Tiotropium May Increase Time to Severe Exacerbation in Patients with Poorly Controlled Asthma

DynaMed Weekly Update - Volume 7, Issue 36

Many patients with asthma have poorly controlled disease despite combined use of inhaled glucocorticoids and long-acting beta-2 agonists (LABAs), and for these patients, few treatment options exist. Anticholinergic agents, such as tiotropium, have been widely used for bronchodilation in COPD, but have been less commonly used for asthma. A recent report of 2 identical randomized trials evaluated the efficacy of tiotropium for controlling exacerbations in patients with poorly controlled asthma.

A total of 912 patients (mean age 53 years) who were taking inhaled glucocorticoids and LABAs were randomized to inhaled tiotropium 5 mcg (in 2 puffs) vs. placebo by Respimat Soft Mist inhaler once daily for 48 weeks. All patients had an Asthma Control Questionnaire score ≥ 1.5 (on 7 point scale) and had at least 1 exacerbation treated with systemic glucocorticoids within the last year. The primary outcome was time to severe asthma exacerbation defined as either the initiation of systemic glucocorticoids for ≥ 3 days or a doubling of systemic glucocorticoid dose for ≥ 3 days in patients with ongoing or preexisting systemic treatment.

Data from the 2 trials were pooled for analysis. Median time to severe exacerbation was not reached in either the tiotropium or placebo groups. The time until 25% of the group had a severe exacerbation was 282 days with tiotropium vs. 226 days with placebo (hazard ratio 0.79, 95% CI 0.62-1) (level 2 [mid-level] evidence). The tiotropium group had 0.53 severe exacerbations per patient year, compared to 0.66 with placebo (p = 0.046). Tiotropium was associated with significant improvements in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) in both trials. There were no significant differences in hospitalizations for asthma or adverse events, and no deaths occurred in either group (N Engl J Med 2012 Sep 2 early online). It should be noted that tiotropium delivered via Respimat Soft Mist inhaler has previously been associated with increased risk of all-cause and cardiovascular mortality in patients with COPD (BMJ 2011 Jun 14;342:d3215). This inhaler is currently available in 55 countries, but not in the United States.

For more information, see the Tiotropium topic in DynaMed.