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.).

Remdesivir, a broad-spectrum antiviral agent administered intravenously, was developed and studied as a potential treatment for Ebola virus disease and Marburg virus infection. In vitro and in vivo preclinical studies found antiviral activity for remdesivir against corona-like viruses, including Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV-1), the circulating human coronaviruses HCoV-OC42 and HCoV-229E, and SARS-CoV-2. Currently, the effectiveness of remdesivir is being tested as a treatment for patients infected with SARS-CoV-2 (COVID-19) and has been authorized for emergency use for treating COVID-19, by the U.S. Food and Drug Administration in the United States, and in other countries. The American College of Physicians (ACP) Scientific Medical Policy Committee (SMPC) based these rapid and living practice points on a systematic evidence review conducted by the U.S. Department of Veterans Affairs (VA) Evidence Synthesis Program in Minneapolis, Minnesota. This version of the practice points, based on a search completed on 3 June 2020 and updated through 31 August 2020, was approved by the ACP's Executive Committee of Board of Regents on behalf of the Board of Regents on 14 August 2020 and submitted to Annals of Internal Medicine on 13 August 2020. Because many studies are planned or under way, literature surveillance is ongoing, with updates currently planned for every 2 months through December 2021. The target audience for these practice points includes clinicians and the public. The target patient population includes all nonpregnant patients with COVID-19.

This is an update of the American College of Physicians' living, rapid practice points on the use of remdesivir for treatment of COVID-19. This update is based on an updated living, rapid systematic review that included studies published through 19 October 2021 and identified 2 new studies meeting inclusion criteria.