Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
(Journal Article;Multicenter Study)
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.).
Kalil, AC; Patterson, TF; Mehta, AK; Tomashek, KM; Wolfe, CR; Ghazaryan, V; Marconi, VC; Ruiz-Palacios, GM; Hsieh, L; Kline, S; Tapson, V; Iovine, NM; Jain, MK; Sweeney, DA; El Sahly, HM; Branche, AR; Regalado Pineda, J; Lye, DC; Sandkovsky, U; Luetkemeyer, AF; Cohen, SH; Finberg, RW; Jackson, PEH; Taiwo, B; Paules, CI; Arguinchona, H; Erdmann, N; Ahuja, N; Frank, M; Oh, M-D; Kim, E-S; Tan, SY; Mularski, RA; Nielsen, H; Ponce, PO; Taylor, BS; Larson, L; Rouphael, NG; Saklawi, Y; Cantos, VD; Ko, ER; Engemann, JJ; Amin, AN; Watanabe, M; Billings, J; Elie, M-C; Davey, RT; Burgess, TH; Ferreira, J; Green, M; Makowski, M; Cardoso, A; de Bono, S; Bonnett, T; Proschan, M; Deye, GA; Dempsey, W; Nayak, SU; Dodd, LE; Beigel, JH; ACTT-2 Study Group Members,
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