Study Finds Underuse of Dexamethasone in COVID Patients

By Megan Brooks

August 17, 2021

NEW YORK (Reuters Health) - Dexamethasone, now an evidence-based treatment for severe COVID-19, is under-utilized in the United States, a new analysis shows.

"Since dexamethasone is an inexpensive and widely available drug, we were surprised at its potential underuse among people who might have benefited from it," Dr. Hemalkumar Mehta, with Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland, told Reuters Health by email.

"Although the use of dexamethasone increased rapidly, nearly one out of five patients who may have benefited from dexamethasone use did not receive it," he added.

The study also found that use of dexamethasone and remdesivir, which is recommended in current guidelines, varies across health systems, "suggesting variation in patient case mix, drug access, treatment protocols, and quality of care," the study team says in Annals of Internal Medicine.

The landscape of treatment for COVID-19 changed rapidly during the pandemic, they note in their paper.

In March 2020, the U.S. Food and Drug Administration (FDA) granted emergency use authorization (EUA) for hydroxychloroquine (HCQ), but rescinded it three months later based on emerging evidence of no benefit and potential harm.

The antiviral remdesivir received an EUA in May 2020 and full approval in October 2020 for COVID-19.

Dexamethasone, already approved for a variety of indications, has been shown to reduce COVID-19 deaths among hospitalized patients requiring oxygen therapy alone or mechanical ventilation.

The National Institutes of Health (NIH) recommends both remdesivir and dexamethasone as treatments for some adults hospitalized with clinically suspected or laboratory-confirmed SARS-CoV-2 infection.

Using the National COVID Cohort Collaborative (N3C), Dr. Mehta and colleagues assessed temporal trends in the use of HCQ, remdesivir, and dexamethasone in the U.S. over a 13-month period beginning in February 2020.

Among more than 137,800 adults hospitalized at 43 centers with confirmed or suspected COVID-19, 8,754 (6%) received HCQ, 29,272 (21%) remdesivir, and 53,909 (39%) dexamethasone during the study period.

According to the study team, "brisk uptake and abandonment of HCQ early in the pandemic has been offset by increases in use of remdesivir and, to an even greater degree, dexamethasone."

Yet, despite publication in mid-June of the RECOVERY trial results, which showed a survival benefit for dexamethasone in mechanically ventilated patients, roughly one fifth of potentially eligible patients did not receive dexamethasone or other glucocorticoids.

Further, they found substantial variation in dexamethasone use across sites, as well as in use of dexamethasone plus remdesivir.

"Dexamethasone and remdesivir combination are recommended in the NIH guideline based on theoretical benefits and expert opinion. Further research is needed to understand the potential benefit of this combined treatment. However, we noted a remarkable increase in combination drug use, with as many as one out four patients receiving combination treatment by February 2021," Dr. Mehta told Reuters Health.

He said some possible reasons for potential underuse may include drug shortages, hospital protocols or variation in quality of care provided by the hospitals.

"Given that we have compelling evidence from well controlled trials that dexamethasone reduces mortality among those who require supplemental oxygen, it is vital that our health system is getting the right drug to the right patient at the right time," Dr. Mehta said.

"These findings are important because of continued high levels of morbidity and mortality in the United States due to COVID-19, as well as a robust evidence base supporting the value of dexamethasone in reducing the likelihood of death among persons with COVID-19 who require mechanical ventilation," the study team wrote in their paper.

One limitation of the study is the inclusion of predominantly academic medical centers, suggesting that the findings may not generalize to community-based hospitals, the site of most care in the U.S. The authors also lacked patient-level data, limiting the analysis of the appropriateness of corticosteroid use.

Weighing in on the study in an editorial, Dr. Marshall Glesby and Dr. Roy Gulick from Weill Cornell Medicine in New York say the data clearly show how rapidly clinicians navigated a "cacophony of data" to incorporate "important and meaningful" trial results into practice during an infectious-disease pandemic.

"Clinicians adopted a drug with a mortality benefit (dexamethasone), abandoned a drug with no benefit and the potential for harm (hydroxychloroquine), and recognized the nuances of a third drug (remdesivir) that had FDA approval based on decreased clinical progression but lacked a demonstrated mortality benefit," Drs. Glesby and Gulick write.

"There have been and will continue to be refinements in the clinical care of COVID-19 based on new evidence that emerges from other carefully conducted trials, including global platform trials. Real-time updates of online treatment guidelines and recent innovations, such as living systematic reviews, will help clinicians keep pace with emerging data and continue to improve clinical outcomes. Lessons learned from COVID-19 will improve how we assess and disseminate emerging data, leading to efficient implementation (or deimplementation) of evidence-based treatments," they conclude.

The study had no commercial funding.

SOURCE: https://bit.ly/3g4zhAo and https://bit.ly/3iPOC9s Annals of Internal Medicine, online August 16, 2021.

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