Dupilumab improves in diverse aspects of eosinophilic oesophagitis

 

Weekly dupilumab demonstrated significant and clinically meaningful improvements in histologic, symptomatic, endoscopic, and molecular aspects of eosinophilic oesophagitis (EoE). In addition, dupilumab was well tolerated. That was found in part A of an ongoing 3-part, randomised, placebo-controlled, phase 3 study [1].

EoE is a chronic type 2 inflammatory disease of the oesophagus that can substantially impair the quality of life. Only a few treatment options are currently available and the response to the current therapy is generally suboptimal.

Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13. These cytokines are key drivers of type 2 inflammation in EoE. In a previous phase 2 proof-of-concept study, dupilumab significantly improved histological and clinical outcomes of EoE with an acceptable safety profile. In the current, ongoing, phase 3 trial, the efficacy and safety of weekly dupilumab 300 mg are compared with placebo in 81 adult and adolescent patients with EoE with a treatment duration of 24 weeks.

The first primary endpoint was the proportion of patients achieving a peak oesophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field. At week 24, a significantly higher proportion of patients treated with dupilumab versus placebo achieved:

• a peak eosinophil count of ≤6 eosinophils per high-power field: 59.5% versus 5.1% (P<0.001); and
• a peak eosinophil count of <15 eosinophils per high-power field: 64.3% versus 7.7% (P<0.001).

Furthermore, dupilumab-treated versus placebo-treated patients had a significantly greater percent change from baseline in:

• peak eosinophil count: LS mean difference -68.26 (P<0.001);
• Dysphagia Symptom Questionnaire score: LS mean difference -12.32 (P<0.001); and
• total EoE Endoscopic Reference Score: LS mean difference -2.9 (P<0.001).

Dupilumab was generally well tolerated with an acceptable safety profile. The most common treatment-emergent adverse events for dupilumab versus placebo were injection-site reactions (16.7% vs 10.3%) and nasopharyngitis (11.9% vs 10.3%).

1. Dellon ES. Dupilumab efficacy and safety in adult and adolescent patients with eosinophilic esophagitis: results from part A of a randomized, placebo-controlled three-part, phase 3 study. UEG Week Virtual Symposium 2020, abstract LB22.

Posted on 2 November, 20202 November, 2020