title: Efficacy of Tiotropium + Olodaterol in Patients with Chronic Obstructive Pulmonary Disease by Initial Disease Severity and Treatment Intensity: A Post Hoc Analysis.
abstract: BACKGROUND
  The once-daily long-acting muscarinic antagonist (LAMA) tiotropium and once-daily long-acting β2-agonist (LABA) olodaterol have been studied as a once-daily fixed-dose combination (FDC) in patients with chronic obstructive pulmonary disease (COPD). Two large, 52-week, double-blind, parallel-group studies in patients with moderate-very severe COPD demonstrated that tiotropium + olodaterol significantly improved lung function and symptoms versus the monocomponents. This post hoc analysis determined effects on lung function by prior LAMA or LABA maintenance treatment and initial disease severity.
  
  
  METHODS
  5162 patients were randomized and treated with olodaterol 5 µg, tiotropium 2.5 µg, tiotropium 5 µg, tiotropium + olodaterol 2.5/5 µg, or tiotropium + olodaterol 5/5 µg (all once daily via Respimat(®) inhaler). Primary efficacy (lung-function) end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) and trough FEV1 responses (i.e., change from baseline). Pooled data are presented for the following subgroups: prior maintenance treatment with LAMA or LABA, Global initiative for chronic Obstructive Lung Disease (GOLD) 2 (predicted FEV1 50% to <80%) and 3 (30% to <50%)/4 (<30%), sex, age, and prior use of inhaled corticosteroids.
  
  
  RESULTS
  Tiotropium + olodaterol FDC improved lung function over the monocomponents in patients with GOLD 2 and 3-4 disease, irrespective of prior LAMA or LABA maintenance therapy; most comparisons between FDCs and their respective monocomponents were statistically significant (P < 0.05). FEV1 AUC0-3 and trough FEV1 responses for the individual treatments were generally greater in patients with less severe COPD at baseline.
  
  
  CONCLUSIONS
  Tiotropium + olodaterol 5/5 µg significantly improved FEV1 AUC0-3 and trough FEV1 in all GOLD severity groups compared to olodaterol 5 µg and tiotropium 5 µg alone, irrespective of whether patients had received prior LAMA or LABA maintenance treatment. Improvements from baseline in lung function were generally greater in patients with less severe disease.
  
  
  BACKGROUND
  Boehringer Ingelheim.
  
  
  BACKGROUND
  ClinicalTrials.gov numbers, NCT01431274 and NCT01431287.
authors.affiliation: Pulmonary Research Institute of Southeast Michigan, Livonia, MI, USA, garytferguson@msn.com.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
authors.forename: Matjaž
authors.initials: M
authors.lastname: Fležar
authors.forename: Stephanie
authors.initials: S
authors.lastname: Korn
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korducki
authors.forename: Lars
authors.initials: L
authors.lastname: Grönke
authors.forename: Roger
authors.initials: R
authors.lastname: Abrahams
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000368:Aged; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012720:Severity of Illness Index; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000318:Adrenergic beta-Agonists; D048588:Benzoxazines; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; C549647:olodaterol; D000069447:Tiotropium Bromide