Study on Dupilumab for Eosinophilic Esophagitis

A new study published in The New England Journal of Medicine suggests that subcutaneous dupilumab given weekly to individuals with eosinophilic esophagitis improved histologic results and relieved symptoms of illness.

Dupilumab is a completely human monoclonal antibody that inhibits interleukin-4 and interleukin-13 signaling, both of which play important roles in eosinophilic esophagitis. As a result, Evan Dellon and colleagues undertook this trial to investigate the effectiveness of dupilumab in persons with eosinophilic esophagitis.

Patients 12 years of age and older participated in a three-part phase 3 trial, in which they were randomized in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every two weeks or weekly placebo (Part B) up to week 24. The Part A-C group, which consisted of the eligible patients from Part B, got dupilumab at a weekly dose of 300 mg until week 52. Part C, which also included the eligible patients from Part A, is still ongoing. Histologic remission (6 eosinophils per high-power field) and the Dysphagia Symptom Questionnaire (DSQ) score change from baseline were the two main end objectives at week 24. (range, 0 to 84, with raised values denoting more frequent or more severe dysphagia).

Key Findings

• Histologic remission occurred in Part A in 2 of 39 patients (5%) who got placebo and in 25 of 42 patients (60%) who received weekly dupilumab.
• In Part B, histologic remission was seen in 49 of 81 patients (60%) who received dupilumab every two weeks, 47 of 80 patients (59%) who received weekly dupilumab, and 5 of 79 patients (6%) who received placebo (deviation between weekly dupilumab and placebo, 54 percentage points; 95% CI, 41 to 66 [P0.001]; difference among both dupilumab and placebo, 56 percentage points; 95%).
• At baseline, the mean (SD) DSQ scores were 33.6±12.41 in Part A and 36.7±11.22 in Part B.
• The scores improved with weekly dupilumab compared to placebo, with differences of -12.32 in Part A and -9.92 in Part B, but not with dupilumab every two weeks.
• Serious side effects happened in 9 patients during the Part A or B treatment periods (7 patients who received weekly dupilumab, 1 patient who received dupilumab every 2 weeks, and 1 patient who received placebo), as well as in 1 patient in the Part A-C group during the Part C treatment period who received weekly dupilumab in Part A and placebo in Part C.

Reference

Dellon, E. S., Rothenberg, M. E., Collins, M. H., Hirano, I., Chehade, M., Bredenoord, A. J., Lucendo, A. J., Spergel, J. M., Aceves, S., Sun, X., Kosloski, M. P., Mannent, L. P., Laws, E., Akinlade, B., … Shabbir, A. (2022). Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. In New England Journal of Medicine (Vol. 387, Issue 25, pp. 2317–2330). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2205982