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 Tapson, Nicole M Iovine, Mamta K Jain, Daniel A Sweeney, Hana M El Sahly, Angela R Branche, Justino Regalado Pineda, David C Lye, Uriel Sandkovsky, Anne F LuetkemeyerStuart H Cohen, Robert W Finberg, Patrick E H Jackson, Babafemi Taiwo, Catharine I Paules, Henry Arguinchona, Nathaniel Erdmann, Neera Ahuja, Maria Frank, Myoung-Don Oh, Eu-Suk Kim, Seow Y Tan, Richard A Mularski, Henrik Nielsen, Philip O Ponce, Barbara S Taylor, LuAnn Larson, Nadine G Rouphael, Youssef Saklawi, Valeria D Cantos, Emily R Ko, John J Engemann, Alpesh N Amin, Miki Watanabe, Joanne Billings, Marie-Carmelle Elie, Richard T Davey, Timothy H Burgess, Jennifer Ferreira, Michelle Green, Mat Makowski, Anabela Cardoso, Stephanie Bono, de, Tyler Bonnett, Michael Proschan, Gregory A Deye, Walla Dempsey, Seema U Nayak, Lori E Dodd, John H Beigel, ACTT-2 Study Group Members, Jens Dilling Lundgren (Medlem af forfattergruppering), Daniel D. Murray (Medlem af forfattergruppering), Tomas Østergaard Jensen (Medlem af forfattergruppering)

1354 Citationer (Scopus)

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.).

OriginalsprogEngelsk
TidsskriftThe New England journal of medicine
Vol/bind384
Udgave nummer9
Sider (fra-til)795-807
Antal sider13
ISSN0028-4793
DOI
StatusUdgivet - 4 mar. 2021

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