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

• DOI: 10.1101/2022.03.02.22271623
• Publication Date: 2022-03-03T17:20:16Z
• Authors: Peter W Horby; Jonathan R Emberson; Marion Mafham; Mark Campbell; Leon Peto; Guilherme Pessoa-...; Enti Spata; Natalie Staplin; Catherine Lowe; David R Chadwick; Christopher Brigh...; Richard Stewart; Paul Collini; Abdul Ashish; Christopher A Green; Benjamin Prudon; Tim Felton; Anthony Kerry; J Kenneth Baillie; Maya H Buch; Jeremy N Day; Saul N Faust; Thomas Jaki; Katie Jeffery; Edmund Juszczak; Marian Knight; Wei Shen Lim; Alan Montgomery; Andrew Mumford; Kathryn Rowan; Guy Thwaites; Richard Haynes; Martin J Landray
• Keywords: Intention-to-treat analysis

SUMMARY Background We evaluated the use of baricitinib, a Janus kinase (JAK) 1/2 inhibitor, for treatment patients admitted to hospital because COVID-19. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in hospitalised Eligible and consenting were randomly allocated (1:1) either usual standard care alone (usual group) or plus baricitinib 4 mg once daily by mouth 10 days until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed intention-to-treat population. A meta-analysis conducted that included results from RECOVERY all previous randomised controlled trials other JAK inhibitor with registered ISRCTN (50189673) clinicaltrials.gov ( NCT04381936 ). Findings Between 2 February 2021 29 December 2021, 8156 receive versus alone. At randomisation, 95% receiving corticosteroids 23% tocilizumab (with planned within next 24 hours recorded further 9%). Overall, 513 (12%) 4148 546 (14%) 4008 died 28 (age-adjusted rate ratio 0·87; CI 0·77-0·98; p=0·026). 13% proportional reduction somewhat smaller than seen 8 (involving 3732 425 deaths) which allocation associated 43% (rate 0.57; 0.45-0.72). Including into an updated 9 completed 11,888 1484 20% 0.80; 0.71-0.89; p<0.001). In RECOVERY, there no significant excess death infection due non-COVID-19 causes thrombosis, safety outcomes. Interpretation COVID-19, significantly reduced risk but size benefit suggested trials. total evidence date suggests inhibitors (chiefly baricitinib) reduce about one-fifth. Funding UK Research Innovation (Medical Council) National Institute Health (Grant ref: MC_PC_19056).