Treatment Patterns, Healthcare Utilization and Clinical Outcomes of Patients with Chronic Obstructive Pulmonary Disease Initiating Single-Inhaler Long-Acting β₂-Agonist/Long-Acting Muscarinic Antagonist Dual Therapy in Primary Care in England

Abstract

Purpose

Selection of treatments for patients with chronic obstructive pulmonary disease (COPD) may impact clinical outcomes, healthcare resource use (HCRU) and direct healthcare costs. We aimed to characterize these outcomes along with treatment patterns, for patients with COPD following initiation of single-inhaler long-acting muscarinic antagonist/long-acting β₂-agonist (LAMA/LABA) dual therapy in the primary care setting in England.

Patients and Methods

This retrospective cohort study used linked primary care electronic medical record data (Clinical Practice Research Datalink-Aurum) and secondary care administrative data (Hospital Episode Statistics) in England to assess outcomes for patients with COPD who had a prescription for one of four single-inhaler LAMA/LABA dual therapies between 1st June 2015–31st December 2018 (indexing period). Outcomes were assessed during a 12-month follow-up period from the index date (date of earliest prescription of a single-inhaler LAMA/LABA within the indexing period). Incident users were those without previous LAMA/LABA dual therapy prescriptions prior to index; this manuscript focuses on a subset of incident users: non-triple therapy users (patients without concomitant inhaled corticosteroid use at index).

Results

Of 10,991 incident users included, 9888 (90.0%) were non-triple therapy users, indexed on umeclidinium/vilanterol (n=4805), aclidinium/formoterol (n=2109), indacaterol/glycopyrronium (n=1785) and tiotropium/olodaterol (n=1189). At 3 months post-index, 63.3% of non-triple therapy users remained on a single-inhaler LAMA/LABA, and 22.1% had discontinued inhaled therapy. Most patients (86.9%) required general practitioner consultations in the first 3 months post-index. Inpatient stays were the biggest contributor to healthcare costs. Acute exacerbations of COPD (AECOPDs), adherence, time-to-triple therapy, time-to-first on-treatment moderate-to-severe AECOPD, time-to-index treatment discontinuation, HCRU and healthcare costs were similar across indexed therapies.

Conclusion

Patients initiating treatment with single-inhaler LAMA/LABA in primary care in England were unlikely to switch treatments in the first three months following initiation, but some may discontinue respiratory medication. Outcomes were similar across indexed treatments.

Keywords:

• COPD
• single-inhaler LAMA/LABA dual therapy
• primary care setting
• treatment patterns
• clinical outcomes

Abbreviations

A&E, accident and emergency; ACL, aclidinium; AECOPD, acute exacerbation of COPD; BDP, beclomethasone; BUD, budesonide; CAT, COPD Assessment Test; COPD, chronic obstructive pulmonary disease; CPRD-Aurum, Clinical Practice Research Datalink; FEV₁, forced expiratory volume in 1 second; FOR, formoterol fumarate; FP, fluticasone propionate; GLY, glycopyrronium; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GP, general practitioner; HCRU, healthcare resource utilization; HES, Hospital Episode Statistics; ICS, inhaled corticosteroid; IMT, initial maintenance therapy; IND, indacaterol; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified British Medical Research Council; NICE, National Institute for Health Care and Excellence; OLO, olodaterol; PDC, proportion of days covered; SABA, short-acting β₂-agonist; SABD, short-acting bronchodilator; SAL, salmeterol; SAMA, short-acting muscarinic antagonist; TIO, tiotropium bromide; UMEC, umeclidinium; VI, vilanterol.

Data Sharing Statement

This study is based in part on data from the CPRD obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the NHS as part of their care and support. The interpretation and conclusions contained in this study are those of the author/s alone.

Data from HES Copyright ^© (2022), re-used with the permission of The Health & Social Care Information Centre. All rights reserved. Authors had access to the study data for the purposes of this work only. Data were accessed through an existing GSK license to address pre-specified research questions only. Therefore, the data cannot be broadly disclosed or made publicly available at this time. Access to each database can be requested via the respective websites.

Ethics Approval and Informed Consent

Approval of this study was provided by the GSK Protocol Review Committee and by the Independent Scientific Advisory Committee (ISAC), which reviewed the protocol and approved access to CPRD data (ISAC study no. 20_000145). No personal subject contact or primary collection of individual human data occurred, and anonymized patient-level data were used in this analysis; patient consent was therefore not required.

This study complied with all applicable laws regarding subject privacy. No direct subject contact or primary collection of individual human subject data occurred. Personal identifiers, and personal identifiable information was removed by the database provider prior to receipt by the study team. Study results are in tabular form and aggregate analyses that omits subject identification, therefore informed consent, ethics committee or institutional review board (IRB) approval were not required. This study was designed, implemented, and reported in accordance with the Guidelines for Good Pharmacoepidemiology Practices (GPP) of the International Society for Pharmacoepidemiology (ISPE 2008), the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines, and with the ethical principles laid down in the Declaration of Helsinki.

Acknowledgments

Editorial support in the form of writing assistance including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Maria Guillermina Casabona, PhD, and Christopher Heath, PhD, at Fishawack Indicia Ltd, UK, part of Fishawack Health, and was funded by GSK. Two abstracts based on this study were previously presented as poster presentations at the ERS 2021 congress and at the Virtual ISPOR Europe 2021 congress.

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

AC, GR, CC, and ASI are employees of GSK and hold stock and shares at GSK. ASI is also a part-time member of the McMaster university faculty. TT, RWo and RWi are employees of Adelphi Real World, which received funding from GSK to conduct the study, but not for manuscript development. VB was an employee of Adelphi Real World at the time of the study, and is currently an employee of Bayer AG UK, and holds stock and shares in Bayer AG UK. Adelphi Real World is a business that provides consulting and other research services to pharmaceutical, device, government, and non-government organizations. Adelphi Real World employees work with a variety of companies and organizations and are expressly prohibited from receiving any payment or honoraria directly from these organizations for services rendered. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study/analysis was funded by GSK (GSK study: 214731). GSK-affiliated authors had a role in study design, data analysis, data interpretation, and writing of the report and GSK funded the article processing charges and open access fee.