SAFETY AND CLINICAL EFFICACY OF ZILEUTON IN PATIENTS WITH CHRONIC ASTHMA

Zileuton, a leukotriene pathway inhibitor used to treat asthma, improv es lung function, relieves symptoms, and is well tolerated. The purpos e of this 12-month, parallel-group, open-label study was to assess the efficacy of zileuton and evaluate liver function in patients treated with this drug (approximately 2% of patients treated with zileuton in controlled trials had reversible liver enzyme elevations). A total of 2,947 patients at 233 centers in the United States were randomly assig ned in a 5:1 ratio to treatment with zileuton plus usual asthma care o r usual asthma care alone. Efficacy variables included asthma exacerba tions; need for alternative treatment, steroid rescue, emergency care, and hospitalizations; forced expiratory volume in 1 second (FEV1); an d asthma symptom scores. The safety evaluation included measurement of alanine aminotransferase levels. Patients treated with zileuton had s ignificantly fewer corticosteroid rescues (P < 0.001), required less e mergency care (P < 0.05), had fewer hospitalizations, and had greater increases in FEV1 (P = 0.048). They also had significantly greater imp rovements in asthma symptoms. Increases in alanine aminotransferase le vels to three times or more the upper limit of normal occurred in 4.6% of patients treated with zileuton and 1.1% of those receiving usual c are (P < 0.001); most increases occurred during the first 2 to 3 month s. Alanine aminotransferase levels decreased to less than two times th e upper limit of normal or to baseline levels during zileuton treatmen t or after drug cessation. jaundice or chronic liver disease did not d evelop in any patient. Adding zileuton to the therapeutic regimens of patients with asthma is likely to improve asthma control and lower uti lization of healthcare resources.