PURPOSE: Frequent COPD exacerbations are associated with significant patient and healthcare burden. In this analysis, the effect of roflumilast on exacerbation outcomes was examined.
METHODS: A post-hoc analysis was conducted on pooled data from two replicate, randomized, placebo-controlled, double-blind, multicenter trials (M2-124 and M2-125) in COPD patients with severe-to-very severe airflow obstruction, a history of exacerbations, and chronic bronchitis. Patients were randomized to roflumilast 500μg QD or placebo for 52 weeks. Exacerbation rate, time to exacerbation, and proportion of patients experiencing frequent exacerbations were analyzed for the overall population, in patients who had a history or who experienced frequent exacerbations, and by COPD severity. Exacerbations were defined as new or worsening COPD symptoms requiring oral or parenteral glucocorticoids (moderate) or hospitalization and/or leading to death (severe).
RESULTS: A total of 3091 COPD patients were randomized to roflumilast (n=1537; 943 severe, 463 very severe) or placebo (n=1554; 989 severe, 440 very severe). Compared with placebo, roflumilast was associated with a lower exacerbation rate in patients with a history (1 year prior to enrollment) of frequent (≥2 exacerbations/year) exacerbations (1.51 vs 1.95, respectively; -22.3%; p=0.002). Roflumilast was also associated with longer times to first and second exacerbations (hazard ratio 0.89, p=0.019 and 0.79, p=0.014, respectively). Overall, the proportion of patients experiencing frequent (≥2 exacerbations/year) exacerbations was lower for roflumilast than placebo (21.4% vs 27.7%, respectively). This held true when these patients were grouped by disease severity (severe COPD: 19.3% vs 26.4%; very severe COPD: 27.0% vs 33.4%, respectively). Roflumilast significantly reduced the rate of exacerbations in severe (rate ratio 0.81, -18.7%; p=0.002) and very severe COPD patients (0.80, -19.7%; p=0.013).
CONCLUSION: Roflumilast reduces exacerbation rate in patients with a history of frequent exacerbations. Overall, frequency of exacerbations was lower, and time to first and second exacerbations was longer with roflumilast compared with placebo in severe-to-very severe COPD patients.
CLINICAL IMPLICATIONS: Roflumilast reduces the rate of COPD exacerbations, which may result in a decrease in healthcare burden.
DISCLOSURE: Nicola Hanania, Grant monies (from industry related sources) Nicola Hanania received research grant support from NyComed. Peter Calverly’ s University has received monies from Nycomed, GSK, AstraZeneca, Boehringer Inghelheim and Novartis to support clinical trials of drugs these companies manufacture. Leonardo Fabbri reports having received grant support from Nycomed, Abbott, AstraZeneca, Boehringer Ingelheim, Menarini,, Novartis , Schering Plough, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharp & Dohme, UCB, Pfizer, Italian Ministry of Health, and Italian Ministry for University and Research. Professor Rabe has been consulting, participated in Advisory Board Meetings and received lecture fees from AstraZeneca, Boehringer, Chiesi Pharmaceuticals, Pfizer, Novartis, Nycomed, MSD, and GSK. Professor Rabe holds no stock or other equities in pharmaceutical companies. The Department of Pulmonology, and thereby professor K.F. Rabe as head of the department has received grants from Novartis, AstraZeneca, Boehringer Ingelheim, Nycomed, Roche and GSK in the years 2005 until 2009.; Employee Udo-Michael Goehring is an employees of Nycomed GmbH.; Consultant fee, speaker bureau, advisory committee, etc. Nicola Hanania served on the advisory board for NyComed and Forest. Peter Calverly has received consulting and speaking fees from Nycomed, GSK, AstraZeneca, Boehringer Inghelheim and Novartis. related topics for Nycomed, GSK, Mpex. Eric Bateman has received speaker fees from Nycomed, and honoraria for serving on advisory boards for Nycomed and Forest. Leonardo Fabbri reports having served as a consultant to Nycomed, Forrest, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche and Pfizer; having been paid lecture fees by Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Nycomed, Roche and Pfizer.; 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.