Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19
12/2020
Journal Article
Authors:
Kalil, A. C.;
Patterson, T. F.;
Mehta, A. K.;
Tomashek, K. M.;
Wolfe, C. R.;
Ghazaryan, V.;
Marconi, V. C.;
Ruiz-Palacios, G. M.;
Hsieh, L.;
Kline, S.;
Tapson, V.;
Iovine, N. M.;
Jain, M. K. ;
Sweeney, D. A.;
El Sahly, H. M.;
Branche, A. R.;
Regalado Pineda, J.;
Lye, D. C.;
Sandkovsky, U.;
Luetkemeyer, A. F.;
Cohen, S. H.;
Finberg, R. W.;
Jackson, P. E. H.;
Taiwo, B.;
Paules, C. I.;
Arguinchona, H.;
Erdmann, N.;
Ahuja, N.;
Frank, M.;
Oh, M. D.;
Kim, E. S.;
Tan, S. Y. ;
Mularski, R. A.;
Nielsen, H.;
Ponce, P. O.;
Taylor, B. S.;
Larson, L.;
Rouphael, N. G.;
Saklawi, Y.;
Cantos, V. D.;
Ko, E. R.;
Engemann, J. J.;
Amin, A. N.;
Watanabe, M.;
Billings, J.;
Elie, M. C.;
Davey, R. T.;
Burgess, T. H. ;
Ferreira, J.;
Green, M.;
Makowski, M.;
Cardoso, A.;
de Bono, S.;
Bonnett, T. ;
Proschan, M.;
Deye, G. A.;
Dempsey, W.;
Nayak, S. U.;
Dodd, L. E.;
Beigel, J. H.
Volume:
384
Pagination:
795-807
Issue:
9
Journal:
N Engl J Med
PMID:
33306283
URL:
https://www.ncbi.nlm.nih.gov/pubmed/33306283
Keywords:
Adenosine Monophosphate/adverse effects/*analogs & derivatives/therapeutic use Adult Aged Alanine/adverse effects/*analogs & derivatives/therapeutic use Antiviral Agents/adverse effects/*therapeutic use
Azetidines/adverse effects/*therapeutic use COVID-19/mortality/therapy Double-Blind Method Drug Therapy, Combination Female Hospital Mortality Hospitalization Humans Janus Kinase Inhibitors/adverse effects/therapeutic use
Male Middle Aged Oxygen Inhalation Therapy Purines/adverse effects/*therapeutic use Pyrazoles/adverse effects/*therapeutic use Respiration, Artificial Sulfonamides/adverse effects/*therapeutic use Treatment Outcome *COVID-19 Drug Treatment
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.).
