The American Journal of Managed Care January 2011
Relationship Between Short-Acting β-Adrenergic Agonist Use and Healthcare Costs
Overuse of rescue medication among asthma patients is associated with increased exacerbations and higher total and asthma-related healthcare costs.
Objective: To assess whether increased short-acting β2-adrenergic agonist (SABA) claims are associated with asthma exacerbations and increased healthcare costs.
Study Design: Cross-sectional study.
Methods: Patients (N = 93,604) were health plan members aged 6-56 years with at least 2 years of enrollment between July 1, 2003, and June 30, 2007, an asthma diagnosis, and at least 1 asthma medication claim per study year. Two years of administrative claims were collected. SABA use was categorized as 0 (none), ½ to 2 (low), 2½ to 6 (moderate), 6½ to 12 (high), and more than 12 (excessive) canister equivalents per year. Multivariate analyses were adjusted for age, sex, geographic region, comorbidities, specialist consultation, controller medication use, and asthma severity.
Results: Half of high and excessive SABA users had few or no controller claims. Compared with SABA nonusers, high and excessive SABA users had significantly higher odds (odds ratio [95% confidence interval]) of asthma-related emergency department/urgent care visits (6.47 [5.25, 7.98] and 7.68 [6.04, 9.76], respectively), hospitalizations (5.37 [6.04, 9.76]; 6.90 [4.90, 9.73]), and oral corticosteroid use (2.89 [2.72, 3.08]; 3.71 [3.41, 4.03]). Excessive SABA users had 3.0 times ($1791) and high SABA users had 2.2 times ($1326) higher asthma-related healthcare costs than low SABA users ($595). Total costs also increased with higher SABA use, but with smaller incremental differences between excessive and high SABA users and low SABA users.
Conclusions: Increased SABA use is associated with higher total and asthma-related healthcare costs. Opportunity exists to lessen overreliance on SABAs.
(Am J Manag Care. 2011;17(1):19-27)
Although National Asthma Education and Prevention Program guidelines for asthma management recommend a stepwise approach to pharmacologic therapy, short-acting b2-adrenergic agonist (SABA) rescue medications remain overused, while controller medications are underprescribed.
- Overuse of SABA is a measure of poor asthma control, is associated with increased asthma severity and inappropriate or inadequate controller therapy, and is negatively associated with specialist care and comorbidity management.
- Patients with increased SABA use are at increased risk for exacerbations and incur greater total and asthma-related costs.
- Substantial opportunity exists to improve asthma management and lower exacerbation-related healthcare costs.
Previous research suggests that increased SABA use is associated with diminished asthma control and an elevated risk of exacerbations.7-11 Moreover, 3 months of elevated SABA use has been associated with higher asthma-related healthcare costs,12 although annual costs associated with SABA use are unknown. Exacerbation-related hospitalizations and ED visits are an important component of these costs. To determine whether increasing SABA use is associated with greater healthcare utilization and costs, we conducted a retrospective study in a large population of health plan members.
Data Source and Patients
Data were obtained from IMS LifeLink, a de-identified, Health Insurance Portability and Accountability Act (HIPAA)–compliant database containing enrollment and claims data for 50 million persons from approximately 70 US health plans. Eligible patients had at least 2 years of continuous enrollment in a health plan during July 1, 2003, to June 30, 2007, were aged 6 to 56 years, had a diagnosis of asthma, and had at least 1 prescription claim for an asthma medication in each of the preindex and postindex years. Asthma diagnosis criteria consisted of (1) at least 1 asthma-related ED visit, urgent care (UC) visit, or hospitalization with a primary International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] diagnosis code of 493.xx, or (2) at least 2 asthma-related physician office visits (ICD-9-CM 493.xx), or (3) at least 2 prescription claims for asthma medication (SABA or controller). Primary controllers included inhaled corticosteroids (ICS), ICS/long-acting β2-agonist combinations (ICS/LABA), and leukotriene modifiers (LMs). Adjunctive controllers included mast cell stabilizers, methylxanthines, and omalizumab. The upper age limit was chosen to exclude patients with a higher likelihood of undiagnosed chronic obstructive pulmonary disease (COPD) and because it is a criterion in the Health Plan Employer Data and Information Set (HEDIS) of the National Committee on Quality Assurance.13 Exclusion criteria were a diagnosis of COPD, emphysema, chronic bronchitis, bronchiectasis, cystic fibrosis, or respiratory tract cancer, and more than 1 drug claim for ipratropium or tiotropium (surrogate markers for COPD).14-18 Patients diagnosed with multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, polymyalgia rheumatica, and temporal arteritis were excluded because these conditions often require long-term treatment with oral corticosteroids (OCS).
Enrollment and claims data were collected for a 2-year period between July 1, 2003, and June 30, 2007. When more than one 2-year observation period was available for a patient, the most recent period was selected. The index date was defined as the date occurring 1 year after the beginning of the 2-year continuous enrollment period and did not otherwise correspond to the dispensing of any medication or any specific event. The observation period was divided into 12-month preindex and postindex periods, similar to other studies.8,19-22 Baseline characteristics of the population were identified in the preindex period, and the relationships between SABA exposure, exacerbations, and healthcare costs were analyzed in the postindex period. Data collected included demographics, outpatient prescription drug claims (National Drug Code, dispensing date, quantity dispensed, days of supply, and billed charges), and inpatient and outpatient claims (service date, ICD-9-CM diagnosis codes, Current Procedural Terminology-4 procedure codes, and billed charges). Costs were imputed by IMS LifeLink for claims with missing cost information that were due to capitation arrangements negotiated with participating plans.23 Pharmacy fills for metered-dose inhaler (MDI) and nebulized SABA and other asthma medications were identified using National Drug Codes.
Asthma exacerbations were identified using primary diagnosis codes in healthcare claims, with an exacerbation defined as an asthma-related (ICD-9-CM 493.xx) ED or UC visit; an asthma-related hospitalization; or a pharmaceutical claim for an OCS. Each OCS claim, regardless of days of supply, was counted as 1 dispensing (90% of OCS fills had a supply of 21 days or fewer). Proxy variables for asthma severity were created based on the presence of 1 or more claims in the preindex period for OCS and asthma-related ED/UC visits and hospitalizations. Healthcare costs were derived from billed charges in inpatient, outpatient, and pharmaceutical claims in the postindex period.8,19-22
SABA exposure was calculated using methods similar to those previously published.24,25 Canister equivalents (CEs) were assigned to each dispensed SABA product to account for MDI and nebulized SABA use. A standard MDI canister size, or 1 CE, was defined as 200 metered actuations of albuterol; levalbuterol was considered to be equivalent in potency to albuterol. For pirbuterol, in which a standard dispensing contains 400 actuations, 1 canister was considered to be 2 CEs. For claims in which canister size was unclear, CEs were imputed based on days of supply. We considered a 3-mL ampule of nebulized albuterol to be equivalent to 4 actuations of albuterol from an MDI, so 50 3-mL ampules of nebulized SABA was considered 1 CE. For analysis, CEs were rounded to the nearest one-half CE. A categorical variable adapted from a previously validated risk stratification scheme19 was created to characterize SABA exposure as 0 CE (no use), ½ to 2 CEs (low use), 2½ to 6 CEs (moderate use), 6½ to 12 CEs (high use), or >12 CEs (excessive use).
Data Analyses and Statistical Methods
Cross-sectional bivariate analyses and multivariate regression models were used to determine the relationships between SABA use, asthma exacerbations, and asthma-related and total (all-cause) healthcare costs in the postindex period. In the bivariate analyses, differences between groups were assessed using the 2-tailed t test or analysis of variance test for continuous variables and the β2 test for categorical variables. These methods also were used to evaluate the association between SABA exposure, outcomes, and covariates. Potential comorbidities for multivariate models were tested using the β2 test; comorbidities demonstrated to be significant in previous research and/or significant at the 5% level in our bivariate analyses were included. The comorbid conditions included in the multivariate regression models were allergies/rhinitis, chronic sinusitis, diabetes mellitus, gastroesophageal reflux disease, obstructive sleep apnea syndrome, tonsil and adenoid disease, acute pharyngitis, acute sinusitis, and upper respiratory infection.5,8,26-30 Logistic regression models were used to determine adjusted associations between SABA use and exacerbations, and generalized linear models with a gamma family distribution and log-link were used to estimate asthma-related and all-cause healthcare costs by SABA strata. Cost differences were calculated between the means of the predicted costs, and 95% confidence intervals (CIs) were calculated using the percentile method with 1000 bootstrapped simulations. All analyses were conducted with SAS version 9.1.3 for Windows (SAS Institute, Cary, NC) or Stata version 10 for Windows (Stata-Corp LP, College Station, TX).
In the postindex period, 26.6% of patients had no drug claims for SABAs, 40.9% were dispensed between ½ and 2 CEs, 21.4% were dispensed between 2½ and 6 CEs, 7.8% were dispensed between 6½ and 12 CEs, and 3.4% were dispensed more than 12 CEs. Nebulized SABAs were prescribed to 12.9% of patients and were used 3 times as often in excessive SABA users (31.6%) and 2.4 times as often in high SABA users (25.9%) compared with low SABA users (10.6%) (data not shown). In general, SABA use by patients did not vary greatly from preindex year to postindex year (Table 1).
Out of an initial pool of 946,859 patients with asthma, 93,604 met study eligibility criteria (eAppendix available at www.ajmc.com). Demographic and baseline clinical characteristics of the cohort are shown in Table 2. The study population was 45.2% male, and the largest proportion of patients (48.9%) resided in the midwestern United States. More than one-third of the population was pediatric, but only 22% of subjects in the high and excessive SABA use groups were children. The most frequent chronic comorbidities in the preindex or postindex periods were allergies/allergic rhinitis and chronic sinusitis. The prevalence of comorbid conditions generally decreased with increasing SABA exposure. This relationship was especially apparent for allergies/rhinitis; non-SABA users had this diagnosis 70% more often than excessive users. Specialist consultations were obtained by 30.9% of subjects, with a 33% higher occurrence in non-SABA users than excessive users. In the preindex period, 2046 members (2.2%) had an asthma-related ED/UC visit, 876 (0.9%) had an asthma-related hospitalization, and 28,892 (30.9%) had OCS treatment. The frequency of these exacerbation events increased with greater postindex SABA exposure.
Controller Medication Use
Controller medication dispensed in the postindex period varied substantially by SABA exposure (Table 3, Figure 1). In general, controller use (primary or any) was highest in excessive SABA users, followed closely by nonusers and high users. Excessive SABA users had nearly twice as many mean days of supply of any controller medication as low SABA users (209 days versus 111 days). Despite elevated levels of controller use as a group, almost half of high and excessive SABA users had either low (1 to 120 days of supply) or no use of any controller medication.