Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus fixed-dose budesonide/formoterol plus terbutaline in patients with asthma: phase III study results.

BACKGROUND AND OBJECTIVE:To evaluate the efficacy and tolerability of budesonide/formoterol as maintenance and reliever therapy versus budesonide/formoterol maintenance plus terbutaline in adults with persistent asthma not adequately controlled with inhaled corticosteroid (ICS) therapy alone. METHODS:In this 12-month, randomized, double-blind, parallel-group, phase III study (NCT00839800), patients (age ≥ 16 years; receiving maintenance ICS; ≥ 1 severe exacerbation in the 12 months prior to study entry) were randomized to either budesonide/formoterol 160/4.5 μg 1 inhalation twice daily plus budesonide/formoterol 160/4.5 μg as-needed or budesonide/formoterol 160/4.5 μg 1 inhalation twice daily plus terbutaline 0.4 mg as-needed for 12 months. PRIMARY OUTCOME:time to first severe asthma exacerbation; secondary outcomes included: lung function, asthma symptom variables and tolerability. RESULTS:Two thousand and ninety-one patients were randomized: 170 (16%) receiving budesonide/formoterol maintenance and reliever therapy experienced 259 severe exacerbations versus 229 patients (22%) receiving budesonide/formoterol plus terbutaline who experienced 363 severe exacerbations. Budesonide/formoterol maintenance and reliever therapy prolonged the time to first severe exacerbation versus budesonide/formoterol plus terbutaline (P = 0.0007) and reduced the instantaneous risk of an exacerbation by 30% (hazard ratio 0.70, 95% confidence interval 0.57-0.85, P = 0.0003). Times to first oral steroid use, first hospitalization and first emergency room treatment were all significantly prolonged in the budesonide/formoterol maintenance and reliever group versus budesonide/formoterol plus terbutaline. Both treatment groups were well tolerated. CONCLUSIONS:Budesonide/formoterol maintenance and reliever therapy provided more effective asthma control, including a prolonged time to first severe asthma exacerbation, than budesonide/formoterol plus terbutaline and was well tolerated. Budesonide/formoterol maintenance and reliever therapy also improved lung function and asthma symptoms.