Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study

被引:302
作者
Rabe, Klaus F.
Atienza, Tito
Magyar, Pal
Larsson, Per
Jorup, Carin
Lalloo, Umesh G.
机构
[1] Leiden Univ, Med Ctr, Dept Pulmonol, NL-2333 ZA Leiden, Netherlands
[2] Vet Mem Med Ctr, Dept Pulm Med, Quezon City, Philippines
[3] Semmelweis Univ, Dept Pulmonol, Budapest, Hungary
[4] AstraZeneca, Res & Dev, Lund, Sweden
[5] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa
关键词
D O I
10.1016/S0140-6736(06)69284-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The contributions of as-needed inhaled corticosteroids and long-acting beta 2 agonists (LABA) to asthma control have not been fully established. We compared the efficacy and safety of three reliever strategies: a traditional short-acting beta 2 agonist; a rapid-onset LABA (formoterol); and a combination of LABA and an inhaled corticosteroid (budesonide-formoterol) in symptomatic patients receiving budesonide-formoterol maintenance therapy. Methods We did a 12-month, double-blind, parallel-group study in 3394 patients (aged 12 years or older), in 289 centres in 20 countries, who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol (160 mu g and 4.5 mu g, respectively), one inhalation twice daily, during a 2-week run-in. After run-in, patients were randomly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline (0.4 mg), formoterol (4.5 mu g), or budesonide-formoterol (160 mu g and 4.5 mu g). The primary outcome was time to first severe exacerbation, defined as an event resulting in hospitalisation, emergency room treatment, or both, or the need for oral steroids for 3 days or more. Findings Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol (p=0.0048; log-rank test) and with as-needed formoterol versus terbutaline (p=0.0051). The rate of severe exacerbations was 37, 29, and 19 per 100 patients per year with as-needed terbutaline, formoterol, and budesonide-formoteroll respectively (rate ratios budesonide-formoterol versus formoterol 0.67 [95% CI 0.56-0.80; p<0.0001]; budesonide-formoterol versus terbutaline 0.52 [0.44-0.62; p<0.0001]; formoterol versus terbutaline 0.78 [0.67-0.91; p=0.0012]). Asthma control days increased to a similar extent in all treatment groups. As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline. All treatments were well tolerated. Interpretation Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance.
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页码:744 / 753
页数:10
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