Roflumilast for asthma: Efficacy findings in mechanism of action studies

Abstract Background The efficacy profile of roflumilast, a phosphodiesterase-4 inhibitor used for the treatment of chronic obstructive pulmonary disease (COPD), is well known. In asthma treatment, much less is understood about the role of roflumilast, particularly its mechanism of action and potenti...

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Published in:Pulmonary pharmacology & therapeutics 2015-12, Vol.35, p.S4-S10
Main Authors: Bardin, P, Kanniess, F, Gauvreau, G, Bredenbröker, D, Rabe, K.F
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Allergen
Aminopyridines - adverse effects
Aminopyridines - pharmacology
Aminopyridines - therapeutic use
Asthma
Asthma - drug therapy
Asthma - physiopathology
Benzamides - adverse effects
Benzamides - pharmacology
Benzamides - therapeutic use
Cross-Over Studies
Cyclopropanes - adverse effects
Cyclopropanes - pharmacology
Cyclopropanes - therapeutic use
Double-Blind Method
Eosinophil
FEV1
Forced Expiratory Volume - drug effects
Humans
Medical Education
Middle Aged
Phosphodiesterase 4 Inhibitors - therapeutic use
Pulmonary/Respiratory
Roflumilast
Sputum - cytology
Young Adult
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Summary:Abstract Background The efficacy profile of roflumilast, a phosphodiesterase-4 inhibitor used for the treatment of chronic obstructive pulmonary disease (COPD), is well known. In asthma treatment, much less is understood about the role of roflumilast, particularly its mechanism of action and potential bronchodilatory effects. Aim To evaluate the therapeutic efficacy and mechanism of action of roflumilast in patients with asthma using data from eight placebo-controlled, double-blind phase I–III studies. Methods The studies were conducted at 14 sites in Europe, North America and South Africa from 1997 to 2005. The effect of treatment with 250 μg, 500 μg or 1000 μg roflumilast was compared with placebo in seven cross-over studies and one parallel-group study in 197 patients 18–70 years of age. Primary endpoints focused on the extent of the late allergic response after an allergen challenge, change in sputum cell eosinophil counts or exhaled nitric oxide (eNO), forced expiratory volume in 1 s (FEV1 ) and exercise-induced bronchoconstriction. Secondary endpoints included the extent of the early allergic response and measurements of tumour necrosis factor α (TNFα), sputum cells and inflammatory markers. Results Roflumilast attenuated allergen-induced bronchoconstriction (FEV1 ) in patients with asthma. Significant reductions in allergen-induced airway inflammation, including a reduction in both eosinophil and neutrophil counts were also observed and physiologic responses to allergen-induced challenge were confirmed by a significant reduction in TNFα. Side effects were similar to COPD, but did not include weight loss. Conclusions The results from these studies indicate that the anti-inflammatory effects of roflumilast observed in COPD are also seen in asthma and advance our understanding of its mechanism of action. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov : NCT01365533.
ISSN:1094-5539
1522-9629
DOI:10.1016/j.pupt.2015.08.006