Comparison of Corticosteroid Regimens for COVID-19 and Non-COVID-19 ARDS

Although previous trials suggest that systemic corticosteroids improve survival in ARDS, the optimal dose remains uncertain. Which corticosteroid dose offers the greatest efficacy, safety, or both in ARDS? We conducted a model-based dose-response network meta-analysis (NMA) that pooled randomized controlled trials (RCTs) of dexamethasone, hydrocortisone, and methylprednisolone, converting regimens to cumulative methylprednisolone-equivalent doses. For short-term mortality, we fitted agent-specific dose-response curves and estimated the 95% effective dose (ED 95 ) as a near-maximal dose. A Bayesian equal-dose NMA compared treatment effects at ED 95 and at a nonspecific dose of NMA. Certainty of evidence was assessed using Confidence in Network Meta-Analysis. Six thousand five hundred two participants from 28 RCTs were analyzed. ED 95 (cumulative methylprednisolone-equivalent doses) was 840 mg for dexamethasone and 1,400 mg for methylprednisolone. At ED 95 , dexamethasone reduced short-term mortality by 87 deaths per 1,000 patients vs placebo (95% credible interval [CrI], 148 fewer-7 fewer; low certainty) and methylprednisolone reduced mortality by 98 deaths per 1,000 patients vs placebo (95% CrI, 172 fewer-26 fewer; low certainty). Hydrocortisone, primarily evaluated at lower cumulative doses, showed an ED 95 of 270 mg methylprednisolone-equivalent doses, based on a log-linear model, with a mortality reduction of 73 deaths per 1,000 patients vs placebo (95% CrI, 152 fewer-22 more; low certainty). Escalating to pulse-dose regimens provided no additional benefit. In the equal-dose NMA, dexamethasone and methylprednisolone improved ventilator-free days vs placebo, whereas hydrocortisone did not. No meaningful differences were observed in safety outcomes across agents. Our results suggest that dexamethasone and methylprednisolone, when administered at ED 95 , are associated with lower mortality and more ventilator-free days in patients with ARDS. Hydrocortisone’s lower mortality benefit likely reflects suboptimal doses in RCTs; its log-linear dose response suggests potential for greater benefit at higher doses.