A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler

Abstract

Background: New inhaled glucocorticosteroids and inhalers are being developed. Their clinical equipotency is difficult to assess and is often discussed.

Objective: This study was carried out to compare the effect of budesonide Turbuhaler and fluticasone propionate (FP) Diskhaler in a dose reduction study in children (ages 5 to 16 years) with asthma.

Methods: Children treated with budesonide administered through a pressurized metered-dose inhaler with a large volume spacer had their budesonide dose gradually reduced to define the minimal effective dose with this delivery system. After this period, 217 children were randomly allocated to treatment with half the dose of either budesonide Turbukaler or FP Diskhaler for 5 weeks in a double-blind trial. If no deterioration in asthma control was seen, the dose was further reduced by 50% at 5-week intervals until deterioration in asthma control was seen. Throughout the study, morning and evening peak expiratory flow, symptoms, and use of rescue beta 2-agonist were recorded in diaries. Lung function tests and a standardized exercise test were performed at the clinic at the end of each treatment period. Urine cortisol excretion (24 hours) was measured before and after the first 5-week treatment period. Standardized criteria for deterioration in asthma control, based on diary card variables and exercise testing, were used to determine the minimal effective dose for each patient; and from this, the number of dose reduction steps was calculated.

Results: No statistically significant difference was seen in number of dose reduction steps from baseline or in minimal effective dose between the two treatments; mean reduction was 1.59 dose steps for budesonide Turbuhaler and 1.65 dose steps for FP Diskhaler (p = 0.52), and minimal effective dose was 188 micrograms for budesonide Turbuhaler and 180 micrograms for FP Diskhaler. After these dose reductions, the same level of asthma control was observed in the budesonide Turbuhaler and FP Diskhaler groups. Furthermore, no statistically significant differences between the two inhaler-drug combinations were seen in daytime or nighttime symptoms, morning and evening peak expiratory flow, use of rescue beta 2-agonist, lung functions at the clinic, exercise-induced fall in lung function, or 24-hour urinary cortisol excretion during the first 5-week period.

Conclusion: Microgram for microgram, budesonide Turbuhaler and FP Diskhaler are equally effective in treatment of children with moderate asthma.