title: Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.
abstract: BACKGROUND
  Roflumilast, a phosphodiesterase 4 inhibitor, has been shown to improve lung function and reduce exacerbation rates, but is associated with adverse events (AEs). The purpose of this study was to systematically review the clinical effectiveness and safety of roflumilast.
  
  
  METHODS
  A systematic search was made of MEDLINE, Cochrane trials database, DARE and CINAHL. Randomized, controlled trials of more than 12 weeks' duration comparing roflumilast with placebo were reviewed. Studies were pooled to yield relative risk (RR), incident rate difference or weighted mean differences with 95% confidence intervals (CIs).
  
  
  RESULTS
  Eight trials (8698 patients) met the inclusion criteria. Roflumilast significantly reduced moderate to severe exacerbations (RR 0.85; 95% CI 0.80-0.91) compared with placebo, but not severe exacerbations (RR 0.83; 95% CI 0.68-1.01) or mortality (RR 0.90; 95% CI 0.63-1.28). Roflumilast significantly improved lung function relative to placebo, but not quality of life measures. AEs (RR 1.11; 95% CI 1.03-1.19) and discontinuations of treatment due to AEs (RR 1.63; 95% CI 1.45-1.84) were significantly more frequent with roflumilast than placebo. In the chronic obstructive pulmonary disease (COPD) Safety Pool (12,054 patients), the overall incidence of serious AEs did not differ between groups. However, atrial fibrillation (0.4% versus 0.2%; p = 0.02) and suicidality (0.08% versus 0%) were more frequent with roflumilast than placebo.
  
  
  CONCLUSIONS
  The efficacy of roflumilast appears modest compared with other available therapies for COPD. Further studies are needed to investigate the risk-benefit ratio and long-term safety of roflumilast before its wider use.
authors.affiliation: Division of Pulmonary, Critical Care and Environmental Medicine, University of Missouri, School of Medicine, One Hospital Drive, CE 412 Columbia, MO 65212, USA. obay@health.missouri.edu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oba
authors.forename: Nazir A
authors.initials: NA
authors.lastname: Lone
mesh_terms: D000368:Aged; D000631:Aminopyridines / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast