Baricitinib has better safety profile than dexamethasone when added to remdesivir for COVID-19
NEW YORK 09/06 - For patients with severe COVID-19 requiring supplemental oxygen, combining remdesivir with either baricitinib or dexamethasone led to similar survival rates off mechanical ventilation by day 29, but dexamethasone was associated with significantly more side effects, in the ACTT-4 randomized controlled trial.
Previous studies have shown improved outcomes with baricitinib or dexamethasone in hospitalized patients with COVID-19.
"The difference in the safety profile for dexamethasone suggests that clinicians need to weigh up the potential benefits in each patient to decide if the higher rate of dexamethasone adverse events is acceptable," Dr. Andre Kalil of the University of Nebraska Medical Center, in Omaha, and colleagues report in The Lancet Respiratory Medicine.
The double-blind ACTT-4 trial assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in 1,047 patients (mean age, 58; 58% male) with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non- invasive ventilation.
Survival free of mechanical ventilation at day 29 (the primary outcome) was similar between the study groups (87.0% in the baricitinib group and 87.6% in the dexamethasone group; P=0.91).
The odds of improved status were also similar in the two groups, as were mortality and other efficacy measures.
But the baricitinib plus remdesivir showed a "significantly better" safety profile compared with dexamethasone plus remdesivir.
At least one adverse event occurred in 30% of patients in the baricitinib group and 37% of patients in the dexamethasone group (P=0.014), and at least one treatment-related adverse events occurred in 4% and 10%, respectively (P=0.0004).
Severe or life-threatening grade-3 or -4 adverse events occurred in 28% of patients on baricitinib versus 36% of those on dexamethasone (P=0.012).
Given that both drugs combined with remdesivir appear to be equally effective, "a more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered," the investigators write.
Funding for the ACTT-4 study was provided by the National Institute of Allergy and Infectious Diseases. The authors have declared no relevant conflicts of interest.
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