The medical community expressed caution when researchers in England said the widely used steroid dexamethasone could save the lives of seriously ill COVID-19 patients. Health experts demanded a full report to be convinced. Now, they have more data to consider, though not yet from a peer-reviewed journal.
According to results published on the preprint site medRxiv, use of 6mg dexamethasone for up to 10 days indeed led to a 35% reduction in death rate among patients on invasive mechanical ventilation after 28 days of treatment.
That said, the 29% death rate for these critically ill patients is still not low, though significantly lower than 40.7% with usual care.
In patients receiving oxygen without invasive ventilation, the drug cut the 28-day death rate by 20%. But among patients who weren't on oxygen or ventilation, the death rate was 22% higher with dexamethasone.
The data invited comparisons to Gilead Sciences’ on its antiviral remdesivir, but at least one analyst cautioned against drawing conclusions until after the two drugs are pitted against each other—and perhaps against a combination of the two—in a clinical trial.
There is an argument for dexamethasone performing better at least in ventilated patients. Dexamethasone’s benefit started showing after seven days of treatment in the U.K. trial dubbed Recovery, “when inflammatory lung damage is likely to have been more common,” the researchers noted. Besides, the greater effect in more serious patients later in their illness “suggests that at this stage the disease is dominated by immunopathology, with active virus replication playing a secondary role.”
Regulators in the U.K. have already granted dexamethasone an approval in hospitalized patients requiring oxygen.
In a large study run by the National Institutes of Health, remdesivir showed it could cut the time to recovery by 47% compared with placebo in patients who required oxygen support but were not mechanically ventilated. However, it didn’t shorten recovery time for patients receiving mechanical ventilation.
As for mortality rates among patients categorized as severe, there were 31 deaths (7.7%) by day 14 in the remdesivir arm, versus 53 cases (13.0%) for placebo. That translated into a 29% reduction, a difference that was not statistically significant.
By comparing the death and hospital discharge ratios in Gilead’s own Simple trial with a known baseline patient study, Bernstein analyst Ronny Gal recently estimated that remdesivir offered around 30% benefit to COVID-19 patients. More in line with the Recovery researchers’ observation, Gal did estimate that dexamethasone works “possibly a bit better in ventilated patients where the response to antivirals is somewhat lower.”
Will dexamethasone replace remdesivir as a new standard treatment? That would depend on a combination trial comparing solo dexa, remdesivir and a pairing of the two, Gal said in a Monday note. Such a study isn't yet planned, but he expects something along those lines from the NIH in the coming months.