TY - JOUR
T1 - Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
AU - Kalil, Andre C.
AU - Patterson, Thomas F.
AU - Mehta, Aneesh K.
AU - Tomashek, Kay M.
AU - Wolfe, Cameron R.
AU - Ghazaryan, Varduhi
AU - Marconi, Vincent C.
AU - Ruiz-Palacios, Guillermo M.
AU - Hsieh, Lanny
AU - Kline, Susan
AU - Tapson, Victor
AU - Iovine, Nicole M.
AU - Jain, Mamta K.
AU - Sweeney, Daniel A.
AU - El Sahly, Hana M.
AU - Branche, Angela R.
AU - Regalado Pineda, Justino
AU - Lye, David C.
AU - Sandkovsky, Uriel
AU - Luetkemeyer, Anne F.
AU - Cohen, Stuart H.
AU - Finberg, Robert W.
AU - Jackson, Patrick E.H.
AU - Taiwo, Babafemi
AU - Paules, Catherine I.
AU - Arguinchona, Henry
AU - Goepfert, Paul
AU - Ahuja, Neera
AU - Frank, Maria
AU - Oh, Myoung-don
AU - Kim, Eu S.
AU - Tan, Seow Y.
AU - Mularski, Richard A.
AU - Nielsen, Henrik
AU - Ponce, Philip O.
AU - Taylor, Barbara S.
AU - Larson, LuAnn
AU - Rouphael, Nadine G.
AU - Saklawi, Youssef
AU - Cantos, Valeria D.
AU - Ko, Emily R.
AU - Engemann, John J.
AU - Amin, Alpesh N.
AU - Watanabe, Miki
AU - Billings, Joanne
AU - Elie, Marie-Carmelle
AU - Davey, Richard T.
AU - Burgess, Timothy H.
AU - Ferreira, Jennifer
AU - Green, Michelle
AU - ACTT-2 Study Group Members
N1 - The authors represent the ACTT-2 Study Group. A complete list of members of the
ACTT-2 Study Group is provided in the Supplementary Appendix, available at
NEJM.org.
PY - 2021/3/4
Y1 - 2021/3/4
N2 - 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.).
AB - 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.).
UR - http://www.scopus.com/inward/record.url?scp=85102545545&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2031994
DO - 10.1056/NEJMoa2031994
M3 - Journal article
C2 - 33306283
SN - 0028-4793
VL - 384
SP - 795
EP - 807
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 9
ER -