The oral, selective phosphodiesterase 4 inhibitor roflumilast can improve lung function in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate whether roflumilast provided additional benefits to COPD patients with moderate-to-severe disease when co-administered with the long-acting bronchodilator salmeterol.
Patients with moderate-to-severe COPD were recruited to this double-blind, randomized, parallel-group study. After a single-blind, 4-week baseline period with salmeterol, 50αg twice daily, plus oral placebo, once daily, patients continued salmeterol treatment and were randomized to receive roflumilast, 500αg once daily (n=466), or placebo, once daily (n=467), concomitantly for 24 weeks. The primary outcome variable was mean change in pre-bronchodilator forced expiratory volume in 1 second (FEV1) from baseline to each post-randomization visit. Other outcomes included post-bronchodilator FEV1, other lung function measurements and time to first exacerbation.
Compared with salmeterol plus placebo, roflumilast plus salmeterol significantly improved mean pre-bronchodilator FEV1 by 49mL (95%CI: 27, 71; p<0.001) and mean post-bronchodilator FEV1 by 60mL (95%CI: 38,82; p<0.001). Similarly, roflumilast plus salmeterol significantly improved pre- and post-bronchodilator FEV1/forced vital capacity (FVC) by 1.18% (standard error [SE] 0.27%; p<0.001) and 1.13% (SE 0.25%, p<0.001), respectively, compared with salmeterol plus placebo. The concomitant regimen also increased the median time to first moderate or severe exacerbation (hazard ratio 0.6; 95%CI: 0.4, 0.9; p=0.007), and reduced the proportion of patients experiencing a moderate or severe exacerbation (risk ratio 0.6; 95%CI 0.43, 0.82; p=0.002) compared with salmeterol plus placebo. The safety profile of the concomitant treatment was consistent with that previously reported for roflumilast. Adverse events occurred in 63.1% of patients receiving roflumilast concomitant with salmeterol compared with 59.1% receiving salmeterol plus placebo.
Roflumilast provides additional clinical benefits to COPD patients receiving salmeterol by statistically significantly improving lung function, increasing time to moderate or severe exacerbation and reducing the proportion of patients experiencing a moderate or severe exacerbation.
In COPD patients already receiving salmeterol, addition of roflumilast can provide further improvements in pulmonary function and clinical outcomes.
K. R. Chapman, MD & EOS Study Team, Grant monies (from industry related sources) Kenneth Chapman has received grant monies from AstraZeneca, Boehringer-Ingelheim, CSL Behring, GlaxoSmithKline, Merck Frosst, Novartis, Nycomed, Parangenix, Roche, Telacris.; Consultant fee, speaker bureau, advisory committee, etc. Kenneth Chapman has provided consultancy to Astra Zeneca, Boehringer-Ingelheim, CSL Behring, GlaxoSmithKline, Merck Frosst, Novartis, Nycomed, Pfizer, Roche, Schering Plough, Telacris. Kenneth Chapman has advised on CME activities for AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck Frosst, Novartis, Nycomed, Pfizer, Telacris. 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.; 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.