Budesonide/formoterol maintenance and reliever therapy versus conventional best practice.

Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART) reduces asthma exacerbations and symptoms versus fixed-dose regimens plus short-acting beta(2)-agonists (SABA) in double-blind trials. Information is lacking regarding its effectiveness versus conventional best practice (CBP). This pooled analysis of six 6-month, randomized, open-label studies examined asthma control and exacerbation risk in asthmatics (aged> or =12 years). Patients (N=7855) symptomatic on inhaled corticosteroids (ICS) or stable/symptomatic on ICS/long-acting beta(2)-agonists (LABA) received budesonide/formoterol maintenance and reliever therapy (160/4.5microg bid and as needed) or CBP (ICS or ICS/LABA+/-other agents at an approved dose plus as-needed SABA). Overall asthma control was assessed comparing the incidence of exacerbations and levels of asthma control using the asthma control questionnaire (ACQ). Budesonide/formoterol maintenance and reliever therapy did not significantly reduce time to first severe exacerbation (primary variable) versus CBP (P=0.062). However, patients in this group experienced 15% fewer exacerbations (0.20 versus 0.24/patient/year; P=0.021) and used 27% less ICS (P<0.0001). Odds of remaining well controlled (ACQ< or =0.75) over 6 months were higher with budesonide/formoterol maintenance and reliever therapy versus CBP (45% versus 41%, odds ratio [OR] 1.29; P<0.01) while risk of remaining uncontrolled decreased (25% versus 29%, OR 0.81; P<0.01). Budesonide/formoterol maintenance and reliever therapy improves key aspects of asthma control versus physicians' choice of CBP.

Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol.

BACKGROUND: Budesonide/formoterol maintenance and reliever therapy maintains asthma control and reduces exacerbation frequency compared with higher fixed-dose combination regimens. Its effects on eosinophilic airway inflammation and structure are unknown. OBJECTIVE: We sought to compare the effects of budesonide/formoterol 200/6 microg twice daily plus as-needed with budesonide/formoterol 800/12 microg twice daily on airway eosinophils and remodeling. METHODS: This 52-week, parallel-group, randomized, double-blind study of 127 asthma patients who were symptomatic despite therapy compared (1) the change between induced sputum percent eosinophils at baseline and the geometric mean of 4 on-treatment values and (2) the change in endobronchial biopsy eosinophil counts pre- and post-treatment. RESULTS: Mean daily doses of budesonide/formoterol were 604/18 microg in the maintenance and reliever therapy group and 1,600/24 microg in the high fixed-dose group. In the former, the geometric mean percent sputum eosinophils remained unchanged (1.6% to 1.9%), whereas biopsy specimen subepithelial eosinophils increased (6.2 to 12.3 cells/mm(2)). Sputum and biopsy eosinophil counts decreased with high fixed-dose treatment (2.2% to 1.2% and 7.7 to 4.8 cells/mm(2), respectively), resulting in significant treatment differences of 0.7% (ratio, 1.8; 95% CI, 1.2-2.8; P = .0038) and 7.5 cells/mm(2) (ratio, 2.9; 95% CI, 1.6-5.3; P < .001), respectively. There were no between-treatment differences in reticular basement membrane thickness, exhaled nitric oxide, exacerbation frequency, or FEV(1). CONCLUSION: Compared with fixed-dose combination treatment containing a 4-fold higher maintenance dose of budesonide, budesonide/formoterol maintenance and reliever therapy is associated with higher eosinophil counts, but these remain within the range associated with stable clinical control.

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 beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone (Seretide) plus a short-acting beta(2)-agonist (SABA). METHODS: Patients (N=2309) with symptomatic asthma (aged 12 years; forced expiratory volume in 1s 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed, or one inhalation of salmeterol/fluticasone 50/500 microg 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 microg/day budesonide [1238 microg/day beclomethasone dipropionate (BDP) equivalent] versus 1000 microg/day fluticasone [2000 microg/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.