https://orcid.org/0000-0002-1889-6656
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Abstract
Purpose
Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England.
Patients and Methods
This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed.
Results
In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were <1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and <1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments.
Conclusion
UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.
Plain Language Summary
Sudden exacerbations, or flare-ups, of chronic obstructive pulmonary disease (COPD) are linked with worsening health and increased risk of death, as well as increased healthcare costs for people with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) dual therapy is recommended for patients with COPD who take LAMA or LABA monotherapy but continue to experience flare-ups or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), in terms of flare-ups in patients with COPD in England.
We used two linked databases of de-identified medical records from general practitioners and hospitals for patients with COPD who had a first prescription for UMEC/VI or IND/GLY between 1 January 2015 and 30 September 2019. We compared the two treatments on COPD flare-ups, healthcare resource utilization and related costs, and changes in medication over the 2 years following starting treatment.
We found that the treatments were comparable for moderate-to-severe flare-ups. Patients taking UMEC/VI had less Accident and Emergency (A&E) visits in total and less inpatient stays related to their COPD, and had a lower overall cost of healthcare for A&E visits and inpatient stays than patients taking IND/GLY. Changes to treatment and time before their first flare-up were similar for all patients, regardless of their prescribed treatment.
This study showed that UMEC/VI is as effective as IND/GLY at preventing moderate-to-severe flare-ups. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY in reducing the rate of moderate-to-severe exacerbations after starting treatment.
Abbreviations
A&E, Accident and Emergency; ACL, aclidinium; BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; COVID, coronavirus; CPRD, Clinical Practice Research Datalink; FDC, fixed-dose combination; FEV1, forced expiratory volume in one second; FOR, formoterol; FVC, forced vital capacity; GBP, British Pound Sterling; GLY, glycopyrronium; GOLD; Global Initiative for Chronic Obstructive Lung Disease; GP, general practitioner; HCRU, healthcare resource utilization; HES; Hospital Episode Statistics; ICS; inhaled corticosteroid; IND, indacaterol; IPTW, inverse probability of treatment weighting; ITT, intention-to-treat; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; MRC, Medical Research Council; NHS, National Health Service; NI, noninferiority; NICE, National Institute for Health and Care Excellence; PS, propensity score; RR, rate ratio; SABA, short-acting β2-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation; UK, United Kingdom; 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 Clinical Practice Research Datalink (CPRD) Research Data Governance [RDG] process, which reviewed the protocol and approved access to CPRD data (protocol no. 21_000616). 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 were removed by the database provider prior to receipt by the study team. Study results are in tabular form and aggregate analyses that omit 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 Christopher Heath, 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 2022 ERS Congress, 4–6 September 2022, Barcelona, Spain, and then as an encore at the 2023 Kongress der Deutschen Gesellschaft für Innere Medizin (DGIM), 22–25 April 2023, Wiesbaden, Germany.
Author Contributions
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work.
Disclosure
GR, CCo, KJR, and ASI are employees of GSK and hold stocks and shares at GSK. ASI also holds an unpaid faculty position at McMaster University. AC was an employee of GSK and held stocks and shares at GSK at the time of the study. FJFH 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 and has received grants or contracts paid to this institution outside the scope of the submitted work from the Medical Research Council, Health Data Research UK, GSK, Boehringer Ingelheim, Asthma + Lung UK, and AstraZeneca. JKQ has also received payment for advisory board participation, teaching or lectures from GSK, AstraZeneca, and Insmed. CCa, TT, RWo, and RWi are employees of Adelphi Real World. 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.