Effect of roflumilast on chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) of roflumilast effect on chronic obstructive pulmonary disease (COPD) have been reported in the last decade. The current meta-analysis was designed to systematically review and perform meta-analysis of the RCTs of roflumilast treatment in COPD.

METHODS: Electronic databases including PubMed, EMBASE, Web of Science, and Cochrane clinical trials database were searched to identify RCTs of roflumilast treatment on COPD. The primary outcomes were effect of roflumilast on pre-bronchodilator FEV1, post-bronchodilator FEV1, and exacerbation rate. Secondary outcomes were effect of roflumilast on airway inflammation and adverse effect.

RESULTS: A total of 11 RCTs were enrolled into the current analysis. Roflumilast significantly improved both pre-bronchodilator FEV1 (standardized difference in mean ± SD was 0.621 ± 0.161; 95% CI 0.306~0.936, p < 0.001) and post-bronchodilator FEV1 (standardized difference in mean ± SD was 0.563 ± 0.149, 95% CI 0.270~0.855, p < 0.001) compared with placebo. Roflumilast also significantly reduced exacerbation of COPD (standardized difference in mean ± SD 0.099 ± 0.020, 95% CI 0.061~0.138; p < 0.001) and suppressed airway inflammation (standardized difference in mean ± SD 1.354 ± 0.260, 95% CI 0.845~1.862, p < 0.001) compared with placebo. However, roflumilast significantly increased adverse effect such as diarrhea (rate ratio 2.945, 95% CI 2.453~3.536, p < 0.001) and weight loss (rate ratio 3.814, 95% CI 3.091~4.707, p < 0.001) compared with placebo.

CONCLUSION: These findings indicated that roflumilast treatment could improve COPD patients' lung function and reduce exacerbation, and that inhibition of airway inflammation by roflumilast might contribute to the beneficial effect of PDE-4 inhibitors on COPD.