Characteristics of Users and New Initiators of Single- and Multiple-Inhaler Triple Therapy for Chronic Obstructive Pulmonary Disease in Germany

Abstract

Purpose

To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany.

Patients and Methods

Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015–31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting β₂-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period.

Results

In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period.

Conclusion

In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.

Plain Language Summary

Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019.

In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years.

The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).

Keywords:

• COPD
• Germany
• MITT
• patient characteristics
• real-world treatment
• SITT

Abbreviations

ATC, Anatomical Therapeutic Chemical; BDP/GLY/FOR, beclomethasone dipropionate/glycopyrronium bromide/formoterol; BUD/GLY/FOR, budesonide/glycopyrronium bromide/formoterol; CCI, Charlson Comorbidity Index; COPD, chronic obstructive pulmonary disease; EMA, European Medicines Agency; FEV₁, forced expiratory volume in 1 second; FF/UMEC/VI, fluticasone furoate/umeclidinium/vilanterol; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICD-10, International statistical Classification of Diseases and related health problems, 10th revision; ICD-10-GM, International statistical Classification of Diseases and related health problems, 10th revision, German Modification; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MITT, multiple-inhaler triple therapy; PDE-4, phosphodiesterase type 4; SABA, short-acting β₂-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation; SITT, single-inhaler triple therapy.

Data Sharing Statement

The data analyzed in this study are derived from the AOK PLUS German sickness fund database. Authors had access to the study data for the purpose of this work only. Therefore, the data cannot be broadly disclosed or made publicly available at this time. Access to the database can be requested via individual application. The interpretation and conclusions contained in this study are those of the authors alone.

Ethics Approval and Informed Consent

For retrospective analysis of anonymized data there is no requirement for ethical approval and consent to participate according to the German Guidelines for Secondary Data Analysis.

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 Apollo, OPEN Health Communications, and funded by GSK.

A summary of the results of this study was presented as a poster at the 62nd Congress of the German Society for Pneumology and Respiratory Medicine (Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin [DGP]), Leipzig, Germany, 25–28 May 2022. The abstract on the poster was published in Pneumologie 2022;76(Suppl 01):S50 (doi:10.1055/s-0042-1747801).

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

Kai-Michael Beeh is a full-time employee of Insaf Respiratory Research Institute. He has received personal or institutional compensation for services on advisory boards or consulting for AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Chiesi, Elpen, GSK, Mundipharma, Novartis, Pohl Boskamp, Sanofi, sterna, and Zentiva, and compensation for speaker activities in scientific meetings supported by AstraZeneca, Berlin Chemie, Boehringer Ingelheim, ERT, GSK, Novartis, Pfizer, Pohl Boskamp, Sanofi, and Teva, all outside the submitted work. The institution has received compensation for design and performance of clinical trials from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Parexel, Pearl Therapeutics, sterna, and Zentiva. Kieran J Rothnie, Jing Claussen, Chris Compton, and Afisi S Ismaila are employees of and/or hold stocks/shares in GSK. Afisi S Ismaila is also an unpaid part-time member of the McMaster University faculty. Alexandrosz Czira was an employee of GSK at the time of the study and now works for Gedeon Richter PLC. Fränce Hardtstock and Rachel K Knapp participated in this study as employees of Cytel/Ingress-Health. Cytel/Ingress-Health received funding from GSK to conduct the study. Thomas Wilke reports grants from GSK and Cytel/Ingress-Health during the conduct of the study and grants from Apontis, Janssen, and Pfizer outside the submitted work. Thomas Wilke received honoraria and other financial support from Cytel Inc., which does studies with all major pharmaceutical companies. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by GSK (study number 214666). GSK-affiliated authors were involved in study conception and design, data analysis, data interpretation, and the decision to submit the article for publication. GSK funded the article processing charges and Open Access fee.