Tiotropium is Efficacious in 6 to 17 Year-Olds With Asthma, Independent of T2 Phenotype

Exploratory analysis to determine whether treatment with tiotropium added to inhaled corticosteroids (ICS) is effective in children and adolescents regardless of T2 status and phenotype.

Approximately 1500 children with symptomatic moderate or severe asthma ages 6–17 years who had participated in 4 Phase III randomized, double-blind, placebo controlled parallel group trials. Only a minority of patients with moderate asthma were on long-acting bronchodilator (LABA), but the majority of those with severe asthma were using LABAs.

Data were pooled by asthma severity, namely symptomatic moderate persistent and symptomatic severe asthma. Tiotropium 5mcg, 2.5mcg or placebo was added onto ICS, with or without other maintenance therapy. T2 asthma status was determined by total serum IgE and blood eosinophil counts. Primary endpoint was peak FEV1 within 3 hours post-dose measured as change from baseline at week 24 for those with moderate asthma and 12 weeks for those with severe asthma. Secondary endpoints included trough FEV1 responses at 24 or 12 weeks, FEF25-75, Asthma Control Questionnaire (ACQ) responder rate (≥0.5 decrease in total score) and time to first exacerbation.

Total IgE levels were higher in adolescents compared with children and were higher in children with severe asthma compared with moderate asthma. Median eosinophil levels were similar in the different age groups. Lung function improved with both doses of tiotropium compared with placebo, except for the trough response with the 2.5 mcg dose in severe asthmatics. ACQ responder rates improved with both doses but did not reach statistical significance in patients with moderate asthma at the lower doses. Time to first exacerbation improved with both doses, but was only significant in severe asthma with both doses. There were no significant differences in response with respect to total IgE or eosinophil counts.

Improvements in lung function, exacerbation risk and asthma control seen with tiotropium add-on therapy for children and adolescents with symptomatic moderate or severe asthma is independent of systemic markers of T2 inflammation.

The takeaway from this analysis is that tiotropium can be used in children and adolescents with poorly controlled moderate or severe asthma regardless of phenotype, obviating the need for additional evaluations.