COPD is an inflammatory airway disease with progressive decline in lung function and health-related quality of life. Current treatments palliate clinical symptoms rather than target COPD pathophysiology. Roflumilast is an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor with anti-inflammatory activity, which may be beneficial in the treatment of COPD. The present study investigated long-term safety of roflumilast in COPD patients for up to 52 weeks.
After a 2-week single-blind, placebo run-in period, patients (postbronchodilator FEV1 35-75%; FEV1/FVC £ 70 predicted) received roflumilast 250 μg, or 500 μg or placebo for 26 weeks. Per-protocol patients (N=397) continued on to the open-label extension and received roflumilast 500 μg for another 26 weeks. Safety was assessed by monitoring adverse events (AEs), vital signs, ECG, and laboratory testing.
Long-term treatment with roflumilast was well tolerated. The frequency of patients experiencing AEs was 49% during the double-blind period (same frequency for all treatment groups), and 41% during the open-label extension. In both treatment periods, most AEs were mild to moderate in intensity and transient in duration; >90% of all AEs were assessed as unrelated or unlikely related to study drug. During the open-label extension, AEs associated with the digestive, cardiovascular, or nervous systems were reported by few (<2%) of patients. Ten patients (2.5%) experienced 13 AEs that were assessed as likely or definitely related to study drug, and of these, 3 cases led to study discontinuation. No significant changes in laboratory parameters or vital signs occurred and there was no evidence of roflumilast-related effects on the QTc interval.
One year of treatment with oral once-daily roflumilast was associated with a low overall incidence of drug-related, PDE4 inhibitor side effects.
Roflumilast is an oral, well-tolerated anti-inflammatory agent with potential use in the long-term therapy of COPD.
J. van Noord, None.