Background Four trials explored whether tiotropium Respimat® add-on to at least ICS is effective in the TH2 phenotype, determined by high serum immunoglobulin E (IgE) and blood eosinophil values, in reducing risk of severe asthma exacerbation and asthma worsening in adult patients with moderate or severe symptomatic asthma.
Methods Four Phase III, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-asthma® (two 48-week trials; NCT00776984/NCT00772538; n = 912): tiotropium Respimat® 5 µg or placebo Respimat® add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-asthma® (two 24-week trials; NCT01172808/NCT01172821; n = 2100): tiotropium Respimat® 5 µg, tiotropium Respimat® 2.5 µg or placebo add-on to ICS (400–800 µg budesonide or equivalent). Patients had symptomatic asthma requiring treatment with at least ICS for ≥4 weeks before screening; COPD was excluded. Subgroups of allergic and inflammatory status (IgE and eosinophils) were used to analyse risk of severe exacerbation and asthma worsening, post hoc. Cox regression modelling analyses, adjusted for treatment, IgE or eosinophils and treatment by IgE or eosinophil interaction, were applied to calculate hazard ratios and 95% confidence intervals across IgE (2–2000 μg/L) and eosinophil (0.05–7.00 × 109/L) values.
Results Severe exacerbation: in PrimoTinA-asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat® up to an IgE level of ~1000 µg/L, and consistently across all eosinophil values. In MezzoTinA-asthma®, tiotropium Respimat® 5 µg and 2.5 µg reduced risk versus placebo consistently across all IgE and eosinophil levels. Asthma worsening: in PrimoTinA-asthma®, tiotropium Respimat® 5 µg reduced risk in terms of hazard ratio versus placebo Respimat®, independent of IgE and eosinophils. In MezzoTinA-asthma®, tiotropium Respimat® 5 µg reduced risk versus placebo across all IgE and eosinophil values. Tiotropium Respimat® 2.5 µg reduced risk versus placebo across all IgE values and at eosinophil values <3.00×109/L.
Conclusion Tiotropium Respimat® add-on to ICS ± LABA reduces risk of severe exacerbation and asthma worsening in patients across severities of symptomatic asthma and a broad range of IgE and eosinophil values, suggesting efficacy independent of underlying allergic/eosinophilic inflammation. Once-daily tiotropium Respimat® may have potential as add-on to at least ICS maintenance therapy in patients with symptomatic asthma, independent of TH2 phenotype.