Comparison of four-times-a-day and twice-a-day dosing regimens in subjects requiring 1200 μg or less of budesonide to control mild to moderate asthma

AbstractThe aim of this study was to compare the efficacy, compliance and side-effects of budesonide administered twice daily (b.d.) and four times a day (q.d.) with a Turbuhaler® device in asthmatic subjects requiring ≤ 1200 μg daily. The randomized, parallel group study design included a 2-week baseline period followed by a 6–12-month treatment period. Subjects were assessed at regular intervals in hospital through FEV1, PC20 methacholine, adrenal function and throat swabs. They were asked to record their symptoms and PEF values morning and evening at home. An asthmatic flare-up, which was the main outcome resulting in a patient's termination of the study, was defined beforehand as (a) 25% or greater diurnal variability in PEF for 2 consecutive days, and/or (b) nocturnal awakenings due to asthma symptoms 2 days or more in the same week and/or (c) an increase (doubling or more) in the need for inhaled bronchodilator 2 days in the same week.Fifty-eight adult asthmatic subjects (20 males and 38 females) entered the study, one-half being randomly assigned to the b.d. regimen and one-half to the q.d. regimen. Fourteen subjects were on 400 μg, 15 subjects on 800 μg and 29 subjects on 1200 μg of budesonide daily. Seventeen flare-ups were recorded in the b.d. regimen group as opposed to 11 in the q.d. regimen (P=0·05), significant differences being found in the 800 and 1200 μg groups (a total of 13 flare-ups in the b.d. group and eight flare-ups in the q.d. group for the two doses, P=0·01). Kaplan-Meier survival analysis yielded similar results. There was no significant difference in FEV1, PC20 or cortisol levels during the study on either regimen. Throat symptoms and growth of Candida albicans were more common in the q.d. group. Compliance assessed by the number of times the Turbuhaler® device was actuated was significantly better in the b.d. group (95%) as compared with the q.d. group (83%). To conclude, administering inhaled budesonide with a Turbuhaler® device on a q.d. basis results in fewer flare-ups in spite of less satisfactory compliance and more common, local side-effects than on a b.d. regimen at daily doses of 800 and 1200 μg