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 alterna tive treatments for mild persistent asthma; however, information on their l ong-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, mult icenter, open-label extension (OLE) of a previously reported 13-week, rando mized (2:1), double-blind (DB), placebo (P)-controlled trial in mild-to-mod erate asthmatic patients treated previously with beta(2)-agonists alone. Methods: Patients (12 to 76 years; FEV1 greater than or equal to 55% predic ted) elected to enter OLE after completing the DB trial. Safety evaluated b y adverse events (AEs), laboratory tests, and physical and electrocardiogra phic examinations. Efficacy assessed by spirometry measurements [FEV1, FEV1 % predicted, personal-best (post-bronchodilator) FEV1] and treatment failu re rates. Compliance was calculated as percentage of treatment dispensed. A fter a visit at OLE week 3 (week 16), patients had visits every 12 weeks, R esults: A total of 443 patients (n(Z-->Z) = 310, n(P-->Z) = 133) entered th e 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%, resp ectively. reported AEs during quarter 1 (Q1); percentage of Z-treated patie nts reporting AEs during the OLE ranged from 66% (Q2) to 44% (Q3). Review b y 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 signif icant improvements (P less than or equal to .02) in all spirometry measurem ents were noted in Z-->Z and P-->Z groups at OLE week 3, with sustained eff ects noted during OLE period. Treatment failure rates during OLE ranged fro m 7.2% (Q2) to 3.3% (Q4). Mean compliance ranged from 98% (OLE week 3) to 9 5% (OLE week 39). Conclusions: Long-term treatment with zafirlukast was safe and well tolerat ed in asthmatic patients. Sustained efficacy and asthma control and good co mpliance were observed over extended treatment period. Results demonstrate long-term safety and effectiveness of and compliance with this anti-leukotr iene agent.