Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

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Citation

Kalil, A. C., T. F. Patterson, A. K. Mehta, K. M. Tomashek, C. R. Wolfe, V. Ghazaryan, V. C. Marconi, G. M. Ruiz-Palacios, L. Hsieh, S. Kline, V. Tapson, N. M. Iovine, M. K. Jain, D. A. Sweeney, H. M. El Sahly, A. R. Branche, J. Regalado Pineda, D. C. Lye, U. Sandkovsky, A. F. Luetkemeyer, S. H. Cohen, R. W. Finberg, P. E. H. Jackson, B. Taiwo, C. I. Paules, H. Arguinchona, P. Goepfert, N. Ahuja, M. Frank, M. D. Oh, E. S. Kim, S. Y. Tan, R. A. Mularski, H. Nielsen, P. O. Ponce, B. S. Taylor, L. Larson, N. G. Rouphael, Y. Saklawi, V. D. Cantos, E. R. Ko, J. J. Engemann, A. N. Amin, M. Watanabe, J. Billings, M. C. Elie, R. T. Davey, T. H. Burgess, J. Ferreira, M. Green, M. Makowski, A. Cardoso, S. de Bono, T. Bonnett, M. Proschan, G. A. Deye, W. Dempsey, S. U. Nayak, L. E. Dodd, and J. H. Beigel. 2020. "Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19." The New England journal of medicine.

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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