Abstract / Summary
Background: /Objectives: Mepolizumab suppresses eosinophilic inflammation in severe asthma, but its relationship with epithelial injury-repair and remodeling biology is incompletely characterized. We assessed longitudinal serum amphiregulin (AREG) and YKL-40 changes and explored their clinical and biological correlates.
Methods: In this paired real-world study, 19 adults with severe eosinophilic asthma were evaluated before and after 12 months of mepolizumab 100 mg every 4 weeks. Biomarkers were measured by ELISA; paired changes were tested using exact two-sided Wilcoxon signed-rank permutation tests. Exploratory associations between biomarker and lung-function changes used Spearman correlations.
Results: AREG decreased from 13.59 to 11.74 pg/mL (median change, −3.07; p = 0.002) and YKL-40 from 50.69 to 45.02 ng/mL (median change, −8.19; p = 0.036). Blood eosinophils, oral corticosteroid dose, exacerbations, and FeNO decreased, whereas ACT and FEV₁/FVC improved. ΔYKL-40 showed weak inverse associations with ΔFEV₁ (ρ = −0.256; p = 0.291) and ΔFVC (ρ = −0.281; p = 0.244); ΔAREG was not associated with either change. These exploratory analyses did not establish prediction of lung-function change.
Conclusions: Co-ordinated AREG and YKL-40 reductions during clinical improvement support modulation of a broader T2 epithelial-inflammatory and remodeling-related network during IL-5 blockade. The weak, non-significant lung-function associations are hypothesis-generating and require prospective mechanistic validation.