• Andre C Kalil, Thomas F Patterson, Aneesh K Mehta, Kay M Tomashek, Cameron R Wolfe, Varduhi Ghazaryan, Vincent C Marconi, Guillermo M Ruiz-Palacios, Lanny Hsieh, Susan Kline, Victor Tapson, Nicole M Iovine, Mamta K Jain, Daniel A Sweeney, Hana M El Sahly, Angela R Branche, Justino Regalado Pineda, David C Lye, Uriel Sandkovsky, Anne F Luetkemeyer, Stuart H Cohen, Robert W Finberg, Patrick E H Jackson, Babafemi Taiwo, Catharine I Paules, Henry Arguinchona, Nathaniel Erdmann, Neera Ahuja, Maria Frank, Myoung-Don Oh, Eu-Suk Kim, Seow Y Tan, Richard A Mularski, Henrik Nielsen, Philip O Ponce, Barbara S Taylor, LuAnn Larson, Nadine G Rouphael, Youssef Saklawi, Valeria D Cantos, Emily R Ko, John J Engemann, Alpesh N Amin, Miki Watanabe, Joanne Billings, Marie-Carmelle Elie, Richard T Davey, Timothy H Burgess, Jennifer Ferreira, Michelle Green, Mat Makowski, Anabela Cardoso, Stephanie de Bono, Tyler Bonnett, Michael Proschan, Gregory A Deye, Walla Dempsey, Seema U Nayak, Lori E Dodd, John H Beigel, and ACTT-2 Study Group Members.
• From the University of Nebraska Medical Center, Omaha (A.C.K., L.L.); University of Texas Health San Antonio, University Health, and the South Texas Veterans Health Care System, San Antonio (T.F.P., P.O.P., B.S.T.), UT Southwestern Medical Center, Parkland Health and Hospital System (M.K.J.) and Baylor Scott and White Health (U.S.), Dallas, and Baylor College of Medicine, Houston (H.M.E.S.) - all in Texas; Emory University (A.K.M., N.G.R., Y.S., V.C.M., V.D.C.) and Grady Memorial Hospital (V.D.C.), Atlanta, and Atlanta Veterans Affairs Medical Center, Decatur (V.C.M.) - both in Georgia; the National Institute of Allergy and Infectious Diseases, National Institutes of Health (K.M.T., V.G., R.T.D., M.P., G.A.D., W.D., S.U.N., L.E.D., J.H.B.), and the Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences (T.H.B.), Bethesda, and Emmes (J.F., M.G., M.M.) and Clinical Monitoring Research Program Directorate, Frederick National Laboratory (T.B.), Rockville - both in Maryland; Duke University, Durham, NC (C.R.W., E.R.K., J.J.E.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, (G.M.R.-P.) and Instituto Nacional de Enfermedades Respiratorias (J.R.P.), Mexico City; University of California Irvine, Irvine (L.H., A.N.A., M.W.), Cedars-Sinai Medical Center, Los Angeles (V.T.), University of California, San Diego, La Jolla (D.A.S.), University of California, San Francisco, San Francisco (A.F.L.), University of California, Davis, Davis (S.H.C.), and Stanford University, Stanford (N.A.) - all in California; University of Minnesota Medical School, Minneapolis (S.K., J.B.); University of Florida, Gainesville (N.M.I., M.-C.E.); University of Rochester, Rochester, NY (A.R.B.); National Center for Infectious Diseases, Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, and Yong Loo Lin School of Medicine (D.C.L.), and Changi General Hospital (S.Y.T.), Singapore; University of Massachusetts Medical School, Worcester (R.W.F.); University of Virginia, Charlottesville (P.E.H.J.); Northwestern University, Chicago (B.T.); Penn State Health Milton S. Hershey Medical Center, Hershey, PA (C.I.P.); Providence Sacred Heart Medical Center, Spokane, WA (H.A.); University of Alabama at Birmingham, Birmingham (N.E.); Denver Health and Hospital Authority, Denver (M.F.); Seoul National University Hospital, Seoul (M.O.), and Seoul National University Bundang Hospital, Seongnam (E.-S.K.) - both in South Korea; Kaiser Permanente Northwest, Portland, OR (R.A.M.); Aalborg University Hospital, Aalborg, Denmark (H.N.); and Eli Lilly, Indianapolis (A.C., S.B.).
• N. Engl. J. Med. 2021 Mar 4; 384 (9): 795807795-807.

BackgroundSevere 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.MethodsWe 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.ResultsA 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).ConclusionsBaricitinib 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.).Copyright © 2020 Massachusetts Medical Society.

45 keywords...

hide…