Does methylprednisolone reduce the mortality risk in hospitalized COVID-19 patients? A meta-analysis of randomized control trials

ABSTRACT

Objectives: The question remained if mortality benefits with dexamethasone seen in patients with coronavirus disease 2019 (COVID-19) also extend to other systemic corticosteroids such as methylprednisolone. This article presents a meta-analysis of randomized controlled trials (RCTs) to ascertain if methylprednisolone can be recommended for use in patients with COVID-19 to prevent deaths.

Methods: Systematic literature search was performed in PubMed, Scopus, Cochrane Central Register of Controlled Trials, and preprint servers until 13 April 2021. The outcome of interest was all-cause mortality. The random-effects model for the meta-analysis was utilized to estimate the pooled odds ratio (OR) at 95% confidence intervals (CI).

Results: Five RCTs were included in the meta-analysis. The pooled OR for all-cause mortality was 0.64 (95% CI: 0.29 − 1.43, n = 652) comparing methylprednisolone with the control, indicating no mortality benefits. A similar finding was noted with a sub-group analysis including four trials that used low-dose methylprednisolone. However, the only trial that administered high dose methylprednisolone indicated a statistically significant mortality benefit (OR 0.08, 95% CI: 0.02–0.42).

Conclusions: In determining equipotent doses for an acute short-course pulse therapy of corticosteroids, the biological half-life of steroids should also be accounted for besides the potency factor. A short duration (3–5 days) pulse therapy of high-dose methylprednisolone can be a promising alternative to the low-dose dexamethasone therapy in severely ill patients with COVID-19 to prevent deaths.

KEYWORDS:

• Coronavirus
• corticosteroids
• deaths
• dexamethasone
• methylprednisolone
• pandemic
• SARS-CoV-2

Article highlights

• The pulsed high-dose methylprednisolone therapy may offer an alternative to low-dose dexamethasone in preventing deaths in severely ill patients with COVID-19.

• The optimal duration of methylprednisolone pulse therapy may be as short as 3 days to limit its exposure and minimize its impact on viral clearance.

• In determining equipotent doses for an acute short-course pulse therapy of corticosteroids, the biological half-life of steroids (short-, intermediate-, or long-acting) should also be accounted for besides the potency factor. The dose estimation based on potency alone is still suitable for long-term corticosteroids use in chronic conditions.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contribution

SSH, CSK, and HAM conceived the content, retrieved the data, and wrote the first draft of the manuscript. SSH, CSK, ZUM, and HAM reviewed the data and revised the manuscript. All authors read and approved the final version.

Additional information

Funding

This paper was not funded.