S597 Efficacy and Safety of Dupilumab in Patients With Eosinophilic Esophagitis: Pooled Analysis and a Systematic Review

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Introduction: Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophageal mucosa, resulting in symptoms like dysphagia, and food impaction. Dupilumab, a monoclonal antibody targeting interleukin-4 receptor alpha, has emerged as a promising candidate for EoE management, as Interleukin-4 plays a pivotal role in EoE pathogenesis by promoting eosinophil and inflammatory cell activation in the esophagus. This systematic review explores the current research on Dupilumab in EoE, presenting key findings from available studies. Methods: A literature search across PubMed, Embase, and Cochrane identified 2 clinical trials (N=368) and one retrospective cohort study (N=46). Extracted baseline data included Edema, Rings, Exudates Furrows, and Strictures (EREFS) scores, as well as baseline peak eosinophil count. Efficacy outcomes, such as histological remission rate (< 6 eso/hpf), changes in EREFS, peak eosinophil count, and proportion of patients achieving < 15 eso/hpf, were also extracted. Safety assessment covered total and serious adverse events. We combined all patients that received placebo into one group and Dupilumab in one group and analyzed the pooled data. Results: The pooled results from the 3 studies revealed notable outcomes in the efficacy and safety of Dupilumab for the treatment of EoE. Histological remission was achieved in a total of 63% (162/257) of patients receiving Dupilumab, compared to the 4% (7/141) in the placebo groups. Furthermore, 82% (213/257) of Dupilumab-treated patients reached esophageal intraepithelial eosinophil count < 15 eosinophils/hpf, while 6% (9/141) in the placebo groups achieved this outcome. In addition, significant improvements in EREFS score were observed when Dupilumab was administered in comparison to placebo. Although adverse events were more prevalent in the Dupilumab group (81%, 184/227) compared to placebo (72%, 102/141), the overall safety profile remained acceptable. Serious adverse effects were rare in both groups with a pooled rate of 0.7%, (1/141) and 3% (8/227) in Dupilumab and placebo respectively. Conclusion: In summary, this systematic review suggests that Dupilumab effectively induces histological remission and improves clinical outcomes in EoE patients. The safety profile appears favorable when compared to placebo, with low rates of total and serious adverse events. These findings underscore the potential of dupilumab as a promising therapeutic option for managing eosinophilic esophagitis (see Table 1). Table 1. - Results from the 3 studies mentioned in this systematic review Author Name of the study Type of the study Total number of pts Duration Number of patients in placebo group Number of patients in Dupilumab group Baseline EREFS score* in placebo Baseline EREFS score* in Dupilumab Baseline Peak eosinophil count per high-power field in placebo Baseline Peak eosinophil count per high-power field in Dupilumab Number of patients with histological remission in placebo Number of patients with histological remission in Dupilumab Change in EREFS* score in placebo Change in EREFS* score in Dupilumab Percent change in Peak eosinophil count per high-power field from baseline in placebo Percent change in Peak eosinophil count per high-power field from baseline in Dupilumab Number of patients achieving peak esophageal intraepithelial esonophil count < 15 eso/hpf in placebo Number of patients achieving peak esophageal intraepithelial esonophil count < 15 eso/hpf in Dupilumab Number of patients who had Adverse events in placebo Number of patients who had Adverse events in Dupilumab Number of patients who had Serious adverse events placebo Number of patients who had Serious adverse events Dupilumab Dellon et. Al. 2022 Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis Phase 3 clinical trial 321 24 weeks 118 203 6.6 6.9 90.4 86.75 7 121 -0.45 -4.1 2.7% -74% 9 157 87 166 1 8 Hirano et. Al 2020 Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis Phase 2 Clinical trial 47 12 weeks 23 24 4.3 3.9 101.1 102.1 0 15 -0.3 -1.9 14.2% -92.9% 0 19 15 18 0 0 Lee et. Al. 2023 Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis Retrospective cohort study 46 Timing varied N/A 46 N/A 4.62 N/A 70 N/A 26 N/A -2.73 N/A N/A N/A 37 N/A N/A N/A N/A

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