Weekly subcutaneous doses of the fully human monoclonal antibody dupilumab improved histologic outcomes and alleviated symptoms in patients with eosinophilic esophagitis, researchers report. Dupilumab is thought to act in this condition by blocking interleukin-4 and interleukin-13 signaling.
The 3-part, phase 3 trial included patients 12 years of age or older who were randomized to weekly subcutaneous dupilumab 300 mg or placebo (Part A) or dupilumab 300 mg either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. In Part C, those who completed Part A received weekly dupilumab 300 mg up to week 52 (the Part A–C group); Part C with participants eligible patients from Part B is ongoing.
The primary endpoints at week 24 were histologic remission (≤6 eosinophils per high-power field) and the change from baseline on the 84-point Dysphagia Symptom Questionnaire (DSQ). The results showed: “In Part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% confidence interval [CI], 40 to 71; P <0.001). In Part B, histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo (difference between weekly dupilumab and placebo, 54 percentage points; 95% CI, 41 to 66 [P <0.001]; difference between dupilumab every 2 weeks and placebo, 56 percentage points; 95% CI, 43 to 69 [not significant per hierarchical testing]). The mean (± SD) DSQ scores at baseline were 33.6 ± 12.41 in Part A and 36.7 ± 11.22 in Part B; the scores improved with weekly dupilumab as compared with placebo, with differences of –12.32 (95% CI, –19.11 to –5.54) in Part A and –9.92 (95% CI, –14.81 to –5.02) in Part B (both P <0.001) but not with dupilumab every 2 weeks (difference in Part B, –0.51; 95% CI, –5.42 to 4.41). Serious adverse events occurred in 9 patients during the Part A or B treatment period (in 7 who received weekly dupilumab, 1 who received dupilumab every 2 weeks, and 1 who received placebo) and in 1 patient in the Part A–C group during the Part C treatment period who received placebo in Part A and weekly dupilumab in Part C.”
Editorial: “Because of the lack of approved medications, providing therapeutic options to patients with eosinophilic esophagitis remains a priority,” writes an editorialist. “Dupilumab is the first Food and Drug Administration–approved biologic with proven efficacy in reducing inflammation and symptoms in patients with esophageal eosinophilia. However, whether dupilumab is better than the good old topical glucocorticoids in improving disease outcomes, particularly in light of considerable costs associated with this treatment, remains to be demonstrated.”