The aim of this study was to investigate whether the phosphodiesterase 4 inhibitor roflumilast improves lung function and prevents exacerbations in patients with chronic obstructive pulmonary disease (COPD) with cough and sputum (chronic bronchitis), severe airflow obstruction and a history of exacerbations.
This study was one of two replicate, double-blind, randomized, placebo-controlled, parallel-group, multicenter trials (M2-124 and M2-125) that enrolled patients with COPD, severe airflow obstruction, a history of exacerbations and chronic bronchitis. In M2-124, patients were recruited from 246 centers in Australia, New Zealand, Austria, France, Germany, Hungary, Romania, Russia, the UK and the USA. Patients were randomized and received roflumilast, 500 αg once daily (n=765), or placebo (n=758) for 12 months. In the USA, 137 centers randomized 334 patients. Co-primary endpoints were mean change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) from baseline to each post-randomization visit, and the rate of moderate and/or severe exacerbations. Secondary endpoints included post-bronchodilator FEV1 and time to death from any cause.
The mean difference in pre-bronchodilator FEV1 between roflumilast- and placebo-treated patients was 39 mL (46 mL vs 8 mL, respectively; p<0.001). The mean rate of moderate and/or severe exacerbations per patient per year was 1.1 in the roflumilast group and 1.3 with placebo (rate ratio 0.85; 95% CI 0.74, 0.98; p=0.028). The safety profile of roflumilast was consistent with that seen in previous studies. Adverse events were reported in 68.3% of patients receiving roflumilast and 62.9% receiving placebo.
Roflumilast significantly improved lung function, decreased exacerbations, and was generally well tolerated in this patient population with symptomatic COPD. These findings are consistent with those of the matched study M2-125.
Roflumilast represents an important potential addition to the armamentarium of drugs available for the treatment of COPD.
F. Martinez, MD & AURA Study Team, Grant monies (from sources other than industry) Nicola Hanania has received grant monies from NIH, ALA.; Grant monies (from industry related sources) Nicola Hanania has received grant monies from GlaxoSmithKline, Nycomed, BI, Dey, Novartis.; Consultant fee, speaker bureau, advisory committee, etc. Fernando Martinez has served on advisory boards for Nycomed. Nicola Hanania has provided services for Nycomed, Dey, GlaxoSmithKline, Novartis; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The contribution describes effects of roflumilast, the oral and once daily PDE4 inhibitor currently in development for COPD at NYCOMED GmbH.