Adverse outcomes more common with dry-powder vs. metered-dose inhaler, study finds

Fluticasone-salmeterol dry-powder inhaler therapy may lead to worse outcomes than budesonide-formoterol metered-dose inhaler therapy in patients with chronic obstructive pulmonary disease (COPD) and asthma, according to a recent study.

Researchers used data from the Veterans Affairs health care system (January 2018 through December 2022) to perform a self-controlled case series and matched observational cohort study examining whether outcomes differed after a July 2021 formulary change replacing budesonide-formoterol metered-dose inhalers with fluticasone-salmeterol dry-powder inhalers for patients with COPD and asthma. Both the case series and the cohort study included patients who were prescribed a combination inhaler before and after the formulary change. The main outcome measures were rescue medication use (i.e., albuterol and prednisone fills), ED visits, and all-cause, respiratory-related, and pneumonia-specific hospitalizations. The results were published July 7 by JAMA Internal Medicine.

A total of 260,268 patients switched from budesonide-formoterol metered-dose therapy to fluticasone-salmeterol dry-powder therapy after the formulary change and were included in the self-controlled case series (median age, 71 years; 91% male). Treatment with fluticasone-salmeterol dry-powder inhaler therapy was associated with a decrease in albuterol fills (incidence rate ratio [IRR], 0.90; 95% CI, 0.90 to 0.91) and increases in prednisone fills (IRR, 1.02; 95% CI, 1.01 to 1.03), all-cause ED visits (IRR, 1.05; 95% CI, 1.04 to 1.06), all-cause hospitalizations (IRR, 1.08; 95% CI, 1.06 to 1.09), respiratory-related hospitalizations (IRR, 1.10; 95% CI, 1.07 to 1.14), and pneumonia-specific hospitalizations (IRR, 1.24; 95% CI, 1.17 to 1.31).

The cohort study included 258,557 patients (median age, 68.9 years; 94% male), 167,331 who switched to fluticasone-salmeterol dry-powder inhaler therapy and 91,226 matched patients who did not. There was no difference in mortality at 180 days after the switch (1.89% vs. 1.90%), but the group who switched had higher all-cause hospitalizations (16.14% vs. 15.64%) respiratory-related hospitalizations (3.15% vs. 2.74%), and pneumonia-related hospitalizations (1.15% vs. 1.03%).

Limitations include that the study involved mostly older men and that inhaler use could not be directly measured, the authors noted. They concluded that the change from a budesonide-formoterol metered-dose inhaler to a fluticasone-salmeterol dry-powder inhaler for treatment of COPD and asthma was associated with increased health care utilization and potential clinical harm in this study population.

“Our results highlight the tension between reducing inhaler costs, improving clinical outcomes, and addressing the environmental impact of care delivery. While the formulary change likely lowered inhaler expenditures and reduced direct inhaler-related greenhouse gas emissions—the equivalent of taking approximately 6000 gasoline-powered passenger vehicles off the road for 1 year—higher health care utilization could offset these climate benefits by increasing resource-intensive ED visits and hospitalizations,” they wrote. “For health systems aiming to align with decarbonization goals, interventions must optimize clinical outcomes and net greenhouse gas emissions while balancing costs.”