In patients with symptomatic asthma receiving ICS or ICS+LABA, phase III studies have demonstrated improved lung function with Tiotropium ( Spiriva ) 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.
Researchers have 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, patients with moderate symptomatic asthma, using medium-dose ICS ( 400-800 mcg Budesonide equivalent ), were administered once-daily Tiotropium Respimat 5 mcg or 2.5 mcg, 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 less than or equal to or greater than 430 mcg/L or blood eosinophils less than or equal to or greater than 0.6×109/L.
Of 1545 patients in the full analysis set who received Tiotropium or placebo, 915/1455 were reported with IgE greater than 430 mcg/L and 300/1461 with an eosinophil count of greater than 0.6×109/L.
Peak FEV1 improved with Tiotropium versus placebo, independent of IgE ( p less than 0.0001 both doses ) and eosinophil count ( p less than 0.0001 both doses ).
Trough FEV1 also improved with Tiotropium versus placebo, independent of IgE ( p less than 0.0001 both doses ) and eosinophil count ( p less than 0.005 both doses ).
In conclusion, 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. ( Xagena )
Casale TB et al, AAAAI Meeting, 2014