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 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. Patients were recruited from 221 sites in Canada, Germany, India, Italy, Poland, South Africa, Spain and the USA. Patients were randomized and received roflumilast, 500 μg once daily (n = 772), or placebo (n = 796) for 12 months; median age 64 and 65 years, respectively. Patients could use short-acting beta2-agonists as needed and could continue treatment with long-acting beta agonists or short-acting anticholinergics at stable doses; inhaled corticosteroids and long-acting anticholinergics were not allowed. Co-primary endpoints were mean change in pre-bronchodilator 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.
Mean (SD) baseline FEV1 was 0.95 (0.3) and 0.98 (0.4) L in the roflumilast and placebo groups, respectively. The mean difference in pre-bronchodilator FEV1 between roflumilast- and placebo-treated patients was 58 mL (33 mL vs –25 mL, respectively; p < 0.001). The mean rate of moderate and/or severe exacerbations/patient/year was 1.2 in the roflumilast group and 1.5 with placebo (rate ratio 0.82; 95% CI 0.71, 0.95; p = 0.004). The safety profile of roflumilast was consistent with that seen in previous studies. Adverse events were mostly mild and reported in 66.2% of patients receiving roflumilast and 61.8% 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 M2-124.
Roflumilast represents an important potential addition to the armamentarium of drugs available for COPD treatment.
Andrew & HERMES Study Team, Consultant fee, speaker bureau, advisory committee, etc. Andrew McIvor has received honoraria for providing CME and attendance at Advisory Boards of pharmaceutical companies involved in COPD management including AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, and Nycomed. Fernando Martinez has served on advisory boards for Nycomed.; 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.