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; TDI; lung function; rescue medication.

Figure 1

OTEMTO^® (1237.5 [NCT01431274] + 1237.6 [NCT01431287]) and TONADO^® (1237.25 [NCT01964352] + 1237.26 [NCT02006732]) study designs. Note: ^aPrimary end point assessment. Abbreviations: O, olodaterol; R, randomization; T, tiotropium.

Figure 2

FEV₁ AUC_0–3 response (A) and trough FEV₁ response (B) by age group after 12 weeks (OTEMTO^®) and 24 weeks (TONADO^®). Abbreviations: AUC_0–3, area under the curve from 0 hour to 3 hours; FEV₁, forced expiratory volume in 1 second; O, olodaterol; SE, standard error; T, tiotropium.

Figure 3

Impact of treatment on FEV₁ AUC_0–3 response (A) and trough FEV₁ response (B) by age group after 12 weeks (OTEMTO^®) and 24 weeks (TONADO^®). Abbreviations: AUC_0–3, area under the curve from 0 hour to 3 hours; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; O, olodaterol; T, tiotropium.