Budesonide vs Fluticasone in COPD

In a recent study published in BMJ, a team of researchers from the United States (US) and Canada investigated the comparative effectiveness and safety of two single-inhaler triple therapies for chronic obstructive pulmonary disease (COPD).

Background
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder characterized by restricted airflow and exacerbations that reduce patients’ quality of life and increase the healthcare burden.

Certain individuals have been offered triple inhaler therapy, which contains an inhaled corticosteroid, a long-acting beta-agonist, and a long-acting muscarinic antagonist, to manage symptoms and prevent exacerbations. While randomized trials have demonstrated the efficacy of individual triple treatment components, direct comparisons of these three components in various formulations are still limited.

Observational studies have shown that fluticasone-based treatments may be associated with a higher incidence of pneumonia but fewer exacerbations than budesonide-based therapies. However, these studies frequently lack direct comparisons, use diverse definitions of symptoms and outcomes, and focus solely on selected population.

Concerns regarding the environmental impact of metered-dose inhalers have led to the evaluation of alternatives such as dry powder inhalers. As a result, extensive real-world evidence is required to inform clinical and environmental decision-making for COPD care.

About the study
In the current cohort study, the researchers used real-world data from US health claims from 2021 to 2023 to compare the effectiveness and safety of two single-inhaler triple therapies for COPD: budesonide-glycopyrrolate-formoterol (administered twice daily through metered-dose inhalers) and fluticasone-umeclidinium-vilanterol (administered once daily via dry powder inhaler).

The trial comprised people aged 40 and up who had a valid COPD diagnosis and were new to either therapy. Patients with prior triple therapy exposure, concurrent inhalers, or incomplete baseline data were excluded.

The study’s key outcomes were the first moderate or severe aggravation of COPD symptoms, which indicated the efficacy of the therapy, and the first pneumonia-related hospitalization, which demonstrated the safety of the inhaler treatment.

Moderate exacerbations required brief doses of systemic steroids, whereas severe exacerbations resulted in hospitalizations. In addition, diagnostic codes were used to identify hospital admissions for pneumonia. The patients were monitored for up to one year, or until treatment was discontinued or switched, an outcome occurred, or they were lost to follow-up.

Major findings

The researchers discovered that dry powder triple inhaler therapy with fluticasone-umeclidinium-vilanterol caused fewer COPD exacerbations than metered dose triple inhaler therapy with budesonide-glycopyrrolate-formoterol. Among the 20,388 matched pairs, budesonide-glycopyrrolate-formoterol users had a 9% greater risk of a moderate or severe exacerbation (hazard ratio 1.09).

Although budesonide-glycopyrrolate-formoterol use increased moderate exacerbations by 7% and severe exacerbations by 29%, the rate of pneumonia hospitalization was the same across the two regimens (hazard ratio 1.00).

Furthermore, the subgroup analysis revealed that budesonide-glycopyrrolate-formoterol posed increased hazards in patients with past exacerbations, severe illness, or elevated eosinophil counts. However, those lacking these risk factors showed fewer differences.

The sensitivity analyses, which altered follow-up time and exacerbation definitions, confirmed the core findings. However, both regimens had comparable rates of all-cause death.

These results revealed that fluticasone-umeclidinium-vilanterol triple inhaler therapy had a small advantage in reducing exacerbations while posing no increased pneumonia risk. This was also consistent with its potential environmental benefits from its dry powder format.

Conclusion
To summarize, the trial found that fluticasone-umeclidinium-vilanterol triple inhaler medication provided a minor clinical advantage in reducing COPD exacerbations while not raising the incidence of adverse events such as pneumonia. These findings showed the necessity of considering both clinical outcomes and environmental implications when selecting COPD inhaler therapy.

The findings also supported the use of dry powder inhalers, such as fluticasone-umeclidinium-vilanterol, as effective replacements for metered-dose inhalers. These findings also supported existing healthcare initiatives to reduce greenhouse gas emissions while maintaining patient care standards.

For more information: Feldman, W. B., Suissa, S., Kesselheim, A. S., Avorn, J., Russo, M., Schneeweiss, S., & Wang, S. V. (2024). Comparative effectiveness and safety of single inhaler triple therapies for chronic obstructive pulmonary disease: new user cohort study. BMJ, 387. doi:10.1136/bmj-2024-080409, https://www.bmj.com/content/387/bmj-2024-080409