Long-term safety and efficacy of zafirlukast in the treatment of asthma: Interim results of an open-label extension trial

Background: Current guidelines recommend anti-leukotriene agents as alternative treatments for mild persistent asthma; however, information on their long-term safety and efficacy is needed. Objective: To evaluate long- term safety and efficacy of and compliance with oral zafirlukast (Z; 20 mg BID) during the first 39 weeks of ongoing, multicenter, open-label extension (OLE) of a previously reported 13-week, randomized (2:1), double-blind (DB), placebo (P)-controlled trial in mild-to-moderate asthmatic patients treated previously with β₂-agonists alone. Methods: Patients (12 to 76 years; FEV₁ ≥ 55% predicted) elected to enter OLE after completing the DB trial. Safety evaluated by adverse events (AEs), laboratory tests, and physical and electrocardiographic examinations. Efficacy assessed by spirometry measurements [FEV₁, FEV₁% predicted, personal-best (post-bronchodilator) FEV₁] and treatment failure rates. Compliance was calculated as percentage of treatment dispensed. After a visit at OLE week 3 (week 16), patients had visits every 12 weeks. Results: A total of 443 patients (n(z→z) = 310, n(p→z) = 133) entered the OLE. Results through the OLE period showed that 80% of patients overall reported AEs. Of patients randomized to Z and P during DB period, 68% and 67%, respectively, reported AEs during quarter 1 (Q1); percentage of Z-treated patients reporting AEs during the OLE ranged from 66% (Q2) to 44% (Q4). Review by quarters showed occurrence of AEs in Z- treated groups (Q2-4) was similar to that in P group (Q1). Compared with baseline (week 0), modest yet significant improvements (P ≤ .02) in all spirometry measurements were noted in Z→Z and P→Z groups at OLE week 3, with sustained effects noted during OLE period. Treatment failure rates during OLE ranged from 7.2% (Q2) to 3.3% (Q4). Mean compliance ranged from 98% (OLE week 3) to 95% (OLE week 39). Conclusions: Long-term treatment with zafirlukast was safe and well tolerated in asthmatic patients. Sustained efficacy and asthma control and good compliance were observed over extended treatment period. Results demonstrate long-term safety and effectiveness of and compliance with this anti-leukotriene agent.