Efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Currently, several large studies showed that roflumilast has been demonstrated efficacy during treatment chronic obstructive pulmonary disease (COPD) patients, but also caused some side effects. AIM: To assess the efficacy and safety of roflumilast in COPD patients. METHODS: A computerized search through electronic databases included PubMed, EMBASE, CINAHL, the Cochrane clinical trials database, Physiotherapy Evidence Database and ClinicalTrials.gov was performed to identify randomized controlled trials. The primary outcomes were trough forced expiratory volume in 1 s (FEV(1)) (reported pre-bronchodilator values) and exacerbation rate. Secondary outcomes included other spirometric parameters, health-related quality of life, the overall mortality rate and adverse events. Weighted mean differences (WMDs), relative risks (RRs) and 95% confidence intervals (CIs) were calculated and pooled using a random effects model. RESULTS: Eleven trials involving 9675 patients met the inclusion criteria. Roflumilast significantly reduced the mean exacerbation rate (mild, moderate or severe) (WMD = -0.23; 95% CI = -0.33 to -0.13; p < 0.00001) and improved trough FEV(1) (WMD = 53.52 ml; 95% CI = 42.49 to 64.55; p < 0.00001), and other post-bronchodilator spirometric parameters (e.g., forced vital capacity, etc.). Roflumilast did not improve St George's Respiratory Questionnaire total score (WMD = -0.70 units; 95% CI = -2.65 to 1.26; p = 0.49) and decrease the overall mortality rate (RR = 0.90; 95% CI = 0.63 to 1.29; p = 0.56). Roflumilast increased some adverse events including diarrhea, headache, nausea, weight loss, and insomnia. CONCLUSIONS: Roflumilast significantly reduces the mean exacerbation rate in COPD patients. Although there are insufficient clinical evidence on other clinical endpoints and high risk of some adverse events, roflumilast therapy may benefit COPD patients. Further studies are needed to pay more attention to the long-term efficacy and safety of roflumilast.