Dupilumab Efficacy in Eosinophilic Oesophagitis Patients Treated With Prior Therapy and Inadequate Response, Intolerance, or Contraindication to Swallowed Topical Corticosteroids

Abstract Background Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation. Methods This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, 15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores. Results Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and 15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile. Conclusion Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.