Abstract
Serum periostin, blood eosinophils, and FeNO are biomarkers of Type 2 airway inflammation in asthma. Elevated levels of these biomarkers are associated with increased clinical benefit from lebrikizumab, an anti-IL13 mAb, in uncontrolled asthma despite standard of care. We recently developed a highly specific serum IL-13 assay with a lower limit of quantification of 14 fg/ml (IMPACTTM). We measured serum IL-13 levels in healthy volunteers (N=228), in uncontrolled moderate to severe asthma patients from three independent lebrikizumab Phase 2 clinical studies (n=499 total)at baseline, and in uncontrolled severe asthma patients from an observational bronchoscopy study (n=62). Serum IL-13 levels were significantly elevated in severe asthma patients (median 0.87 pg/ml) relative to healthy volunteers (median 0.54 pg/ml). In addition, serum IL-13 levels strongly correlated with a Type 2 gene signature in bronchial epithelium from severe asthma patients in the observational bronchoscopy study (Spearman ρ=0.66). In moderate to severe asthma patients, serum IL-13 at baseline strongly correlated with blood eosinophils (Spearman ρ=0.61) and weakly correlated with FeNO and serum periostin (Spearman ρ=0.32 and 0.24, respectively). The elevated serum IL-13 levels at baseline enriched for future asthma exacerbations and predicted increased clinical benefits from lebrikizumab treatment with respect to both FEV1 improvement and asthma exacerbations reduction. In conclusion, we have developed a highly sensitive and specific assay for serum IL-13, which may be an additional biomarker for identification of asthma patients with underlying Type 2 airway inflammation.
- Copyright ©ERS 2015