Tiotropium respimat® add-on therapy reduces airflow obstruction in patients with symptomatic moderate asthma, independent of TH2 inflammatory status

S A T U R D A Y 16 Tiotropium Respimat Add-On Therapy Reduces Airflow Obstruction In Patients With Symptomatic Moderate Asthma, Independent Of TH2 Inflammatory Status Dr. Thomas B. Casale, MD, FAAAAI, Dr. Eric Donn Bateman, MD, Prof. Ronald Dahl, MD, Dr. Emilio Pizzichini, Dr. Mark L. Vandewalker, MD, Dr. Johann Christian Virchow, Dr. Michael Engel, MD, Dr. Petra Moroni-Zentgraf, Dr. Hendrik Schmidt, Huib A. M. Kerstjens; Univeristy Of South Florida Morsani College Of Medicine, Tampa, FL, University of Cape Town Lung Institute, Cape Town, South Africa, Odense University Hospital, Odense, Denmark, NUPAIVA (Asthma Research Centre), Universidade Federal de Santa Catarina, Florian opolis, Brazil, Clinical Research of the Ozarks, Columbia, MO, University Clinic Rostock, Rostock, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim Am Rhein, Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. RATIONALE: In patients with symptomatic asthma receiving ICS or ICS+LABA, Phase III studies have demonstrated improved lung function with tiotropium Respimat , a once-daily long-acting anticholinergic bronchodilator. The efficacy of some treatments (e.g. 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. We explored whether TH2 biomarker status influenced responses to tiotropium in patients with moderate symptomatic asthma. METHODS: In two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group trials (NCT01172808/NCT01172821), patients with moderate symptomatic asthma, using medium-dose ICS (400-800 mg budesonide equivalent), were administered once-daily tiotropium Respimat 5 mg or 2.5 mg, placebo, or salmeterol (active comparator without inferential analysis). Co-primary endpoints included peak and trough FEV1 response (difference from baseline) at 24 weeks. Pre-planned analyses (pooled population) were performed in TH2-low and TH2-high subgroups defined at baseline as total serum IgE 430 mg/L or blood eosinophils 0.6310/L. RESULTS: Of 1545 patients in the full analysis set who received tiotropium or placebo, 915/1455 were reported with IgE >430 mg/L and 300/1461 with an eosinophil count of >0.6310/L. Peak FEV1 improved with tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and eosinophil count (p<0.0001 both doses). Trough FEV1 also improved with tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and eosinophil count (p<0.005 both doses). CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS reduces airflow obstruction in patients withmoderate symptomatic asthma, independent of TH2 phenotype, and thus may potentially provide an important therapeutic option.