Phase III Results: Tiotropium Respimat® Is Effective In Symptomatic Asthma Patients Irrespective Of Their Allergic Status
Tiotropium delivered once daily via Respimat™ significantly improved lung function and reduced asthma exacerbations in patients who remain symptomatic despite treatment with at least ICS/LABA, irrespective of their allergic status.1
These were the main findings from a new subset of data1 from the Phase III UniTinA-asthma® programme presented for the first time today at the 2013 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in San Antonio, Texas.
“Patients with asthma may respond differently to treatment based on their allergic status, therefore it is important to investigate new therapies in both allergic and non-allergic patients,” said Dr. Mark Vandewalker, MD, director, Clinical Research of the Ozarks, Columbia, Missouri. “The results of these trials show that tiotropium provides additional bronchodilation and reduces exacerbation rates in asthmatics who are uncontrolled on current therapy with at least ICS/LABA regardless of their allergic status, demonstrating its potential benefit for patients who need additional asthma control.”
The PrimoTinA-asthmaTM studies (1 and 2) were two replicate double-blind parallel-group trials including asthma patients with post-bronchodilator FEV1 <80% predicted and Asthma Control Questionnaire score ≥1.5 while on at least ICS/LABA. A total of 912 patients were randomised to additional tiotropium Respimat® 5 mg (n=256) or placebo (n=256) for 48 weeks.
In addition to ICS/LABA, patients in the trials were permitted to receive additional background therapy, including antihistamines, anti-allergic agents, nasal steroids and omalizumab.
To investigate the relationship between response and the patients’ allergic status, a pre-planned sub-group analysis of the data from both PrimoTinA-asthmaTM studies (1 and 2) was carried out.
The subgroup of patients with potentially allergic asthma was identified using three criteria: total serum immunoglobulin E (IgE), blood eosinophils, or clinician judgment. Allergic status was positive if serum IgE was greater than 430 μg/L, blood eosinophilia was greater than 0.6 – 109/L, or clinician judgement was “yes.”
In the overall study population, adding tiotropium Respimat® provided significant lung function improvements at 24 weeks, which were sustained over 48 weeks.1 Also, patients who received tiotropium Respimat® had a 21% risk reduction (HR 0.79, P=0.03) in time to first severe exacerbation. Severe exacerbations were defined as requiring systemic corticosteroids for at least 3 days.1
Furthermore, the addition of tiotropium Respimat® reduced the risk of any asthma exacerbation, defined by a significant increase in symptoms or peak expiratory flow (PEF) drop >30% over >2 days, by 31% (P<0.0001).1
These significant improvements in lung function and reduction in exacerbations were also seen regardless of allergic status in each of the two trials. The pre-planned subgroup analyses showed that peak FEV1 improved with tiotropium in PrimoTinA-asthmaTM 1 irrespective of allergic status for IgE (P=0.86) and eosinophilia (P=0.46), and in PrimoTinA-asthmaTM 2 for IgE (P=0.98) and eosinophilia (P=0.18). There was also an improvement in clinician judgment in PrimoTinA-asthmaTM 2 (P=0.29).
Pre-dose (trough) FEV1 also improved with tiotropium compared with placebo, irrespective of allergic status, across all criteria in Trial 1 (IgE, P=0.85; eosinophilia, P=0.83; clinician judgment, P=0.15) and Trial 2 (IgE, P=0.58; eosinophilia, P=0.38; clinician judgment, P=0.85).
Pooled pre-specified data analyses from the two trials revealed that time to first severe asthma exacerbation and time to first asthma worsening were both increased with tiotropium compared with placebo not just in the overall analysis of the data, but also regardless of the patients’ allergic status, based on the three criteria.
Adverse events (AEs) were balanced between the allergic and non-allergic sub groups. The most frequently reported treatment-emergent AEs in both Phase III studies included asthma, peak expiratory flow (PEF) rate decreased and nasopharyngitis.
“The UniTinA-asthmaTM trial programme is exploring whether tiotropium can address the clear unmet medical need seen in the significant number of asthma patients who remain symptomatic despite the available therapeutic options. This programme demonstrates our commitment to develop tiotropium Respimat® for a wide range of asthma patients,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “We are encouraged by these findings, as they provide us with more information on the potential of tiotropium Respimat® across new subsets of asthma patients,” Professor Dugi concluded.
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 Inhaled corticosteroids
 Long-acting beta2-agonists
 FEV1 Forced Expiratory Volume in one second