Impact of IL-5 Pathway Inhibition on Circulating Eosinophil- and Remodeling-Related Biomarkers in Severe Eosinophilic Asthma.

Abstract

Purpose: To assess the effects of IL-5 pathway inhibition with mepolizumab or benralizumab on circulating eosinophil-related and selected remodeling-associated biomarkers in severe eosinophilic asthma (SEA), and to determine whether these profiles differ according to four-component study-defined early clinical remission (ECR) status.

Patients and methods: This prospective, observational, single-center cohort study included 30 adults with SEA treated with mepolizumab or benralizumab. Clinical assessment, spirometry, and blood sampling were performed at baseline and after 6 months. The primary endpoint was change in circulating biomarker concentrations; secondary endpoints included clinical improvement and ECR rate.

Results: IL-5 pathway inhibition improved asthma control and lung function, with OCS-treated exacerbations occurring in 4 of 30 patients during follow-up. These changes were accompanied by marked reductions in eosinophil-related biomarkers, with median decreases of 95.3% in blood eosinophils, 79.5% in eosinophil-derived neurotoxin, and 32.9% in galectin-10, respectively; false discovery rate (FDR)-adjusted p≤0.003. Significant but smaller decreases were observed in MMP-10, TGF-β1, and TGF-β2, with median reductions of 5.0%, 21.2%, and 10.9%, respectively; FDR-adjusted p≤0.002. No significant group-level changes were observed for eotaxin-1, MMP-9, TIMP-1, fibulin-1, tenascin-C, or periostin. ECR was achieved in 16 of 30 patients (53.3%). Compared with non-ECR patients, those achieving ECR had lower baseline OCS burden and fewer relevant comorbidities, whereas neither baseline biomarker concentrations nor 6-month biomarker changes differed significantly between groups. Exploratory comparisons did not show consistent differences in clinical outcomes or biomarker changes between mepolizumab and benralizumab.

Conclusion: IL-5 pathway inhibition in SEA was associated with marked suppression of eosinophil-related biomarkers, more selective changes in remodeling-associated mediators, and meaningful clinical benefit after 6 months. Similar biomarker responses in patients with and without ECR should be interpreted cautiously, but suggest that incomplete clinical response may reflect broader disease burden, particularly comorbidities, rather than insufficient suppression of eosinophilic inflammation alone.