ArticlesEfficacy and safety of maintenance and reliever combination budesonide–formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial
Introduction
Inhaled corticosteroid plus long-acting β agonist delivered from a combination inhaler is the mainstay of treatment in patients with moderate to severe asthma.1, 2 It can be prescribed either in accordance with a standard fixed-dose maintenance regimen with a short-acting β agonist for relief of symptoms, or according to the SMART (Single combination budesonide–formoterol inhaler Maintenance And Reliever Therapy) regimen, in which a combination budesonide–formoterol inhaler is used for both maintenance and as-needed reliever use. Results of randomised controlled trials show that in patients with moderate to severe asthma, the SMART regimen leads to a reduction in severe exacerbations compared with the standard regimen.3, 4 However, the generalisability of this finding is restricted because patients who had high baseline use of their reliever medication were not eligible for inclusion in these studies.3, 4 Because there are no robust data for the actual patterns of medication use, it is not possible to ascertain whether the reduction in severe exacerbations with the SMART regimen is due to more regular exposure to inhaled corticosteroid through as-needed reliever use in otherwise poorly adherent patients or use of self-titrated budesonide–formoterol during worsening of asthma. Also, whether the SMART regimen leads to delays in patients seeking medical care during severe asthma exacerbations or whether it might result in a greater systemic corticosteroid load is not known.
We report the results of a randomised controlled trial in patients with asthma at risk of severe exacerbations. We used electronic monitoring to assess patterns of actual medication use and this method allowed us to apply β agonist overuse as a marker of the risk of life-threatening asthma.5, 6, 7, 8 Our hypothesis was that treatment of patients with the SMART regimen would lead to a reduction in the risk of high-use episodes of β agonist, but when such episodes did occur the patients would be less likely to seek medical review and that any reduction in severe asthma exacerbations would be at a higher burden of systemic corticosteroid.
Section snippets
Study design and participants
The study was a 24-week, open-label, parallel-group, randomised, controlled, trial undertaken at four primary health-care practices and one hospital in New Zealand (appendix p 2; study protocol).
Participants were eligible for participation in the study if they were aged 16–65 years, had a physician's diagnosis of asthma, a current prescription for inhaled corticosteroid, and at least one asthma exacerbation in the preceding year. This exacerbation was defined as a presentation to a general
Results
303 participants were enrolled between June 29, 2010 (study start), and Sept 14, 2011, with the last participant completing the study on Feb 29, 2012. The characteristics of participants are shown in table 1 and their flow is shown in figure 1. A final-visit assessment was completed for 21 (75%) of 28 participants who had withdrawn from the study. 282 466 actuations from 2642 monitors were recorded in the database over 49 149 days of treatment. After removal of actuations on visit days (11 576
Discussion
The results of this study show that combination budesonide–formoterol delivered through an inhaler and prescribed according to the SMART regimen has favourable safety and efficacy profiles compared with the standard regimen of fixed-dose maintenance budesonide–formoterol and salbutamol as reliever therapy in adult patients with asthma at risk of severe exacerbations. The SMART regimen reduces the risk of severe asthma exacerbations without increasing the risk of β-agonist overuse without
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Dr Black died in January, 2010