Leukotriene Receptor Antagonists or Long-acting Beta Agonists as add-on therapies in asthma

Published Online: April 1, 2013

There is an ongoing debate in the literature as to whether the use of leukotriene receptor antagonists (LTRA) in addition to inhaled corticosteroids (ICS) in patients with asthma provides comparable benefits to the addition of long-acting beta-agonists (LABA) to ICS. Most of the evidence on the comparative effectiveness of ICS+LTRA versus ICS+LABA is generated through 'efficacy' randomized controlled trials (RCTs) with strict treatment protocols, inclusion criteria, and follow-up schedules. It is well known that the setting of such RCTs significantly differs from the real-world clinical practice, and as such their results have low external validity. Well-designed observational studies using high quality data and proper statistical methods can provide real-world estimates of adherence and comparative outcomes at a fraction of the cost of a RCT.

In an article published in The Journal of Allergy & Clinical Immunology (JACI), Sadatsafavi et al. used the comprehensive administrative health data of the province of British Columbia (BC), Canada, to study the adherence and outcomes associated with step-up therapies to ICS+LTRA versus ICS+LABA in patients with asthma in a real world clinical and practice setting.

Adherence was better in patients who stepped up their medication from ICS to ICS+LABA than to ICS+LTRA. In addition, ICS+LTRA was associated with more asthma-related outpatient visits, asthma-related medication dispensations, and dispensation of reliever medications. Rate of asthma exacerbations was higher in the ICS+LTRA during the time patients were adherent to their medication compared with the rate in the ICS+LABA group, but was similar between the two group after two years of follow-up.

Individuals who stepped up from monotherapy with ICS to ICS+LABA were more adherent to their medication than those who stepped up to ICS+LTRA. In addition, ICS+LABA was associated with better outcomes, even when the effect of differential adherence was accounted for. One hypothesis explaining the overall results of this study is that step-up therapy to ICS+LABA is associated with more improvements in asthma-related impairment versus ICS+LTRA, and consequently patients remain more adherent to ICS+LABA.


The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology