Asthma guidelines recommend reducing inhaled corticosteroids (ICS) to the minimum effective dose, but the timing of long-acting β₂-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. Adults using salmeterol/fluticasone combination (SFC) 50/500 μg bd were randomized to SFC 50/500 μg bd or fluticasone propionate (FP) 500 μg bd, with subsequent ICS down-titration 8-weekly using a clinical algorithm. The primary outcome was mean daily FP dose, including ICS for exacerbations. 82 subjects were randomized. Asthma was well-controlled at baseline, with mean FEV1 84.8% predicted and Asthma Control Questionnaire (ACQ) score 0.9. There was no significant difference in mean daily FP dose (SFC: 721 μg, FP:816 μg, p = 0.3), but final dose was lower with SFC (534 μg cf. 724 μg, p = 0.005). ICS dose was reduced by ≥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 β₂-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. 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. This study was commenced before mandatory registration of clinical trials.
Respiratory Medicine Vol. 104, Issue 8, p. 1110-1120