title: Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial.
abstract: OBJECTIVE
  This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥ 2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 g (R5).
  
  
  METHODS
  TIOSPIR (n=17,135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial.
  
  
  METHODS
  Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤ 0.70, receiving HH18 before study entry, were analysed (n=2784).
  
  
  METHODS
  Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2-3 years.
  
  
  METHODS
  
  
  
  METHODS
  time to death (safety) and time to first COPD exacerbation (efficacy).
  
  
  RESULTS
  number of exacerbations and time to first major adverse cardiovascular event (MACE).
  
  
  RESULTS
  Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89).
  
  
  CONCLUSIONS
  This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch.
  
  
  BACKGROUND
  NCT01126437; Post-results.
authors.affiliation: Allergy Centre, Odense University Hospital, Odense C, Denmark.
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.affiliation: Clinical Science Centre (Aintree Campus), Institute of Ageing and Chronic Disease, University Hospital Aintree, Liverpool, UK.
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Pulmonary/Critical Care Department, University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.affiliation: TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Metzdorf
authors.affiliation: Clinical Research, Boehringer Ingelheim Pharma Ltd, Bracknell, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Fowler
authors.affiliation: Biometrics and Data Management, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riss, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Mueller
authors.affiliation: Johns Hopkins Asthma & Allergy Center, Baltimore, Maryland, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wise
authors.affiliation: Department of Pneumology, Hôpital Cochin, AP-HP, Université Paris Descartes, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dusser
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004311:Double-Blind Method; D004867:Equipment Design; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality*; D012307:Risk Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D000069447:Tiotropium Bromide
keywords: COPD; Efficacy; HandiHaler®; Respimat®; Switching; Tiotropium