Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO^® and OTEMTO^® studies: a subgroup analysis by age

Abstract

Background

Increasing age is associated with poor prognosis in patients with COPD.

Objective

This analysis from the replicate Phase III OTEMTO^® and TONADO^® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β₂-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years.

Methods

In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO only). This analysis used the approved doses of tiotropium + olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George’s Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV₁) area under the curve from 0 hour to 3 hours (AUC_0–3) response, and trough FEV₁ response.

Results

A total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ≥85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ≥85 years, n=13) in TONADO. FEV₁ AUC_0–3 and trough FEV₁ responses improved with tiotropium + olodaterol 5/5 μg at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups. SGRQ scores generally improved with tiotropium + olodaterol 5/5 μg after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO. In all age groups receiving tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved.

Conclusion

No differences were noted in relative responses to treatment or safety when using tiotropium + olodaterol 5/5 μg compared to monotherapies or placebo across all age groups.

Keywords:

• FEV₁
• SGRQ
• lung function
• TDI
• rescue medication

Acknowledgments

The reported studies were supported by Boehringer Ingelheim Pharma GmbH & Co. KG. The authors received no compensation related to the development of the manuscript. Medical writing assistance was provided by Laura Badtke, PhD, on behalf of Complete HealthVizion, which was contracted and compensated by Boehringer Ingelheim Pharmaceuticals, Inc.

Author contributions

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

Disclosure

GTF has received consulting and advisory board fees from Boehringer Ingelheim, AstraZeneca, Pearl Therapeutics, Novartis, Forest, Sunovion, and Verona, consulting fees from Receptos, speaker fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Pearl Therapeutics, Forest, and Sunovion, and is in receipt of research grants from Boehringer Ingelheim, AstraZeneca, Pearl Therapeutics, Sunovion, Novartis, Theravance, Sanofi, Forest, and GlaxoSmithKline. JPK discloses no conflicts of interest. ECB, LG, and FV are employees of Boehringer Ingelheim. RB reports grants from Boehringer Ingelheim, GlaxoSmithKline, Roche, and the German Research Foundation. RB also reports consulting, Speaker Bureau, and advisory committee fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Grifols, Novartis, Roche, and Takeda. The authors report no other conflicts of interest in this work.