Inhaled steroid/long-acting β2 agonist combination products provide 24 hours improvement in lung function in adult asthmatic patients

Background: The combination of inhaled corticosteroids (ICS) and long-acting beta 2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide(TM) GSK, UK) and formoterol/budesonide (FBC, Symbicort(TM), AstraZeneca, UK) are commercially available. Objectives: The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. Methods: Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400 - 1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800 - 1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide T followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. Results: In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L ( 95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (- 0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2 - 24 hours post dose was - 16.0 ml/hr for SFC and - 14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively Conclusion: Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.