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

Abstract

ObjectivesThis 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 µg (R5).SettingTIOSPIR (n=17 135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial.ParticipantsPatients 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).InterventionsPatients 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 measuresPrimary 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).ResultsBaseline 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).ConclusionsThis 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 numberNCT01126437; Post-results.

A review of nebulized drug delivery in COPD

“…Tiotropium bromide SMI provides a solution form of tiotropium bromide 55 that is efficacious at lower doses compared with the tiotropium bromide HandiHaler ® (Boehringer Ingelheim). 56 In patients with COPD, tiotropium SMI improved lung function, health-related quality of life, and dyspnea, reduced acute exacerbations of COPD, and was as effective and safe as the tiotropium HandiHaler 57 , 58 Tiotropium is generally well tolerated in patients with COPD, but antimuscarinic side effects (eg, dry mouth) are among the most commonly reported adverse events. 59 …”

A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?

“…An analysis of patients treated with tiotropium HandiHaler® 18 μg at TIOSPIR® baseline, and who were randomized and subsequently received tiotropium Respimat® 5 μg during the study, showed that they had similar risks for all-cause mortality (HR 0.79; 95% CI 0.58–1.07), fatal MACE (HR 0.67; 95% CI 0.33–1.34), MACE (HR 0.69; 95% 0.44–1.08) and exacerbations (HR 0.96; 95% CI 0.86−1.08) as patients who continued to be treated with tiotropium HandiHaler® 18 μg [ 27 , 29 ].…”

“…For physicians who may be considering whether patients are suitable candidates to switch from tiotropium HandiHaler® to tiotropium Respimat®, TIOSPIR® data show that in patients who switched from tiotropium HandiHaler® to tiotropium Respimat®, mortality, cardiac safety and exacerbation outcomes were similar to those who remained on tiotropium HandiHaler® [ 27 , 29 ]. From the patient’s perspective, studies have suggested that they find it easy to switch from tiotropium HandiHaler® to tiotropium Respimat®, and have reported high levels of preference for, and adherence to, tiotropium Respimat® [ 61 – 65 ].…”

Effectiveness and safety of concurrent beta-blockers and inhaled bronchodilators in COPD with cardiovascular comorbidities

“…The TIOSPIR study (TIOtropium Safety and Performance In Respimat) also showed that different formulations of tiotropium (Respimat at a dose of 2.5 or 5 μg and HandiHaler at 18 μg; both from Boehringer Ingelheim GmbH) had a similar risk of death [30]. Furthermore, the risk of exacerbation and major adverse cardiovascular events did not differ significantly among the three treatment groups [30], or upon switching patients from tiotropium HandiHaler to tiotropium Respimat [31].…”