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Original Research: COPD |

Efficacy of Roflumilast in the COPD Frequent Exacerbator PhenotypeRoflumilast for the Frequent Exacerbator Phenotype

Jadwiga A. Wedzicha, MD; Klaus F. Rabe, MD; Fernando J. Martinez, MD; Dirk Bredenbröker, MD; Manja Brose, MS; Udo-Michael Goehring, MD; Peter M. A. Calverley, MD
Author and Funding Information

From the Centre for Respiratory Medicine (Dr Wedzicha), University College London, Royal Free Campus, London; the School of Clinical Sciences (Dr Calverley), University Hospital Aintree, Liverpool, England; University Kiel (Dr Rabe), Kiel; Krankenhaus Grosshansdorf (Dr Rabe), Center for Pulmonology and Thoracic Surgery, Grosshansdorf; the Department of Respiratory Medicine (Drs Bredenbröker and Goehring) and the Department of Data Science (Ms Brose), Nycomed: a Takeda Company, Konstanz, Germany; the Department of Pulmonology C3-P (Dr Rabe), Leiden University Medical Center, Leiden, The Netherlands; and the Department of Internal Medicine (Dr Martinez), University of Michigan Medical Center, Ann Arbor, MI.

Correspondence to: Jadwiga A. Wedzicha, MD, Centre for Respiratory Medicine, University College London, Royal Free Campus, London, NW3 2PF, England; e-mail: j.wedzicha@ucl.ac.uk


Funding/Support: This study was supported financially by Nycomed: a Takeda Company, Konstanz, Germany, which holds the license for roflumilast.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(5):1302-1311. doi:10.1378/chest.12-1489
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Background:  COPD exacerbations are associated with increased morbidity and mortality and can accelerate disease progression. The best predictor of future exacerbations is a history of previous exacerbations, which helps identify a frequent exacerbator phenotype. This post hoc analysis evaluated the effect of roflumilast, a drug known to reduce the COPD exacerbation rate, on exacerbation status.

Methods:  Pooled data from two 1-year, placebo-controlled, roflumilast (500 μg once daily) studies in patients with symptomatic COPD and severe airflow obstruction were evaluated (studies M2-124 and M2-125, ClinicalTrials.gov identifiers NCT00297102 and NCT00297115). A total of 3,091 patients were included in this analysis (62.5% with GOLD [Global Initiative for Chronic Obstructive Lung Disease] III COPD and 29.2% with GOLD 4 COPD). Based on their exacerbation frequency status in the previous year, patients were classified as frequent (two or more events) or infrequent (fewer than two events) exacerbators. Exacerbation frequency was analyzed at baseline and at year 1.

Results:  Among frequent exacerbators treated with roflumilast, 32.0% still had frequent exacerbations at year 1 compared with 40.8% of placebo-treated patients (risk ratio, 0.799; P = .0148). Among infrequent exacerbators, 17.5% of roflumilast-treated patients became frequent exacerbators at year 1 compared with 22.9% of those taking placebo (risk ratio, 0.768; P = .0018). The reduction in severe exacerbations leading to hospitalization/death was similar between subgroups and occurred independently of concomitant long-acting β2-agonists or previous inhaled corticosteroid treatment. When analyzed by severity of airflow limitation, 26.4% of roflumilast-treated frequent exacerbators with GOLD III COPD remained frequent exacerbators at year 1 compared with 38.9% of those taking placebo (P = .0042).

Conclusions:  Treatment with roflumilast shifts patients from the frequent to the more stable infrequent exacerbator state.

Trial registry:  ClinicalTrials.gov; No.: NCT00297102 and NCT00297115; URL: www.clinicaltrials.gov

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