Baricitinib reduces mortality in patients with COVID-19 on mechanical ventilation, ECMO

Treatment with baricitinib reduced mortality in critically ill patients with COVID-19 receiving invasive mechanical ventilation or extracorporeal membrane oxygenation, researchers reported in The Lancet Respiratory Medicine.

“The FDA issued an emergency use authorization (EUA) for the use of baricitinib to treat COVID-19 in hospitalized adults and pediatric patients aged 2 years or older requiring supplemental oxygen, noninvasive mechanical ventilation or invasive mechanical ventilation, or ECMO. The EUA was first issued in November 2020 on the basis of ACTT-2 results and later updated in July 2021 based on COV-BARRIER NIAID-OS 4-6 results,” E. Wesley Ely, MD, professor of medicine and critical care at Vanderbilt University Medical Center and associate director of aging research at the Veterans Affairs Tennessee Valley Geriatric Research and Education Clinical Center, Nashville, and colleagues wrote. “In October 2020, the FDA requested further evaluation of baricitinib for the treatment of critically ill adult patients with COVID-19 requiring invasive mechanical ventilation or ECMO.”

The researchers conducted an exploratory trial that included 101 adults enrolled from December 2020 to April 2021 across 18 hospitals in Argentina, Brazil, Mexico and the U.S. The trial followed the design of the COV-BARRIER trial, looking at critically ill patients who were not included in the main trial.

All participants were hospitalized with COVID-19 and were receiving invasive mechanical ventilation or ECMO. Participants were randomly assigned to receive baricitinib 4 mg (Olumiant, Eli Lilly; n = 51) or placebo (n = 50) once daily for up to 14 days plus standard of care, which included systemic corticosteroids in 86% of patients.

The primary outcomes were all-cause mortality at 28 and 60 days, number of ventilator-free days, hospitalization duration and time to recovery through 28 days.

Baricitinib reduced all-cause mortality at 28 days compared with placebo (39% vs. 58%; HR = 0.54; 95% CI, 0.31-0.96; P = .03).

Researchers also observed a reduction in all-cause mortality at 60 days among those assigned baricitinib compared with placebo (45% vs. 62%; HR = 0.56; 95% CI, 0.33-0.97; P = .027).

One in six additional deaths were prevented among participants treated with baricitinib compared with placebo at 28 and 60 days, according to the researchers.

Ely and colleagues reported no significant difference in ventilator-free days between those assigned baricitinib or placebo (mean, 8.1 days vs. 5.5 days; P = .21). In addition, duration of hospitalization among those assigned baricitinib was not significantly shorter than for those assigned placebo (mean, 23.7 days vs. 26.1 days; P = .05).

Rates of treatment-emergent infections were similar (70% vs. 71%) as were positively adjudicated venous thromboembolic events (6% vs. 6%) between those assigned baricitinib and placebo. Serious treatment-emergent infections occurred in 44% of those assigned baricitinib compared with 53% assigned placebo.

“Baricitinib, when used to treat critically ill patients with COVID-19, might represent a novel option to reduce mortality, even if the disease process has progressed to the point of already receiving corticosteroids, invasive mechanical ventilation and ECMO,” the researchers wrote. “However, further well-designed phase 3 trials are necessary to provide additional data to support routine use of baricitinib in the studied population.”