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SAN FRANCISCO -- For hospitalized COVID-19 patients, pulsed methylprednisolone was not a good alternative to dexamethasone, based on the worse outcomes seen with it in a large Japanese study.

Among 1,197 propensity-matched pairs of patients, those receiving high-dose pulses of IV methylprednisolone were a relative 42% more likely to die before discharge than were those who got the standard course of IV dexamethasone (12.0% vs 8.8%, OR 1.42, 95% CI 1.09-1.85), reported Atsuyuki Watanabe, MD, of the University of Tsukuba Hospital in Japan, at the Society of Critical Care Medicine Critical Care Congress.

Hyperglycemia was also more common for the pulsed methylprednisolone group (16.3% vs 9.7%, OR 1.81, 95% CI 1.42-2.32), and hospital stay was a median of 1 day longer (13 vs 12, P=0.002).

"Providers should be aware of the potential benefit and risks of the type and dose of corticosteroids," Watanabe said.

Dexamethasone was the first drug shown to cut mortality for severe COVID-19, with a 35% relative reduction in deaths in the . However, it was only effective for patients on mechanical ventilation or oxygen, not those who needed no respiratory support, and a high dose was associated with elevated mortality risk. A also supported no benefit and possible harm from dexamethasone in hospitalized COVID-19 patients on room air or nasal cannula oxygen.

In the study by Watanabe and colleagues, none of the differences were notable in the subgroup of 171 severe COVID-19 patients who went straight onto mechanical ventilation on the day of or day after admission. However, pulsed methylprednisolone held a significant disadvantage for all the measures in those not on mechanical ventilation, with the addition of a more than doubled rate of fungal infections (5.3% vs 2.1%, P<0.001).

These findings were not surprising, given the earlier RECOVERY and VA results, commented SCCM congress co-chair Amy Dzierba, PharmD, of NewYork-Presbyterian Hospital/Columbia Irving Medical Center in New York City.

"It made sense that there was no difference in patients who were mechanically ventilated -- they were the ones who benefited from the steroids regardless of the dose or the drug," she told MedPage Today, "whereas people who are less sick, don't require mechanical ventilation ... they're benefiting from the lower dose of steroid as compared with the higher dose, maybe because the side effects may have overshadowed any benefit."

Methylprednisolone is recommended for acute respiratory distress syndrome (ARDS), but "the effect of its high-dose therapy on COVID-19 has not been firmly established," Watanabe noted.

He pointed to prior studies in which methylprednisolone was associated with better biomarker measures. And a 68-patient showed better clinical improvement and numerically higher survival rates with pulsed methylprednisolone for hospitalized severe COVID-19 patients.

In a small, observational , though, 3-day pulses of methylprednisolone had shown a relative 89% higher risk of death among intubated patients whereas non-intubated patients had much shorter duration of hospitalization and a trend towards earlier extubation. A single-center U.S. showed no impact on mortality but more renal failure with pulsed methylprednisolone in hospitalized COVID-19 patients.

The worse outcomes in the Japanese cohort on pulsed methylprednisolone might be chalked up to increased adverse events with high-dose steroids, Watanabe suggested.

He cautioned, though, about the potential for unmeasured confounding as well as the lack of data on laboratory measures or ventilator settings. He also warned that the observational study could not determine causality.

The study included adults in an inpatient claim database hospitalized for COVID-19 across more than 350 acute care hospitals in Japan. They received either pulsed methylprednisolone (250 mg/day or more) or IV dexamethasone on the day of admission or the day afterward. Patients were propensity matched for patient characteristics, baseline comorbidities, hospitalized periods, treatments received on the day of or day after admission, and hospital size.

Of the study population, 30% were female, 58% had diabetes, 35% had hypertension, and 13% had obesity. The mean age was 62. Among them, 17% of patients were in the ICU, 15% were on mechanical ventilation, and 1% on extracorporeal membrane oxygenation (ECMO).

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