Long-acting beta-agonist in combination or separate inhaler as step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids

Background: Adding a long-acting β2-agonist (LABA) to inhaled corticosteroids (ICS) using a fixed-dose combination (FDC) inhaler containing ICS and LABA is the UK guideline-recommended step-up option for children aged >4 years with uncontrolled asthma on ICS monotherapy. The evidence of benefit of FDC inhalers over adding a separate LABA inhaler to ICS therapy is limited. Objective: Our aim was to compare outcomes for FDC versus separate LABA+ICS inhalers for children by analyzing routinely-acquired clinical and prescribing data. Methods: This matched cohort study used large UK primary care databases to study children prescribed their first step-up from ICS monotherapy at 5–12 years of age as add-on LABA, either via separate LABA inhaler or FDC inhaler. A baseline year was examined to characterize patients and identify potential confounders; outcomes were examined during the subsequent year. The primary outcome was adjusted odds ratio for overall asthma control, defined as no asthma-related hospital admission, emergency room visit prescription for oral corticosteroids and ≤200 μg/day salbutamol. Results: After matching, there were 1330 children in each cohort (mean age [SD] 9 [2] years; 59% male). All measures of asthma exacerbations and control improved during the outcome year in both cohorts. In the separate ICS+LABA cohort, the odds of achieving overall asthma control were lower (adjusted odds ratio, 0.77 [95% CI 0.66-0.91] P = 0.001) compared with the FDC cohort. Conclusion: Our results demonstrate a small but significant benefit of add-on LABA therapy as FDC over separate inhaler and support current recommendations.