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1. In this randomized controlled trial, benralizumab, an anti-interleukin-5 receptor (anti-IL-5R) monoclonal antibody, demonstrated histologic depletion of eosinophils among patients with eosinophilic esophagitis (EoE) compared to placebo.
2. Patients receiving benralizumab did not experience fewer dysphagia symptoms when compared to those receiving a placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: EoE is a chronic disease characterized by eosinophil-driven inflammation causing scarring and narrowing of the esophagus. This results in progressive dysphagia and impairs quality of life. Current therapies have variable and inadequate responses, including proton pump inhibitors, corticosteroids, and biologics. Benralizumab is an anti-IL-5R monoclonal antibody that depletes eosinophils through cytotoxic immunity, previously approved for eosinophilic asthma. This phase three trial assessed benralizumab in adolescent and adult patients with EoE. By week 24, patients receiving benralizumab were found to have a significantly higher histologic response of eosinophil depletion in their esophageal epithelium compared to the placebo group. Nevertheless, there was no appreciable difference in dysphagic symptoms from baseline between the two groups, nor was there a difference in endoscopic abnormalities between the groups. Benralizumab and placebo were associated with similar rates and profiles of adverse events. The study was limited by the lack of a placebo control during the open-label period after week 24. The discordance between histologic and symptomatic responses underpinned the complex pathophysiology of EoE, highlighting a need for further investigation into other therapeutic approaches.
Click to read the study in NEJM
In-Depth [randomized controlled trial]: This current study was a phase three multi-center, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of benralizumab for treating patients with symptomatic EoE. Patients between 12 and 65 years of age diagnosed with EoE via endoscopic biopsy and active dysphagic symptoms were eligible for inclusion. Exclusion criteria included pregnancy, other active gastrointestinal diseases, malignancy, and immunosuppressed status. In total, 211 patients were randomized 1:1 to receive subcutaneous benralizumab (30mg) or placebo every four weeks for 24 weeks, followed by an open-label period where placebo recipients were switched to benralizumab until week 52. The primary outcomes were a histologic response and a change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score. Secondary outcomes included change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score (EREFS) for endoscopic abnormalities, Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) for tissue abnormalities, and quality of life assessments. By week 24, patients from the benralizumab group (87.4%) demonstrated a significantly higher rate of histologic response than the placebo group (6.5%) (difference 80.8 percentage points, 95% confidence interval [CI] 72.9-89.8, p<0.001). Notwithstanding, the changes from baseline in the DSQ score did not differ significantly between the groups (difference in least-squares means 3.0 points, 95% CI -1.4-7.4, p=0.18). There was also no appreciable difference between the benralizumab and placebo groups in changes from baseline EREFS and EoE-HSS scores or quality of life at 24 weeks. Benralizumab (64.1%) was associated with a comparable rate of adverse events to placebo (61.7%), including coronavirus disease 2019, headache, and nasopharyngitis, with none resulting in discontinuations. In summary, these results highlighted the need for further investigation into other therapeutic approaches.
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