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

Int J Chron Obstruct Pulmon Dis. 2016 Oct 31:11:2701-2710. doi: 10.2147/COPD.S108758. eCollection 2016.

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 (AUC0-3) 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 AUC0-3 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.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Benzoxazines / adverse effects
  • Benzoxazines / therapeutic use*
  • Bronchodilator Agents / adverse effects
  • Bronchodilator Agents / therapeutic use*
  • Cholinergic Antagonists / adverse effects
  • Cholinergic Antagonists / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Drug Combinations
  • Forced Expiratory Volume
  • Health Status
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Randomized Controlled Trials as Topic
  • Recovery of Function
  • Severity of Illness Index
  • Time Factors
  • Tiotropium Bromide / adverse effects
  • Tiotropium Bromide / therapeutic use*
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Benzoxazines
  • Bronchodilator Agents
  • Cholinergic Antagonists
  • Drug Combinations
  • tiotropium-olodaterol
  • Tiotropium Bromide