Intraclass Comparison of Inhaled Corticosteroids for the Risk of Pneumonia in Chronic Obstructive Pulmonary Airway Disorder: a Network Meta-analysis and Meta-regression

Background: Inhalational corticosteroids (ICS) were observed to increase the pneumonia risk in chronic obstructive pulmonary airway disorder (COPD). However, it is unknown whether any differences exist between the drugs within the ICS class.

Aim: This study aimed to evaluate the risk of pneumonia associated with different ICS and identify factors that predict pneumonia in patients with moderate-to-severe COPD using a network meta-analysis.

Method: Electronic databases (Medline, Cochrane CENTRAL and Google Scholar) were searched for trials comparing ICS in COPD patients. The outcomes were pneumonia and serious pneumonia. Odds ratios (OR) with 95% confidence interval (95% CI) were estimated. Meta-regression was used to identify the predictors. The strength of evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluations approach.

Results: Sixty-six studies (103,347 participants) were included. Fluticasone (OR: 1.46; 95% CI: 1.26, 1.7), mometasone (OR: 2.2; 95% CI: 1.05, 4.6), and beclometasone (OR: 1.7; 95% CI: 1.1, 2.6) were observed with an increased pneumonia risk compared to placebo. Fluticasone (OR: 1.5; 95% CI: 1.3, 1.7) was observed with an increased risk of serious pneumonia. High doses (OR: 1.2; 95% CI: 1.03, 1.4), BMI ≥ 25 kg/m (OR: 1.6; 95% CI: 1.1, 2.2), and history of exacerbations in the preceding year predicted the pneumonia risk. Evidence strength was moderate.

Conclusion: ICS class differences in pneumonia risk were observed in terms of pooled effect estimates but it is unlikely that any clinically relevant differences exist. Risk-benefit analysis supports ICS use in moderate-severe COPD.