title: 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 potential bronchodilatory effects.
  
  
  OBJECTIVE
  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.
authors: Monash Lung & Sleep, Monash Medical Center and University, Melbourne, Australia. Electronic address: philip.bardin@monash.edu.
authors: P
authors: P
authors: Bardin
authors: Practice for Allergy and Family Medicine, Reinfeld, Germany. Electronic address: f.kanniess@gpr-reinfeld.de.
authors: F
authors: F
authors: Kanniess
authors: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. Electronic address: gauvreau@mcmaster.ca.
authors: G
authors: G
authors: Gauvreau
authors: Takeda Pharmaceuticals International GmbH, Zurich, Switzerland. Electronic address: dirk.bredenbroeker@takeda.com.
authors: D
authors: D
authors: Bredenbröker
authors: Lung Clinic Großhansdorf, Germany; Department of Medicine, Christian Albrecht University Kiel, Germany. Electronic address: k.f.rabe@lungenclinic.de.
authors: K F
authors: KF
authors: Rabe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001549:Benzamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003521:Cyclopropanes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000627:therapeutic use*; D013183:Sputum / Q000166:cytology; D055815:Young Adult
chemical_list: D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast
keywords: Allergen; Asthma; Eosinophil; FEV(1); Roflumilast