title: Efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease: a meta-analysis.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Clinical Medical Technology, Affiliated Hospital of Binzhou Medical College, Binzhou, PR China.
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Yan
authors.affiliation: Department of Anaesthesiology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, PR China.
authors.forename: Wan-Jie
authors.initials: WJ
authors.lastname: Gu
authors.affiliation: Department of Respiratory Medicine, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical College, 151 Yanjiang Road, Guangzhou 510120, PR China. Electronic address: zypl781102@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Pan
mesh_terms: D000631:Aminopyridines / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D006801:Humans; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D014797:Vital Capacity
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast
keywords: Chronic obstructive pulmonary disease; Efficacy; Meta-analysis; Roflumilast; Safety