BACKGROUND: Asthma management guidelines recommend patients with persistent asthma use asthma controller therapy in addition to as-needed short-acting beta-agonist therapy to improve symptom control, maintain pulmonary function, and decrease exacerbations. This study compared 2 asthma controllers, inhaled fluticasone and oral montelukast, with respect to clinical efficacy, patient preference, asthma-specific quality of life, and safety.
POPULATION STUDIED: The patients in this study were men and women aged 15 years and older with asthma recruited from multiple centers across the United States. Nonsmoking patients were included with a forced expiratory volume in 1 second (FEV 1 ) of 50% to 80% of predicted that reversed by at least 15% with bronchodilator use. Patients were then eligible for randomization if, after an 8- to 14-day run-in period, their FEV 1 remained within 15% of initial values, they used albuterol at least 6 of the last 7 days, and they had asthma symptom scores of 2 (on a 0 to 5 scale) for at least 4 of the last 7 days.
STUDY DESIGN AND VALIDITY: This study was a double-blinded, randomized trial sponsored by the makers of fluticasone. Patients meeting initial inclusion criteria underwent an 8- to 14-day run-in period in which only short-acting beta-agonist use was allowed. Patients were then randomized to 1 of 2 treatment groups if they met the secondary inclusion criteria. Personal communication with the lead author confirmed that allocation assignment was concealed. Patients received either fluticasone 88 μg twice daily via metered dose inhaler (MDI) and montelukast placebo, or montelukast 10 mg daily with a placebo MDI. Patients kept daily records and had clinical evaluations at regular intervals for 24 weeks. Seventy-six percent of the patients completed the study.
OUTCOMES MEASURED: The primary outcome was percent change in FEV 1 . Other outcomes included peak flow rate, symptom-free days, daily albuterol use, asthma symptom scores, asthma quality-of-life scores, and patient-rated satisfaction with treatment. Safety was also assessed by reports of clinical adverse events and number of asthma exacerbations.
RESULTS: Using an intent-to-treat analysis, the fluticasone group had a significantly greater sustained change in FEV 1 (22% vs 14%; P < .001). Significant differences were noted after just 2 weeks of treatment. Significant differences favoring fluticasone were also found in all secondary outcomes including the patient-oriented outcomes of change in asthma symptom scores (–0.91 vs –0.57; P < .001), asthma quality-of-life scores (1.3 vs 1.0; P = .004), and patient-rated satisfaction with treatment (83% of fluticasone patients satisfied vs 66% of montelukast patients satisfied; P < .001). No differences were noted in overall incidence of adverse events between treatment groups, but significantly more fluticasone-treated patients reported hoarseness (9 vs 0; P = .002) and oral pharyngeal candidiasis (8 vs 0; P = .008). The incidence of asthma exacerbations was similar (19 fluticasone-treated patients vs 21 montelukast-treated patients).
This study confirms earlier studies indicating that inhaled steroids should be first-line treatment for moderate-to-severe persistent asthma. When compared with montelukast, inhaled fluticasone showed greater improvements in clinical measures of asthma, as well as patient-oriented measures such as symptom scores, quality-of-life scores, and patientrated satisfaction. However, moderate-to-severe persistent asthma appears to require more therapeutic measures than just low-dose fluticasone. Despite treatment, patients still used albuterol on more than half of the days, only one third of days were symptom-free, and symptom scores improved by less than 1 point on a 6-point scale.