Tiotropium Respimat® Add-on to at Least Ics Therapy Demonstrates Reduced Risk of Severe Asthma Exacerbation and Asthma Worsening in Symptomatic Asthma, Independent of IgE or Blood Eosinophil Levels

Abstract

Once-daily tiotropium Respimat® add-on therapy has been shown, in conventional subgroup analyses, to reduce the risk of severe exacerbation and asthma worsening in patients with symptomatic asthma, independent of TH2 phenotypes (low and high) defined as total IgE ≤ or >430 μg/L and blood eosinophils ≤ or >0.6×109/L. We further investigated treatment effects by modeling estimates of risk reduction across the whole continuous range of IgE and eosinophil values following tiotropium Respimat® add-on therapy. Four Phase III double-blind, placebo-controlled, parallel-group trials: PrimoTinA-asthma® (2× 48-week trials; NCT00776984/NCT00772538; n=912) tiotropium Respimat® 5 μg or placebo Respimat® add-on to ICS (≥800 μg budesonide or equivalent) + LABA; MezzoTinA-asthma® (2× 24-week trials; NCT01172808/NCT01172821; n=2100) tiotropium Respimat® 5 μg or 2.5 μg or placebo Respimat® add-on to ICS (400-800 μg budesonide or equivalent). Patients had symptomatic asthma, with at least ICS treatment for ≥4 weeks before screening; COPD was excluded. Post hoc Cox regression modeling was performed to investigate hazard ratios versus placebo Respimat® across continuous ranges of IgE 2-2000 μg/L and eosinophils 0.05-2.00×109/L. Overall, tiotropium Respimat® 5 μg and 2.5 μg reduced the risk of severe exacerbation and asthma worsening at all levels of IgE and eosinophils compared with placebo Respimat® (hazard ratio <1). Once-daily tiotropium Respimat® add-on to at least ICS maintenance therapy reduces the risk of severe exacerbation and asthma worsening in patients with moderate or severe symptomatic asthma, independent of IgE or blood eosinophil levels. These results support the use of tiotropium Respimat® in both TH2-high and TH2-low patients.