Zileuton added to low-dose inhaled beclomethasone for the treatment of moderate to severe persistent asthma

Objective: To assess the therapeutic effects of oral zileuton tablets combined with low-dose beclomethasone compared to doubling the dose of beclomethasone, in improving lung function and reducing asthma symptoms. Methods: Randomized, active-controt, double-blind, parallel, multi-center study of zileuton (400 or 600mg QID)+200 mu g beclomethasone dipropionate (BDP) BID versus ptacebo+BDP 400pg BID in asthmatics with baseline FEV, percent predicted values between 40% and 80% following a single-blind ICS (BDP 200 mu g BID) 2-week run-in. During the 3-month double-blind treatment period, assessments included safety, daytime and nighttime symptoms, acute asthma exacerbations, beta(2)-agonist use, AM and PM peak expiratory flow (PEF) and FEV1. Results: The addition of a 5-lipoxygenase (5-LO) inhibitor added to a tow-dose of BDP showed no significant difference in FEV1 compared to doubling the dose of BDR FEV1 improved in all 3 treatment groups, with mean increases of 10% with zileuton 600mg QID+BDP 200 mu g BID, 12% with ziteuton 400 mg QID+BDP 200 mu g BID, and 11% with BDP 400 mu g BID by study end. Within each treatment group, there were significant improvements in asthma symptoms and AM and PM PEF compared to baseline. No significant differences were observed between groups with regards to salbutamol use, acute asthma exacerbations, the requirement for oral/parenteral corticosteroids and adverse clinical events. Conclusions: The addition of a 5-LO inhibitor added to low-dose beclomethasone may be an alternative to higher-doses of ICS in patients unable to achieve sufficient asthma control on tow-dose ICS therapy. (c) 2007 Elsevier Ltd. All rights reserved.