Effect of Corticosteroid Therapy on Influenza-Related Mortality: A Systematic Review and Meta-analysis

Background. Most studies have reported that corticosteroid therapy adversely influences influenza-related outcomes. Methods. Electronic databases were searched from inception to March 2013 for experimental and observational studies investigating systemic corticosteroid therapy for presumed influenza-associated complications. Meta-analysis of Observational Studies in Epidemiology guidelines were adopted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models, and heterogeneity was assessed using the I-2 statistic. Quality of evidence was assessed using the Grading Assessment, Development, and Evaluation system. Results. We identified 16 eligible studies (3039 individuals), all of which were observational; 10 (1497 individuals) were included in the meta-analysis of mortality, of which 9 studied patients with 2009 pandemic influenza A virus subtype H1N1. Risk of bias was greatest in the comparability domain of the Newcastle-Ottawa scale, consistent with potential confounding by indication, and data specific to mortality were of low quality. Meta-analysis found an increased odds of mortality (OR, 2.12; 95% CI, 1.36-3.29) associated with corticosteroid therapy. Subgroup analysis of adjusted estimates from 4 studies with very low statistical heterogeneity found a similar association (OR, 2.58; 95% CI, 1.39-4.79). Conclusions. No completed clinical trials were identified. Evidence from observational studies, with important limitations, suggests that corticosteroid therapy for presumed influenza-associated complications is associated with increased mortality.