Once-Daily Tiotropium Respimat® Add-on to at Least Ics Maintenance Therapy Demonstrates Improved Lung Function in Patients with Symptomatic Asthma, Independent of Serum IgE or Blood Eosinophil Levels

Tashkin, Donald

Rationale: In adults with moderate or severe symptomatic asthma, once-daily tiotropium Respimat^® add-on to at least ICS maintenance therapy has demonstrated lung-function improvements in conventional subgroup analyses, independent of serum IgE ≤ or >430μg/L (equivalent to 179.2 IU/L) and blood eosinophils ≤ or >0.6×10⁹/L (equivalent to 600/μL). We investigated whether these improvements in lung function were also observed in modeling estimates across a continuous range of IgE and eosinophil values following tiotropium Respimat^® 5µg add-on therapy.

Methods: Four Phase III double-blind, placebo-controlled, parallel-group trials: PrimoTinA-asthma^® (2× 48-week trials; NCT00776984/NCT00772538; n=912) tiotropium Respimat^® 5µg or placebo Respimat^® add-on to ICS (≥800μg budesonide or equivalent) + LABA; MezzoTinA-asthma^® (2× 24-week trials; NCT01172808/NCT01172821; n=2100) tiotropium Respimat^® 5µg or 2.5µg or placebo add-on to ICS (400-800μg budesonide or equivalent). Patients had symptomatic asthma requiring treatment with at least ICS for ≥4 weeks before screening; COPD was excluded. Post hoc mixed model with repeated measures modeling analyses of peak and trough FEV₁ were performed across continuous ranges of IgE 0-2000μg/L and eosinophils 0-2.00×10⁹/L following treatment with tiotropium Respimat^®5µg.

Results: Tiotropium Respimat^® 5µg consistently improved peak and trough FEV₁, compared with placebo, across all IgE and eosinophil ranges in all trials (mean difference >0).

Conclusions: Once-daily tiotropium Respimat^® add-on to at least ICS improved lung function in patients with moderate or severe symptomatic asthma, independent of serum IgE or blood eosinophil levels. These results support the lung-function improvements previously reported from subgroup analyses using binary cut-offs of serum IgE ≤ and >430μg/L and blood eosinophils ≤ and >0.6×10⁹/L.