Inhaled versus systemic corticosteroids for acute exacerbations of COPD: a systematic review and meta-analysis

This meta-analysis compares the efficacy and safety of inhaled systemic corticosteroids for COPD exacerbations.Following a pre-registered protocol, we appraised eligible randomised controlled trials (RCTs) according to Cochrane methodology, performed random-effects meta-analyses for all outcomes prioritised in the European Respiratory Society COPD core outcome set and rated the certainty of evidence as per Grading of Recommendations Assessment, Development and Evaluation methodology.We included 20 RCTs totalling 2140 participants with moderate or severe exacerbations. All trials were at high risk of methodological bias. Low-certainty evidence did not reveal significant differences between inhaled and systemic corticosteroids for treatment failure rate (relative risk 1.75, 95% CI 0.76-4.02, n=569 participants); breathlessness (mean change: standardised mean difference (SMD) -0.11, 95% CI -0.36-0.15, n=239; post-treatment scores: SMD -0.18, 95% CI -0.41-0.05, n=293); serious adverse events (relative risk 1.47, 95% CI 0.56-3.88, n=246); or any other efficacy outcomes. Moderate-certainty evidence implied a tendency for fewer adverse events with inhaled compared to systemic corticosteroids (relative risk 0.80, 95% CI 0.64-1.0, n=480). Hyperglycaemia and oral fungal infections were observed more frequently with systemic and inhaled corticosteroids, respectively.Limited available evidence suggests potential noninferiority of inhaled to systemic corticosteroids in COPD exacerbations. Appropriately designed and powered RCTs are warranted to confirm these findings.