The Mepo for EoE trial revealed mepolizumab’s efficacy in reducing eosinophil counts and endoscopic severity, although the primary endpoint was not met.

Treatments for eosinophilic esophagitis (EoE), which encompass dietary modifications, steroids, and biologics, often fail to fully address the condition. Mepolizumab’s effect on eosinophilic-related inflammation led researchers to explore its potential to enhance symptoms of dysphagia and lower esophageal eosinophil counts in adolescents and adults with active EoE. These findings were presented at DDW 2023.

From 2018 to 2022, the randomized, double-blind, placebo-controlled Mepo for EoE trial was conducted across four research centers in the United States. A total of 66 participants with EoE, aged 16 to 75 years, received either a 300 mg dose of mepolizumab for 6 months or a placebo. After 3 months, placebo recipients switched to a 100 mg dose of mepolizumab until month 6. The primary outcome was a change in dysphagia from the baseline to month 3, assessed by the Eosinophilic Esophagitis Activity Index (EEsAI).

At month 3, the EEsAI decreased more in the mepolizumab group compared with the placebo group (-15.4 vs -8.3; P=0.14), although this difference did not reach statistical significance. This trend persisted up to month 6. Secondary outcomes demonstrated a promising trend. At month 3, mepolizumab significantly reduced peak eosinophil counts (-77.5 in the mepolizumab group vs 16.7 in the placebo group; P<0.001), leading to a better histologic response (<15 eos/hpf in 3% of the placebo group vs 42% in the mepolizumab group; P<0.001). Mepolizumab also reduced endoscopic severity compared with placebo (-1 vs -0.4, respectively; P=0.03). At month 6, the higher dose of mepolizumab showed lower peak eosinophil counts than the 100 mg dose (26.0 ± 19.7 vs 50.2 ± 42.2, respectively; P=0.008), although the histologic response remained similar.

In conclusion, mepolizumab emerged as a potential treatment for difficult-to-treat EoE participants. While it did not significantly impact dysphagia symptoms, it improved eosinophil counts and endoscopic severity, suggesting potential use in severe cases. Future studies are needed to determine how best to incorporate this treatment into EoE management strategies.

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