Tiotropium respimat® add-on therapy reduces airflow obstruction in patients with symptomatic moderate asthma, independent of TH2 inflammatory status
© Yang et al; licensee BioMed Central Ltd. 2014
Published: 18 December 2014
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 (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. We explored whether TH2 biomarker status influenced responses to tiotropium in patients with moderate symptomatic asthma.
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 µg budesonide equivalent), were administered once-daily tiotropium Respimat® 5 µg or 2.5 µg, 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-high and TH2-low subgroups defined at baseline as total serum IgE ≤ or >430 µg/L) or blood eosinophils ≤ or >0.6×109/L.
Of 1545 patients in the full analysis set who received tiotropium or placebo, 915/1455 were reported with IgE >430 µg/L and 300/1461 with an eosinophil count of >0.6×109/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, irrespective of IgE (p<0.0001 both doses) and eosinophil count (p<0.005 both doses).
Once-daily tiotropium Respimat® as add-on to ICS reduces airflow obstruction in patients with moderate symptomatic asthma, independent of TH2 phenotype, and thus may potentially provide an important therapeutic option.
Study supported by Boehringer Ingelheim. Previously presented at AAAAI 2014 in San Diego, CA, USA.
We thank Dr W.H. Yang for presenting this study on behalf of the authors.
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