Discontinuation of Inhaled Corticosteroids from Triple Therapy in COPD: Effects on Major Outcomes in Real World Clinical Practice

Abstract

Recent reports provide evidence-based guidelines for the withdrawal of inhaled corticosteroids (ICS) in COPD, but data on patients treated with ICS-based triple therapy are sparse and contradictory. We assessed the effect of ICS discontinuation on the incidence of severe exacerbation and pneumonia in a real-world population of patients with COPD who initiated triple therapy. We identified a cohort of patients with COPD treated with LAMA-LABA-ICS triple therapy during 2002–2018, age 50 or older, from the UK’s CPRD database. Subjects who discontinued ICS were matched 1:1 on time-conditional propensity scores to those continuing ICS and followed for one year. Hazard ratios (HR) of severe exacerbation and pneumonia were estimated using Cox regression. The cohort included 42,667 patients who discontinued ICS matched to 42,667 who continued ICS treatment. The hazard ratio of a severe exacerbation with ICS discontinuation relative to ICS continuation was 0.86 (95% CI: 0.78–0.95), while for severe pneumonia it was 0.96 (95% CI: 0.88–1.05). The incidence of severe exacerbation after ICS discontinuation was numerically higher than after continuation among patients with two or more exacerbations in the prior year (HR 1.09; 95% CI: 0.94–1.26) and among those with FEV₁ <30% predicted (HR 1.29; 95% CI: 1.04–1.59). This large real-world study in the clinical setting of COPD treatment suggests that certain patients on triple therapy can be safely withdrawn from ICS and remain on bronchodilator therapy. As residual confounding cannot be ruled out, ICS discontinuation is not warranted for patients with multiple exacerbations and with very severe airway obstruction.

Keywords:

• Databases
• new user cohort design
• observational research
• real-world evidence
• long-acting bronchodilators
• COPD exacerbations
• pneumonia

Acknowledgements

This study was not funded but was conducted thanks to infrastructure funding from the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI). Dr. Suissa is the recipient of the Distinguished James McGill Professorship award. These sponsors had not input in the study.

Authors’ contributions

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

Data sharing 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).

Disclosure statement

Dr. Suissa attended scientific advisory committee meetings for Atara, Merck, Pfizer and Seqirus, and received speaking fees from Boehringer-Ingelheim and Novartis. Ms Dell’Aniello and Dr Ernst have no conflict of interest to report.

Funding

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