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Initiation of Inhaled Corticosteroid and Long-Acting b2-adrenergic Agonist (ICS/LABA) in Asthma
Ozgur Tunceli, PhD; David M. Kern, MS; Setareh A. Williams, PhD; Ned Pethick, MBA; Lisa Suchower, MA; and Sulabha Ramachandran, PhD

Initiation of Inhaled Corticosteroid and Long-Acting b2-adrenergic Agonist (ICS/LABA) in Asthma

Ozgur Tunceli, PhD; David M. Kern, MS; Setareh A. Williams, PhD; Ned Pethick, MBA; Lisa Suchower, MA; and Sulabha Ramachandran, PhD
This study compares the initiation of asthma therapies in a real-world population.
Concomitant asthma medication use was defined as at least 1 fill of the medication of interest during the 12-month pre-index period, as shown in Table 2. Previous asthma medication use was consistently higher in the BFC group across all classes (ICS, LTRA, SABA, and OSC) and for individual medications in each class. The largest difference in prior asthma medication use was for ICS medication use, with 24.9% of BFC patients versus 14.8% of FSC patients taking those medications.

Appropriate Use of Combination Therapies

In both BFC and FSC cohorts, approximately 32% of patients met asthma exacerbation high-risk criteria within the year prior to initiating combination therapies (Table 3). Prior controller therapy (ICS and/or LTRA) was prescribed to 42% of BFC and 31% of FSC patients. Compared with FSC patients (52%), a higher percentage of BFC patients (57%) appropriately initiated ICS/LABA therapy.

After controlling for selected confounders, as shown in the footnotes to Table 3, the odds that the BFC cohort of patients with asthma appropriately initiated ICS/LABA combination therapy was 1.21 times higher compared with those who initiated FSC (adjusted OR 1.21; P <.0001).

An asthma-related hospitalization during the 12-month pre-index period was considered a proxy of high risk for asthma exacerbations. Asthma-related hospitalizations were determined from the occurrences of any asthmarelated claims during an event. This entailed using any occurrence of asthma diagnosis (primary or secondary positions) as a proxy for identifying asthma-related hospitalizations, which could lead to overestimation. To address this, a post hoc sensitivity analysis was performed to explore whether study outcomes were sensitive to the definition of asthma-related inpatient visits by using occurrences of asthma diagnoses in the primary position only. The results showed that the proportion of patients with asthma-related hospitalizations decreased by more than 50% for each cohort (6.3% to 2.8% for FSC, 4.9% to 2.3% for BFC). The overall effect on the proportion of patients who appropriately initiated ICS/LABA combination therapy, however, decreased only slightly for both cohorts, and the direction of the relationships remained unchanged (51.6% to 49.7% for FSC, 57.3% to 56.1% for BFC). The new definition had a slightly higher impact on FSC than BFC, as reflected in the model that showed the crude OR for appropriate initiation of BFC to FSC increasing from 1.26 to 1.30 and the adjusted OR changing from 1.21 to 1.24.

The evaluation of appropriate initiation by calendar year showed a decline over the entire study period in the percentage of patients considered appropriately initiated on BFC, but showed fairly consistent results over the study period for FSC patients (Table 4). These results were based on crude percentages, not adjusted for covariates, and need to be interpreted within the context of these limitations.

DISCUSSION

The current study evaluated the appropriateness of ICS/LABA treatment initiation among commercially insured patients with asthma in accordance with EPR-3 guideline recommendations.

Over the 3.5-year study period, greater than 50% of patients met the appropriate initiation criteria outlined in this study. Compared with FSC patients (52%), BFC patients (57%) were significantly more likely to initiate ICS/LABA therapy appropriately (adjusted OR, 1.21; P <.0001).

A prior study, also utilizing a large retrospective US insurance claims database, demonstrated a significant difference in the percentage of patients appropriately initiating BFC and FSC therapies during the study period of January 2007 to December 2007 (58.4% vs 36.7%, respectively; P <.0001).18 In another analysis of US insurance claims data, Blanchette and colleagues reported 39.2% of patients met at least 1 criterion for appropriate initiation of ICS/LABA combination therapy, with a significantly larger percentage of patients in the BFC group (55.6%) initiating treatment appropriately versus 37.7% in the FSC group (P <.001) during the study period of July 2007 to June 2008.19

This study provides an updated perspective on the appropriate initiation of ICS/LABA by utilizing the extensive HIRD claims database for 3.5 years (June 2007-December 2010) after BFC became available in the United States. The findings of the current study were consistent with those of Ye and Blanchette, all of which showed higher appropriate initiation rates for BFC patients versus FSC patients over the time periods investigated in the respective studies. 18,19 The greater difference observed between the treatment cohorts in the earlier published literature may be due to the higher appropriate initiation of therapy coinciding with the time of BFC launch. Additional post hoc analysis was performed to investigate appropriate initiation rates for BFC and FSC within each calendar year of the study period (Table 4). This evaluation showed a decline over the entire study period in the percentage of patients considered appropriately initiated on BFC, but the results over the study period were fairly consistent for FSC patients. These results were based on crude percentages, not adjusted for covariates, and need to be interpreted within the context of these limitations of the study period, which could have been influenced by physician specialty. The greater difference observed between the 2 cohorts may also be due to the level of physician education during marketing of the drug or safety concerns about LABA use which may affect the prescribing behavior.

In our study population, BFC patients were more likely than FSC patients to have allergic rhinitis, sinusitis, and higher previous asthma controller medication use across all medication classes and for individual medications in those classes. The difference was greatest for prior ICS use, which could be the driver for the differences in appropriate initiation of BFC and FSC therapies.

The appropriate initiation of ICS/LABA was evaluated based on selected criteria in the EPR-3 guidelines, per claims data availability such as prior asthma controller medication use. For this study, 1 or more prescription fill for ICS or LTRA during the 12-month pre-index period was considered an indicator of persistent asthma. Patients with 1 or more prescription fill for ICS or LTRA during the 12-month pre-index period were considered appropriately initiated on ICS/LABA combination regardless of whether they met any other high-risk criteria during that time period. Overall, 21% of study patients (10,612 of 50,541; 19.6% FSC, 25.6% BFC) received ICS or LTRA monotherapy before initiating ICS/LABA combination treatment, but had no other studydefined high-risk criteria. In addition, 17.2% of the patients in the total sample—14.8% in the FSC cohort and 24.9% in the BFC cohort—received any ICS during the 12-month pre-index period. Substantially larger proportions of patients received OSCs during the pre-index period: 40.8% in the total sample, 39.8% in the FSC cohort, and 44.1% in the BFC cohort (Table 2). Nonetheless, it is not known how many of those patients were well controlled on ICS or LTRA alone before initiating ICS/LABA combination, as disease severity could not be assessed from the claims data due to lack of availability of information on asthma symptoms and lung function. Thus, overall, 38% (7566 of 19,966) of FSC and 45% (2999 of 6714) of BFC patients identified in this study as appropriately initiating ICS/LABA therapy did not have simultaneous high-risk criteria, and it is not known whether they were controlled on their ICS or LTRA monotherapy prior to stepping up to ICS/LABA combination.

In this study, a higher percentage of patients had BFC prescribed by a specialist physician (allergists/immunologists and pulmonologists) compared with the FSC patients. The specialty of the prescribing physician should be considered when interpreting differences in appropriate initiation between BFC and FSC, as this may play a role in the appropriateness of the initial therapy selected; in general, specialists are more likely to treat more severely affected patients who are in need of ICS/LABA treatment. It is likely that specialists will be more aware of and adhere to treatment guidelines. Physician specialty was controlled for in the statistical models as a covariate in this study.

Limitations

The results should be interpreted within the context of limitations inherent to administrative claims data, including the absence of clinical indicators of disease severity or progression, which may have underestimated the appropriateness of ICS/LABA combination therapy initiation. The absence of data on lung function and asthma symptoms does not allow a full assessment of disease severity. It is therefore likely that appropriate initiation of therapy was underestimated, as only proxies for disease severity were used from the database. Further, limiting the study to ICS/LABA treatment-naïve patients and the exclusion of patients with compromised and/or reduced lung function is likely to have contributed to an underestimation of appropriateness of treatment initiation.

Given that the same criteria were used for both patient cohorts, this misclassification is likely to be nondifferential and should not impact the comparisons between treatment cohorts. Asthma-related utilization in this study was based on the occurrence of asthma claim codes, which could lead to erroneous estimates of the actual utilization levels for any patient or population. Study medications were identified based on pharmacy claims for each medication, which indicate medication dispensing but remain uncertain on whether treatment was initiated, and on what date. This study was conducted among commercially insured subjects aged between 12 and 64 years in a managed care setting. Thus, the ability to generalize these results may be limited to similar patient groups. Patients older than 64 years were not included in this analysis because data in the HIRD were collected from a commercially insured population, generally younger than 65 years. Nonetheless, because the majority of patients with asthma are younger than 65 years, the exclusion of patients who are 65 years and older resulted in the loss of only a minimal number of true asthmatics, while likely excluding a large number of possible COPD patients.

CONCLUSIONS

Over the 3.5-year study period, greater than 50% of patients were appropriately initiated on ICS/LABA combination therapy criteria as defined in this study to correspond with EPR-3 guidelines.

The percentage of patients considered appropriately initiated was significantly higher among BFC-treated patients than among FSC-treated patients. After controlling for selected potential confounders/baseline differences, the odds of patients with asthma initiating BFC appropriately were 1.21 times greater compared with patients initiating FSC. However, there was a decrease over the study period in the appropriate initiation rate for BFC, while the rate was fairly consistent for FSC. While these results were consistent with earlier reported patterns, further evidence, including a more accurate assessment of disease severity using multiple data sources with additional clinical information, could provide a more reliable estimation of appropriate treatment initiation.

Author Affiliations: HealthCore, Inc, Wilmington, DE (OT, DMK); AstraZeneca LP, Wilmington, DE (SAW, NP, LS, SR).

Source of Funding: Astra Zeneca LP funded this research.

Author Disclosures: SAW, NP, LS, and SR have disclosed that they are employed by Astra Zeneca LP. OT, DMK, and BBT have disclosed that they are employed by HealthCore Inc, which received funding from Astra Zeneca LP for this study.

Authorship Information: Concept and design (OT, DMK, SAW, NP, SR); acquisition of data (OT, DMK, SR); analysis and interpretation of data (OT, DMK, SAW, NP, LS, SR); drafting of the manuscript (OT, SAW, NP, LS, SR); critical revision of the manuscript for important intellectual content (OT, DMK, SAW, LS, SR); statistical analysis (OT, DMK, SR); provision of study materials or patients (SR); obtaining funding (NP, SR); administrative, technical, or logistic support (SAW, NP); supervision (OT, SR).

Address correspondence to: Ozgur Tunceli, PhD, Director, HealthCore, Inc, 800 Delaware Ave, Fifth Fl, Wilmington, DE 19801. E-mail: otunceli@healthcore.com.
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