Siglec-8 as a Biomarker for Predicting Anti-IL-5 Response in Severe Asthma

Purpose: Biologic therapies have revolutionized the management of severe asthma (SA), yet the variability in patient responses necessitates identification/verification of predictive biomarkers. Siglec-8, a sialic acid-binding immunoglobulin-like lectin 8 selectively that is expressed on eosinophils, could serve as a biomarker for predicting responsiveness to biologics in patients with SA. It is necessary to evaluate the predictive value of baseline serum Siglec-8 levels compared to other parameters, including blood eosinophil counts, in determining clinical responses to anti-interleukin 5 (IL-5) therapies in patients with SA. Methods: This study included 68 patients with SA from the Precision Medicine Intervention in Severe Asthma study, who had initiated anti-IL-5 therapies and whose baseline serum Siglec-8 levels were measured. Clinical outcomes were assessed at 6 and 12 months following treatment. Excellent responders were defined as patients with zero exacerbations during follow-up. Multivariable logistic regression and receiver operating characteristic curve analyses were performed to compare the predictive performance of serum Siglec-8 levels versus that of other parameters. Results: Data from 29 patients treated with mepolizumab and 39 patients treated with reslizumab were analyzed. Baseline serum Siglec-8 levels showed a trend toward better diagnostic performance compared to blood eosinophil counts for predicting 6- and 12-month clinical responses (area under the curve, 0.931 vs. 0.836; P = 0.08 for 6-month responders; and 0.811 vs. 0.628, P = 0.05 for 12-month excellent responders). Additionally, the ratio of serum Siglec-8 levels to blood eosinophil counts significantly increased after 6 months of anti-IL-5 therapy (P < 0.001). Conclusions: Baseline serum Siglec-8 levels showed a trend toward better predictive performance than other parameters for predicting 6- and 12-month responses to anti-IL-5 therapies in patients with SA. These findings suggest that Siglec-8 may have the potential as a biomarker for guiding treatment decisions, although further validation in larger, prospective studies is warranted. Trial Registration: ClinicalTrials.gov