Study objectives: We evaluated the efficacy of the leukotriene receptor antagonist zafirlukast (Accolate), 20 mg twice daily, as monotherapy in patients with severe persistent asthma (defined by an FEV1 < 60% of predicted before treatment and frequent night-time symptoms).
Design: Data were analyzed from a subgroup of 261 steroid-naive patients (zafirlukast, n = 149; placebo, n = 112) from four randomized, double-blind, placebo-controlled, 13-week trials with similar experimental designs, entry criteria, and clinical assessments.
Patients: These patients were mostly men (57%) older than 30 years (56%) with pulmonary obstruction, ie, FEV1/FVC ratio < 0.7 (79%), and reversible airway disease demonstrated by a 15% increase in FEV1 after inhaled bronchodilator use.
Results: At end point, patients who received zafirlukast monotherapy had significant (p < 0.05) improvements from baseline, and compared with placebo, in FEV1, morning and evening peak expiratory flow (PEF), daytime asthma symptoms, nighttime awakenings, and beta2-agonist use. A stratified analysis based on the FEV1/FVC ratio showed an interaction between treatment and the amount of airflow obstruction for nighttime awakenings and mornings with asthma. Moreover, 37% of patients in both treatment groups had PEF variability > or = 20% (an indirect measure of airway inflammation). Zafirlukast patients with PEF variability > or = 20% had increases from baseline in the morning and evening PEF of approximately 40 and 11 L/min, respectively. For patients who take zafirlukast and who have a PEF variability of < 20%, the morning and evening PEF increased by 25 and 30 L/min, respectively. Regardless of the degree of PEF variability, zafirlukast significantly (p < 0.05) increased morning and evening PEF compared with placebo.
Conclusion: Patients with severe persistent asthma who received zafirlukast as monotherapy had clinically significant improvements across all efficacy measures compared with placebo and significant reductions in PEF variability.