The Centers for Disease Control and Prevention reports that in 2009, there were 2.1 million emergency room visits with asthma as the primary diagnosis.1 The National Asthma Education and Prevention Program, Expert Panel Report 3 Guidelines for the Diagnosis and Management of Asthma recommends a stepwise approach to treating asthma, which suggests that all chronic asthma patients start with an inhaled corticosteroid with add-on treatment as needed to achieve control. Current add-on therapies include inhaled long-acting beta-2 adrenergic agonists, oral leukotriene modifiers, systemic corticosteroids, mast cell stabilizers, and methylxanthines.2 For the many asthma patients who do not present with adequate response to the guideline recommended treatments, novel treatment modalities such as inhaled anticholinergic medications are attractive options for both patients and practitioners.
Inhaled anticholinergic medications (IACs) have been available for the treatment of chronic obstructive pulmonary disease (COPD) for many years. Tiotropium, an IAC, is a plausible alternative for patients with asthma that is uncontrolled with conventional therapies, though there is no formal recommendation regarding its use. The study by Kerstjens and colleagues examined the benefit of inhaled tiotropium in two randomized, placebo controlled replicate trials. They treated patients with characteristics including a score on the Asthma Control Questionnaire 7 (ACQ-7) of 1.5 or higher, post-bronchodilator forced expiratory volume in one second (FEV1) of 80% or less of predicted, and less than or equal to 70% of forced vital capacity (FVC) 30 minutes post inhalation of albuterol. Patients included were already treated with a daily inhaled corticosteroid (ICS) plus a long acting beta-2 adrenergic agonist (LABA) and had at least one severe exacerbation treated with oral or parenteral corticosteroids in the previous year. They excluded patients who had a past history of COPD, were current smokers or who had a 10 pack year or more history of smoking or had concurrent IAC use. In each replicate trial, patients were randomized to receive either 5 micrograms of tiotropium inhaled via a Respimat® Soft Mist™ Inhaler or placebo. Participants were allowed to continue using their individualized asthma regimen. Primary endpoints included peak FEV1 after 24 weeks compared to baseline, trough FEV1 after 24 weeks compared to baseline, and time to first severe asthma exacerbation.3
Results included 912 patients across the two replicate trials with a mean age of 53 years and median duration of asthma of 28 years (5-72 years); patient characteristics were similar between the trials. The mean baseline FEV1 was 62%. Tiotropium therapy improved the peak FEV1 compared to the placebo group at week 24 with mean differences of 86±34mL (p=0.01) in trial 1 and 154±32mL (p<0.001) in trial 2 compared to placebo. The trough FEV1 improvement between the treatment and placebo group was 88±31mL (p=0.01) in trial 1 and 111±30mL (p≤0.001) in trial 2. At least one severe exacerbation occurred in 26.9% of the tiotropium group and 32.8% of placebo. The time to the first severe asthma exacerbation was 56 days longer in the tiotropium group versus placebo (HR 0.79, p=0.03). Researchers also evaluated the change in ACQ-7 scores, which only reached statistical significance in trial two with a difference of -0.2 (p=0.003). This trial was not sufficiently powered to detect any difference in adverse drug reactions; however, the adverse events experienced were consistent with those found with IAC use in COPD and no serious adverse events occurred.3 The authors concluded that the addition of tiotropium via a Respimat® Soft Mist™ Inhaler in patients on ICS and LABA therapy provided sustained bronchodilation and increased the time to exacerbation.
This trial showed promise for the use of tiotropium added to symptomatic asthmatics on ICS and LABA therapy. The exact place in therapy for tiotropium in the management of ...