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

SummaryObjectiveTo 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.MethodsRandomized, active-control, double-blind, parallel, multi-center study of zileuton (400 or 600 mg QID)+200 μg beclomethasone dipropionate (BDP) BID versus placebo+BDP 400 μg BID in asthmatics with baseline FEV1 percent predicted values between 40% and 80% following a single-blind ICS (BDP 200 μg BID) 2-week run-in. During the 3-month double-blind treatment period, assessments included safety, daytime and nighttime symptoms, acute asthma exacerbations, β2-agonist use, AM and PM peak expiratory flow (PEF) and FEV1.ResultsThe addition of a 5-lipoxygenase (5-LO) inhibitor added to a low-dose of BDP showed no significant difference in FEV1 compared to doubling the dose of BDP. FEV1 improved in all 3 treatment groups, with mean increases of 10% with zileuton 600 mg QID+BDP 200 μg BID, 12% with zileuton 400 mg QID+BDP 200 μg BID, and 11% with BDP 400 μg 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.ConclusionsThe 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 low-dose ICS therapy.