The oral, selective phosphodiesterase 4 inhibitor roflumilast can improve lung function in patients with chronic obstructive pulmonary disease (COPD). This study aimed to determine whether roflumilast provides benefit to COPD patients with moderate-to-severe disease and cough and sputum (chronic bronchitis) regularly treated with tiotropium.
In a double-blind, randomized, parallel-group study, patients with moderate-to-severe COPD (forced expiratory volume in 1 second [FEV1] 40–70% predicted) associated with chronic bronchitis entered a single-blind, 4-week baseline treatment period with tiotropium 18 αg once daily, followed by randomization to concomitant roflumilast 500 αg once daily (n=371) or placebo once daily (n=372) with continued tiotropium therapy for 24 weeks. The study met its primary endpoint of change in pre-bronchodilator FEV1 [Rabe KF et al. Submitted 2009]. The effect of treatment on change in breathlessness, measured using the Shortness of Breath Questionnaire (SOBQ), from baseline to each post-randomization visit was a secondary outcome.
Baseline characteristics were similar in the two groups. Improvements (reduced scores) in SOBQ total score were seen in both groups at all visits, and between-treatment differences showed the superiority of tiotropium plus roflumilast compared with tiotropium plus placebo over 24 weeks (LS Mean: –2.6, 95% CI: –4.5, –0.8, p=0.005). The potential for a clinically relevant improvement (5-unit score reduction) in SOBQ total score was higher with roflumilast than with placebo; risk 0.70 and 0.58 on log-binomial regression analysis, respectively. The risk ratio for the proportion of patients with clinically relevant improvement in SOBQ total score in each treatment group was greater than one (1.195; 95% CI: 1.070, 1.335; p=0.002) confirming that roflumilast was superior to placebo for this measurement.
Roflumilast further increases the possibility of clinically relevant improvement in SOBQ total score in patients with COPD receiving tiotropium.
Roflumilast may improve breathlessness in COPD patients treated with tiotropium.
Pierluigi Paggiaro, University grant monies Pierluigi Paggiaro has received funding from the Italian Ministry of the University for research projects.; Grant monies (from sources other than industry) Pierluigi Paggiaro has received funding from the Italian Agency of the Drug (AIFA) for independent research.; Grant monies (from industry related sources) Pierluigi Paggiaro has received grants from Boehringer, Chiesi, and MerckSharp&Dohme to support research activities of the Cardio-Thoracic and Vascular Department.; Consultant fee, speaker bureau, advisory committee, etc. Alwyn Foden has provided services for GlaxoSmithKline and AstraZeneca.; 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.