Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

Kalil, Andre C.; Patterson, Thomas F.; Mehta, Aneesh K.; Tomashek, Kay M.; Wolfe, Cameron R.; Ghazaryan, Varduhi; Marconi, Vincent C.; Ruiz-Palacios, Guillermo M.; Hsieh, Lanny; Kline, Susan; Tapson, Victor; Iovine, Nicole M.; Jain, Mamta K.; Sweeney, Daniel A.; El Sahly, Hana M.; Branche, Angela R.; Regalado Pineda, Justino; Lye, David C.; Sandkovsky, Uriel; Luetkemeyer, Anne F.; Cohen, Stuart H.; Finberg, Robert W.; Jackson, Patrick E.H.; Taiwo, Babafemi; Paules, Catherine I.; Arguinchona, Henry; Goepfert, Paul; Ahuja, Neera; Frank, Maria; Oh, Myoung-don; Kim, Eu S.; Tan, Seow Y.; Mularski, Richard A.; Nielsen, Henrik; Ponce, Philip O.; Taylor, Barbara S.; Larson, LuAnn; Rouphael, Nadine G.; Saklawi, Youssef; Cantos, Valeria D.; Ko, Emily R.; Engemann, John J.; Amin, Alpesh N.; Watanabe, Miki; Billings, Joanne; Elie, Marie-Carmelle; Davey, Richard T.; Burgess, Timothy H.; Ferreira, Jennifer; Green, Michelle; Makowski, Mat; Cardoso, Anabela; de Bono, Stephanie; Bonnett, Tyler; Proschan, Michael; Deye, Gregory A.; Dempsey, Walla; Nayak, Seema U.; Dodd, Lori E.; Beigel, John H.

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.)