Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study

Background For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines. Objective To compare montelukast, a oncedaily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting β-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year. Methods A randomized, doubleblind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 μg/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 μg/d) or montelukast (10 mg/d) for 48 weeks. Results Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated. Conclusions Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.