VA Inhaler Formulary Change for COPD and Asthma Treatment Is Associated with Potential Clinical Harm
BACKGROUND:
This study evaluated the clinical impact associated with a July 2021 VA formulary change that replaced budesonide–formoterol metered-dose inhaler therapy with fluticasone–salmeterol dry-powder inhaler therapy for the treatment of chronic obstructive pulmonary disease (COPD) and asthma among 260,268 Veterans (median age 71, 91% male; “case series cohort”) in the VA healthcare system from January 2018 through December 2022 who switched from budesonide–formoterol metered-dose inhaler therapy to fluticasone–salmeterol dry-powder inhaler therapy following the formulary change. In a second cohort (mean age 69, 94% male; “comparison study cohort”) from the same time period, investigators compared the outcomes of 167,331 Veterans who switched to fluticasone–salmeterol dry-powder inhaler therapy with the outcomes of 91,226 Veterans who continued to receive non-fluticasone–salmeterol dry-powder inhaler therapy. Outcomes of interest were rescue medication use (albuterol and prednisone fills), emergency department visits, and hospitalizations (all-cause, respiratory-related, and pneumonia-specific).
FINDINGS:
- Changing from budesonide–formoterol metered-dose inhaler therapy to fluticasone–salmeterol dry-powder inhaler therapy for the treatment of COPD and asthma was associated with increased healthcare utilization and adverse clinical outcomes.
- Among Veterans in the case series cohort who experienced adverse outcomes of interest, fluticasone–salmeterol dry-powder inhaler therapy was associated with a decrease in albuterol fills (10%) but increased prednisone fills (2%), all-cause emergency department visits (5%), all-cause hospitalizations (8%), respiratory-related hospitalizations (10%), and pneumonia-specific hospitalizations (24%).
- In the comparison study cohort, Veterans who switched to fluticasone–salmeterol dry-powder inhaler therapy vs. those who did not switch had increased all-cause hospitalizations (16.1% vs. 15.6%), respiratory-related hospitalizations (3.2% vs. 2.7%), and pneumonia-related hospitalizations (1.2% vs. 1.0%) at 180 days.
IMPLICATIONS:
- Changing from budesonide–formoterol metered-dose inhaler therapy to fluticasone–salmeterol dry-powder inhaler therapy may result in clinical harm and need for VA to re-evaluate this inhaler formulary change.
- VA Pharmacy Benefits Management is incorporating this new data into upcoming contracting for inhalers, as well as in the development of new criteria-for-use of budesonide-formoterol.
LIMITATIONS:
- Investigators could not measure inhaler use directly (instead using pharmacy fills as an indirect measure of use) and focused only on short-term clinical outcomes (ED and hospitalization use), not longer-term impacts or quality of life.
AUTHOR/FUNDING INFORMATION:
This study was funded by HSR (IIR 23-032). Drs. Rabin and Prescott are with the VA Ann Arbor Healthcare System. Drs. Seelye and Prescott, Mss. Hogan, Cano, and Whittington, and Mr. Weinstein are with HSR’s Center for Clinical Management Research (CCMR). Dr. Kelley is with VA Pharmacy Benefits Management Service.
Rabin AS, Seelye SM, Weinstein JB, Hogan CK, Whittington TN, Cano J, Miller SA, Kelley C, Prescott HC. Budesonide-Formoterol Metered-Dose Inhaler vs. Fluticasone-Salmeterol Dry-Powder Inhaler. JAMA Internal Medicine. July 7, 2025; online ahead of print.
