Reduction of exacerbations by the PDE4 inhibitor roflumilast - the importance of defining different subsets of patients with COPDReport as inadecuate




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Respiratory Research

, 12:18

First Online: 01 December 2011Received: 23 November 2010Accepted: 27 January 2011

Abstract

BackgroundAs 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.

MethodsThe 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.

ResultsThe 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%.

ConclusionsThis 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 registrationClinicalTrials.gov identifiers: NCT00076089 and NCT00430729.

AbbreviationsANCOVAAnalysis of covariance

COPDchronic obstructive pulmonary disease

FEV1forced expiratory volume in 1 second

ICSinhaled corticosteroids

PDE4phosphodiesterase 4

SDstandard deviation

SEstandard error

SGRQSt George-s Respiratory Questionnaire.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-18 contains supplementary material, which is available to authorized users.

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Author: Stephen I Rennard - Peter MA Calverley - Udo M Goehring - Dirk Bredenbröker - Fernando J Martinez

Source: https://link.springer.com/







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