Abstract
Thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine produced in response to pro-inflammatory stimuli, drives allergic inflammatory responses mostly through its effect on dendritic and mast cells. TSLP reportedly is increased in the airways of asthmatic subjects. AMG 157 is a human anti-TSLP monoclonal antibody that blocks interaction between TSLP and its receptor.
The goal of this study was to evaluate AMG 157 effects on asthma biomarkers in mild atopic asthmatic subjects after an inhaled allergen challenge.
The study consisted of 31 subjects who received three doses, at monthly intervals, of 700mg AMG 157 (n=16) or placebo (n=15). Allergen challenges were performed pre-dose, and 6 and 12 weeks after initiation of dosing. Sputum eosinophil counts, blood mRNA and fractional exhaled nitric oxide (FeNO) were collected before and after allergen challenge and blood eosinophil counts and Th2/Th1 ratio were followed prior to allergen challenge through the treatment period.
AMG 157 attenuated allergen-induced airway responses. Pre-allergen FeNO and blood and sputum eosinophil counts decreased significantly with AMG 157. In whole blood transcript analysis, genes highly expressed in eosinophils were elevated after allergen challenge. Pre-dose gene expression and eosinophil count were well-correlated. However, no AMG 157 effects on blood transcript profiles were detected. Treatment with AMG 157 was associated with a decreased Th2/Th1 cell ratio, driven mostly by a decrease in Th2 cells.
The reduction in these markers of airway and systemic inflammation in AMG 157-treated subjects supports a role of TSLP in allergen-induced responses in patients with allergic asthma.
- © 2014 ERS