A new study of outcomes among more than 33,000 hospitalized COVID-19 patients shows that remdesivir plus dexamethasone administration is associated with lower mortality rates at 14 and 28 days compared with dexamethasone alone, according to findings in Clinical Infectious Diseases.
The retrospective, comparative effectiveness study used data on 33,037 US patients to compare outcomes of the anti-inflammatory drug dexamethasone alone or co-administered with the antiviral medication remdesivir.
All patients were hospitalized when the Omicron variant was the most dominant strain in the United States: December 2021 to April 2023. The main outcome was all-cause inpatient mortality at 14 and 28 days after the baseline period.
The study began with 61,236 patients who were given remdesivir and dexamethasone within 2 days of hospitalization and 36,489 who initiated dexamethasone monotherapy in the first 2 days of hospitalization. For the final analysis, 33,037 remdesivir and dexamethasone patients were matched to 33,037 dexamethasone monotherapy patients.
Most patients received supplemental oxygen
For both treatment groups, most patients were over 65 (67% to 70%), White (77% to 78%), and 45% did not receive supplemental oxygen. Among those who did receive oxygen, 37% received low-flow, 17% high-flow, and 3% either invasive mechanical ventilation or extracorporeal membrane oxygenation.
For those who did not use supplemental oxygen, 5.6% and 7.2% of remdesivir and dexamethasone patients died within 14 and 28 days, respectively, compared with 6.1% and 7.7% of dexamethasone monotherapy patients.
For patients receiving low-flow oxygen, 6.1% and 8.1% of combination patients died within 14 and 28 days, respectively, compared with 7.7% and 9.7% of dexamethasone monotherapy patients. For patients receiving high-flow oxygen, 12.7% and 17.6% of remdesivir and dexamethasone patients died within 14 and 28 days, respectively, compared with 15.7% and 20.7% of dexamethasone monotherapy patients, the authors said.
Findings update outdated RCTs
For patients ventilated or on extracorporeal membrane oxygenation, 23.5% and 32.7% of remdesivir and dexamethasone patients died within 14 and 28 days, respectively, compared with 27.1% and 35.4% of dexamethasone monotherapy patients.
"Our study highlights that the addition of remdesivir to dexamethasone is associated with a significant survival benefit compared to dexamethasone without remdesivir use," the authors concluded. "This finding is seen in patients without supplemental oxygen requirement (a group for whom dexamethasone usage is contraindicated unless for a pre-existing or for treatment of a non-COVID-19 condition) as well as in patients with hypoxemia across the spectrum of oxygen support requirements, for whom the addition of remdesivir improves outcomes further."
In a commentary on the study from Todd C. Lee, MD, MPH, of McGill University, Lee said the study updated the understanding and clinical use of the drugs in a post-vaccine era. Most data on the efficacy of remdesivir and dexamethasone came from randomized control trails (RCTs) early in the pandemic, before vaccination, boosters, and widespread natural immunity. To assess these drugs in the post-COVID-emergency era, observational studies must be used.
"Both the observational and RCT level evidence shows that if you have COVID pneumonia with a real requirement for oxygen, you should receive dexamethasone, remdesivir, and potentially an IL-6or JAK inhibitor," Lee said.
If you have COVID pneumonia with a real requirement for oxygen, you should receive dexamethasone, remdesivir, and potentially an IL-6or JAK inhibitor.
For patients who are hospitalized but do not require supplemental oxygen therapy, "It is probable that remdesivir still shortens the duration of illness, and it may reduce mortality, but the benefit is almost certainly less striking than in the initial non-immune population in the RCTs."
