Remdesivir plus dexamethasone reduces death in COVID-19 hospitalizations
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Key takeaways:
- The combination treatment reduced the need for supplemental oxygen and risk for mortality.
- In a related editorial, an expert questioned some aspects of the study.
A combination of remdesivir plus dexamethasone significantly reduced the risk for death among people hospitalized with COVID-19 with baseline oxygen requirements compared with dexamethasone alone, according to a study.
“Evolving evidence generated during the later stages of the pandemic shows a lack of benefit, or even harm, of dexamethasone monotherapy in patients not receiving oxygen,” Andre Kalil, MD, MPH, FACP, FIDSA, FCCM, professor of internal medicine at the University of Nebraska Medical Center, and colleagues wrote in the study.
“This new finding 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 remdesivir,” they wrote.
Kalil and colleagues analyzed data from the PINC AI Healthcare Database on more than 33,000 patients who were hospitalized between December 2021 and April 2023 with COVID-19 and received combination remdesivir and dexamethasone treatment, matching them in a 1:1 ratio with patients who had received only dexamethasone.
According to the researchers, mortality was significantly lower among groups of patients receiving combination therapy compared with monotherapy in nearly every treatment group regardless of supplemental oxygen requirements have a lower risk for death. The combination therapy reduced the odds of death by between 21% (adjusted HR = 0.79; 95% CI, 0.72-0.87) among people who received no supplemental oxygen and 31% (aHR = 0.69; 95% CI, 0.62-0.76) among those receiving high-flow oxygen/noninvasive ventilation, the researchers reported.
In a related editorial, Todd C. Lee, MD, MPH, FIDSA, a researcher and associate professor of medicine in the division of infectious diseases at McGill University Health Centre in Montreal, questioned why nearly half of the patients in the study were on dexamethasone despite not requiring oxygen, giving that corticosteroids may increase mortality among people not on oxygen.
“Is this an issue with validity of the oxygen exposure data, an issue with the quality of practice, or something else?” Lee wrote. “Whatever the reason, dexamethasone in patients not requiring oxygen should not represent a standard of care. So, it becomes challenging to know what to make of this population.”
Lee noted several reasons that the results “may overstate the benefits of remdesivir,” including that the study excluded anyone receiving tocilizumab and baricitinib.
Although Kalil and colleagues noted that the results should not be used to encourage the use of glucocorticosteriods in patients with COVID-19 without hypoxemia or other unrelated conditions, they contended that the drug combination has a place in the right patient populations.
We asked Kalil about the study. His answers have been edited for clarity and length.
Healio: Based on the effectiveness of combination therapy with remdesivir and dexamethasone found in the study, why aren’t clinicians using it more?
Kalil: In part, because fewer patients are progressing to more severe COVID-19 due to hybrid immunity. However, for patients who require hospitalization and supplemental oxygen for COVID-19 pneumonia (ie, previous immunity and/or vaccine failure), either remdesivir plus dexamethasone, or remdesivir plus baricitinib, are the most effective and evidence-based therapies, as demonstrated by our new study and by the placebo-controlled randomized ACTT-4 trial, as reported by Wolfe and colleagues).
Healio: Considering the risk of dexamethasone monotherapy in some patients, why is remdesivir not being included in their treatment regimens?
Kalil: Dexamethasone monotherapy should not be administered to patients hospitalized for COVID-19 who are not requiring respiratory support with supplemental oxygen because multiple studies — randomized and observational — have shown a higher risk of death with dexamethasone in this patient population.
In addition, our study finding of significantly lower mortality across all respiratory support levels in patients receiving remdesivir plus dexamethasone vs. dexamethasone alone matches not only the expected biologic course of the infections — faster viral clearance leads to short disease duration and improved survival — but is also highly consistent with all infectious disease evidence in which steroids’ survival benefits are present only when given together with antimicrobials in severe infections such as Streptococcus pneumoniae meningitis, Pneumocystis jirovecii and septic shock.
Healio: Should remdesivir be used more often overall in patients with COVID-19?
Kalil: All patients who are hospitalized for COVID-19 pneumonia, independent of the need for supplemental oxygen, should benefit from remdesivir.
Healio: What is the main takeaway from the study’s findings for clinicians?
Kalil: Remdesivir plus dexamethasone shows significantly better survival than dexamethasone alone in patients hospitalized for COVID-19 across all levels of respiratory support.
References:
- Lee TC. Clin Infect Dis. 2024;doi:10.1093/cid/ciae478.
- Mozafarri E, et al. Clin Infect Dis. 2024;doi:10.1093/cid/ciae477.
- Wolfe CR, et al. Lancet Respir Med. 2022;doi:10.1016/S2213-2600(22)00088-1.
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