PURPOSE: The M2-112 (RATIO) study found that the beneficial effects of roflumilast on lung function, exacerbation rate, and quality of life was independent of concomitant therapy with inhaled corticosteroids (ICS) in moderate COPD patients. This pre-specified analysis of two pivotal trials (M2-124 and M2-125) examined the effect of prior ICS use on roflumilast efficacy in severe COPD patients with bronchitic symptoms and a history of exacerbations.
METHODS: In this pooled, pre-specified analysis comparing roflumilast 500μ g QD with placebo, patients using ICS prior to study enrollment were compared to those without ICS pre-treatment. All patients were required to discontinue ICS treatment after a 4-week run-in period for each trial. Pre- and post-bronchodilator FEV1 change from baseline, percentage of subjects experiencing an exacerbation, and the rate of moderate or severe exacerbations were examined.
RESULTS: Of 3091 randomized patients, 1307 (650 roflumilast, 657 placebo) received ICS pre-treatment and 1784 (887 roflumilast, 897 placebo) did not. Baseline characteristics were similar between treatment groups and between ICS pre-treatment strata. Differences between roflumilast and placebo for pre-bronchodilator FEV1 change from baseline were comparable with ICS pre-treatment (LS Mean 47 mL increase [95% CI, 28-67] P< 0.0001) and without (49 mL increase [30-68] P< 0.0001). Compared with placebo, roflumilast had similar effects on post-bronchodilator FEV1 change from baseline in patients with ICS pre-treatment (44 mL increase [23-66], P< 0.0001) and without (63 mL increase [44-82], P< 0.0001). Compared with placebo, decreases in moderate/severe exacerbation rates with roflumilast treatment were similar with or without ICS pre-treatment (rate ratio 0.807 [95% CI 0.698-0.933], -19.3%, P=0.0038 vs. 0.832 [0.723-0.957], -16.8%, P=0.0102, respectively). Compared with placebo, fewer roflumilast patients experienced ≥1 moderate/severe exacerbation during the one year studies: 52.5% and 59.2% with ICS pre-treatment vs. 42.4% and 48.2% without ICS pre-treatment respectively, based on post-hoc analyses.
CONCLUSION: Roflumilast is effective at improving lung function and reducing the rate of moderate or severe COPD exacerbations independent of previous ICS treatment.
CLINICAL IMPLICATIONS: Roflumilast efficacy does not appear to be influenced by prior ICS treatment.
DISCLOSURE: Andrew McIvor, Employee Manja Brose and Udo-Michael Goehring are employees of , Nycomed GmbH.; Consultant fee, speaker bureau, advisory committee, etc. Fernando Martinez has participated in a Speaker’s Bureau on COPD related topics for GSK, BI and in Steering Committees on COPD related topics for Nycomed, GSK, and Advisory Boards for Nycomed/Forest, GSK, Novartis; Andrew McIvor is on the speaker bureau for AstraZeneca, GlaxoSmithKlein, Boehringer Ingelheim, Pfizer, Nycomed, Novartis, and Merck .; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Roflumilast is approved in the European Union for patients with COPD and is under consideration from the FDA in the US.