Baricitinib and remdesivir combination therapy was superior to remdesivir alone in reducing recovery time and accelerating clinical status improvement in patients with coronavirus disease 2019 (COVID-19), according to results published in The New England Journal of Medicine.
In this double-blind, randomized, placebo-controlled trial (ACTT-2; ClinicalTrials.gov identifier: NCT04401579), investigators assessed the effectiveness of the baricitinib in combination with remdesivir. All patients in the study (N=1033) received remdesivir for 10 days or less in addition to either baricitinib (combination group; n=515) or placebo (placebo group; n=518) for 14 days or less. The primary outcome was time to recovery; key secondary outcome was clinical status at day 15.
In the combination group, 498 patients completed the trial through day 29, recovered, or died, compared with 495 in the control group. Patients in the combination group recovered a mean of 1 day faster compared with the control group (median, 7 vs 8; P =.03). When analyzed based on severity at randomization (moderate vs severe), the hazard ratio [HR] was 1.15 (95% CI, 1.00-1.31; P =.047).
For patients receiving noninvasive ventilation or high-flow oxygen, recovery time was 10 days with combination therapy and 18 days with remdesivir monotherapy. At day 15, the odds of improvement in clinical status were greater for patients in the combination group compared with patients in the control group (odds ratio for improvement, 1.3; 95% CI, 1.0-1.6). Estimates of mortality at day 28 post-randomization were 5.1% (95% CI, 3.5-7.6) and 7.8% (95% CI, 5.7-10.6) in the combination and control groups, respectively (HR for death, 0.65; 95% CI, 0.39-1.09).
A total of 207 patients in the combination group (40.7%) and 238 patients in the control group (46.8%) experienced grade 3 or 4 adverse events, of which 25 cases and 28 cases were determined to be related to treatment, respectively. Most common grade 3 and 4 adverse events were hyperglycemia, anemia, decreased lymphocyte count, and acute kidney injury.
In total, 81 patients in the combination group (16.0%) and 107 patients in the control group (21.0%) experienced serious adverse events (P= .03). Patients in the combination group experienced less new infections compared to the control group (5.9% vs 11.2%; P =.003).
“[C]ombination treatment with the anti-inflammatory drug baricitinib and the antiviral drug remdesivir was safe and superior to remdesivir alone for the treatment of hospitalized patients with COVID-19 pneumonia,” the study authors concluded. Combination therapy patients had a 1-day shorter recovery time and greater improvement in clinical status.
Study authors found that despite concerns of immunosuppression, adding baricitinib was not associated with a significantly higher incidence of adverse events or thromboembolic events.
Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus Remdesivir for hospitalized adults with Covid-19. N Engl J Med. Published online December 11, 2020. doi:10.1056/NEJMoa2031994.