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Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD.
Respir Res. 2011 Jan 27; 12:18.RR

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.

Authors+Show Affiliations

Nebraska Medical Center, Omaha, Nebraska, USA. srennard@unmc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21272339

Citation

Rennard, Stephen I., et al. "Reduction of Exacerbations By the PDE4 Inhibitor Roflumilast--the Importance of Defining Different Subsets of Patients With COPD." Respiratory Research, vol. 12, 2011, p. 18.
Rennard SI, Calverley PM, Goehring UM, et al. Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD. Respir Res. 2011;12:18.
Rennard, S. I., Calverley, P. M., Goehring, U. M., Bredenbröker, D., & Martinez, F. J. (2011). Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD. Respiratory Research, 12, 18. https://doi.org/10.1186/1465-9921-12-18
Rennard SI, et al. Reduction of Exacerbations By the PDE4 Inhibitor Roflumilast--the Importance of Defining Different Subsets of Patients With COPD. Respir Res. 2011 Jan 27;12:18. PubMed PMID: 21272339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD. AU - Rennard,Stephen I, AU - Calverley,Peter M A, AU - Goehring,Udo M, AU - Bredenbröker,Dirk, AU - Martinez,Fernando J, Y1 - 2011/01/27/ PY - 2010/11/23/received PY - 2011/01/27/accepted PY - 2011/1/29/entrez PY - 2011/1/29/pubmed PY - 2011/5/5/medline SP - 18 EP - 18 JF - Respiratory research JO - Respir Res VL - 12 N2 - 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. SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/21272339/Reduction_of_exacerbations_by_the_PDE4_inhibitor_roflumilast__the_importance_of_defining_different_subsets_of_patients_with_COPD_ DB - PRIME DP - Unbound Medicine ER -