Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD.


METHODS
This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 microg (n=576), roflumilast 500 microg (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat.


RESULTS
1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 microg group, and 124 (22%) from the roflumilast 500 microg group. Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 microg (by 74 mL [SD 18]) and roflumilast 500 microg (by 97 mL [18]) compared with placebo (p<0.0001). Improvement in health-related quality of life was greater with roflumilast 250 microg (-3.4 units [0.6]) and roflumilast 500 microg (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 microg, and roflumilast 500 microg, respectively. Most adverse events were mild to moderate in intensity and resolved during the study.


CONCLUSIONS
Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life.
Rabe
Klaus F
KF
Leiden University Medical Centre, Leiden, Netherlands. k.f.rabe@lumc.nl
Bateman
Eric D
ED
O'Donnell
Denis
D
Witte
Stephan
S
Bredenbröker
Dirk
D
Bethke
Thomas D
TD
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000631:Aminopyridines / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D003521:Cyclopropanes / Q000008:administration & dosage; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008450:Maximal Midexpiratory Flow Rate; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D014797:Vital Capacity
D000631:Aminopyridines; D000893:Anti-Inflammatory Agents; D001549:Benzamides; D003521:Cyclopropanes; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast