The inhaled corticosteroid/long-acting β-agonist maintenance and reliever therapy regimen: where to from here?
Authors: Richard Beasley, Irene Braithwaite, James Fingleton, Mark Weatherall
Journal: European Respiratory Journal (2018)

Combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) inhaler therapy (ICS/LABA therapy) represents the mainstay of the management of moderate and severe asthma, recommended in the Global Initiative for Asthma (GINA) guidelines for steps 3, 4 and 5 [1]. Indeed, in some countries, such as Australia, ICS/LABA therapy now represents the default ICS treatment, with a recent survey reporting that just over four out of every five adults with asthma who are prescribed ICS receive ICS/LABA therapy [2, 3]. As a result, the optimal use of ICS/LABA therapy is a priority in the management of asthma and this requires the consideration of a number of key issues. First, ICS and LABA should not be prescribed as separate inhalers in asthma due to the risks associated with LABA monotherapy in patients who are non-adherent with their ICS inhaler [4]. This recommendation reflects concern that LABA monotherapy increases the risk of mortality in patients with poorly controlled asthma, in contrast to ICS/LABA treatment for which no such risk has been identified [5]. Secondly, there are two main management regimens by which ICS/LABA inhalers can be prescribed. The most common "standard" regimen is fixed-dose ICS/LABA maintenance with a short-acting β-agonist (SABA) as reliever. The alternative option is to use a combination ICS/LABA inhaler as both maintenance and reliever therapy (referred to as the MART regimen). To implement the MART regimen it is necessary for the LABA component to have a fast onset of action, which allows for its use as a reliever as well as a maintenance therapy. The efficacy of the MART regimen has been illustrated with budesonide/formoterol using both turbuhaler [6] and metered dose inhaler (MDI) [7] devices for delivery, as well as with beclometasone/formoterol using the MDI device [8]. Thirdly, there is evidence that turbuhaler administration of budesonide/formoterol according to the MART regimen is more effective than the regimen comprising fixed-dose ICS/LABA maintenance (at a higher maintenance ICS dose) with "as required" SABA therapy in adults and children with chronic asthma [9]. In the Cochrane systematic review and meta-analysis summarising this evidence, the point estimates for the magnitude of the greater efficacy of the MART regimen were large. For the MART regimen versus the higher fixed-dose ICS/LABA regimen, the odds ratio for risk of exacerbations requiring hospitalisation or a visit to the emergency room was 0.72 (95% CI 0.57–0.90) while the odds ratio for exacerbations requiring oral corticosteroids was 0.75 (95% CI 0.65–0.87). This knowledge-base has now been extended by the publication, by jorup et al. [10] in this issue of the European Respiratory Journal , of an individual patient data subgroup meta-analysis which reports on the efficacy of the MART regimen in children aged 12–17 years. This meta-analysis includes 1847 adolescents from six double-blind randomised controlled trials comparing MART with an active comparator. Five trials required patients to have had at least one asthma exacerbation in the previous year at randomisation, thereby ensuring that the findings could be generalised to high risk adolescents with asthma. Comparator treatments used a SABA or LABA as the reliever therapy and included maintenance ICS at a dose of at least double the equivalent daily maintenance dose of ICS used in the MART regimen, or maintenance ICS/LABA at the same or a higher equivalent daily maintenance ICS dose, thereby representing the main treatment options from GINA steps 2, 3, 4 and 5 [1]. ICS/LABA maintenance and reliever therapy is recommended for adolescents with asthma at risk of severe exacerbations <http://ow.ly/xhhO30gKZ6W>