Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

André C. Kalil(The University of Texas Health Science Center at San Antonio), Thomas F. Patterson(The University of Texas Health Science Center at San Antonio), Aneesh K. Mehta(The University of Texas Health Science Center at San Antonio), Kay M Tomashek(The University of Texas Health Science Center at San Antonio), Cameron R. Wolfe(The University of Texas Health Science Center at San Antonio), Varduhi Ghazaryan(The University of Texas Health Science Center at San Antonio), Vincent C. Marconi(The University of Texas Health Science Center at San Antonio), Guillermo M. Ruiz‐Palacios(The University of Texas Health Science Center at San Antonio), Lanny Hsieh(The University of Texas Health Science Center at San Antonio), Susan Kline(The University of Texas Health Science Center at San Antonio), Victor F. Tapson(The University of Texas Health Science Center at San Antonio), Nicole M. Iovine(The University of Texas Health Science Center at San Antonio), Mamta K. Jain(The University of Texas Health Science Center at San Antonio), Daniel A Sweeney(The University of Texas Health Science Center at San Antonio), Hana M. El Sahly(The University of Texas Health Science Center at San Antonio), Angela R Branche(The University of Texas Health Science Center at San Antonio), Justino Regalado Pineda(The University of Texas Health Science Center at San Antonio), David Chien Lye(The University of Texas Health Science Center at San Antonio), Uriel Sandkovsky(The University of Texas Health Science Center at San Antonio), Anne F. Luetkemeyer(The University of Texas Health Science Center at San Antonio), Stuart H. Cohen(The University of Texas Health Science Center at San Antonio), Robert W. Finberg(The University of Texas Health Science Center at San Antonio), Patrick Jackson(The University of Texas Health Science Center at San Antonio), Babafemi Taiwo(The University of Texas Health Science Center at San Antonio), Catharine I. Paules(The University of Texas Health Science Center at San Antonio), Henry Arguinchona(The University of Texas Health Science Center at San Antonio), Nathaniel Erdmann(The University of Texas Health Science Center at San Antonio), Neera Ahuja(The University of Texas Health Science Center at San Antonio), Maria G. Frank(The University of Texas Health Science Center at San Antonio), Myoung‐don Oh(The University of Texas Health Science Center at San Antonio), Eu Suk Kim(The University of Texas Health Science Center at San Antonio), Seow Yen Tan(The University of Texas Health Science Center at San Antonio), Richard A. Mularski(The University of Texas Health Science Center at San Antonio), Henrik Nielsen(The University of Texas Health Science Center at San Antonio), Philip O. Ponce(The University of Texas Health Science Center at San Antonio), Barbara S. Taylor(The University of Texas Health Science Center at San Antonio), LuAnn Larson(The University of Texas Health Science Center at San Antonio), Nadine Rouphael(The University of Texas Health Science Center at San Antonio), Youssef Saklawi(The University of Texas Health Science Center at San Antonio), Valeria D Cantos(The University of Texas Health Science Center at San Antonio), Emily R. Ko(The University of Texas Health Science Center at San Antonio), John J. Engemann(The University of Texas Health Science Center at San Antonio), Alpesh Amin(The University of Texas Health Science Center at San Antonio), Miki Watanabe(The University of Texas Health Science Center at San Antonio), Joanne Billings(The University of Texas Health Science Center at San Antonio), Marie‐Carmelle Elie(The University of Texas Health Science Center at San Antonio), Richard T. Davey(The University of Texas Health Science Center at San Antonio), Timothy Burgess(The University of Texas Health Science Center at San Antonio), Jennifer Ferreira(The University of Texas Health Science Center at San Antonio), Michelle Green(The University of Texas Health Science Center at San Antonio), Mat Makowski(The University of Texas Health Science Center at San Antonio), Anabela Cardoso(The University of Texas Health Science Center at San Antonio), Stephanie de Bono(The University of Texas Health Science Center at San Antonio), Tyler Bonnett(The University of Texas Health Science Center at San Antonio), Michael A. Proschan(The University of Texas Health Science Center at San Antonio), Gregory A. Deye(The University of Texas Health Science Center at San Antonio), Walla Dempsey(The University of Texas Health Science Center at San Antonio), Seema Nayak(The University of Texas Health Science Center at San Antonio), Lori E. Dodd(The University of Texas Health Science Center at San Antonio), John H. Beigel(The University of Texas Health Science Center at San Antonio)
New England Journal of Medicine
December 11, 2020
10.1056/nejmoa2031994
Cited by 1,910Open Access
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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.).

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