Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid nonadherence

Abstract

Background: Asthma is an inflammatory condition often punctuated by episodic symptomatic worsening, and accordingly, patients with asthma might have waxing and waning adherence to controller therapy.

Objective: We sought to measure changes in inhaled corticosteroid (ICS) adherence over time and to estimate the effect of this changing pattern of use on asthma exacerbations.

Methods: ICS adherence was estimated from electronic prescription and fill information for 298 participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity. For each patient, we calculated a moving average of ICS adherence for each day of follow-up. Asthma exacerbations were defined as the need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization. Proportional hazard models were used to assess the relationship between ICS medication adherence and asthma exacerbations.

Results: Adherence to ICS medications began to increase before the first asthma exacerbation and continued afterward. Adherence was associated with a reduction in exacerbations but was only statistically significant among patients whose adherence was greater than 75% of the prescribed dose (hazard ratio, 0.61; 95% CI, 0.41-0.90) when compared with patients whose adherence was 25% or less. This pattern was largely confined to patients whose asthma was not well controlled initially. An estimated 24% of asthma exacerbations were attributable to ICS medication nonadherence.

Conclusions: ICS adherence varies in the time period leading up to and after an asthma exacerbation, and nonadherence likely contributes to a large number of these exacerbations. High levels of adherence are likely required to prevent these events.

Figure 1

Change in corticosteroid adherence over time with respect to the first asthma exacerbation in SAPPHIRE study participants. The first asthma exacerbation (i.e., burst oral steroid use, asthma-related emergency room visit, or asthma-related hospitalization) is aligned at time zero. Average adherence for the 180 days preceding and following the exacerbation are shown.

Figure 2

Relationship between level of inhaled corticosteroid (ICS) adherence (i.e., the percent of prescribed ICS medication taken) and the likelihood of an asthma exacerbation (i.e., burst oral steroid use, asthma-related emergency room visit, or asthma-related hospitalization). The relationship between adherence and outcomes is shown for all study participants (A), for those whose asthma was uncontrolled at the initial visit (B), and for those whose asthma was controlled at the initial visit (C). Participants with an ICS adherence of 0–25% are the referent group against which the other adherence categories are compared. Effect estimates are adjusted for all covariates included in Table 2 and in Model 5 from Table E1.