Long-term safety of mometasone furoateformoterol combination for treatment of patients with persistent asthma

Objective: The combination of inhaled corticosteroid (ICS) and long-acting β2-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoateformoterol (MFF) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium-to high-dose ICS. Methods: This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MFF (20010 or 40010 μg) or fluticasone propionatesalmeterol (FPS; 25050 or 50050 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC0-24 h) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored. Results: The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MFF 20010 μg, 77.3 [n =109]; FPS 25050 μg, 82.4 [n= 56]; MFF 40010 μg, 79.2 [n =103]; FPS 50050 μg, 76.9 [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MFF 20010 μg, 28.4; FPS 25050 μg, 23.5; MFF 40010 μg, 23.1; FPS 50050 μg, 20.0). Headache (3.7) and dysphonia (2.7) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC0-24 h observed with MFF treatment were similar to those observed with FPS treatment. Ocular events were rare (26 overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MFF 40010 μg group; one for reduced visual acuity in the FPS 25050 μg group) and no asthma-related deaths occurred. Furthermore, MFF showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use. Conclusions: One-year treatment with the new combination therapies twice-daily MFF-MDI 20010 and 40010 μg is safe and well tolerated in patients with persistent asthma.