美国内布拉斯加大学医学中心Andre C. Kalil研究了巴瑞替尼联合瑞德西韦治疗成人Covid-19住院患者的疗效。2020年12月11日，该研究发表在《新英格兰医学杂志》上。

Covid-19与炎症失调有关。尚不清楚Janus激酶抑制剂巴瑞替尼和瑞德西韦联合治疗的效果。研究组进行了一项双盲、随机、安慰剂对照试验，招募了1033例成人Covid-19住院患者，其中515例接受巴瑞替尼和瑞德西韦联合治疗，518例接受安慰剂治疗。主要结局是康复时间，关键次要结局是第15天的临床状态。

联合治疗组患者的中位康复时间为7天，而对照组为8天，康复比率为1.16；联合治疗组第15天临床状况改善的几率比对照组高出30％。对于入组时接受高流量氧气或无创通气的患者，联合治疗组的康复时间为10天，显著短于对照组（18天），康复比率为1.51。

联合治疗组的28天死亡率为5.1％，显著低于对照组（7.8％），风险比为0.65。联合治疗组的严重不良事件发生率为16.0％，显著低于对照组（21.0％）；新发感染率为5.9％，显著低于对照组（11.2％）。

综上，对于Covid-19患者，尤其是接受高流量氧气或无创通气的患者，采用巴瑞替尼和瑞德西韦联合治疗，与单独瑞德西韦治疗相比，可缩短恢复时间并加快临床状况的改善，同时严重不良事件较少。

附：英文原文

Title: Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

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

Issue&Volume: 2020-12-11

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.

DOI: 10.1056/NEJMoa2031994

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2031994