title: Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease.
abstract: BACKGROUND
  The oral phosphodiesterase-4 (PDE4) inhibitor, roflumilast, can improve lung function in moderate chronic obstructive pulmonary disease (COPD). Whether treatment is effective in more severe COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages III and IV) over a longer period is unknown.
  
  
  OBJECTIVE
  To determine whether roflumilast improves lung function and decreases exacerbation frequency over 1 year in patients with stable COPD.
  
  
  METHODS
  We conducted a randomized, placebo-controlled, double-blind, parallel-group trial for 1 year. We recruited 1,513 patients (mean post-bronchodilator FEV1 41% predicted), 760 receiving oral 500 microg roflumilast and 753 receiving placebo once daily.
  
  
  RESULTS
  We recorded post-bronchodilator FEV1, exacerbation rate, St. George's Respiratory Questionnaire total score at the study end point, and number and type of reported adverse events during treatment. Post-bronchodilator FEV1 increased by 39 ml with roflumilast compared with placebo by 52 weeks (p=0.001). The mean exacerbation rate was low and comparable in both treatment groups (0.86 vs. 0.92 exacerbations/patient/yr for roflumilast and placebo, respectively). In a retrospective analysis, the exacerbation rate in patients in GOLD stage IV disease was 36% lower in patients treated with roflumilast than in those treated with placebo (1.01 vs. 1.59 exacerbations/patient/year, respectively; p=0.024). The St. George's Respiratory Questionnaire total score did not differ between treatments. The commonest adverse events related to roflumilast treatment were diarrhea, nausea, and headache, which usually subsided during continued treatment. However, roflumilast resulted in more withdrawals within the first 3 to 4 weeks of administration.
  
  
  CONCLUSIONS
  In severe, stable COPD, PDE4 inhibition with roflumilast produced a modest but significant improvement in lung function without changing the exacerbation rate or health status. However, patients with very severe disease experienced fewer exacerbations with roflumilast.
authors.affiliation: Department of Medicine, Clinical Sciences, University Hospital Aintree, Liverpool L97AL, UK. pmacal@liverpool.ac.uk
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.forename: Fernando
authors.initials: F
authors.lastname: Sanchez-Toril
authors.forename: Andrew
authors.initials: A
authors.lastname: McIvor
authors.forename: Peter
authors.initials: P
authors.lastname: Teichmann
authors.forename: Dirk
authors.initials: D
authors.lastname: Bredenbroeker
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Fabbri
mesh_terms: D000368:Aged; D000631:Aminopyridines / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D015331:Cohort Studies; D003521:Cyclopropanes / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast