Document Type

Article

Journal Title

Respiratory Research

Publication Date

2011

Volume

12

Abstract

BACKGROUND: As chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive. This led to the question of whether a responsive subset existed that could be investigated further.

METHODS: The datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.

RESULTS: The pooled analysis included 2686 randomized patients. Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026). Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014). The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).

CONCLUSIONS: This post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS. These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.

TRIALS REGISTRATION: ClinicalTrials.gov identifiers: NCT00076089 and NCT00430729.

MeSH Headings

Administration, Oral, Aged, Aminopyridines, Anti-Inflammatory Agents, Benzamides, Clinical Trials, Phase III as Topic, Cyclopropanes, Double-Blind Method, Drug Administration Schedule, Female, Forced Expiratory Volume, Humans, Lung, Male, Middle Aged, Multicenter Studies as Topic, Patient Selection, Phosphodiesterase 4 Inhibitors, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive, Randomized Controlled Trials as Topic, Research Design, Risk Assessment, Risk Factors, Treatment Outcome

ISSN

1465-993X

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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