Zafirlukast Improves Asthma Control in Patients Receiving High-Dose Inhaled Corticosteroids

• Published in: American journal of respiratory and critical care medicine Vol. 162; no. 2; pp. 578 - 585
• Main Authors: CHRISTIAN VIRCHOW, J., Jr, PRASSE, ANTJE, NAYA, IAN, SUMMERTON, LINDA, HARRIS, ALLAN, The Zafirlukast Study Group
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.08.2000; American Lung Association
• Subjects: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones - administration & dosage; Adrenergic beta-Agonists - therapeutic use; Adult; Aged; Anti-Asthmatic Agents - therapeutic use; Asthma - drug therapy; Beclomethasone - administration & dosage; Biological and medical sciences; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Leukotriene Antagonists - therapeutic use; Male; Medical sciences; Middle Aged; Patient Compliance; Peak Expiratory Flow Rate; Pharmacology. Drug treatments; Respiratory system; Safety; Tosyl Compounds - therapeutic use; Treatment Outcome; Human; Corticosteroid; Respiratory disease; Treatment efficiency; Zafirlukast; Antiinflammatory agent; Leukotriene D4; Leukotriene E4; Antiasthma agent; Asthma; Inhalation; Symptomatology; Chemotherapy; Lung function; Treatment; Leukotriene C4; Combined treatment; Antagonist; Obstructive pulmonary disease; High dose; Biological receptor
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/ajrccm.162.2.9905041

Not all asthma can be adequately controlled, despite the use of high-dose inhaled corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in the pathogenesis of asthma, we hypothesized that the leukotriene receptor antagonist zafirlukast, in combination with high-doses of inhaled corticosteroids, might be efficacious in severe asthma. In a double-blind, parallel group study, 368 chronic adult asthmatic patients treated with inhaled corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of asthma symptoms during the run in period of the study, were randomly assigned to receive additional treatment with a high dose of zafirlukast (80 mg twice daily) (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p < 0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2 to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids, zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk of an asthma exacerbation, suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids.