Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease.
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.
Calverley
Peter M A
PM
Department of Medicine, Clinical Sciences, University Hospital Aintree, Liverpool L97AL, UK. pmacal@liverpool.ac.uk
Sanchez-Toril
Fernando
F
McIvor
Andrew
A
Teichmann
Peter
P
Bredenbroeker
Dirk
D
Fabbri
Leonardo M
LM
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
D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast