Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions

J Allergy Clin Immunol. 2005 Aug;116(2):292-8. doi: 10.1016/j.jaci.2005.04.023.


Background: Asthma is a chronic inflammatory disease with increasing incidence worldwide. Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 that prevents the breakdown of cyclic adenosine monophosphate levels, leading to inhibition of proinflammatory signaling.

Objective: The objective of this study was to investigate the effects of repeated doses of 250 or 500 microg of roflumilast on asthmatic airway responses to allergen.

Methods: Twenty-three patients with mild asthma with an FEV1 of 70% of predicted value or greater were enrolled in a randomized, double-blind, placebo-controlled, 3-period crossover study. Patients participated in 3 treatment periods (7-10 days) separated by washout periods (2-5 weeks). Patients received 250 microg of oral roflumilast, 500 microg of roflumilast, or placebo once daily. Allergen challenge was performed at the end of each treatment period, followed by FEV1 measurements over the ensuing 24 hours.

Results: Late asthmatic reactions (LARs) were reduced by 27% (P = .0110) and 43% (P = .0009) in patients treated with 250 and 500 microg of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 microg, also attenuated early asthmatic reactions by 25% (P = .0038) and 28% (P = .0046), although not to the same extent as LAR attenuation. Roflumilast was well tolerated. No serious adverse events or discontinuations caused by adverse events were reported.

Conclusion: Once-daily oral roflumilast modestly attenuated early asthmatic reactions and, to a greater extent, LARs to allergen in patients with mild allergic asthma. Pronounced suppression of late responses in an allergen challenge model suggests that roflumilast might have anti-inflammatory activity, which could provide clinical efficacy in chronic inflammatory pulmonary diseases, such as asthma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Administration, Oral
  • Adult
  • Allergens / immunology*
  • Aminopyridines / adverse effects
  • Aminopyridines / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Benzamides / adverse effects
  • Benzamides / therapeutic use*
  • Cross-Over Studies
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclopropanes / adverse effects
  • Cyclopropanes / therapeutic use
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Phosphodiesterase Inhibitors / therapeutic use*


  • Allergens
  • Aminopyridines
  • Benzamides
  • Cyclopropanes
  • Phosphodiesterase Inhibitors
  • Roflumilast
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4