Managing Pediatric Eosinophilic Esophagitis with Dupilumab
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 21st, 2024
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Eosinophilic esophagitis is an inflammatory condition driven by type 2 Helper T-cells and its associated cytokines such as Interleukin-4 and Interleukin-13. In children, the inflammation can lead to fibrosis and stricture that can result in dysphagia and impact development. Dupilumab is a monoclonal antibody that can be used to treat asthma and atopic dermatitis by blocking the signaling pathway of IL-4 and IL-13. As a result, Sanofi and Regeneron Pharmaceuticals had sponsored a study to assess the effect of dupilumab in managing eosinophilic esophagitis in pediatric patients.
The phase 3 clinical trial included a total of 102 participants between the age of 1 and 11 years old who had been diagnosed with eosinophilic esophagitis for an mean duration of 4.1 years with an average peak esophageal intraepithelial eosinophil count of 83.3 cells per field. Baseline assessment using the 3-point eosinophilic esophagitis histology scoring system (EoS-HSS) yielded a mean value of 1.3 for the group, with 3 being the most severe. Almost all of the participants in the study had other coexisting atopic or allergic conditions ranging from asthma, atopic dermatitis, food allergy, and allergic rhinitis. The participants were randomly assigned to receive intradermal injection of either placebo or 2 dose levels of dupilumab: one high-exposure regimen and one low-exposure regimen that is adjusted to match the body weight of the participant. Authors of the article did not provide further information about the dose. After the first 16 weeks of treatment, the researchers noted that high-level usage of dupilumab increased the chance of histological remission by 65% when compared to the placebo group. In addition, dupilumab significantly reduced the disease severity as reflected by a 0.88 reduction in EoE-HSS grade. Endoscopic examination and transcriptomic analysis also reflect the same conclusion.
The phase 3 clinical trial included a total of 102 participants between the age of 1 and 11 years old who had been diagnosed with eosinophilic esophagitis for an mean duration of 4.1 years with an average peak esophageal intraepithelial eosinophil count of 83.3 cells per field. Baseline assessment using the 3-point eosinophilic esophagitis histology scoring system (EoS-HSS) yielded a mean value of 1.3 for the group, with 3 being the most severe. Almost all of the participants in the study had other coexisting atopic or allergic conditions ranging from asthma, atopic dermatitis, food allergy, and allergic rhinitis. The participants were randomly assigned to receive intradermal injection of either placebo or 2 dose levels of dupilumab: one high-exposure regimen and one low-exposure regimen that is adjusted to match the body weight of the participant. Authors of the article did not provide further information about the dose. After the first 16 weeks of treatment, the researchers noted that high-level usage of dupilumab increased the chance of histological remission by 65% when compared to the placebo group. In addition, dupilumab significantly reduced the disease severity as reflected by a 0.88 reduction in EoE-HSS grade. Endoscopic examination and transcriptomic analysis also reflect the same conclusion.