title: 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 (AUC0-3) response, and trough FEV1response.
  
  
  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. FEV1AUC0-3and trough FEV1responses 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
authors.affiliation: North Shore Medical Arts LLP, Great Neck, NY.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Karpel
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Clerisme-Beaty
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein.
authors.forename: Lars
authors.initials: L
authors.lastname: Grönke
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein.
authors.forename: Florian
authors.initials: F
authors.lastname: Voß
authors.affiliation: Pulmonary Department, Mainz University Hospital, Mainz, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004338:Drug Combinations; D005541:Forced Expiratory Volume; D006304:Health Status; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D012720:Severity of Illness Index; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations; C000611386:tiotropium-olodaterol; D000069447:Tiotropium Bromide
keywords: FEV1; SGRQ; TDI; lung function; rescue medication