Pulse Methylprednisolone Versus Dexamethasone in COVID-19: A Multicenter Cohort Study

IMPORTANCE: Although pulse (high-dose) methylprednisolone therapy can hypothetically control immune system flare-ups effectively, the clinical benefit of pulse methylprednisolone compared with dexamethasone in COVID-19 remains inconclusive. OBJECTIVES: To compare pulse methylprednisolone to dexamethasone as a COVID-19 treatment. DESIGN, SETTING, AND PARTICIPANTS: Using a Japanese multicenter database, we identified adult patients admitted for COVID-19 and discharged between January 2020 and December 2021 treated with pulse methylprednisolone (250, 500, or 1,000 mg/d) or IV dexamethasone (≥ 6 mg/d) at admission day 0 or 1. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, new ICU admission, insulin initiation, fungal infection, and readmission. Multivariable logistic regression was conducted to differentiate the dose of pulse methylprednisolone (250, 500, or 1,000 mg/d). Additionally, subgroup analyses by characteristics such as the need for invasive mechanical ventilation (IMV) were also conducted. RESULTS: A total of 7,519, 197, 399, and 1,046 patients received dexamethasone, 250, 500, and 1,000 mg/d of methylprednisolone, respectively. The crude in-hospital mortality was 9.3% (702/7,519), 8.6% (17/197), 17.0% (68/399), and 16.2% (169/1,046) for the different doses, respectively. The adjusted odds ratio (95% CI) was 1.26 (0.69-2.29), 1.48 (1.07-2.04), and 1.75 (1.40-2.19) in patients starting 250, 500, and 1,000 mg/d of methylprednisolone, respectively, compared with those starting dexamethasone. In subgroup analyses, the adjusted odds ratio of in-hospital mortality was 0.78 (0.25-2.47), 1.12 (0.55-2.27), and 1.04 (0.68-1.57) in 250, 500, and 1,000 mg/d of methylprednisolone, respectively, among patients with IMV, whereas the adjusted odds ratio was 1.54 (0.77-3.08), 1.62 (1.13-2.34), and 2.14 (1.64-2.80) among patients without IMV. CONCLUSIONS AND RELEVANCE: Higher doses of pulse methylprednisolone (500 or 1,000 mg/d) may be associated with worse COVID-19 outcomes when compared with dexamethasone, especially in patients not on IMV.