title: Down-titration from high-dose combination therapy in asthma: Removal of long-acting beta(2)-agonist.
abstract: BACKGROUND
  Asthma guidelines recommend reducing inhaled corticosteroids (ICS) to the minimum effective dose, but the timing of long-acting beta(2)-agonist (LABA) withdrawal is unclear. Recent FDA guidelines recommend LABA withdrawal once asthma is well-controlled. This 13-month double-blind study of patients taking high-dose combination therapy investigated the effect of discontinuation of LABA before ICS down-titration.
  
  
  METHODS
  Adults using salmeterol/fluticasone combination (SFC) 50/500 microg bd were randomized to SFC 50/500 microg bd or fluticasone propionate (FP) 500 microg bd, with subsequent ICS down-titration 8-weekly using a clinical algorithm. The primary outcome was mean daily FP dose, including ICS for exacerbations.
  
  
  RESULTS
  82 subjects were randomized. Asthma was well-controlled at baseline, with mean FEV(1) 84.8% predicted and Asthma Control Questionnaire (ACQ) score 0.9. There was no significant difference in mean daily FP dose (SFC: 721 microg, FP:816 microg, p = 0.3), but final dose was lower with SFC (534 microg cf. 724 microg, p = 0.005). ICS dose was reduced by >or=80% in 41% SFC and 15% FP patients. Ambulatory lung function was significantly higher with SFC, but there were no differences between groups in rescue beta(2)-agonist use, clinic spirometry, airway responsiveness, ACQ, sputum eosinophils or FeNO. Baseline airway responsiveness, and pre-reduction blood eosinophils, were significant predictors of mean daily FP dose and dose reduction failure respectively.
  
  
  CONCLUSIONS
  Many patients prescribed high-dose combination therapy may be over-treated. Substantial reductions in dose can be achieved with a clinical algorithm, reaching lower FP doses with SFC than FP without losing asthma control or increasing disease activity.
  
  
  BACKGROUND
  This study was commenced before mandatory registration of clinical trials.
authors.affiliation: Woolcock Institute of Medical Research, PO Box M77, Missenden Rd PO, Camperdown NSW 2050, Australia. hkr@med.usyd.edu.au
authors.forename: Helen K
authors.initials: HK
authors.lastname: Reddel
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Peters
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Sand
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Hoyos
authors.forename: Christine R
authors.initials: CR
authors.lastname: Jenkins
mesh_terms: D000293:Adolescent; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D017410:Practice Guidelines as Topic; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000420:Albuterol