The lung function profile of once-daily tiotropium and olodaterol via Respimat^® is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler^® (ENERGITO^® study)

Abstract

Background

Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting β₂-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.

Objective

The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.

Methods

This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat^® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler^® for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV₁) area under the curve from 0 hour to 12 hours (AUC_0–12) relative to the baseline after 6 weeks.

Results

Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV₁ AUC_0–12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV₁ area under the curve from 0 hour to 24 hours (AUC_0–24).

Conclusion

Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.

Keywords:

• COPD
• maintenance treatment
• lung function
• tiotropium
• FEV₁
• inhaled corticosteroid

Supplementary materials

Table S1 Additional exclusion criteria

Table S2 Adjusted mean FVC AUC_0–12, AUC_0–24, and AUC_12–24 responses after 6 weeks of treatment: treatment differences (full analysis set)

Table S3 Adjusted mean FVC AUC_0–3, trough FVC, and peak_0–3 FVC responses after 6 weeks of treatment: treatment differences (full analysis set)

Acknowledgments

This work was supported by Boehringer Ingelheim Pharma GmbH & Co. KG. The authors received no compensation related to the development of the manuscript. This work was supported by Boehringer Ingelheim Pharma GmbH & Co. KG. Medical writing assistance was provided by Tanja Torbica and Claire Scofield, on behalf of Complete Health-Vizion, and was contracted and compensated by Boehringer Ingelheim Pharma GmbH & Co. KG.

Disclosure

The institution where KMB is employed has received compensation for organizing or participating in advisory boards for Almirall Hermal, Cytos, Chiesi, Boehringer Ingelheim, AstraZeneca, Mundipharma, Novartis, and Revotar Biopharmaceuticals, and for participation in scientific meetings or courses supported by various pharmaceutical companies (Almirall Hermal, AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, and Takeda) in the past 3 years. KMB’s institution has also received consulting fees from Ablynx, Apellis Pharmaceuticals, Chiesi, and Cytos. The institution has received compensation for the design, performance or participation in single or multi-center clinical trials in the past 3 years from several companies including Almirall, Boehringer Ingelheim, Cytos, GSK, Mundipharma, Novartis, Pfizer, Revotar Biopharmaceuticals, Sterna AG, and TEVA. ED reports consultancy fees from Actelion, Boehringer, AstraZeneca, and Cipla, advisory board fees for Chiesi, AstraZeneca, and CSL Behring, and speaker fees for Glaxo-SmithKline and Boehringer. LG and AH are employees of Boehringer Ingelheim. JES, DZ, and LB report no conflicts of interest in this work.

Author Contributions

The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. They take full responsibility for the scope, direction, content of, and editorial decisions relating to, the manuscript, and were involved at all stages of development. All authors contributed toward data analysis, drafting and critically revising the paper, and they have approved the submitted manuscript and agree to be accountable for all aspects of the work.