The relationship between combination inhaled corticosteroid and long-acting β-agonist use and severe asthma exacerbations in a diverse population

Abstract

Background: Safety concerns surround the use of long-acting β-agonists (LABAs) for the treatment of asthma, even in combination with inhaled corticosteroids (ICSs) and particularly in high-risk subgroups.

Objective: To estimate the effect of ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population.

Methods: ICS and ICS/LABA exposure was estimated from pharmacy data for patients with asthma aged 12 to 56 years who were members of a large health maintenance organization. ICS and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (ie, use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization).

Results: Among the 1828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio, 0.65 vs 0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy.

Conclusion: Treatment with ICS/LABA fixed-dose combination therapy appeared to perform as well as or better than ICS treatment alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups.

Figure 1

Unweighted (A) and weighted (B) relationship between inhaled corticosteroid (ICS) use alone (solid line) and fixed-dose combination ICS and long-acting beta-agonist (LABA) use and severe asthma exacerbation (i.e., burst oral corticosteroid use, asthma-related emergency department visit, or asthma-related hospitalization). The unweighted analysis does not account for ICS strength, whereas the weighted analysis does account for ICS strength (see Table E1 in the Online Repository of ICS weights).