tetano
Editor, Senior Moderator
N Engl J Med
. 2020 Dec 11.
doi: 10.1056/NEJMoa2031994. Online ahead of print.
Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
Andre C Kalil[SUP] 1 [/SUP], Thomas F Patterson[SUP] 1 [/SUP], Aneesh K Mehta[SUP] 1 [/SUP], Kay M Tomashek[SUP] 1 [/SUP], Cameron R Wolfe[SUP] 1 [/SUP], Varduhi Ghazaryan[SUP] 1 [/SUP], Vincent C Marconi[SUP] 1 [/SUP], Guillermo M Ruiz-Palacios[SUP] 1 [/SUP], Lanny Hsieh[SUP] 1 [/SUP], Susan Kline[SUP] 1 [/SUP], Victor Tapson[SUP] 1 [/SUP], Nicole M Iovine[SUP] 1 [/SUP], Mamta K Jain[SUP] 1 [/SUP], Daniel A Sweeney[SUP] 1 [/SUP], Hana M El Sahly[SUP] 1 [/SUP], Angela R Branche[SUP] 1 [/SUP], Justino Regalado Pineda[SUP] 1 [/SUP], David C Lye[SUP] 1 [/SUP], Uriel Sandkovsky[SUP] 1 [/SUP], Anne F Luetkemeyer[SUP] 1 [/SUP], Stuart H Cohen[SUP] 1 [/SUP], Robert W Finberg[SUP] 1 [/SUP], Patrick E H Jackson[SUP] 1 [/SUP], Babafemi Taiwo[SUP] 1 [/SUP], Catherine I Paules[SUP] 1 [/SUP], Henry Arguinchona[SUP] 1 [/SUP], Paul Goepfert[SUP] 1 [/SUP], Neera Ahuja[SUP] 1 [/SUP], Maria Frank[SUP] 1 [/SUP], Myoung-Don Oh[SUP] 1 [/SUP], Eu S Kim[SUP] 1 [/SUP], Seow Y Tan[SUP] 1 [/SUP], Richard A Mularski[SUP] 1 [/SUP], Henrik Nielsen[SUP] 1 [/SUP], Philip O Ponce[SUP] 1 [/SUP], Barbara S Taylor[SUP] 1 [/SUP], LuAnn Larson[SUP] 1 [/SUP], Nadine G Rouphael[SUP] 1 [/SUP], Youssef Saklawi[SUP] 1 [/SUP], Valeria D Cantos[SUP] 1 [/SUP], Emily R Ko[SUP] 1 [/SUP], John J Engemann[SUP] 1 [/SUP], Alpesh N Amin[SUP] 1 [/SUP], Miki Watanabe[SUP] 1 [/SUP], Joanne Billings[SUP] 1 [/SUP], Marie-Carmelle Elie[SUP] 1 [/SUP], Richard T Davey[SUP] 1 [/SUP], Timothy H Burgess[SUP] 1 [/SUP], Jennifer Ferreira[SUP] 1 [/SUP], Michelle Green[SUP] 1 [/SUP], Mat Makowski[SUP] 1 [/SUP], Anabela Cardoso[SUP] 1 [/SUP], Stephanie de Bono[SUP] 1 [/SUP], Tyler Bonnett[SUP] 1 [/SUP], Michael Proschan[SUP] 1 [/SUP], Gregory A Deye[SUP] 1 [/SUP], Walla Dempsey[SUP] 1 [/SUP], Seema U Nayak[SUP] 1 [/SUP], Lori E Dodd[SUP] 1 [/SUP], John H Beigel[SUP] 1 [/SUP]
Affiliations
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.).
. 2020 Dec 11.
doi: 10.1056/NEJMoa2031994. Online ahead of print.
Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
Andre C Kalil[SUP] 1 [/SUP], Thomas F Patterson[SUP] 1 [/SUP], Aneesh K Mehta[SUP] 1 [/SUP], Kay M Tomashek[SUP] 1 [/SUP], Cameron R Wolfe[SUP] 1 [/SUP], Varduhi Ghazaryan[SUP] 1 [/SUP], Vincent C Marconi[SUP] 1 [/SUP], Guillermo M Ruiz-Palacios[SUP] 1 [/SUP], Lanny Hsieh[SUP] 1 [/SUP], Susan Kline[SUP] 1 [/SUP], Victor Tapson[SUP] 1 [/SUP], Nicole M Iovine[SUP] 1 [/SUP], Mamta K Jain[SUP] 1 [/SUP], Daniel A Sweeney[SUP] 1 [/SUP], Hana M El Sahly[SUP] 1 [/SUP], Angela R Branche[SUP] 1 [/SUP], Justino Regalado Pineda[SUP] 1 [/SUP], David C Lye[SUP] 1 [/SUP], Uriel Sandkovsky[SUP] 1 [/SUP], Anne F Luetkemeyer[SUP] 1 [/SUP], Stuart H Cohen[SUP] 1 [/SUP], Robert W Finberg[SUP] 1 [/SUP], Patrick E H Jackson[SUP] 1 [/SUP], Babafemi Taiwo[SUP] 1 [/SUP], Catherine I Paules[SUP] 1 [/SUP], Henry Arguinchona[SUP] 1 [/SUP], Paul Goepfert[SUP] 1 [/SUP], Neera Ahuja[SUP] 1 [/SUP], Maria Frank[SUP] 1 [/SUP], Myoung-Don Oh[SUP] 1 [/SUP], Eu S Kim[SUP] 1 [/SUP], Seow Y Tan[SUP] 1 [/SUP], Richard A Mularski[SUP] 1 [/SUP], Henrik Nielsen[SUP] 1 [/SUP], Philip O Ponce[SUP] 1 [/SUP], Barbara S Taylor[SUP] 1 [/SUP], LuAnn Larson[SUP] 1 [/SUP], Nadine G Rouphael[SUP] 1 [/SUP], Youssef Saklawi[SUP] 1 [/SUP], Valeria D Cantos[SUP] 1 [/SUP], Emily R Ko[SUP] 1 [/SUP], John J Engemann[SUP] 1 [/SUP], Alpesh N Amin[SUP] 1 [/SUP], Miki Watanabe[SUP] 1 [/SUP], Joanne Billings[SUP] 1 [/SUP], Marie-Carmelle Elie[SUP] 1 [/SUP], Richard T Davey[SUP] 1 [/SUP], Timothy H Burgess[SUP] 1 [/SUP], Jennifer Ferreira[SUP] 1 [/SUP], Michelle Green[SUP] 1 [/SUP], Mat Makowski[SUP] 1 [/SUP], Anabela Cardoso[SUP] 1 [/SUP], Stephanie de Bono[SUP] 1 [/SUP], Tyler Bonnett[SUP] 1 [/SUP], Michael Proschan[SUP] 1 [/SUP], Gregory A Deye[SUP] 1 [/SUP], Walla Dempsey[SUP] 1 [/SUP], Seema U Nayak[SUP] 1 [/SUP], Lori E Dodd[SUP] 1 [/SUP], John H Beigel[SUP] 1 [/SUP]
Affiliations
- PMID: 33306283
- DOI: 10.1056/NEJMoa2031994
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.).