ArticlesBeclometasone–formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial
Introduction
International treatment guidelines for asthma1, 2 recommend the combination of an inhaled corticosteroid and a long-acting β2 agonist with the addition of a short-acting β2 agonist for relief of symptoms in patients who are not adequately controlled with an inhaled corticosteroid alone. All available combinations of inhaled corticosteroid plus long-acting β2 agonist have similar efficacies in patients with moderate-to-severe asthma when given with a short-acting β2 agonist as reliever.3, 4
Budesonide–formoterol is more effective in reducing asthma exacerbations when given as maintenance and reliever than when given regularly as maintenance with a short-acting β2 agonist terbutaline or the rapid-onset, long-acting β2 agonist formoterol as reliever.5, 6 These findings suggest that treatment of symptoms with an inhaled corticosteroid and rapid-onset, long-acting β2 agonist combination might provide better clinical control than a short-acting β2 agonist alone for symptom relief. Whether patients should be left in need of rescue medication is debatable,7 partly because of concerns about the safety of a long-acting β2 agonist in asthma.8
The use of regular inhaled beclometasone dipropionate–formoterol combination in an extrafine hydrofluoroalkane formulation plus salbutamol as a reliever is non-inferior to equivalent doses of both regular inhaled budesonide–formoterol3 or fluticasone–salmeterol combinations plus salbutamol as reliever4 in improving lung function in patients with asthma uncontrolled with inhaled corticosteroid alone. The clinical effectiveness of low-dose extrafine beclometasone–formoterol combination in a single pressurised metered-dose inhaler (pMDI) as maintenance led us to speculate that a similar effectiveness could also be shown if this combination was used as a reliever medication, particularly considering the increased penetration of particles in the peripheral airways, a site of important acute inflammation during exacerbations. This method of treating asthma, initially introduced as SMART (Single inhaler Maintenance And Reliever Therapy), seems to be a generally effective management strategy in patients with asthma, with particular effectiveness in the prevention of exacerbations. It might also have ramifications for the development of other affordable formulations worldwide. However, whether the extrafine beclometasone–formoterol combination is suitable as both maintenance and relief of asthma exacerbations has never been tested.
The main objective in our study was to investigate whether the inhaled extrafine hydrofluoroalkane fixed combination of beclometasone 100 μg and formoterol 6 μg was more effective when given as both maintenance and reliever than when given as maintenance with a short-acting β2 agonist as reliever in adults with asthma that was not fully controlled by inhaled corticosteroid alone or low-dose inhaled corticosteroid plus a long-acting β2 agonist.
Section snippets
Study design and patients
The study was a multinational, multicentre, double-blind, randomised, parallel group, active-controlled trial. Additional details about the study design are provided in the appendix p 3. Patients were recruited between March 20, and Nov 20, 2009, in 183 centres in 14 European countries (appendix p 2). They were eligible for inclusion if they were aged 18 years or older, and had a clinical diagnosis of asthma for at least 6 months, prebronchodilator forced expiratory volume in 1 s (FEV1) of at
Results
The start and end dates for the study were March 20, 2009, and Dec 7, 2010, respectively. Figure 1 shows the trial profile; 2079 patients signed the informed consent and entered the study, 1714 were randomly assigned to the as-needed beclometasone–formoterol and as-needed salbutamol groups, and 1701 patients were included in the efficacy analysis (intention-to-treat population). The safety population consisted of all randomly assigned patients who took at least one dose of study medication (854
Discussion
We have shown that an extrafine inhaled combination of beclometasone 100 μg and formoterol 6 μg is more effective in reducing asthma exacerbations when given as both maintenance and reliever treatment than when given only as maintenance with salbutamol 100 μg as needed to patients who do not have fully controlled asthma. The two treatment regimens are equally safe and well tolerated. These findings confirm the efficacy of the inhaled corticosteroid (beclometasone) given as reliever with a
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