Comparison of Rescue Medication Prescriptions in Patients with Chronic Obstructive Pulmonary Disease Receiving Umeclidinium/Vilanterol versus Tiotropium Bromide/Olodaterol in Routine Clinical Practice in England

Abstract

Purpose

Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting β₂-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO.

Patients and Methods

This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics. Patients with a COPD diagnosis at age ≥35 years were included (indexed) following initiation of single-inhaler UMEC/VI or TIO/OLO between July 1, 2015, and September 30, 2019. Outcomes included the number of rescue medication prescriptions at 12-months (primary), and at 6-, 18- and 24-months (secondary), adherence at 6-, 12-, 18- and 24-months post-index, defined as proportion of days covered ≥80% (secondary), and time-to-initiation of triple therapy (exploratory). Inverse probability of treatment weighting (IPTW) was used to balance potential confounding baseline characteristics. Superiority of UMEC/VI versus TIO/OLO for the primary outcome of rescue medication prescriptions was assessed using an intention-to-treat analysis with a p-value < 0.05.

Results

In total, 8603 patients were eligible (UMEC/VI: n = 6536; TIO/OLO: n = 2067). Following IPTW, covariates were well balanced across groups. Patients initiating UMEC/VI had statistically significantly fewer (mean [standard deviation]; p-value) rescue medication prescriptions versus TIO/OLO in both the unweighted (4.84 [4.78] vs 5.68 [5.00]; p < 0.001) and weighted comparison (4.91 [4.81] vs 5.48 [5.02]; p = 0.0032) at 12 months; consistent results were seen at all timepoints. Adherence was numerically higher for TIO/OLO versus UMEC/VI at all timepoints. Time-to-triple therapy was similar between treatment groups.

Conclusion

UMEC/VI was superior to TIO/OLO in reducing rescue medication prescriptions at 12 months after treatment initiation in a primary care cohort in England, potentially suggesting improvements in symptom control with UMEC/VI compared with TIO/OLO.

Keywords:

• COPD treatment
• LABA/LAMA
• primary care setting
• rescue medication
• treatment escalation

Abbreviations

AECOPD, acute exacerbations of COPD; ACL, aclidinium; ATE, average treatment effect; BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CPRD, Clinical Practice Research Datalink; FDC, fixed-dose combination; FEV₁, forced expiratory volume in 1 second; FOR, formoterol; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GP, general practitioner; HES, Hospital Episode Statistics; ICS, inhaled corticosteroid; IPTW, inverse probability of treatment weighting; ITT, intention-to-treat; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MRC, Medical Research Council; NICE, National Institute for Health and Care Excellence; NR, not reported; OLO, olodaterol; PDC, proportion of days covered; PS, propensity score; SABA, short-acting β₂-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation; SMD, standardized mean difference; TIO, tiotropium bromide; UMEC, umeclidinium; VI, vilanterol.

Data Sharing Statement

This study is based in part on data from the CPRD 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. Data from HES Copyright^© (2022), re-used with the permission of the Health and 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 (EMIS Web^® electronic patient record system and CPRD-Aurum).

Ethics Approval and Informed Consent

Approval of this study was provided by the GSK Protocol Review Committee and by the Clinical Practice Research Datalink (CPRD) Research Data Governance, which reviewed the protocol and approved access to CPRD data (protocol no. 21_000618). 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 approval were not required. This study was designed, implemented, and reported in accordance with the 2008 Guidelines for Good Pharmacoepidemiology Practices of the International Society for Pharmacoepidemiology, the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, and 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 Alexandra Berry, PhD, of Fishawack Indicia Ltd, UK, part of Fishawack Health, and was funded by GSK. An abstract based on this study was previously presented as a poster presentation at the ERS 2022 Congress, 4–6 September 2022, Barcelona, Spain.

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

GR, AC, CC, KJR, and ASI are employees of GSK and hold stock and shares at GSK. ASI also holds an unpaid faculty position at McMaster University. FH is an employee of the Translational Lung Research Center Heidelberg, part of the Germany lung research Foundation (DZL). JKQ holds a position at Imperial College London. CMC, TT, RWo, and RWi are employees of Adelphi Real World. VB is currently an employee of Bayer AG UK, and holds stock and shares in Bayer AG UK. VB and JY were employees of Adelphi Real World at the time of the study. Adelphi Real World is a business that provides consulting and other research services to pharmaceutical, device, government, and non-government organizations which received funding from GSK to conduct the study. 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 was funded by GSK (GSK study 217815) and approved by Clinical Practice Research Datalink (CPRD) Research Data Governance process. 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.