PURPOSE: Nocturnal awakening is an important asthma-related outcome that significantly burdens patients and impacts quality of life. It is a component of several measures of asthma control recognized by the American Thoracic and European Respiratory Societies. Nocturnal awakenings were assessed in 3 studies of mometasone furoate/formoterol (MF/F), a newly-developed inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination.
METHODS: Nocturnal awakenings requiring rescue medication were investigated in 3 randomized multicenter trials of different MF/F strengths administered twice-daily. MF/F-100/10μg was tested in moderate asthmatics previously receiving low-dose ICS±LABA (N=746; 26-weeks; 2−3-week-run-in MF-100μg) vs MF-100μg, F-10μg, or placebo. MF/F-200/10μg was evaluated in moderate asthmatics previously receiving medium-dose ICS±LABA (N=781; 26-weeks; 2−3-week-run-in MF-200μg) vs MF-200μg, F-10μg, or placebo. MF/F-400/10μg was tested in severe asthmatics previously receiving high-dose ICS±LABA (N=728; 12-weeks; 2−3-week-run-in MF-400μg) vs MF/F-200/10μg or MF-400μg. The proportion of subjects with awakenings on 2 consecutive nights was also measured.
RESULTS: Baseline awakenings ranged from 0.84−1.05, 1.05−1.26, and 1.33−1.61 nights/week in the 100/10μg, 200/10μg, and 400/10μg studies, respectively. MF/F-100/10μg reduced awakenings 0.42 nights/week vs 0.21 for both MF-100μg, and F-10μg; placebo increased awakenings 0.14 nights/week (MF/F-100/10μg vs placebo and F-10μg: P≤0.035). MF/F-200/10μg reduced awakenings 0.56 nights/week vs MF-200μg=0.35, F-10μg increased awakenings 0.07; placebo awakenings did not change (MF/F-200/10μg vs placebo and F-10μg: P<0.001). MF/F-400/10μg reduced awakenings 0.70 nights/week vs MF/F-200/10μg=0.70 and MF-400μg=0.35 nights/week. Proportions of subjects experiencing awakenings on 2 consecutive nights was 20.9%, 27.7%, 33.5%, and 47.3% in the MF/F-100/10μg, MF-100μg, F-10μg, and placebo groups (MF/F vs F and placebo: P≤0.006); 27.7%, 29.2%, 43.6%, and 46.4% in the MF/F-200/10μg, MF-200μg, F-10μg, and placebo groups (MF/F vs F and placebo: P≤0.001); 39.6%, 36.1%, and 40.6% in the MF/F-400/10μg, MF/F-200/10μg, and MF-400μg groups.
CONCLUSION: MF/F reduces nocturnal awakenings in asthmatic subjects compared to placebo; trends favored MF/F-100/10μg−200/10μg over MF-100μg−200μg. In the high-dose study, the reduction was significant (P≤0.006) and 2-fold higher for both MF/F doses (−0.70/week) vs MF (−0.35/week).
CLINICAL IMPLICATIONS: MF/F combination therapy reduces nocturnal awakenings in moderate/severe asthma patients.
DISCLOSURE: Hendrik Nolte, Grant monies (from industry related sources) Dr. Nathan has received grants and research support from Abbott, Alcon, AstraZeneca, Ception, Dey, Dyax, Genentech, GlaxoSmithKline, MAP, MedImmune, Novartis, Sanofi-Aventis, Schering-Plough, and TEVA.Dr. Meltzer has received research/grant support and served as a consultant and on speaker bureau for Schering-Plough. Dr. Weinsteinhas received grants from Schering-Plough, Merck, GSK, Amgen, and Novartis, served on Advisory Boards for GSK, Schering-Plough, and Sepracor and participated in Speaker’s Bureaus for Teva, Schering-Plough, Merck, Sanofi-Aventis, and Astra-Zeneca.; Employee Dr. Nolte is a full-time Employee of Merck Research Laboratories; Consultant fee, speaker bureau, advisory committee, etc. Dr. Nathan has served as consultant or scientific advisor for Genentech, GlaxoSmithKline, Merck, Novartis, Schering-Plough, and TEVA. Dr. Nathan has also participated in Speaker’s Bureaus for AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Sanofi-Aventis, Schering-Plough and UCB. Dr. Meltzer received research/grant support and served as a consultant and on speaker bureau for Schering-Plough.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Mometasone furoate/formoterol is a new ICS/LABA combination treatment currently under review by the US Food and Drug Administration as a potential new treatment for persistent asthma.