Down-titration from high-dose combination therapy in asthma: Removal of long-acting beta(2)-agonist.
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.
Reddel
Helen K
HK
Woolcock Institute of Medical Research, PO Box M77, Missenden Rd PO, Camperdown NSW 2050, Australia. hkr@med.usyd.edu.au
Gibson
Peter G
PG
Peters
Matthew J
MJ
Wark
Peter A B
PA
Sand
Ingrid B
IB
Hoyos
Camilla M
CM
Jenkins
Christine R
CR
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
D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000420:Albuterol