Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone

Background: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART^®) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting β₂-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide™) plus a short-acting β₂-agonist (SABA). Methods: Patients (N=2309) with symptomatic asthma (aged ≥12 years; forced expiratory volume in 1 s ≥50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 μg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 μg twice daily plus terbutaline as needed, for 6 months. Results: Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 μg/day budesonide [1238 μg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 μg/day fluticasone [2000 μg/day BDP equivalent] with salmeterol/fluticasone therapy; P<0.0001). Both treatments were well tolerated. Conclusion: In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure.