Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
Andre C. Kalil,Thomas F. Patterson,Aneesh K. Mehta,Kay M. Tomashek,Cameron R. Wolfe,Varduhi Ghazaryan,Vincent C. Marconi,Guillermo M. Ruiz-Palacios,Lanny Hsieh,Susan Kline,Victor F. Tapson,Nicole M. Iovine,Mamta K. Jain,Daniel A. Sweeney,Hana M. El Sahly,Angela Branche,Justino Regalado Pineda,David C. Lye,Uriel Sandkovsky,Anne F Luetkemeyer,Stuart H. Cohen,Robert W. Finberg,Patrick E. H. Jackson,Babafemi Taiwo,Catharine I. Paules,Henry Arguinchona,Nathaniel B. Erdmann,Neera Ahuja,Maria G. Frank,Myoung Don Oh,Eu-Suk Kim,Seow Y Tan,Richard A. Mularski,Henrik Nielsen,Philip O Ponce,Barbara S. Taylor,LuAnn Larson,Nadine Rouphael,Youssef Saklawi,Valeria D Cantos,Emily R Ko,John J. Engemann,Alpesh Amin,Miki Watanabe,Joanne Billings,Marie-Carmelle Elie,Richard T. Davey,Timothy Burgess,Jennifer Ferreira,Michelle Green,Mat Makowski,Anabela Cardoso,Stephanie de Bono,Tyler Bonnett,Michael A. Proschan,Gregory A. Deye,Walla Dempsey,Seema U Nayak,Lori E. Dodd,John H. Beigel +59 more
TLDR
Baricitinib plus remdesivir was superior to remdes Vivir 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.Abstract:
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.).read more
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