Finding a Role for Remdesivir as Part of Combo Therapy for COVID-19


Regimen reduces mortality and recovery time in patients severely ill with pneumonia caused by the virus.


As we reported in this space, finding an effective treatment for COVID-19 using older-line antiviral drugs has proved elusive—at least to date.

A notable exception, though, may be remdesivir. Although hardly a cure, the drug originally developed as an option for Ebola virus may yet find a life in the management of patients with pneumonia caused by severe COVID-19, as part of a combination regimen with the rheumatoid arthritis drug baricitinib. A study published in the New England Journal of Medicine (NEJM) found that patients treated with the regimen recovered slightly faster and had 30% higher odds of clinical improvement than those given a placebo.

That hardly makes the baricitinib/remdesivir regimen a “miracle cure” for the disease caused by SARS-CoV-2 but, given that outcomes in infected patients who become seriously ill are generally poor, any approach that offers some benefit—with minimal risk—is welcome.

“Baricitinib plus remdesivir is effective and safe for the treatment of hospitalized patients with moderate-severe COVID-19 pneumonia,” study co-author Andre Kalil, MD, MPH, FACP, FIDSA, FCCM, a professor of internal medicine and director of the Transplant ID Program at University of Nebraska Medical Center, told Contagion®. “This combination is associated with a shorter time to recovery and hospital discharge, faster clinical status improvement, decrease in the need for supplemental oxygen, reduction in the progression to intubation or death, and also reduction in mechanical ventilation duration. In addition, the combination therapy is associated with fewer serious adverse events and less new secondary infections. All these findings were statistically significant and clinically meaningful to our patients with COVID-19 pneumonia.”

In general, repurposed drugs (think: hydroxychloroquine or lopinavir) have demonstrated little efficacy in the treatment of COVID-19, and/or have been deemed not worth the risks, given severe adverse events. Remdesivir, though, has been the notable exception. On November 19, the US Food and Drug Administration granted the combination approach used in the NEJM study an emergency use authorization for the treatment of COVID-19. Still, in November, the World Health Organization formally recommended against using remdesivir monotherapy, citing lack of evidence supporting clinical benefit.

For their research, Dr. Kalil and his colleagues enrolled 1,033 hospitalized adults, with 515 receiving the combination regimen and 518 being administered a placebo. Those treated with the study regimen received remdesivir intravenously as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily on days 2 through 10 (or until hospital discharge or death). Baricitinib, meanwhile, was administered as a 4-mg daily dose—either orally or through a nasogastric tube—for 14 days (or until hospital discharge).

Patients on the combination regimen had a median time to recovery of 7 days vs 8 days for placebo and a 30% higher odds of improvement in clinical status at day 15. Those treated with high-flow oxygen or noninvasive ventilation in addition to the study regimen had a time to recovery of 10 days vs 18 days with placebo. The 28-day mortality was 5.1% in the combination group and 7.8% in the placebo group. Notably, serious adverse events were less frequent in the combination group (16%) than in the placebo group (21%; P=0.03), as were new infections (5.9% vs. 11.2%; P=0.003), according to the researchers.

“Remdesivir is the only antiviral medication that has proven to significantly speed up recovery and allow patients to leave the hospital almost 1 week earlier, decreases the need for noninvasive and invasive ventilation, and reduces mortality by half within the first 2 weeks of treatment,” Kalil said. “This robust evidence supports the FDA approval of remdesivir as a standard of care [for COVID-19], as well as the recommendation to use remdesivir by the Infectious Diseases Society of America and the National Institutes of Health Guidelines.”

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