Lower mortality in COVID-19 with remdesivir plus dexamethasone than dexamethasone alone
An industry-funded retrospective study found that COVID-19 patients who got both remdesivir and dexamethasone had lower inpatient mortality than matched patients who got dexamethasone alone, across all levels of respiratory support.
Patients who received both remdesivir and dexamethasone during the omicron variant period had lower mortality than those getting dexamethasone alone, regardless of respiratory status, a retrospective, industry-funded study found.
The study used a U.S. hospital database to identify hospitalized adult patients with a primary discharge diagnosis of COVID-19 (which was present on admission) who were treated with remdesivir plus dexamethasone or dexamethasone alone from December 2021 to April 2023. They were matched between interventions and stratified by baseline oxygen requirements to look at outcomes of 14- and 28-day in-hospital all-cause mortality. The study was funded by Gilead Sciences, and results were published by Clinical Infectious Diseases on Sept. 20.
A total of 33,037 patients were matched (72% ≥65 years of age, 78% White). Those who received remdesivir plus dexamethasone had lower mortality rates at 14 days, regardless of their need for oxygen (adjusted hazard ratios, 0.79 [95% CI, 0.72 to 0.87] with no oxygen, 0.70 [95% CI, 0.64 to 0.77] with low-flow oxygen, 0.69 [95% CI, 0.62 to 0.76] with high-flow oxygen or noninvasive ventilation, and 0.78 [95% CI, 0.64 to 0.94] with invasive mechanical ventilation/extracorporeal membrane oxygen [IMV/ECMO]). The results at 28 days were similar.
The study authors concluded that the combination of drugs was associated with better survival in patients ranging from those requiring IMV/ECMO to those without hypoxemia. The benefit in the least sick patients “strongly suggests that viral clearance delay is likely the reason for worse survival outcomes with dexamethasone in the early course of COVID-19 (before patients require supplemental oxygen), and that this may be mitigated by the antiviral activity of remdesivir,” the study authors said, although they cautioned that steroids should not be prescribed to patients not on oxygen without another indication.
Limitations of the study included the risk of residual confounding inherent in observational research and lack of data on any prehospital treatments, they said.
“Findings from this research suggest that more effort is needed to update guidelines recommending the use of remdesivir+dexamethasone in patients requiring supplemental oxygen according to best practice guidelines for oxygen use, and the strong clinical rationale to avoid dexamethasone monotherapy in all levels of respiratory support, especially those not receiving supplemental oxygen,” the study authors said.
An accompanying editorial offered “several reasons why the findings in this observational study may overstate the benefits of remdesivir.” These include the exclusion of patients well enough to go home or sick enough to receive tocilizumab/baricitinib and confounding by indication.
“Both the observational and [randomized controlled trial] level evidence shows that if you have COVID pneumonia with a real requirement for oxygen, you should receive dexamethasone, remdesivir, and potentially an IL-6 or JAK inhibitor,” the editorialist said, noting that decision making for patients without hypoxemia, with deteriorating status, or on IMV/ECMO remains more uncertain.
