Mixed treatment analysis comparing tiotropium HandiHaler ® and Respimat ®

Background: Tiotropium is available in the once-daily formulations HandiHaler ® 18 µg (HH) and Respimat ® 5 µg (R5) for the treatment of chronic obstructive pulmonary disease (COPD). Both formulations have been compared to placebo (PBO) in Phase III trials and directly compared in a recent Phase IIIb trial (TIOSPIR™). Methods: This post-hoc analysis of HH vs R5 identified all trials with vital status follow up (analyzed for death) and those with a duration ≥1 year (analyzed for exacerbations). A frequentist mixed treatment comparison (MTC) was used to collate direct and indirect evidence for HH, R5 and PBO. Results: In the six trials that were analyzed for deaths, 8680 patients were treated with HH, 8760 with R5 and 6053 with PBO. Five trials were included in the exacerbations analysis: 8673 patients were treated with HH, 8314 with R5 and 5612 with PBO. Using a random-effects model of MTC for HH vs R5, odds ratios (ORs) were 1.01 (95% confidence interval CI: 0.89-1.15) for deaths and 0.90 (95% CI: 0.81-1.01) for exacerbations; fixed-effects model measures were similar with a smaller CI for exacerbations: deaths, 1.01 (95% CI: 0.89-1.15); exacerbations, 0.92 (95% CI: 0.86-0.98). ORs versus PBO (random-effects model) for deaths were 0.91 (95% CI: 0.80-1.04) for HH and 0.92 (95% CI: 0.77-1.10) for R5; for exacerbations 0.87 (95% CI: 0.78-0.98) for HH and 0.79 (95% CI: 0.70-0.88) for R5. Conclusions: When compared, HH and R5 showed similar effects on survival and exacerbations in this meta-analysis. Prolongation of survival was not statistically significant vs PBO, while risk of exacerbation was lower for both formulations with a numerically higher efficacy for R5. Funded by Boehringer Ingelheim.