Original Research

Clinical Implications of a Formulary Conversion From Budesonide/formoterol to Fluticasone/salmeterol at a VA Medical Center

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Background: Chronic obstructive pulmonary disease (COPD) is a respiratory disorder associated with chronic and slowly progressive systemic inflammation. The Global Initiative for Chronic Obstructive Lung Disease recommends a combination inhaler of a long-acting β-2 agonist and inhaled corticosteroid for patients with a history of frequent exacerbations. In 2021, the US Department of Veterans Affairs transitioned patients who were prescribed budesonide/formoterol inhaler to a fluticasone/salmeterol inhaler.

Methods: The primary objective of this study was to compare clinical outcomes including COPD exacerbations and hospitalizations 6 months before vs 6 months after the inhaler transition. Secondary outcomes included adverse effects, treatment failure, tobacco use, and antimicrobial/systemic corticosteroid use. A retrospective chart review was conducted on patients with a prescription for a budesonide/formoterol or fluticasone/salmeterol inhalers between February 1, 2021, and May 30, 2022, at the Hershel “Woody” Williams Veterans Affairs Medical Center, Huntington, West Virginia.

Results: In a convenience sample of 100 patients who transitioned from the budesonide/formoterol inhaler to the fluticasone/salmeterol inhaler, exacerbations increased from 24 before the transition to 29 after the transition, which was not a statistically significant change (P = .56). There were no statistically significant differences in the secondary endpoints including active tobacco use. Three patients had adverse reactions to fluticasone/salmeterol, while 18 patients experienced a therapeutic failure to fluticasone/salmeterol.

Conclusions: Patients with COPD that transitioned from budesonide/formoterol to fluticasone/salmeterol during the formulary conversion yield no clinical or statistically significant change in their clinical outcomes. Switching between these inhalers in the same therapeutic class may not impact clinical efficacy of the therapy for veterans with COPD but some intolerances and treatment failures should be expected.


 

References

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder associated with slowly progressive systemic inflammation. It includes emphysema, chronic bronchitis, and small airway disease. Patients with COPD have an incomplete reversibility of airway obstruction, the key differentiating factor between it and asthma.1

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend a combination inhaler consisting of a long-acting β-2 agonist (LABA) and inhaled corticosteroid (ICS) for patients with a history of COPD exacerbations.2 Blood eosinophil count is another marker for the initiation of an ICS in patients with COPD. According to the 2023 GOLD Report, ICS therapy is appropriate for patients who experience frequent exacerbations and have a blood eosinophil count > 100 cells/μL, while on maximum tolerated inhaler therapy.3 A 2019 meta-analysis found an overall reduction in the risk of exacerbations in patients with blood eosinophil counts ≥ 100 cells/µL after initiating an ICS.4

Common ICS-LABA inhalers include the combination of budesonide/formoterol as well as fluticasone/salmeterol. Though these combinations are within the same therapeutic class, they have different delivery systems: budesonide/formoterol is a metered dose inhaler, while fluticasone/salmeterol is a dry powder inhaler. The PATHOS study compared the exacerbation rates for the 2 inhalers in primary care patients with COPD. Patients treated long-term with the budesonide/formoterol inhaler were significantly less likely to experience a COPD exacerbation than those treated with the fluticasone/salmeterol inhaler.5

In 2021, The Veteran Health Administration transitioned patients from budesonide/formoterol inhalers to fluticasone/salmeterol inhalers through a formulary conversion. The purpose of this study was to examine the outcomes for patients undergoing the transition.

Methods

A retrospective chart review was conducted on patients at the Hershel “Woody” Williams Veterans Affairs Medical Center in Huntington, West Virginia, with COPD and prescriptions for both budesonide/formoterol and fluticasone/salmeterol inhalers between February 1, 2021, and May 30, 2022. In 2018, the prevalence of COPD in West Virginia was 13.9%, highest in the US.6 Data was obtained through the US Department of Veteran Affairs (VA) Corporate Data Warehouse and stored on a VA Informatics and Computing Infrastructure server. Patients were randomly selected from this cohort and included if they were aged 18 to 89 years, prescribed both inhalers, and had a confirmed COPD diagnosis. Patients were excluded if they also had an asthma diagnosis, if they had an interstitial lung disease, or any tracheostomy tubes. The date of transition from a budesonide/formoterol inhaler to a fluticasone/salmeterol inhaler was collected to establish a timeline of 6 months before and 6 months after the transition.

The primary endpoint was to assess clinical outcomes such as the number of COPD exacerbations and hospitalizations within 6 months of the transition for patients affected by the formulary conversion. Secondary outcomes included the incidence of adverse effects (AEs), treatment failure, tobacco use, and systemic corticosteroid/antimicrobial utilization.

Statistical analyses were performed using STATA v.15. Numerical data was analyzed using a Wilcoxon signed rank test. Categorical data was analyzed by a logistic regression analysis.

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