Down-titration from high-dose combination therapy in asthma: Removal of long-acting β2-agonist

Reddel, Helen K.; Gibson, Peter G.; Peters, Matthew J.; Wark, Peter A.B.; Sand, Ingrid B.; Hoyos, Camilla M.; Jenkins, Christine R.

doi:10.1016/j.rmed.2010.04.003

« Previous Next »Respiratory Medicine
Volume 104, Issue 8 , Pages 1110-1120, August 2010

Down-titration from high-dose combination therapy in asthma: Removal of long-acting β₂-agonist

Helen K. Reddel
- Woolcock Institute of Medical Research, PO Box M77, Missenden Rd PO, Camperdown NSW 2050, Australia
- Corresponding author. Tel.: +61 2 9114 0437; fax: +61 2 9114 0014.
Peter G. Gibson
- Hunter Medical Research Institute, John Hunter Hospital, Lookout Road, New Lambton NSW 2305, Australia
Matthew J. Peters
- Concord Repatriation General Hospital, Hospital Rd, Concord NSW 2139, Australia
Peter A.B. Wark
- Hunter Medical Research Institute, John Hunter Hospital, Lookout Road, New Lambton NSW 2305, Australia
Ingrid B. Sand
- GlaxoSmithKline Australia, 1061 Mountain Hwy, Boronia, Victoria 3155, Australia
Camilla M. Hoyos
- Woolcock Institute of Medical Research, PO Box M77, Missenden Rd PO, Camperdown NSW 2050, Australia
Christine R. Jenkins
- Woolcock Institute of Medical Research, PO Box M77, Missenden Rd PO, Camperdown NSW 2050, Australia

Received 9 October 2009; accepted 5 April 2010. published online 30 April 2010.

Summary

Background

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.

Methods

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.

Results

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.

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.