Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma

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Abstract

This study compared the efficacy and safety of budesonide/formoterol (Symbicort® Turbuhaler®) with salbutamol pressurized metered-dose inhaler (pMDI) with spacer for relief of acute bronchoconstriction in patients with asthma. In this randomized, double-blind, parallel-group study, patients (n=104 allocated to treatment; n=103 received treatment; mean age 45 years) seeking medical attention for acute asthma (mean FEV1 43% of predicted) received two doses repeated at t=−5 and 0 min of either budesonide/formoterol (320/9 μg, two inhalations) or salbutamol (100 μg×eight inhalations); total doses 1280/36μg and 1600 μg, respectively. All patients received prednisolone 60 mg at 90 min and FEV1 was assessed over 3 h. FEV1 90 min after dosing (primary variable) increased compared with pre-dose FEV1 by an average of 30% and 32% for budesonide/formoterol and salbutamol, respectively (P=0.66), with similar increases at all timepoints from 3 to 180 min for both groups. Mean pulse rate over 3 h was significantly higher in the salbutamol group versus the budesonide/formoterol group (92 vs. 88 bpm; P<0.01). No treatment differences were seen for other vital signs, including ECG. High-dose budesonide/formoterol was effective and well tolerated for the treatment of acute asthma, with rapid onset of efficacy and a safety profile over 3 h similar to high-dose salbutamol.

Introduction

Short-acting β2-agonists are currently the gold standard for relief of acute asthma symptoms in all severities of asthma [1], [2]. Inhaled corticosteroids (ICS) are the recommended maintenance therapy for the majority of patients with persistent asthma [1] because of their anti-inflammatory effects. In patients with persistent asthma, where low doses of ICS alone do not provide optimal control, the combination of ICS and long-acting β2-agonists is more effective than increasing the dose of ICS [1], [3], [4].

Combination inhalers containing an ICS and a long-acting β2-agonist are a relatively new addition to the pharmacological management of asthma. Currently, there are two single-inhaler combination products on the market: budesonide/formoterol (Symbicort® Turbuhaler®) and salmeterol/fluticasone (Seretide® Diskus®). Budesonide/formoterol has been shown to be effective and well tolerated as maintenance therapy in adults and children with persistent asthma [5], [6], [7], [8], [9], [10]. Formoterol, the long-acting β2-agonist component, causes rapid bronchodilation within 1–3 min of inhalation [11], [12], [13]—comparable with that of salbutamol [13]—and is as well tolerated as short-acting β2-agonists in patients with stable asthma [13], [14], [15], [16]. Moreover, high-dose formoterol is as effective and well tolerated as high doses of terbutaline and salbutamol in treating patients with acute asthma [17], [18]. In addition to rapid bronchodilation, the use of formoterol as reliever medication has now been shown to be well tolerated in long-term studies of over 18,000 patients [19], [20].

Budesonide/formoterol has a rapid onset of effect [21]. Indeed, it has been demonstrated that patients can feel relief from asthma symptoms (bronchodilation) within 1 min of inhalation with budesonide/formoterol [22]. Palmqvist and colleagues reported that, in addition to its more rapid onset of effect, two inhalations of budesonide/formoterol (160/4.5 μg) resulted in a more pronounced improvement in lung function than salmeterol/fluticasone (50/250 μg) at 3 h post-dosing [21]. In addition, previous studies have shown improvements in lung function within hours of a single dose of budesonide [23], [24], [25]. There is, therefore, favourable evidence to support the efficacy of both formoterol and budesonide in patients with acute bronchoconstriction.

Budesonide/formoterol has previously been found to be highly effective in a model of acute asthma whereby severe bronchoconstriction was induced in patients using methacholine provocation [22]. A recent study by Ankerst and co-workers [26] also demonstrated that budesonide/formoterol has a favourable tolerability profile following administration of high doses over 1 h (1600/45 μg in addition to a maintenance dose of 160/4.5 μg, two inhalations twice daily) corresponding to doses that might occasionally be used by patients for the relief of acute severe asthma. Budesonide/formoterol was as well tolerated as formoterol, and neither formoterol nor budesonide/formoterol was considered to produce clinically important differences in safety variables compared with placebo [26].

The efficacy and tolerability of budesonide/formoterol in real-life acute asthma have not been investigated. Consequently, the current study examined the efficacy and safety of reliever therapy with budesonide/formoterol compared with salbutamol—administered via pressurized metered-dose inhaler (pMDI) with spacer—in patients seeking medical attention for acute asthma.

Section snippets

Patients

Male and female patients aged ≥12 years seeking medical attention for acute asthma were enrolled into the study. Eligible patients had asthma as defined by the American Thoracic Society criteria [27], a forced expiratory volume in 1 s (FEV1) 30–60% of the predicted normal and were able to use a Turbuhaler® and pMDI with spacer correctly. Patients with acute severe asthma—defined as patients either unable to generate an FEV1 value, with an FEV1 <30% of predicted normal or those who required

Results

In total, 112 patients were enrolled at 10 centres in five countries (China, Indonesia, The Philippines, Taiwan and Vietnam) and 104 patients were randomized to study treatment: 55 in the budesonide/formoterol group and 49 in the salbutamol group. One patient in the salbutamol group did not receive any study drug. Therefore, the analysis was based on data from 103 patients: 55 and 48 patients in the budesonide/formoterol and salbutamol groups, respectively. In total, 102 patients completed the

Discussion

The efficacy and tolerability of budesonide/formoterol for the management of stable asthma have been extensively documented [5], [6], [7], [8], [9], [10]. This is the first study to compare the use of budesonide/formoterol for the relief of acute asthma bronchoconstriction with that of salbutamol, which is widely used both as a day-to-day reliever medication and in the hospital/emergency room management of exacerbations. Our study in patients seeking medical attention for acute asthma shows

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