巴瑞替尼联合瑞德西韦治疗住院的新冠成年患者

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

作者信息

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 Catharine I, Arguinchona Henry, Erdmann Nathaniel, Ahuja Neera, Frank Maria, Oh Myoung-Don, Kim Eu-Suk, 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

机构信息

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.).

出版信息

N Engl J Med. 2021 Mar 4;384(9):795-807. doi: 10.1056/NEJMoa2031994. Epub 2020 Dec 11.

DOI:10.1056/NEJMoa2031994

PMID:33306283

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7745180/

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.).

摘要

背景

2019年冠状病毒病（Covid-19）重症患者存在炎症调节异常。尚不清楚Janus激酶抑制剂巴瑞替尼联合瑞德西韦治疗的效果。

方法

我们开展了一项双盲、随机、安慰剂对照试验，评估巴瑞替尼联合瑞德西韦用于住院的Covid-19成年患者的疗效。所有患者均接受瑞德西韦治疗（≤10天），并随机接受巴瑞替尼治疗（≤14天）或安慰剂治疗（对照组）。主要结局为恢复时间。关键次要结局为第15天时的临床状态。

结果

共有1033例患者接受随机分组（515例接受联合治疗，518例接受对照治疗）。接受巴瑞替尼治疗的患者恢复时间中位数为7天（95%置信区间[CI]，6至8天），而对照组为8天（95%CI，7至9天）（恢复率比为1.16；95%CI，1.01至1.32；P = 0.03），且在第15天时临床状态改善的几率高30%（优势比为1.3；95%CI，1.0至1.6）。入组时接受高流量吸氧或无创通气的患者，联合治疗组的恢复时间为10天，对照组为18天（恢复率比为1.51；95%CI，1.10至2.08）。联合治疗组28天死亡率为5.1%，对照组为7.8%（死亡风险比为0.65；95%CI，0.39至1.09）。联合治疗组严重不良事件的发生频率低于对照组（16.0%对21.0%；差异为-5.0个百分点；