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

Gary T Ferguson,¹ Jill P Karpel,² Emmanuelle Clerisme-Beaty,³ Lars Grönke,⁴ Florian Voß,⁴ Roland Buhl<sup>5

1</sup>Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, ²North Shore Medical Arts LLP, Great Neck, NY, ³Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; ⁴Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, ⁵Pulmonary Department, Mainz University Hospital, Mainz, Germany

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