The Efficacy and Tolerability of Inhaled Montelukast Plus Inhaled Mometasone Compared with Mometasone Alone in Patients with Chronic Asthma

Abstract

Background. The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone. Methods. This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 μg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 μg. Men and women aged 15–85 years with chronic asthma, forced expiratory volume in 1 second (FEV₁) 50–80% of the predicted value, and β-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV₁ over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting β-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count. Results. A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV₁, inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated. Conclusion. Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV₁, symptoms, asthma control, and blood eosinophil count.

• asthma
• control
• FEV₁
• inhaled corticosteroids
• mometasone
• montelukast

Acknowledgments

The authors thank Tracey Varnell for her contributions to the conduct of the study and Jennifer Pawlowski for her help with the preparation of the manuscript.

Protocol 386 Investigators: Issachar Ben-Dov, Donald M. Brandon, Shari A. Brazinsky, Raphael Breuer, Guido Cardona, Amarjit S. Cheema, Adrian Darrah, Tony Egerton, Gershon Fink, Alejandro Flores, John T. Given, Sandra Gonzales, Alfredo Gilberto Guerreros Benavides, Sam Henein, Hector Oswaldo Jave Castillo, Damien McNally, David S. Miller, Michael Redmond, Diego Leon Severiche, Shailen R. Shah, Lawrence D. Sher, Ivan Solarte, Jose William Torres Sales, Cesar Villaran Ferreyros, James D. Wolfe.

Declaration of Interest

This study was sponsored by Merck & Co., Inc. Drs. Philip and Smugar and Ms. Vandormael are employees of Merck, who may own or hold options to own stock in the company. Dr. Reiss is a former employee of Merck. Dr. Villaran has served as a scientific advisor and has received research support from Merck, GlaxoSmithKline, AstraZeneca, Pfizer, Novartis, and Schering-Plough. Dr. Shah has served as a paid lecturer or served as a scientific advisor or consultant to or received research support from Alcon, AstraZeneca, GlaxoSmithKline, Genentech, Novartis, Meda, Merck, Sepracor, and Teva.

All authors are responsible for the work described in this article, and they contributed to the conception, data interpretation, and drafting of the manuscript and/or revising the manuscript for important intellectual content. All authors provided final approval of the version to be published.