Once-Daily Tiotropium Reduces Risk of Exacerbations and Asthma Worsening in Patients With Symptomatic Asthma Despite Treatment With Inhaled Corticosteroids and Long-Acting β 2 -Agonists

Abstract

PURPOSE: To evaluate the effect of once-daily tiotropium (5 mu g [morning] via Respimat Soft MistTM Inhaler) on asthma exacerbations in patients with symptomatic asthma despite receiving ICS+LABA. METHODS: Two replicate, double-blind, placebo-controlled studies (NCT00772538; NCT00776984). Eligible patients had: >5-year history of asthma diagnosed before aged 40 years; Asthma Control Questionnaire 7 score >1.5; experienced >1 exacerbation during previous year. Patients were either life-long non-smokers or ex-smokers (<10 pack-years) who quit smoking >1 year before study enrollment. Co-primary endpoint was time to first severe exacerbation from combined study data after 48 weeks (asthma deterioration necessitating initiation or doubling of systemic glucocorticosteroids for >3 days). Secondary endpoints included time to first episode of asthma worsening (either progressive increase in symptoms or decline of >30% in best morning peak expiratory flow for >2 consecutive days). Subgroup analysis of these endpoints was performed on a range of baseline characteristics. RESULTS: 912 patients were randomized to receive either tiotropium (n=456) or placebo (n=456) for 48 weeks. Time to first severe exacerbation was 56 days longer with tiotropium versus placebo, corresponding to a 21% risk reduction (hazard ratio [HR] 0.79; p=0.03). A lower proportion of tiotropium patients (26.9%) experienced >1 severe exacerbation versus placebo (32.8%). From post hoc calculation, 15 patients were needed to treat to prevent one severe exacerbation during the treatment period. Fewer tiotropium patients (3.5%) were hospitalized due to asthma versus placebo (4.4%). Tiotropium also reduced risk of first asthma worsening (31%; HR 0.69; p<0.001). Improvement in time to first severe asthma exacerbation and first asthma worsening did not differ across subgroups subdivided by hospitalizations within past year, percentage predicted FEV 1, age class, sex, allergic status, or disease duration. CONCLUSIONS: Once-daily tiotropium as add-on to ICS+LABA reduced the risk of severe asthma exacerbation and asthma worsening compared with placebo. Findings were consistent across various subgroups.