The US Food and Drug Administration's drug safety recommendations and long-acting beta2-agonist dispensing pattern changes in adult asthma patients: 2003-2012

Abstract

Background: Emerging safety issues associated with long-acting beta₂-agonist (LABA) have led to multiple regulatory activities by the US Food and Drug Administration (FDA) since 2003, including Drug Safety Communications (DSCs) in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment.

Methods: We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1) contraindicated use of single-ingredient (SI)-LABA without an asthma controller medication (ACM); 2) a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs) or ACM; and 3) step-down asthma therapy (e.g., discontinue LABA) when asthma control is achieved.

Results: There were 477,922 adults (18-64 years old) dispensed a new LABA during 2003-2012. Among LABA initiators, patients who initiated an SI-LABA and who did "not" have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change) to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model). The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period.

Conclusion: Although the decrease in SI-LABA initiation is consistent with FDA's recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts to move toward the recommended safe practices.

Keywords: LABA; US FDA; dispensing pattern; regulatory activities.

Figure 1

Percentage of adult asthma patients dispensed non-LABA ACM in 3 months (solid color) or 6 months (solid color plus upward diagonal pattern) prior to LABA initiation or having poor asthma control, by time segment: 2003–2004, 2005–2009, and 2010–2012. Notes: ^aPoor asthma control is defined as follows: within 3 months prior to the LABA index date, ≥1 dispensing of an ICS or LM dispensed, or ≥1 asthma-related ED visit or hospitalization, or ≥2 oral corticosteroids of ≤21 days’ supply, or within 6 months prior to the LABA index date, ≥3 canisters of an SABA dispensed. Abbreviations: ACM, asthma controller medication; ED, emergency department; ICS, inhaled corticosteroid; LABA, long-acting beta₂-agonist; LM, leukotriene modifier.

Figure 2

Percentage of SI-LABA initiators among all LABA initiators, by age group, 2003–2012 (by half-year). Abbreviations: LABA, long-acting beta₂-agonist; SI-LABA, single-ingredient-LABA; Y.O., years old.

Figure 3

Trend of percentage of LABA initiators among adult asthma patients who had longer than 2 months or longer than 4 months of continuous days’ supply^a of LABA dispensing, 2003–2012. Note: ^aBased on continuous treatment of the first treatment episode. Abbreviation: LABA, long-acting beta₂-agonist.