Mepolizumab shows potential in eosinophilic oesophagitis treatment

Mepolizumab 300 mg was administered monthly to participants with active eosinophilic oesophagitis (EoE) in the Mepo for EoE trial (NCT03656380). Although the primary endpoint of dysphagia symptom improvement was not met, the study revealed mepolizumab’s effectiveness in reducing eosinophil counts and endoscopic severity.

Treatments for EoE, which encompass dietary modifications, steroids, and biologics, often fail to fully address the condition [1]. Mepolizumab’s effect on eosinophilic-related inflammation led researchers to explore its potential to improve symptoms of dysphagia and lower oesophageal eosinophil counts in adolescents and adults with active EoE.

From 2018 to 2022, a randomised, double-blind, placebo-controlled trial was conducted across 4 research centres in the US. A total of 66 participants with EoE, aged between 16 and 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 the sixth month.

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 histological 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 histological 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.

1. Dellon E, et al. Mepolizumab for treatment of adolescents and adults with eosinophilic esophagitis: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Lecture 463, DDW 2023, 6–9 May, Chicago, IL, USA.

 

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Posted on 13 June, 202329 February, 2024