BACKGROUND AND OBJECTIVE The dose-response relationship of inhaled corticosteroid (ICS)/fast-onset long acting beta agonist (LABA) reliever therapy has not been formally addressed. The objective of this retrospective analysis is to ascertain from the available evidence whether ICS/fast-onset LABA administered as reliever therapy has a different dose-response relationship than maintenance fixed dose ICS/fast-onset LABA therapy in reducing risk of severe exacerbations. METHODS A systematic literature review was undertaken to identify randomised controlled trials (RCTs) in which randomised treatments included either i) budesonide/formoterol reliever monotherapy versus budesonide/formoterol fixed dose maintenance with short acting beta agonist (SABA) reliever therapy, or ii) budesonide/formoterol reliever therapy in addition to budesonide/formoterol maintenance versus higher fixed dose maintenance budesonide/formoterol with SABA as reliever therapy. Eligible studies were reviewed to allow determination of the relative potency and efficacy of the comparator regimens to reduce the risk of a severe exacerbation. RESULTS The one RCT of budesonide/formoterol reliever monotherapy showed a 4.6-fold (95% CI 2.9 to 7.3) greater potency than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of severe exacerbations. In the one RCT that compared budesonide/formoterol maintenance and reliever therapy with higher fixed dose maintenance budesonide/formoterol plus SABA reliever therapy, there was an additional 26% (95% CI 4 to 42%) reduction in severe exacerbation risk with the addition of budesonide/formoterol reliever therapy to maintenance budesonide/formoterol, despite a 25% lower total budesonide/formoterol dose. CONCLUSION The limited available evidence suggests that budesonide/formoterol reliever therapy has greater potency and efficacy than budesonide/formoterol fixed dose maintenance plus SABA reliever therapy in reducing the risk of a severe exacerbation. This is an important concept which has the potential to guide clinical practice in asthma, although the small number of studies available highlights the need for further research to better define these pharmacological properties.

中文翻译：

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ICS /速效LABA作为哮喘缓解药物的剂量反应关系。

背景与目的吸入皮质类固醇（ICS）/速效长效β受体激动剂（LABA）缓解剂的剂量反应关系尚未得到正式解决。这项回顾性分析的目的是从现有证据中确定，作为缓解剂治疗的ICS /快速发作LABA与维持固定剂量ICS /快速发作LABA治疗在降低严重加重风险方面是否具有不同的剂量反应关系。方法进行了系统的文献综述，以确定随机对照试验（RCT），其中随机治疗包括：i）布地奈德/福莫特罗缓解剂单药治疗与布地奈德/福莫特罗固定剂量维持用短效β受体激动剂（SABA）缓解剂治疗，或ii）除布地奈德/福莫特罗维持治疗之外，布地奈德/福莫特罗缓解治疗与以SABA替代的布地奈德/福莫特罗较高固定剂量维持治疗。对合格的研究进行了审查，以便确定比较方案的相对效力和功效，以降低严重加重的风险。结果布地奈德/福莫特罗缓解剂单一疗法的一项RCT在降低严重加重风险方面显示出比布地奈德/福莫特罗固定剂量维持疗法加SABA缓解剂疗效高4.6倍（95％CI 2.9至7.3）。在一项将布地奈德/福莫特罗维持和缓解治疗与更高的固定剂量维持布地奈德/福莫特罗和SABA缓解治疗进行比较的RCT中，尽管布地奈德/福莫特罗的总剂量降低了25％，但在维持布地奈德/福莫特罗的基础上加用布地奈德/福莫特罗缓解剂治疗，严重急性发作的风险又降低了26％（95％CI 4至42％）。结论有限的现有证据表明，布地奈德/福莫特罗缓解剂疗法在降低严重加重风险方面比布地奈德/福莫特罗固定剂量维持疗法加SABA缓解剂疗法具有更高的效力和功效。这是一个重要的概念，具有指导哮喘临床实践的潜力，尽管少数可用的研究突出了需要进一步研究以更好地定义这些药理特性的需求。结论有限的现有证据表明，布地奈德/福莫特罗缓解剂疗法在降低严重加重风险方面比布地奈德/福莫特罗固定剂量维持疗法加SABA缓解剂疗法具有更高的效力和功效。这是一个重要的概念，具有指导哮喘临床实践的潜力，尽管少数可用的研究突出了需要进一步研究以更好地定义这些药理特性的需求。结论有限的现有证据表明，布地奈德/福莫特罗缓解剂疗法在降低严重加重风险方面比布地奈德/福莫特罗固定剂量维持疗法加SABA缓解剂疗法具有更高的效力和功效。这是一个重要的概念，具有指导哮喘临床实践的潜力，尽管少数可用的研究突出了需要进一步研究以更好地定义这些药理特性的需求。