Long-Term Safety of Mometasone Furoate/Formoterol Combination for Treatment of Patients with Persistent Asthma

Abstract

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 furoate/formoterol (MF/F) 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 MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 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 (AUC_{0−24 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 (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 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 AUC_{0−24 h} observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2–6% 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 MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F 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 MF/F-MDI 200/10 and 400/10 μg – is safe and well tolerated in patients with persistent asthma.

Keywords:

• asthma
• formoterol
• long-term safety
• metered-dose inhaler
• mometasone furoate
• mometasone furoate/formoterol

Acknowledgments

This study was sponsored by Merck & Co. The authors acknowledge the statistical assistance of Davis F. Gates Jr., Ph.D., and Wen-Ling Kuo, Ph.D., Merck & Co. Original editorial support was provided by Mariko Nagashima, Ph.D., of UBC Scientific Solutions; additional editorial support was provided by Tracy Wetter, Ph.D., of Complete Publication Solutions, LLC. Editorial support was funded by Merck & Co. We would like to thank all the investigators (Appendix 1) who participated in this study.

Declaration of Interest

J. Maspero has served as a speaker and consultant for Merck & Co., and GlaxoSmithKline. H. Nolte is an employee of Merck Research Laboratories. I. Chérrez-Ojeda does not have any relevant financial interests in this manuscript.