TY - JOUR
T1 - Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY)
T2 - a randomised, controlled, open-label, platform trial and updated meta-analysis
AU - RECOVERY Collaborative Group
AU - Abani, Obbina
AU - Abbas, Ali
AU - Abbas, Fatima
AU - Abbas, Joshua
AU - Abbas, Kasim
AU - Abbas, Mustafa
AU - Abbasi, Sadia
AU - Abbass, Hakam
AU - Abbott, Alfie
AU - Abbott, Alison
AU - Abdallah, Nabeel
AU - Abdelaziz, Ammar
AU - Abdelaziz, Ashraf
AU - Abdelfattah, Mohamed
AU - Abdelqader, Bushra
AU - Abdul, Audrey
AU - Abdul, Basir
AU - Abdul, Siddiqui
AU - Abdul Rasheed, Althaf
AU - Abdulakeem, Ajibode
AU - Abdul-Kadir, Rezan
AU - Abdullah, Abdullah
AU - Abdulmumeen, Abdulfatahi
AU - Abdul-Raheem, Rasheed
AU - Abdulshukkoor, Niyaz
AU - Abdusamad, Kula
AU - Abed El Khaleq, Yazeed
AU - Abedalla, Mai
AU - Ul Amna, Abeer
AU - Abel, Lynn
AU - Abernethy, Katrina
AU - Abeywickrema, Movin
AU - Abhinaya, Chandra
AU - Abidin, Affyarsyah
AU - Aboaba, Adebanke
AU - Aboagye-Odei, Abigail
AU - Aboelela, Heba
AU - Abo-Leyah, Hani
AU - Abouelela, Karim
AU - Abou-Haggar, Ahmed
AU - Abouibrahim, Mahmoud
AU - Abousamra, Ahmed
AU - Abouzaid, Mona
AU - Abraham, Miriam
AU - Abraham, Tizzy
AU - Abraheem, Abraheem
AU - Abrams, Judith
AU - Abrams, Rebecca
AU - Abu, Hyacinth John
AU - Faulkner, Maria
N1 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85135019586&partnerID=8YFLogxK
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 -