Tiotropium for asthma appears to be an effective adjunct in phase 3 studies

Phase 3 clinical trial data demonstrate tiotropium’s potential benefit as an add-on treatment for asthma patients.

At the 2014 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting recently in San Diego, Boehringer Ingelheim presented the results from phase 3 studies of the UniTinA-asthma clinical trial program, which evaluated tiotropium in adults, teens, and children with persistent asthma at various levels of severity. Tiotropium is not currently approved for asthma.

In the United States, more than 25 million people are known to have asthma. Approximately 40% of asthma patients remain symptomatic even while receiving treatment with currently available options and remain at risk for asthma exacerbations.

In the phase 3 GraziaTinA-asthma study (NCT01316380), tiotropium delivered via the Respimat SoftMist Inhaler improved lung function response, as measured by forced expiratory volume in one second (FEV₁), in patients with mild asthma who remained symptomatic while receiving low-dose inhaled corticosteroid (ICS) treatment.

The primary end point of the study was peak FEV₁ response within three hours post-dosing (change from baseline) at 12 weeks. The 5-ug dose showed an adjusted mean difference in peak FEV₁ response of 128 mL (P=.0005) and the 2.5-ug dose showed an adjusted mean difference in peak FEV₁ response of 159 mL (P<.0001).

According to a pre-specified subset of data from the phase 3 MezzoTinA-asthma trials (NCT01172808/NCT01172821), enrolled patients had moderate asthma and remained symptomatic while receiving medium-dose ICS therapy. With the addition of once-daily tiotropium, these patients demonstrated reduced airflow obstruction independently of allergic status, as measured by the Th2 phenotype biomarkers.

In another subset of data presented at AAAAI, the addition of once-daily tiotropium in the phase 3 PrimoTinA-asthma trials (NCT00772538/NCT00776984) improved lung function responses independently of concomitant use of a leukotriene receptor antagonist (LTRA) in patients with severe asthma.

Patients with prior use of LTRA showed an adjusted mean difference in peak FEV₁ of 103 ± 51 mL (P=.0454) and those without prior LTRA use showed an adjusted mean difference in peak FEV₁ of 111 ± 28 mL (P<.0001).

“Despite currently available therapies and detailed guidelines, many people with even mild asthma remain symptomatic; therefore, it is important to establish new treatments for this patient population,” said Tunde Otulana, MD, senior vice president, clinical development and medical affairs, Boehringer Ingelheim. “The GraziaTinA-asthma data found both tiotropium doses were statistically significant compared to placebo in mildly symptomatic asthma patients.”

Additionally, Dr. Otulana said, the efficacy of some asthma treatments (eg, ICS and omalizumab) appears higher in Th2-high phenotypes, but no specific treatments are available that work equally well in both Th2-high and Th2-low phenotypes.

“That is why it was important . . . to explore whether Th2 biomarker status influenced responses to tiotropium in pre-specified subgroups of patients with moderate symptomatic asthma in the MezzoTinA-asthma studies,” he said.

“Leukotriene modifiers are part of the standard treatment of asthma, as noted in the Global Initiative for Asthma [GINA] guidelines, so it assessed whether pre-screening and concomitant LTRA use in severe symptomatic asthma patients in the PrimoTinA-asthma trials affected lung function improvements seen with tiotropium,” he added.