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Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response
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Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response
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Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response
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Journal Article
Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response
2024
Overview
INTRODUCTION:We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.METHODS:Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.RESULTS:A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation.DISCUSSION:The dupilumab 300 mg weekly regimen approved for adults and adolescents with EoE weighing ≥ 40 kg is supported by dose- and exposure-response relationships.
