EFFECTIVENESS OF THE LEUKOTRIENE RECEPTOR ANTAGONIST ZAFIRLUKAST FOR MILD-TO-MODERATE ASTHMA - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background: The increasing costs of managing asthma are due in part to the introduction of new medications, such as leukotriene receptor ant agonists. These antagonists interfere with the action of leukotrienes, which are implicated in bronchoconstriction and the formation of airw ay edema in patients with asthma. Leukotriene receptor antagonists mus t be shown to be clinically and economically effective for their clini cal use to be justified. Objective: To assess the clinical and economi c effectiveness of zafirlukast, a leukotriene receptor antagonist, in patients with mild-to-moderate asthma who might benefit from regular a nti-inflammatory therapy. Design: Randomized, double-blind, multicente r, placebo-controlled trial. Setting: 28 outpatient clinics. Patients: 146 patients with mild-to-moderate asthma who were 12 years of age or older, had not smoked cigarettes in the previous 6 months, had a smok ing history of less than 10 pack-years, had an FEV(1) at least 55% of the predicted value with no upper limit, had demonstrated bronchial hy perresponsiveness, and were symptomatic during the 7-day run-in period . All patients were seen every 2 to 3 weeks for 13 weeks. Intervention : 103 patients received zafirlukast (20 mg twice daily), and 43 patien ts received placebo (twice daily). All patients received inhaled beta- agonists as needed. Measurements: Data were obtained from medical exam inations, patient questionnaires, and daily diaries. The clinical effe ctiveness outcomes were days per month without asthma symptoms, limita tion of activity, use of beta-agonists, sleep disturbance, and episode s of asthma (the latter was a composite measure made up of the first f our outcomes plus the occurrence of adverse events). The economic effe ctiveness outcomes were frequency and type of unscheduled health care contacts, use of beta-agonist inhalers, consumption of nonasthma medic ations, and days of absence from work or school. Results: The zafirluk ast group had 89% more days without symptoms (adjusted rates, 7.0 comp ared with 3.7 days per month; P = 0.03), 89% more days without use of beta-agonists (adjusted rates, 11.3 compared with 6.0 days per month; P = 0.001), and 98% more days without episodes of asthma (adjusted rat es, 10.1 compared with 5.1 days per month; P = 0.003). They also had 5 5% (95% CI, 19% to 74%) fewer health care contacts (18.5 compared with 40.7 per 100 per month; P = 0.007) and 55% (CI, 3% to 79%) fewer days of absence from work or school (15.6 compared with 35.0 per 100 per m onth; P = 0.04). They used 17% fewer canisters of inhaled beta-agonist s (P = 0.17) and 19% less nonasthma medication (P > 0.2). Conclusions: A dairy regimen of zafirlukast added to as-needed inhaled beta-agonis ts is more effective than beta-agonists alone in treating mild-to-mode rate asthma. The clinical and economic effectiveness of zafirlukast, a potential alternative to inhaled corticosteroids, provides further im petus to use regular ''preventive'' therapy in patients with mild-to-m oderate asthma.