Clinical and Economic Impact of Long-Term Inhaled Corticosteroid Withdrawal in Patients with Chronic Obstructive Pulmonary Disease Treated with Triple Therapy in Spain

Abstract

Purpose

To determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting β₂-agonist (LABA), and long-acting muscarinic antagonist (LAMA).

Patients and Methods

This was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted.

Results

Of 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57–0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001).

Conclusion

ICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.

Keywords:

• inhaled corticosteroid withdrawal
• COPD
• exacerbations
• resource use
• health costs

Abbreviations

ANCOVA, analysis of covariance; BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; ICS, inhaled corticosteroids, LABA, long-acting β₂-agonists; LAMA, long-acting muscarinic antagonists; P, percentiles; PSM, propensity score matching; SD, standard deviation; TT, triple therapy.

Ethics Approval and Informed Consent

The study was classified by the Spanish Medicines and Healthcare Products Agency as EPA-OD and subsequently approved by the Research Ethics Committee of the Hospital of Terrassa, Barcelona, Spain (code: 02-20-399-090). Patient consent was not required as anonymized patient-level data were used in this analysis.

Acknowledgments

Editorial support (in the form of writing assistance, grammatical editing, and referencing) was provided by Kathryn Wardle of Aura, a division of Spirit Medical Communications Group Limited (Manchester, UK) and was funded by GlaxoSmithKline.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

VNG, LAV-A, ASI, RC, SS, and MG-P are employees of GlaxoSmithKline; LAV-A and ASI also hold stocks in GlaxoSmithKline. AS-M and AS-N are employees of Real Life Data. Real Life Data received payments from GlaxoSmithKline to perform the study, but not for manuscript development. CG received fees from GlaxoSmithKline for her involvement in the study, but not for manuscript development. The authors report no other conflicts of interest in this work.

Additional information

Funding

The study was funded by GlaxoSmithKline (study number: 213389). The sponsor was involved in study conception and design, data interpretation, and the decision to submit the article for publication. The sponsor was also given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.