Investigational tiotropium reduces exacerbations in severe asthma cases

Once-daily dosing of the investigational drug tiotropium helped to improve lung function over 24 hours in individuals with severe asthma, according to data presented at the 2013 American College of Chest Physicians annual meeting (CHEST 2013) in Chicago.

Boehringer Ingelheim presented clinical trial data from a phase 3 study of tiotropium delivered via the Respimat inhaler in severe adult asthma patients. Tiotropium is currently being evaluated to determine the efficacy and safety in treating asthma patients.

Pooled phase 3 data was presented from the PrimoTinA-asthma studies (NCT00772538 and NCT00776984). The PrimoTinA-asthma studies are two replicate randomized, double-blind, placebo-controlled, parallel-group trials that were designed to evaluate the long-term efficacy and safety of once-daily tiotropium 5 µg delivered via the Respimat inhaler, and placebo, as add-on to stable maintenance treatment of high-dose inhaled corticosteroids (ICS)/long-acting beta-2 agonists (LABA) in adult patients with symptomatic severe persistent asthma over 48 weeks.

A total of 912 patients were randomly assigned to treatment in the paired studies, which included specific inclusion and exclusion criteria to both select patients with asthma and actively exclude patients with COPD. Patients who enrolled had a confirmed diagnosis of severe persistent asthma of at least 5 years duration made prior to age 40 years, documented by confirmatory testing, with a post-bronchodilator FEV₁ ≤80% predicted normal and FEV₁ ≤70% of forced vital capacity (FVC). Patients were never-smokers or ex-smokers for at least 1 year with a history of less than 10 pack-years and symptomatic as measured by an ACQ score ≥1.5 while on at least high-dose ICS/LABA therapy.

The pre-specified co-primary lung function end points included peak and trough FEV₁ at 24 weeks. The third co-primary end point in the pre-specified combined analysis of the 2 trials was the time to first severe exacerbation during the 48-week treatment period. A severe exacerbation was defined as an exacerbation that required treatment with systemic corticosteroids for at least 3 days.

The data showed that in adult asthma patients who remain symptomatic despite treatment with at least ICS/LABA, treatment with tiotropium 5 µg delivered via the Respimat inhaler as add-on to maintenance therapies reduced the risk of both severe asthma exacerbations and any asthma exacerbation, or asthma worsening.

An exacerbation was defined as an increase in one or more of a patient’s asthma symptoms and/or decrease in best morning peak expiratory flow rate (PEFR) for two or more consecutive days compared with a patient’s baseline. Severe exacerbations were defined as requiring systemic corticosteroids for at least three days and a decrease in lung function and/or an increase in symptoms.

In addition, pooled safety data (ie, vital signs and adverse events [AEs]) from the PrimoTinA-asthma studies were presented, which suggest that treatment with once-daily tiotropium 5 µg, delivered via the Respimat inhaler, was comparable to that of placebo in these studies when used as add-on therapy for symptomatic patients with severe persistent asthma on ICS/LABA.

The overall incidence of AEs reported (including SAEs, drug-related AEs, and AEs resulting in discontinuation) with once-daily tiotropium 5 µg delivered via the Respimat treatment was similar to placebo. A lower percentage of patients in the tiotropium-treated group (73.5%, n=335) reported AEs versus placebo (80.3%, n=336). The most commonly reported AEs by patients were asthma (tiotropium group 39.9%, n=182; placebo group 50.9%, n=232), peak expiratory flow (PEF) rate decrease (tiotropium group 20.4%, n=93; placebo group 26.8%, n=122) and nasopharyngitis (tiotropium group 11.2%, n=51; placebo group 12.3%, n=56). Treatment with tiotropium delivered via the Respimat inhaler was associated with fewer AE reports of asthma compared to placebo.

“Importantly, both for physicians and their patients, these data increase our understanding of tiotropium’s potential efficacy as an add-on asthma treatment for severe asthma patients who continue to experience symptoms despite current standard treatments,” said Alan Cohen, MD, executive director, clinical development & medical affairs, respiratory, Boehringer Ingelheim. “There is an unmet need in asthma for patients with severe disease . . . Despite current treatment options, approximately 40% of patients with asthma remain symptomatic.”

According to the Centers for Disease Control and Prevention, in May 2011, about 1 in 12 people (about 25 million) in the United States have asthma, and the numbers are increasing every year.