Clinical question: How do the two available (U.S. market) single triple-therapy inhalers compare in terms of safety and efficacy for patients with chronic obstructive pulmonary disease (COPD), with the background knowledge that one of these inhalers has much lower global warming potential?
Background: Single triple-therapy inhalers containing inhaled corticosteroids, long-acting beta 2-agonists, and long-acting muscarinic antagonists (ICS-LAMA-LABA) confer benefit to certain patient populations with COPD, including patients who experience exacerbations despite dual therapy (LAMA-LABA). In the U.S., there are two such inhalers available: fluticasone-umeclidinium vilanterol as a once daily dry powder inhaler (DPI), and budesonide-glycopyrrolate-formoterol as a twice daily metered dose inhaler (MDI), which have never been compared head-to-head. Notably, MDIs confer an approximately 20 times higher greenhouse-gas footprint as compared to DPIs, related to the potent greenhouse-gas propellants currently used in MDIs, hydrofluoroalkanes. Health systems around the world have been targeting MDIs for replacement with DPI due to the positive impact on climate change.
Study design: One-to-one, propensity score matched, new user, cohort study
Setting: Optum’s database of administrative health claims
Synopsis: Participants had COPD, were at least 40 years old, and were new users of single-inhaler triple therapy. The main outcomes were first moderate or severe COPD exacerbation (effectiveness) and first admission to hospital with pneumonia (safety). There were 20,388 propensity-score-matched pairs of new users. Those who received budesonide-glycopyrrolate-formoterol MDI had a 9% higher incidence of first moderate or severe COPD exacerbation (HR, 1.09; 95% CI, 1.04 to 1.14) and an equivalent incidence of first admission to hospital with pneumonia compared with patients receiving fluticasone-umeclidinium-vilanterol DPIs. The authors pose several possible reasons why the patients receiving fluticasone-umeclidinium-vilanterol DPIs had lower incidence of COPD exacerbations: 1) it was once daily versus twice daily, thus possibly enjoying better adherence; 2) MDIs necessitate timing of breaths with action, but DPIs just need deep breaths; and 3) perhaps it is the medications themselves.
Bottom line: Health systems can “breathe easy” by moving their single-inhaler triple therapy to fluticasone-umeclidinium-vilanterol DPIs; this study demonstrates effectiveness and safety, while reaping the known benefits of a DPI’s lower global warming potential as compared to an MDI that utilizes hydrofluoroalkanes.
Citation: Feldman WB, et al. Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study. BMJ. 2024;387:e080409. doi:10.1136/bmj-2024-080409.
Dr. Gordon is associate program director of Maine Medical Center’s internal medicine residency program, a hospital medicine attending at Maine Medical Center in Portland, Maine, and an assistant professor at Tufts University School of Medicine in Boston.