PURPOSE: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, reduces exacerbation rates and improves lung function in COPD patients. Inhaled corticosteroids (ICS) are commonly used to manage COPD, particularly among individuals at risk for exacerbations. This post-hoc analysis studied the effects of roflumilast vs placebo in COPD patients with or without concomitant ICS treatment.
METHODS: This pooled, post-hoc analysis of two replicate, randomized, double-blind, placebo-controlled studies (M2-111 and M2-112) compared oral roflumilast 500μg QD with placebo over 52 weeks. Stable dose ICS use was permitted. Lung function outcomes and exacerbation rates were examined.
RESULTS: Of 2686 randomized patients, 1622 used concomitant ICS (n=809 roflumilast and n=813 placebo) and 1064 did not (n=518 and n=546, respectively). Among patients receiving concomitant ICS, 65% had severe disease vs 68% without ICS; 28% with ICS vs 21% without ICS had very severe COPD. For the overall population, pre-bronchodilator and post-bronchodilator FEV1 improved (mean±SE) with roflumilast compared to placebo by 51±7 mL (p<0.0001) and 53±8 mL (p<0.0001) and exacerbations were decreased by 14.3% (p=0.026). With concomitant ICS use, pre-bronchodilator FEV1 (53±9 mL; p<0.0001) and post-bronchodilator FEV1 (54±9 mL; p<0.0001) improved with roflumilast vs placebo. Without concomitant ICS use, pre-bronchodilator FEV1 (49±13 mL; p=0.0002) and post-bronchodilator FEV1 (53±13 mL; p<0.0001) improved with roflumilast compared to placebo. Roflumilast+ICS reduced the moderate/severe exacerbation rate vs placebo+ICS (rate ratio 0.72 vs 0.89; -18.8%; p=0.014); the percentage of patients experiencing an exacerbation was numerically lower with roflumilast+ICS vs placebo+ICS (36% vs 42%). Without concomitant ICS, the exacerbation rate (roflumilast 0.42; placebo 0.46; -7.7%; p=0.55) was not affected by roflumilast; the percentage of patients experiencing an exacerbation was numerically lower with roflumilast vs placebo (23% vs 27%).
CONCLUSION: Roflumilast was effective at improving lung function independent of concomitant ICS use and reduced exacerbation rates in patients taking concomitant ICS, who may be recognized by clinicians as more likely to experience exacerbations.
CLINICAL IMPLICATIONS: Roflumilast improves lung function, reduces the rate of exacerbations, and can have an additive effect in patients receiving concomitant ICS.
DISCLOSURE: Stephen Rennard, Grant monies (from industry related sources) Peter Calverly’ s University has received monies from Nycomed, GSK, AstraZeneca, Boehringer Inghelheim and Novartis to support clinical trials of drugs these companies manufacture.; Employee Dirk Bredenbroeker and Udo-Michael Goehring are employees of Nycomed GmbH.; Consultant fee, speaker bureau, advisory committee, etc. Peter Calverly has received consulting and speaking fees from Nycomed, GSK, AstraZeneca, Boehringer Inghelheim and Novartis. Fernando Martinez has participated in Advisory Boards for Nycomed/Forest, GSK, Novartis Speaker’ s Bureau on COPD related topics for GSK, BI Steering Committees on COPD related topics for Nycomed, GSK, Mpex.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Roflumilast is approved in Europe, and under consideration by the FDA in the United States.