Late Breaking Abstract - An assessment of potential predictive biomarkers for the treatment of severe eosinophilic asthma with CRTH2 antagonists

Abstract

<b>Introduction:</b> CRTH2 antagonists are a promising therapy for T2-high disorders, particularly uncontrolled eosinophilic asthma. Biomarkers to identify patients likely to respond to treatment would be a useful advance. We set out to investigate the relationship between the effect of 12 weeks’ treatment with the CRTH2 antagonist timapiprant on the induced sputum eosinophil count and a range of blood and sputum biomarkers. <b>Methods and Materials:</b> Peripheral blood and induced sputum samples were collected from 20 patients with severe eosinophilic asthma at baseline and 12 weeks after oral treatment with 50 mg timapiprant daily. Immune cell counts in blood were determined with flow cytometry. Cell numbers in sputum were determined by slide counting. Correlations were assessed non-parametrically using Prism 7. <b>Results:</b> Timapiprant treatment reduced the geometric mean sputum eosinophils from 11% to 2.5% (Fold reduction 4.5; 95% CI 1.9 to 9.7; p=0.001). Baseline blood total CRTH2+ cells (r=0.75; p&lt;0.001), eosinophils (r=0.76; p&lt;0.001), basophils (r=0.53; p=&lt;0.05), Type-2 cytotoxic T (Tc2) cells (r=0.52; p=&lt;0.05), and sputum eosinophils (r=0.82; p&lt;0.0001) were correlated significantly with the reduction in the sputum eosinophil count with timapiprant treatment. <b>Conclusion:</b> High levels of blood total CRTH2+ cells, eosinophils, basophils, Tc2 cells, and sputum eosinophils are associated with the anti-inflammatory effect of timapiprant treatment and could be potential predictive biomarkers of response.