BACKGROUND Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (=10 days) and either baricitinib (=14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).
Bibliographical noteFunding Information:
The trial was sponsored and primarily funded by the NIAID, National Institutes of Health (NIH), Bethesda, MD. This trial has been funded in part with federal funds from the NIAID and the National Cancer Institute, NIH, under contract HHSN261200800001E 75N910D00024, task order number 75N91019F00130/75N91020F00010, and by the Department of Defense, Defense Health Program. This trial has been supported in part by the NIAID of the NIH under award numbers UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689 and by NIH Stimulating Access to Research in Residency grant 5R38AI140299-02. The trial has also been funded in part by the governments of Japan, Mexico, Denmark, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council (MRC_UU_12023/23).
Dr. Marconi reports receiving grant support from Bayer, grant support and lecture fees from ViiV Healthcare and Gilead Sciences, and grant support and consulting fees from Eli Lilly; Dr. Hsieh, receiving grant support from NeuroRx, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, Octapharma, Fulcrum Therapeutics, and Alexion Pharmaceuticals; Dr. Jain, receiving grant support and advisory board fees from Gilead Sciences and grant support from Regeneron Pharmaceuticals; Dr. Lye, serving on an advisory board for Gilead Sciences; Dr. Sandkovsky, receiving grant support from CytoDyn; Dr. Luetkemeyer, receiving grant support, paid to the University of California, San Francisco, from AstraZeneca and Novartis; Dr. Amin, receiving grant support from Pulmotect, Blade Therapeutics, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, Octapharma, Fulcrum Therapeutics, and NeuroRx, grant support and consulting fees from Novartis, grant support, consulting fees, and lecture fees from Alexion Pharmaceuticals, consulting fees and lecture fees from Bristol Myers Squibb, Pfizer, Portola Pharmaceuticals, Sunovion, and AstraZeneca, and consulting fees from Boehringer Ingelheim, Mylan, Salix Pharmaceuticals, Nabriva Therapeutics, Paratek Pharmaceuticals, Bayer, Tetraphase Pharmaceuticals, Achaogen, La Jolla Pharmaceutical, Millenium Pharmaceuticals, Ferring Pharmaceuticals, PeraHealth, AseptiScope, Heartrite, and Sprightly; Dr. Watanabe, receiving grant support from Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, Octapharma, Fulcrum Therapeutics, and Alexion Pharmaceuticals; and Drs. Cardoso and de Bono, being employed by Eli Lilly. No other potential conflict of interest relevant to this article was reported.
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