anne M.} and Ciaran O'Gorman and Sarah Orr and Robert Patterson and James Quinn and Martin Regan and A. Rehman and Andrew Reid and Jennifer Reid and Matthew Rice and Jane Ritchie and Emma Robinson and Matthew Robinson and John Rogers and Stephen Rowan and Kathryn Ryan and M. Saad and Anne Scott and Stephen Scott and Syed Shah and Christopher Shaw and Richard Simms and Thomas Simpson and Kathryn Simpson and Brendan Sloan and Catherine Smith and Christopher Smith and Oliver Smith and Rachel Smith and Richard Smith and Sally Smith and Stephanie Smith and Susan Smith and John Smith and Shiva Sreenivasan and Andrew Stevenson and Christopher Stewart and Tan, {Wei Teen} and Julie Taylor and Samantha Taylor and Victoria Taylor and Catherine Thompson and Laura Thompson and Luke Thompson and Marianne Tinkler and Elizabeth Walsh and James Walters and Michael Walton and Ran Wang and Christopher Ward and Hannah Ward and Nicola Ward and Thomas Ward and Watson, {J. G.R.} and Robert Watson and Deborah Webster and Ian Webster and Christopher White and Jonathan White and Gina Williams and James Williams and John Williams and Mark Williams and Robin Williams and Williamson, {James D.} and Alison Wilson and Anna Wilson and David Wilson and Mark Wilson and Jing Zhang and Xiaobei Zhao and {RECOVERY Collaborative Group}",

note = "Funding Information: Above all, we thank the thousands of patients who participated in this trial. We also thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056), the Wellcome Trust (grant reference 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. Baricitinib was provided from routine NHS stock. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Funding Information: Above all, we thank the thousands of patients who participated in this trial. We also thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056), the Wellcome Trust (grant reference 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. Baricitinib was provided from routine NHS stock. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license",

year = "2022",

month = jul,

day = "30",

doi = "10.1016/S0140-6736(22)01109-6",

language = "English",

volume = "400",

pages = "359--368",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier B.V.",

number = "10349",

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Abdullah, A, Ahmad, M, Alderdice, D, Alexander, J, Alexander, PDG, Ali, S, Allen, K, Anderson, J, Anderson, S, Anderson, W, Baker, M, Barlow, R, Brady, C, Brown, A, Browne, D, Burns, A, Campbell, M, Carr, S, Chambers, E, Chapman, K, Clark, P, Collins, E, Comer, D, Cooper, D, Craig, V, Cunningham, N, Curran, D, Davies, S, Dawson, E, Doherty, C, Donnelly, E, Donnelly, R, Downey, D, Drain, M, Evans, J, Evans, J, Ferguson, J, Fowler, S, Gallagher, W, Gordon, C, Gosling, R, Grant, D, Green, D, Griffiths, S, Hameed, M, Harrison, T, Hart, D, Heron, E, Hewitt, R, Hughes, S, Ibrahim, A, Jackson, A, Johnson, G, Johnson, M, Johnston, J, Jones, A, Jones, L, Jones, S, Jones, S, Jones, T, Keegan, B, Kelly, D, Kelly, D, Kelly, E, Kelly, M, Kelly, M, Kelly, S, Kerr, A, Khan, W, Kinnear, DJ, Kumar, S, Lee, S, Linden, D, Malone, E, Marshall, A, McCourt, P, McDermott, J, McElwaine, F, McGarvey, L, McGettigan, C, McGrath, B, McMahon, S, McManus, T, McNally, H, Millar, J, Molloy, A, Moore, DAJ, Moore, L, Morgan, P, Morris, P, Murray, C, Murray, L, Murray, T, Nguyen, Q, North, F, Nugent, AM, O'Gorman, C, Orr, S, Patterson, R, Quinn, J, Regan, M, Rehman, A, Reid, A, Reid, J, Rice, M, Ritchie, J, Robinson, E, Robinson, M, Rogers, J, Rowan, S, Ryan, K, Saad, M, Scott, A, Scott, S, Shah, S, Shaw, C, Simms, R, Simpson, T, Simpson, K, Sloan, B, Smith, C, Smith, C, Smith, O, Smith, R, Smith, R, Smith, S, Smith, S, Smith, S, Smith, J, Sreenivasan, S, Stevenson, A, Stewart, C, Tan, WT, Taylor, J, Taylor, S, Taylor, V, Thompson, C, Thompson, L, Thompson, L , Tinkler, M, Walsh, E, Walters, J, Walton, M, Wang, R, Ward, C, Ward, H, Ward, N, Ward, T, Watson, JGR, Watson, R, Webster, D, Webster, I, White, C, White, J, Williams, G, Williams, J, Williams, J, Williams, M, Williams, R, Williamson, JD, Wilson, A, Wilson, A, Wilson, D, Wilson, M, Zhang, J, Zhao, X & RECOVERY Collaborative Group 2022, 'Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis', The Lancet, vol. 400, no. 10349, pp. 359-368. https://doi.org/10.1016/S0140-6736(22)01109-6

TY - JOUR

T1 - Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

AU - Abdullah, Abdullah

AU - Ahmad, Mohammad

AU - Alderdice, David

AU - Alexander, John

AU - Alexander, Peter D.G.

AU - Ali, Syed

AU - Allen, Kerry

AU - Anderson, Julie

AU - Anderson, Samantha

AU - Anderson, Wendy

AU - Baker, Mark

AU - Barlow, Richard

AU - Brady, Clare

AU - Brown, Andrew

AU - Browne, Duncan

AU - Burns, Amy

AU - Campbell, Mark

AU - Carr, Sharon

AU - Chambers, Emma

AU - Chapman, Katie

AU - Clark, Patricia

AU - Collins, Emma

AU - Comer, David

AU - Cooper, David

AU - Craig, Victoria

AU - Cunningham, Nicola

AU - Curran, David

AU - Davies, Simon

AU - Dawson, Elizabeth

AU - Doherty, Conor

AU - Donnelly, Eilish

AU - Donnelly, Ronan

AU - Downey, Damian

AU - Drain, Maire

AU - Evans, Jennifer

AU - Evans, John

AU - Ferguson, Jenny

AU - Fowler, Stephen

AU - Gallagher, William

AU - Gordon, Chris

AU - Gosling, Rebecca

AU - Grant, David

AU - Green, David

AU - Griffiths, Sandra

AU - Hameed, Mohammed

AU - Harrison, Thomas

AU - Hart, Dominic

AU - Heron, Emma

AU - Hewitt, Richard

AU - Hughes, Stephen

AU - Ibrahim, Ahmed

AU - Jackson, Amanda

AU - Johnson, Gillian

AU - Johnson, Mark

AU - Johnston, Janet

AU - Jones, Amy

AU - Jones, Louise

AU - Jones, Samantha

AU - Jones, Sophie

AU - Jones, Tim

AU - Keegan, Breffni

AU - Kelly, David

AU - Kelly, Dominic

AU - Kelly, Emma

AU - Kelly, Martin

AU - Kelly, Michael

AU - Kelly, Stephen

AU - Kerr, A.

AU - Khan, Waleed

AU - Kinnear, Deborah J.

AU - Kumar, Satish

AU - Lee, Simon

AU - Linden, Dermot

AU - Malone, Edward

AU - Marshall, Andrew

AU - McCourt, Paul

AU - McDermott, John

AU - McElwaine, Fred

AU - McGarvey, Lorcan

AU - McGettigan, Clodagh

AU - McGrath, Brendan

AU - McMahon, Stephen

AU - McManus, Terence

AU - McNally, Helen

AU - Millar, Jonathan

AU - Molloy, Aoife

AU - Moore, David A.J.

AU - Moore, Laura

AU - Morgan, Patrick

AU - Morris, Paul

AU - Murray, Clare

AU - Murray, Lisa

AU - Murray, Tracey

AU - Nguyen, Quang

AU - North, Fiona

AU - Nugent, Anne M.

AU - O'Gorman, Ciaran

AU - Orr, Sarah

AU - Patterson, Robert

AU - Quinn, James

AU - Regan, Martin

AU - Rehman, A.

AU - Reid, Andrew

AU - Reid, Jennifer

AU - Rice, Matthew

AU - Ritchie, Jane

AU - Robinson, Emma

AU - Robinson, Matthew

AU - Rogers, John

AU - Rowan, Stephen

AU - Ryan, Kathryn

AU - Saad, M.

AU - Scott, Anne

AU - Scott, Stephen

AU - Shah, Syed

AU - Shaw, Christopher

AU - Simms, Richard

AU - Simpson, Thomas

AU - Simpson, Kathryn

AU - Sloan, Brendan

AU - Smith, Catherine

AU - Smith, Christopher

AU - Smith, Oliver

AU - Smith, Rachel

AU - Smith, Richard

AU - Smith, Sally

AU - Smith, Stephanie

AU - Smith, Susan

AU - Smith, John

AU - Sreenivasan, Shiva

AU - Stevenson, Andrew

AU - Stewart, Christopher

AU - Tan, Wei Teen

AU - Taylor, Julie

AU - Taylor, Samantha

AU - Taylor, Victoria

AU - Thompson, Catherine

AU - Thompson, Laura

AU - Thompson, Luke

AU - Tinkler, Marianne

AU - Walsh, Elizabeth

AU - Walters, James

AU - Walton, Michael

AU - Wang, Ran

AU - Ward, Christopher

AU - Ward, Hannah

AU - Ward, Nicola

AU - Ward, Thomas

AU - Watson, J. G.R.

AU - Watson, Robert

AU - Webster, Deborah

AU - Webster, Ian

AU - White, Christopher

AU - White, Jonathan

AU - Williams, Gina

AU - Williams, James

AU - Williams, John

AU - Williams, Mark

AU - Williams, Robin

AU - Williamson, James D.

AU - Wilson, Alison

AU - Wilson, Anna

AU - Wilson, David

AU - Wilson, Mark

AU - Zhang, Jing

AU - Zhao, Xiaobei

AU - RECOVERY Collaborative Group

N1 - Funding Information: Above all, we thank the thousands of patients who participated in this trial. We also thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056), the Wellcome Trust (grant reference 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. Baricitinib was provided from routine NHS stock. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Funding Information: Above all, we thank the thousands of patients who participated in this trial. We also thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from UK Research and Innovation and NIHR (MC_PC_19056), the Wellcome Trust (grant reference 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Tocilizumab was provided free of charge for this trial by Roche Products. Regeneron Pharmaceuticals supported the trial through provision of casirivimab and imdevimab. Baricitinib was provided from routine NHS stock. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

PY - 2022/7/30

Y1 - 2022/7/30

N2 - Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

AB - Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19.Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing.Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

U2 - 10.1016/S0140-6736(22)01109-6

DO - 10.1016/S0140-6736(22)01109-6

M3 - Article

C2 - 35908569

AN - SCOPUS:85135019586

SN - 0140-6736

VL - 400

SP - 359

EP - 368

JO - The Lancet

JF - The Lancet

IS - 10349

ER -

Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

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