Fluticasone-Based versus Budesonide-Based Triple Therapies in COPD: Real-World Comparative Effectiveness and Safety

Abstract

Triple therapy for chronic obstructive pulmonary disease (COPD) is recommended for some patients, but the inhaled corticosteroids (ICS) may differ in effectiveness and safety. We compared budesonide-based and fluticasone-based triple therapy given in two inhalers on the incidence of exacerbation, mortality and severe pneumonia, using an observational study approach. We identified a cohort of patients with COPD, new users of triple therapy given in two inhalers during 2002–2018, age 50 or older, from the UK’s CPRD database, and followed for one year. The hazard ratio (HR) of exacerbation, all-cause death and pneumonia was estimated using the Cox regression model, weighted by fine stratification of the propensity score of treatment initiation. The cohort included 29,716 new users of fluticasone-based triple therapy and 9,646 of budesonide-based. The HR of a first moderate or severe exacerbation with budesonide-based triple therapy was 0.98 (95% CI: 0.94–1.03), relative to fluticasone-based, while for a severe exacerbation it was 0.97 (95% CI: 0.87–1.07). The incidence of all-cause death was lower with budesonide-based therapy among patients with no prior exacerbations (HR 0.80; 95% CI: 0.66–0.98). The HR of severe pneumonia with budesonide-based therapy was 0.84 (95% CI: 0.75–0.95). In a real-world clinical setting of COPD treatment, budesonide-based triple therapy given in two inhalers was generally as effective at reducing exacerbations as fluticasone-based triple therapy. However, the budesonide-based triple therapy was associated with a lower incidence of severe pneumonia and possibly also of all-cause death, especially among patients with no prior exacerbations for whom triple therapy is not recommended.

Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2035705 .

Keywords:

• New-user cohort design
• observational research
• real-world evidence
• long-acting bronchodilators
• inhaled corticosteroids
• COPD exacerbations
• Pneumonia

Acknowledgments

This study was conducted thanks to infrastructure funding from the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI). Pr. Suissa is the recipient of the Distinguished James McGill Professorship award. These sponsors had no input in the study.

Author’s contributions

Dr Ernst participated in study design, data interpretation, and writing of the manuscript. Ms Dell’Aniello participated in data analysis and writing of the manuscript. Pr. Suissa participated in data acquisition, study design, data interpretation, writing of the manuscript, and acts as guarantor of this entire manuscript.

Declaration of interest

Pr. Suissa has previously received research grants from Boehringer Ingelheim and Novartis and has participated in advisory board meetings or as speaker for AstraZeneca, Boehringer‐Ingelheim, and Novartis. Dr. Ernst and Ms Dell’Aniello have no conflicts of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Data availability statement

This study is based in part on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the UK National Health Service as part of their care and support. The interpretation and conclusions contained in this study are those of the author/s alone. Because electronic health records are classified as “sensitive data” by the UK Data Protection Act, information governance restrictions (to protect patient confidentiality) prevent data sharing via public deposition. Data are available with approval through the individual constituent entities controlling access to the data. Specifically, the primary care data can be requested via application to the Clinical Practice Research Datalink (https://www.cprd.com).