Dupilumab in Adults and Adolescents With Eosinophilic Esophagitis

To determine if dupilumab (a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling) plays any key roles in eosinophilic esophagitis.

Patients 12 years and older with eosinophilic esophagitis and a histologic diagnosis of >15 eosinophils per high-power field despite 8 weeks of high dose protein pump inhibitor (PPI) were enrolled. A Dysphagia Symptom Questionnaire (DSQ) of >10 (range 0–84) was required at baseline. Patients could not initiate PPI or change their elimination diet. Patients could not use swallowed topical corticosteroid for the 8 weeks before or during the trial. Rescue medications or systemic glucocorticoids and esophageal dilation were permitted if medically necessary.

In this 3-part study, endpoints were analyzed at 24 and 52 weeks. Dosing was 300 mg every 1 or 2 weeks subcutaneous or placebo every 1 week subcutaneous. The primary endpoints were histologic response of ≤6 eosinophils per high-power field and the absolute change in DSQ.

The histologic remission rate of 60% occurred with both dosing regimen at 24 weeks. Inflammation persisted in 93% of placebo patients. Relevant reduction in DSQ occurred in the 1 weekly patient (−12.3) compared with every 2 weeks (−0.51) compared with placebo. The side effect profile was good for all dosing regiments.

The histologic remission with swallowed corticosteroids is up to 90% of patients. The histologic response in this study of 60% is puzzling. Note that less effectiveness of dupilumab has been shown in this study.

The addition of Dupilumab to PPI, swallowed corticosteroid and elimination diets remains an effective additive treatment. Further work is needed to tease out the additional benefit to the aforementioned treatments in patients who do not show response. Also cost considerations and insurance coverage need to evolve over time.