Purpose of the Study. Previous studies have shown that the combination of inhaled corticosteroids (ICSs) with long-acting β2 agonists improves asthma control and reduces exacerbations. The authors hypothesized that in patients already receiving daily budesonide/formoterol (B/F), replacing conventional short-acting β2 agonist (SABA) rescue with the B/F combination drug would increase antiinflammatory therapy while simultaneously giving rapid relief of symptoms. The investigators reasoned that using the B/F combination drug in this manner might reduce asthma exacerbations and improve asthma control compared with other possible regimens.
Study Population. Subjects were 2760 patients with asthma (aged 4–80 years), all previously on ICSs.
Methods. A double-blind parallel-group study was performed with subjects randomly assigned to 3 groups: B/F (80 mg/4.5 μg) twice daily for maintenance and also for rescue; B/F (80 mg/4.5 μg) twice daily with terbutaline 0.4 mg for rescue; or budesonide 320 μg twice daily with terbutaline 0.4 mg for rescue. Pediatric patients (11%–13% of each group) received half of the above-stated doses for maintenance. The primary outcome was time to first severe exacerbation, defined as asthma symptoms requiring an emergency department visit or hospitalization; an increase in ICS dose; use of oral steroids; or a morning peak expiratory flow rate ≤70% of baseline on 2 consecutive days.
Results. Multiple positive outcomes were seen in the group using B/F for maintenance and rescue: a significant increase in the time to the first severe and mild exacerbations (P < .001); a 45% to 50% decrease in the number of severe exacerbations; significant decreases in the use of rescue medication, nighttime symptom score, and the number of nighttime awakenings; and fewer courses of oral steroids per year. The average daily dose of ICS received per patient was lower in the 2 B/F groups. All of the medications were well tolerated. Pediatric subjects receiving B/F demonstrated greater linear growth than those on higher-dose budesonide.
Conclusions. Use of B/F for both maintenance and rescue is associated with a lower asthma-exacerbation rate and an improvement in several other indicators of asthma control. In addition, subjects using B/F in this manner have a decreased exposure to oral steroids and require less use of rescue medication. The authors suggest that the timing of the increase in ICS use for asthma exacerbations, rather than the total ICS dose administered, provides the greater improvement in efficacy.
Reviewer Comments. The rapid onset of action of the β2-agonist formoterol suggests that it could be used as a rescue medication, although this is not a licensed indication. Use of the B/F combination as controller and rescue presents an attractive option because of the decrease in asthma morbidity compared with either B/F and SABA or ICS and SABA. Even with the use of B/F for rescue, the mean dose of ICS received was lower than in the ICS-and-SABA group (240 vs 640 μg/day in the adults) and only slightly higher than in the B/F-and-SABA group (240 vs 160 μg/day in the adults). This combination product is not yet licensed in the United States, but if approved, B/F used in this fashion will offer a novel treatment alternative for asthmatic patients. In addition, B/F maintenance and rescue therapy may provide a significant benefit for patients for whom adherence to 2 separate drugs may present serious difficulties or confusion.
- Copyright © 2006 by the American Academy of Pediatrics