The Effect of Anti-Interleukin-5 Benralizumab on Eosinophilic Esophagitis
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 23rd, 2024
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Eosinophilic esophagitis, an inflammatory condition driven by Th2 cells, can be treated with proton pump inhibitors, glucocorticoids, and monoclonal antibodies targeting associated cells and signaling pathways. Interleukin 5 plays a key role in eosinophil activation, making its receptor a potential therapeutic target. Benralizumab, which targets IL-5 receptors, may help alleviate the condition. To explore this potential, AstraZeneca sponsored a study to evaluate the effectiveness of benralizumab in managing eosinophilic esophagitis.
The phase 3 clinical trial included 211 participants diagnosed with eosinophilic esophagitis. Endoscopic examination revealed an average baseline peak esophageal intraepithelial eosinophil count of 83 cells per field, while blood tests showed a mean eosinophil concentration of 310 cells per microliter. Among the cohort, 45.7% reported concurrent use of proton pump inhibitors, and 12.4% were using glucocorticoids. The baseline Dysphagia Symptom Questionnaire (DSQ) score was approximately 35 on a 48-point scale, with higher scores indicating more severe symptoms. Participants were randomly assigned to receive either a placebo or 30 mg of benralizumab subcutaneously every 4 weeks. After 24 weeks, benralizumab proved more effective in reducing the eosinophil count, with 87.4% of participants achieving a peak esophageal intraepithelial eosinophil count of fewer than 6 cells per field, compared to just 6.5% in the placebo group. Despite this histological improvement, there was no significant difference in dysphagia symptoms between the two benralizumab and placebo, as measured by the DSQ. The authors noted that previous studies have shown that biologics targeting cytokine pathways, such as anti-Siglec-8 entelimab and anti-IL-5 mepolizumab and reslizumab, might not effectively reduce symptom severity. However, dupilumab, which targets Interleukin-4 and Interleukin-13 essential for Th2 cells, has been shown to reduce symptom severity. The authors suggest that additional biomarkers beyond eosinophil count should be used to assess the severity of eosinophilic esophagitis.
The phase 3 clinical trial included 211 participants diagnosed with eosinophilic esophagitis. Endoscopic examination revealed an average baseline peak esophageal intraepithelial eosinophil count of 83 cells per field, while blood tests showed a mean eosinophil concentration of 310 cells per microliter. Among the cohort, 45.7% reported concurrent use of proton pump inhibitors, and 12.4% were using glucocorticoids. The baseline Dysphagia Symptom Questionnaire (DSQ) score was approximately 35 on a 48-point scale, with higher scores indicating more severe symptoms. Participants were randomly assigned to receive either a placebo or 30 mg of benralizumab subcutaneously every 4 weeks. After 24 weeks, benralizumab proved more effective in reducing the eosinophil count, with 87.4% of participants achieving a peak esophageal intraepithelial eosinophil count of fewer than 6 cells per field, compared to just 6.5% in the placebo group. Despite this histological improvement, there was no significant difference in dysphagia symptoms between the two benralizumab and placebo, as measured by the DSQ. The authors noted that previous studies have shown that biologics targeting cytokine pathways, such as anti-Siglec-8 entelimab and anti-IL-5 mepolizumab and reslizumab, might not effectively reduce symptom severity. However, dupilumab, which targets Interleukin-4 and Interleukin-13 essential for Th2 cells, has been shown to reduce symptom severity. The authors suggest that additional biomarkers beyond eosinophil count should be used to assess the severity of eosinophilic esophagitis.