The idea of using one inhaler for both maintenance and reliever therapy for asthma, with patients adjusting their dose according to need based on symptoms, was first introduced as SMART (Single inhaler Maintenance And Reliever Therapy), for the fixed combination of budesonide-formoterol in the Turbohaler. 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.
The purpose of the current study was to evaluate use of a single combination inhaler containing extra-fine beclometasone and formoterol in this way. The study enrolled adults with asthma, a forced expiratory volume in 1 second (FEV1) of ≥60% predicted and a history of at least one severe exacerbation in the previous year. A total of 2,079 patients entered the run-in period during which they received open-label treatment with a fixed combination of beclometasone 100mcg and formoterol 6mcg in a single inhaler (Fostair®) as one inhalation twice daily plus salbutamol 100mcg (Ventolin®) on an as-required basis for the relief of symptoms.
Following the run-in period, 1,714 patients were not fully controlled and entered the double-blind phase. They continued regular use of Fostair®, and were randomised to as-required treatment (max 6 doses daily) with the same inhaler (n=857) or with salbutamol (n=857). The primary outcome was the time to first severe exacerbation – this was 75 days longer in the group using beclometasone-formoterol for both maintenance and reliever treatment (hazard ratio [HR] 0.64; 95% CI 0.49 to 0.82]; p=0.0005). The respective rates (number of events per 100 patients per year) were 14.76 and 22.39 (HR 0.66; 0.55-0.80; p<0.0001).
Both treatments improved symptoms, percentage of asthma control days, use of reliever, and lung function, with no statistically significant differences between the two groups for these endpoints. Serious adverse events were reported in a similar number of patients in the two groups (4% for beclometasone-formoterol and 5% for salbutamol); however adverse drug reactions were seen more often in the former (5% versus 2%; p=0.01).
The authors acknowledge that the reduction in exacerbation rate could have been due to the additional dose of inhaled corticosteroid and not of the rapid-onset, long-acting β2 agonist (formoterol). Further research is needed to determine whether the results would be similar if the extra inhaled corticosteroid were given regularly rather than as needed, and also to determine whether the beclometasone–formoterol combination is equally effective as budesonide–formoterol in patients with more severe asthma.
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 budesonide-formoterol combination, show that both of the evaluated SMART regimens were effective and well tolerated in patients with asthma who were not well controlled and at risk of further exacerbations. This study specifically suggests that beclometasone-formoterol reduces the small but significant risk of severe exacerbations and hospital admissions in a population with milder asthma.
They note, as in previous research, that there is a dissociation between no improvements in functional measurements but significant improvements in exacerbations, and suggest based on this that a specific aspect of the disease (increased airway inflammation) may be more responsive to the SMART option.
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.