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 versus 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.
Competing Interests: Conflict of interest: The authors declare no conflict of interest related to this work. E. Papadopoulou, S. Bin Safar, A. Khalil, J. Hansel, R. Wang and A. Corlateanu report no conflicts of interest. K. Kostikas reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuovoAir, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis, Pfizer and Sanofi Genzyme, honoraria from Alector Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GILEAD, GSK, Menarini, MSD, Novartis, Sanofi Genzime, Pfizer and WebMD, and a leadership role as a member of the GOLD assembly, not related to this work. S. Tryfon reports honoraria from ELPEN, GSK, AstraZeneca, Chiesi and Menarini and participation on advisory boards for ELPEN, GSK, AstraZeneca and Menarini, not related to this work. J. Vestbo reports consulting fees from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Teva, and honoraria from AstraZeneca, Chiesi and GSK, not related to this work. A.G. Mathioudakis reports honoraria from GSK not related to this work.
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