Methods: A 2- to 3-week run-in period with twice-daily (BID) MF 100 μg (MF/F 100/10 μg BID study), MF 200 μg (MF/F 200/10 μg BID study), or MF 400 μg (MF/F 400/10 μg BID study) was performed before subjects (aged ≥12 y) were randomized to BID: MF/F 100/10 μg, MF 100 μg, F 10 μg, or placebo for 26 weeks (n=746; MF/F 100/10 μg BID study); MF/F 200/10 μg, MF 200 μg, F 10 μg, or placebo for 26 weeks (n=781; MF/F 200/10 μg BID study); or MF/F 200/10 μg, MF/F 400/10 μg, or MF 400 μg for 12 weeks (n=728; MF/F 400/10 μg BID study). Assessment of asthma deterioration (ie, 20% decrease in forced expiratory volume in 1 s [FEV1], 30% decrease in peak expiratory flow [PEF] on ≥2 consecutive days, or clinically judged deterioration [ie, emergency treatment, hospitalization, or treatment with excluded medications]) was a coprimary endpoint for the MF/F 100/10 µg BID and 200/10 μg BID studies and a secondary endpoint for the MF/F 400/10 μg BID study. Post hoc pair-wise comparisons of pooled MF/F vs pooled MF, F, and placebo treatment groups were performed.
Results: Sample sizes in this pooled analysis were 861 for MF/F, 620 for MF, 390 for F, and 384 for placebo. There was a significantly lower incidence of asthma deterioration with MF/F (17.2%) vs MF (26.1%; P=.002), F (49.5%; P<.001), and placebo (50.8%; P<.001). Incidence of individual asthma deterioration criteria was 7.0% for MF/F, 10.0% for MF, 13.8% for F, and 17.7% for placebo for FEV1 reduction; 7.5%, 12.6%, 27.2%, and 26.3%, respectively, for PEF reduction; and 2.1%, 2.6%, 6.7%, and 5.2% for clinically judged deterioration.
Conclusions: MF/F-treated subjects experienced a significantly lower rate of asthma deterioration compared with MF, F, and placebo in subjects previously not well controlled on low-, medium-, or high-dose ICS.