Real-World Effectiveness of Fluticasone Furoate/Umeclidinium/Vilanterol Once-Daily Single-Inhaler Triple Therapy for Symptomatic COPD: The ELLITHE Non-Interventional Trial

Abstract

Purpose

Real-life effectiveness data on once-daily single-inhaler triple therapy (odSITT) with the inhaled corticosteroid fluticasone furoate (FF), the long-acting muscarinic antagonist umeclidinium (UMEC), and the long-acting β₂-agonist vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) are important to complement evidence from well-controlled randomized clinical trials. Effectiveness of odSITT was quantified by assessing health status and symptoms in usual care.

Patients and Methods

ELLITHE was a single-country (Germany), multicenter, open-label, non-interventional effectiveness study between 2020 and 2022, evaluating the effect of treatment initiation with FF/UMEC/VI 100/62.5/25 µg once-daily via the ELLIPTA inhaler on improvements in clinical outcomes versus baseline in COPD patients. The primary endpoint was the change in the total COPD Assessment Test (CAT) score between baseline and month 12. Key secondary endpoints included change in CAT score over time, occurrence of exacerbations until month 12, changes in forced expiratory volume in one second (FEV₁), inhaler adherence, and safety.

Results

Nine hundred and six patients were included (age 66.6 years, 55.6% male, mean FEV₁ 52.6% of predicted, mean CAT 21.5 units, 1.4 exacerbations/year pre-study). About 63.9% of patients were escalated from dual therapies, and 18% were switched from multiple-inhaler triple therapies. Reductions in CAT score at month 12 were statistically significant and above the threshold of clinical importance (−2.6 units; p < 0.0001). CAT score also improved at interim visits. CAT improvements were more pronounced in patients with high baseline scores and better inhaler adherence. Exacerbations during follow-up were rare (0.2 events/year) compared to pre-study (1.4 events/year). FEV₁ was improved by 93 mL (p < 0.0001). No new safety effects were observed.

Conclusion

In usual care, treatment with odSITT resulted in significant and clinically relevant improvements of CAT score and FEV₁ in COPD patients, regardless of the occurrence of exacerbations. These findings challenge the current guideline recommendations for SITT only in patients experiencing exacerbations.

Keywords:

• CAT score
• real-world evidence
• lung function
• exacerbation
• treatment adherence

Abbreviations

ADR, adverse drug reaction; AE, adverse event; CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; FF, fluticasone furoate; FEV₁, forced expiratory volume in one second; GOLD, The Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MITT, multiple-inhaler triple therapy; mMRC, modified medical research council dyspnea scale; odSITT, once-daily single-inhaler triple therapy; SAE, serious adverse event; SD, standard deviation; TAI, test of the adherence to inhalers; UMEC, umeclidinium; VI, vilanterol.

Data Sharing Statement

Study synopsis and protocol are available at the BfArM-study registry DRKS. The data analyzed in this study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

The study was carried out in accordance with Good Clinical Practice guidelines under the provisions of the latest version of the Declaration of Helsinki (2013) and received approval from the State Chamber of Physicians of Hesse as the ethics committee of the national chief investigator. The study was registered at the German Clinical Trials Register (DRKS00031897).

Acknowledgments

The authors would like to thank Dr. Robert Brinkmann (Medical Department, BERLIN-CHEMIE AG, Berlin, Germany) for support in conducting the study and preparation of manuscript.

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. All authors engaged in drafting, revising or critically reviewing the article. They gave final approval of the version to be published and all versions before submission. All authors 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 has received personal and/or institutional compensation for clinical research, consulting, lecturing fees from AstraZeneca, Boehringer Ingelheim, Bosch AG, GSK, Novartis, Menarini/Berlin Chemie and Chiesi; consulting and lecturing fees from Sanofi and Elpen; and consulting fees from Sterna. The authors report no other conflicts of interest in this work.

Additional information

Funding

The ELLITHE study was funded by BERLIN-CHEMIE AG, Berlin, Germany.