When researchers in the U.K. said in June that the low-cost corticosteroid dexamethasone could reduce death rates in critically ill COVID-19 patients, clinicians still had doubts about whether to change their treatment practice without full data.
But findings from a series of clinical trials from around the world, along with a new meta-analysis—all of which were published on Wednesday in JAMA—will likely change that.
The findings “provide definitive data that corticosteroids should be first-line treatment for critically ill patients with COVID-19,” two researchers wrote in a JAMA editorial accompanying the new papers. Based on the results, the World Health Organization has also updated its guidance with a “strong recommendation” for using corticosteroids in severe and critical COVID-19 cases.
In the meta-analysis supported by WHO, researchers pooled data from seven randomized clinical trials that evaluated corticosteroids—dexamethasone, hydrocortisone, or methylprednisolone—in 1,703 critically ill COVID-19 patients.
Overall, compared with usual care or placebo, steroids lowered the likelihood of all-cause death by day 28 by about one-third. Dexamethasone appeared to be the most effective of the group.
In one trial whose results were published Wednesday in JAMA, the CoDEX trial in Brazil, intensive care patients with moderate to severe acute respiratory distress syndrome (RDS) receiving dexamethasone went ventilator-free for longer than those who got standard care alone—6.6 days versus 4 days, to be specific.
Researchers didn't observe a significant difference in mortality rate between the two groups at 28 days, but 35% of patients in the standard care arm got at least one dose of corticosteroids, potentially narrowing the efficacy gap between the two groups.
Plus, the trial was stopped early after a U.K. trial showed dexamethasone led to a 35% reduction in the death rate among patients on invasive mechanical ventilation after 28 days.
Two other JAMA studies released on Wednesday focused on hydrocortisone and were unable to reach definitive conclusions as they were also stopped early at the U.K. data release. But they both showed promise for the steroid’s use in severely ill patients.
Enrollment to many corticosteroid trials in critically ill COVID-19 patients was halted after that U.K. data release, as investigators started to consider the potential of dexamethasone and that it might be unethical to keep enrolling serious patients to non-steroid placebo.
The new studies published in JAMA, though, “have strengthened confidence, further defined the benefit, and shifted usual care of COVID-19-related RDS to include corticosteroids,” the JAMA editorial said.
Of course, many questions remain, it noted—including how sick patients should be before they get corticosteroids. Still, though, the group of drugs is inexpensive and readily available, two points in its favor as doctors and researchers look for ways to curb the COVID-19 death rate.