Background Assessment of adherence to inhaled corticosteroids and long-acting beta-agonist therapy, allows identification of patients classified as having refractory asthma. It is crucial to ensure that adherence is adequately assessed in clinical practice and in the conduct of clinical trials to target the patients who may benefit from expensive potential add-on therapies. We hypothesised that adherence to inhaled corticosteroids and long acting β₂-agonists is under-assessed and under-reported in clinical trials of add-on drug treatment interventions in adolescent and adult patients with severe asthma.

Methods A systematic literature search of six major databases was performed to identify randomised controlled trials (RCTs) of asthma drug treatment interventions conducted in severe adolescent and adult asthma patients taking inhaled corticosteroids (ICS) alone or in combination with long-acting beta-agonist therapy (ICS/LABA). Identified studies were reviewed concerning key characteristics of the trial and the intervention; reporting and monitoring of adherence to ICS/LABA and the relationship between measuring adherence and study outcomes was assessed. This systematic review had been registered on PROSPERO; registration number CRD42015029611.

Results The electronic search retrieved 5869 articles with an additional 19 identified from references. 4008 articles were screened after removal of duplicates of which 72 RCTs were included and underwent data extraction and quality scoring. Of these, only 12 RCTs reported adherence to ICS or ICS/LABA therapy. Measures of adherence used included; self-report, n = 1; self-report and inhaler technique, n = 1; inhaler technique, n = 1; inhaler technique and FeNO, n = 1; dose counting. n = 1; diary, n = 2; prescription records, n = 1; weighing inhaler canister, n = 1; assumption that primary respiratory physician had assessed adherence, n = 1; and method of adherence assessment not reported but measure of adherence included in n = 2 studies. High levels of heterogeneity across studies with regard to adherence and exacerbation measurements, designs and analysis precluded a formal meta-analysis. Although effect measures varied, good adherence was associated with fewer severe asthma exacerbations in high-quality studies.

Conclusion Good adherence is associated with a lower risk of severe asthma exacerbations. Future studies should use standardised methodology to assess adherence and inhaler technique.