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

Atsuyuki Watanabe; Ryota Inokuchi; Toshiki Kuno; Kazuaki Uda; Jun Komiyama; Motohiko Adomi; Yoshiko Ishisaka; Toshikazu Abe; Nanako Tamiya; Masao Iwagami

doi:10.1097/CCE.0000000000000886

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

Crit Care Explor. 2023 Mar 27;5(4):e0886. doi: 10.1097/CCE.0000000000000886. eCollection 2023 Apr.

Authors

Atsuyuki Watanabe¹, Ryota Inokuchi², Toshiki Kuno³, Kazuaki Uda², Jun Komiyama², Motohiko Adomi⁴, Yoshiko Ishisaka⁵, Toshikazu Abe^{2

6}, Nanako Tamiya², Masao Iwagami^{2

7}

Affiliations

¹ Division of Hospital Medicine, University of Tsukuba Hospital, Tsukuba, Japan.
² Department of Health Services Research, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
³ Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY.
⁴ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
⁵ Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY.
⁶ Department of Emergency and Critical Care Medicine, Tsukuba Memorial Hospital, Tsukuba, Japan.
⁷ Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Abstract

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.

Keywords: COVID-19; dexamethasone; methylprednisolone; mortality; pulse therapy.