Reduction in Asthma Deteriorations in Subjects With Persistent Asthma Uncontrolled on Low-, Medium-, or High-Dose Inhaled Corticosteroids: A Pooled Analysis From Three Clinical Trials Using Combined Mometasone Furoate/Formoterol

RATIONALE: We present a post hoc analysis from 3 phase III clinical trials (P04073/P04334/P04431) examining the effects of mometasone furoate/formoterol (MF/F) combination therapy on asthma deterioration (ie, severe asthma exacerbation) in subjects previously uncontrolled on low-, medium-, or high-dose inhaled corticosteroids (ICS). METHODS: A 2−3-week run-in period with twice daily (BID) MF-100μg (P04073), MF-200μg (P04334), or MF-400μg (P04431) was performed before subject (≥12y) randomization to BID: MF/F-100/10μg, MF-100μg, F-10μg, or placebo for 26weeks (n=746; P04073); MF/F-200/10μg, MF-200μg, F-10μg, or placebo for 26weeks (n=781; P04334); MF/F-200/10μg, MF/F-400/10μg, or MF-400μg for 12weeks (n=728; P04431). Assessment of asthma deterioration (ie, 20% decrease in forced expiratory volume in 1s [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 co-primary endpoint for studies P04073/P04334, and a secondary endpoint for study P04431. Post hoc pair-wise comparisons of pooled MF/F vs MF, F, and placebo treatment groups were performed. RESULTS: Sample sizes in this pooled analysis were: MF/F, n=861; MF, n=620; F, n=390; placebo, n=384. There was a significantly lower incidence of asthma deterioration with MF/F=17.2% vs MF=26.1% (P=0.002), F=49.5% (P<0.001), and placebo=50.8% (P<0.001). Incidence rates for asthma deterioration subtypes were: FEV1 reduction: MF/F=7.0%, MF=10.0%, F=13.8%, placebo=17.7%; PEF reduction: MF/F=7.5%, MF=12.6%, F=27.2%, placebo=26.3%; clinically judged deterioration: MF/F=2.1%, MF=2.6%, F=6.7%, placebo=5.2%. CONCLUSIONS: MF/F-treated subjects experienced a significantly lower rate of asthma deterioration compared with MF, F, and placebo in subjects previously uncontrolled on low-, medium-, or high-dose ICS in this pooled analysis.