Onset of bronchodilation with fluticasone/formoterol combination versus fluticasone/salmeterol in an open-label, randomized study

Abstract

Introduction: The inhaled corticosteroid, fluticasone propionate (fluticasone), and the long-acting beta(2)-agonist, formoterol fumarate (formoterol), have been combined in a single aerosol inhaler (fluticasone/formoterol). In a randomized, open-label study, fluticasone/formoterol showed similar efficacy to fluticasone/salmeterol after 12 weeks of treatment. This post-hoc analysis compared the onset of bronchodilation with the two treatments.

Methods: Adults with mild-to-moderate-severe persistent asthma were randomized to fluticasone/formoterol (100/10 or 250/10 μg twice daily [b.i.d.]) or fluticasone/salmeterol (100/50 or 250/50 μg b.i.d.) for 12 weeks. The onset of bronchodilation (the first post-dose time point at which the forced expiratory volume in 1 second [FEV(1)] was ≥12% greater than the pre-dose value), responder rates (the proportion of patients achieving bronchodilation), and changes in FEV(1) were assessed at days 0 (baseline) and 84.

Results: Fluticasone/formoterol (n = 101) provided more rapid onset of bronchodilation than fluticasone/salmeterol (n = 101) over the first 120 min post-dose on days 0 (hazard ratio [HR] = 1.47 [95% CI 1.05-2.05]) and 84 (HR = 1.77 [95% CI 1.14-2.73]). The odds of a patient achieving bronchodilation within 5 min of dosing were almost four-times higher with fluticasone/formoterol than with fluticasone/salmeterol on day 0 (odds ratio [OR] = 3.97 [95% CI 1.96-8.03]) and almost 10-times higher on day 84 (OR = 9.58 [95% CI 2.14-42.90]); the odds of achieving bronchodilation within 120 min post-dose were approximately twofold higher with fluticasone/formoterol on both days. The overall percentage increase in least-squares (LS) mean FEV1 during the 120-min post-dose period was significantly greater with fluticasone/formoterol than fluticasone/salmeterol on days 0 (LS mean treatment difference: 4.70% [95% CI 1.57-7.83]; P = 0.003) and 84 (2.79% [95% CI 0.65-4.93]; P = 0.011).

Conclusion: These analyses showed that fluticasone/formoterol provided a faster onset of bronchodilation than fluticasone/salmeterol, which was maintained over 12 weeks of treatment. This benefit may facilitate treatment adherence among patients with asthma.

Trial registration: ClinicalTrials.gov NCT00476073.