The SMART (Single combination budesonide–formoterol inhaler Maintenance And Reliever Therapy) regimen involves use of a combination budesonide–formoterol inhaler for both maintenance and as-needed relief for patients with asthma. Although randomised controlled trials have shown this to reduce severe exacerbations compared to standard treatment in patients with moderate to severe asthma, patients who had high baseline use of their reliever medication were not eligible for inclusion and the generalisability of the results have therefore been questioned. In addition it is not known if the reduction in exacerbations could have actually been due to more regular exposure to inhaled corticosteroid through as-needed reliever use in otherwise poorly adherent patients.
The SIGN/BTS guideline on the management of asthma states for adults at step 3 who are poorly controlled or in selected adult patients at step 2 (above BDP 400 micrograms/day and poorly controlled), the use of budesonide/formoterol in a single inhaler as rescue medication instead of a short-acting β2 agonist, in addition to its regular use as controller therapy, has been shown to be an effective treatment regime. When this management option is introduced the total regular dose of daily inhaled corticosteroids should not be decreased. Patients taking rescue budesonide/formoterol once a day or more on a regular basis should have their treatment reviewed. Careful education of patients about the specific issues around this management strategy is required.
This short-term, open-label study (24 weeks; n=303) involved four primary health-care practices and one hospital in New Zealand. Its purpose was to see if the SMART regimen in patients with a recent asthma exacerbation would reduce the risk of overuse of β agonist, reduce the likelihood of patients seeking medical review when such episodes occurred, and if any reduction in severe asthma exacerbations would be at the cost of a higher burden of systemic corticosteroid. Electronic monitoring was used to assess patterns of actual medication use.
Patients randomised to SMART received two actuations of budesonide 200mcg-formoterol 6mcg via a pressurised metered dose inhaler twice daily, with one extra actuation as needed for relief of symptoms (n=151). Those in the standard group received the same maintenance treatment, but with salbutamol (one or two 100mcg actuations) as needed for symptom relief (n=152).
The primary outcome was the proportion of participants with at least one high-use episode of β agonist (>8 as-needed actuations of budesonide-formoterol or >16 as-needed actuations of salbutamol per day). There was no statistically significant difference between the two groups for this endpoint. The SMART regimen was however associated with improvements over standard care for some of the other endpoints studied, including fewer asthma exacerbations and days of high use. It was associated with higher inhaled but lower oral corticosteroid exposure, with no overall significant difference in composite systemic corticosteroid exposure.
The researchers note that patients in the SMART group had fewer days of non-adherence (no maintenance taken) and that this reduction in non-adherence may have contributed to the reduction in risk of severe exacerbations. They discuss the issue of mortality and note that their study and the SMART clinical trial programme have insufficient power to rule out an effect on asthma mortality risk, which requires further investigation. They go on to acknowledge the study’s limitations, including its open-label nature.
The author of a related Comment note how the SMART treatment option has now been incorporated into the Global Initiative for Asthma guidelines; however many still think it to be an option driven by mainly commercial and financial interests. They say that the results of this study, and another in the same journal issue evaluating the beclometasone-formoterol combination, show the evaluated SMART regimens to have been effective and well tolerated in patients with asthma who were not well controlled and at risk of further exacerbations.
For this study specifically, they acknowledge the novel use of an electronic monitoring device to measure the number of actuations, and that this was the first non-pharmaceutical industry sponsored study of its kind.
It is still not known which patients will benefit most from the available treatment options in this setting and they call for real-life studies to be undertaken.