title: Roflumilast for asthma: Efficacy findings in non-placebo-controlled comparator and dosing studies.
abstract: BACKGROUND
  Roflumilast, a phosphodiesterase-4 inhibitor, has an established place in the treatment of chronic obstructive pulmonary disease. Its potential role as a treatment for asthma is unclear.
  
  
  OBJECTIVE
  We report the results from seven double-blind, parallel group, phase II or III studies designed to compare roflumilast with two anti-inflammatory treatments, beclomethasone dipropionate (BDP) and montelukast, in patients with asthma.
  
  
  METHODS
  The studies of 6-12 week duration were conducted at 309 sites in Europe, North America, South Africa and Australia from 1998 to 2005. Data from 3802 patients, aged 12-70 years who received either roflumilast 100 μg, 250 μg or 500 μg once daily, BDP 400 μg or 500 μg twice daily, or 10 mg montelukast once daily was analyzed. Primary endpoints were mean change and time averaged excess area under the curve in forced expiratory volume in one second (FEV1) over the duration of the study. Secondary endpoints included change in forced vital capacity and peak expiratory flow, asthma symptoms and the concomitant use of rescue medication.
  
  
  RESULTS
  Roflumilast was non-inferior to BDP and montelukast and consistently increased FEV1. Use of rescue medication and all asthma symptom scores decreased significantly with all treatments, but no statistically significant between-group differences were observed. Secondary lung function endpoints generally supported the conclusions of the primary outcome measure.
  
  
  CONCLUSIONS
  Roflumilast improves FEV1 and asthma symptoms in patients with mild to moderate asthma, and is non-inferior compared with both BDP and montelukast. It deserves further study as a potentially effective anti-inflammatory treatment for asthma.
authors.affiliation: Division of Pulmonology, Department of Medicine, University of Cape Town Lung Institute, Cape Town, South Africa. Electronic address: Eric.Bateman@uct.ac.za.
authors.forename: E D
authors.initials: ED
authors.lastname: Bateman
authors.affiliation: Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier-Cedex, France. Electronic address: jean.bousquet@orange.fr.
authors.forename: J
authors.initials: J
authors.lastname: Bousquet
authors.affiliation: Service de Pneumologie-allergologie, Hôpital Bichat de Paris, Paris, France. Electronic address: michel.aubier@bch.aphp.fr.
authors.forename: M
authors.initials: M
authors.lastname: Aubier
authors.affiliation: Takeda Pharmaceuticals International GmbH, Zurich, Switzerland. Electronic address: dirk.bredenbroeker@takeda.com.
authors.forename: D
authors.initials: D
authors.lastname: Bredenbröker
authors.affiliation: Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Canada. Electronic address: obyrnep@mcmaster.ca.
authors.forename: P M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D003521:Cyclopropanes / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D005541:Forced Expiratory Volume; D006801:Humans; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D013440:Sulfides; D055815:Young Adult
chemical_list: D000085:Acetates; D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; D011804:Quinolines; D013440:Sulfides; C424423:Roflumilast; D001507:Beclomethasone; C093875:montelukast
keywords: Asthma; Beclomethasone; FEV(1); Montelukast; Roflumilast