Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial

OBJECTIVES 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). SETTING TIOSPIR (n=17,135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial. PARTICIPANTS 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). INTERVENTIONS Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2-3 years. PRIMARY AND SECONDARY OUTCOME MEASURES PRIMARY OUTCOMES time to death (safety) and time to first COPD exacerbation (efficacy). SECONDARY OUTCOMES 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. TRIAL REGISTRATION NUMBER NCT01126437; Post-results.