Comparative Adherence and Persistence of Single- and Multiple-Inhaler Triple Therapies Among Patients with Chronic Obstructive Pulmonary Disease in an English Real-World Primary Care Setting

Abstract

Purpose

Triple therapy comprising a long-acting muscarinic antagonist, long-acting β₂-agonist and inhaled corticosteroid is recommended for patients with chronic obstructive pulmonary disease (COPD) who continue to experience frequent exacerbations or symptoms whilst receiving dual therapy. Adherence and persistence to multiple-inhaler triple therapy (MITT) is known to be poor. This study assessed comparative adherence to single-inhaler triple therapy (SITT) versus MITT in a real-world setting in England.

Patients and Methods

This was a retrospective cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics [HES] Admitted Patient Care) data to identify patients with COPD who were newly initiated on SITT or MITT between November 2017 and June 2019. Eligible patients were aged ≥35 years and had a forced expiratory volume in 1 second/forced vital capacity <0.7, linkage to HES and continuous registration with a general practitioner for 12 months pre- and 6 months post-initiation. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Adherence was measured using the proportion of days covered by days’ supply of SITT or MITT prescriptions. Persistence was measured with a gap of >30 days between the end of a prescription and the following refill used to determine non-persistence.

Results

Overall, 4080 SITT and 6579 MITT users comprised the study cohort. After weighting, the baseline characteristics between the cohorts were comparable (absolute standardized mean difference <10%). SITT users had significantly higher adherence than MITT users at 6, 12, and 18 months post-initiation (p<0.001 for all comparisons). Median persistence was higher among SITT users than MITT users (5.09 months vs 0.99 months).

Conclusion

Patients with COPD in England initiating SITT had significantly better adherence and persistence compared with MITT initiators. These improvements continued at least 18 months following treatment initiation.

Keywords:

• COPD
• Clinical Practice Research Datalink
• Hospital Episode Statistics
• MITT
• proportion of days covered
• SITT

Abbreviations

BDP, beclomethasone; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CPRD, Clinical Practice Research Datalink; FEV1, forced expiratory volume in 1 second; FF, fluticasone furoate; FOR, formoterol; GB, glycopyrronium bromide; HES, Hospital Episode Statistics; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; MITT, multiple-inhaler triple therapy; PDC, proportion of days covered; PS, propensity score; SD, standard deviation; SITT, single-inhaler triple therapy; UMEC, umeclidinium; VI, vilanterol.

Data Sharing Statement

The data analyzed in this publication are derived from the Clinical Practice Research Datalink (www.cprd.com) and Hospital Episode Statistics database (https://digital.nhs.uk/data-and-information/data-tools-and-services/data-services/hospital-episode-statistics). Authors had access to the study data for the purposes of this work only. Data were accessed through an existing GSK license to address the prespecified 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

This study complied with all applicable laws regarding patient privacy. No direct patient contact or primary collection of individual patient data occurred; therefore, informed patient consent was not required. This study was approved by CPRD (study number 20_000121). Generic ethical approval for observational research approved by CPRD has been granted by a Health Research Authority Research Ethics Committee (East Midlands-Derby, UK; REC reference number 05/MRE04/87).

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 Rebecca Cunningham of Aura, a division of Spirit Medical Communications Group Limited, and was funded by GSK.

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 is provided by patients and collected by the NHS as part of their care and support.

Data from this study have previously been presented in abstract/conference presentation form at:

The 2021 European Respiratory Society – 31st Annual congress. The abstract was published in European Respiratory Journal. 2021;58(65):OA2947. Available from https://erj.ersjournals.com/content/58/suppl_65/OA2947 DOI:10.1183/13993003.congress-2021.OA2947

The 2021 British Thoracic Society Winter Meeting. The abstract was published in Thorax 2021;76:A20-A21. Available from: https://thorax.bmj.com/content/thoraxjnl/76/Suppl_2/A20.2.full.pdf

Author Contributions

All authors made a significant contribution to the work reported, whether that was 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 manuscript; 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

Kieran J Rothnie, Alexandrosz Czira, Chris Compton, Kirill Nikitin, Raj Sharma, and Afisi S Ismaila are employees of and/or hold stocks/shares in GSK. Neil Snowise is a previous employee of GSK and holds GSK stocks/shares. Victoria Banks, Robert Wood, Theo Tritton, Olivia Massey, and Rosie Wild are employees of Adelphi Real World. Adelphi Real World received funding from GSK to conduct the study. David MG Halpin reports personal fees from AstraZeneca, personal fees and non-financial support from Boehringer Ingelheim, personal fees from Aerogen, Chiesi, CSL Behring, and GSK, personal fees and non-financial support from Novartis, and personal fees from Pfizer and Sanofi. Claus F Vogelmeier has received research grants from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, and Grifols, and has given presentations at symposia and/or served on scientific advisory boards sponsored by Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, Grifols, Menarini, Novartis, and Nuvaira. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by GSK (study number 208114). The sponsor was involved in study conception and design, 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.