Mepolizumab improves the histologic severity of eosinophilic oesophagitis

Three months of therapy with mepolizumab, a monoclonal antibody against IL-5, significantly improved the eosinophilic oesophagitis (EoE) Histologic Scoring System (HSS) grade and stage scores compared with placebo. A moderate correlation with the post-treatment Endoscopic Reference Score (EREFS) was also observed.

The randomised phase 2 clinical trial (NCT03656380) included participants aged 16–75 years with EoE who were non-responsive to proton pump inhibitors, had ≥15 eosinophils per high-power field on biopsy, and had dysphagia symptoms [1]. Key exclusion criteria were severe stricturing, recent oesophageal dilation, and recent steroid use. Participants were randomised 1:1 to receive mepolizumab 300 mg, administered subcutaneously, or a placebo for 3 months. The randomisation was stratified by prior topical steroid non-response. A post-hoc analysis conducted by Dr Evan Dellon (University of North Carolina School of Medicine, NC, USA) and his team aimed to evaluate the changes in HSS grade and stage scores at 3 months. HSS grade and stage scores assess 8 histopathologic features: eosinophil infiltration (EI), basal zone hyperplasia (BZH), eosinophil abscess (EA), eosinophil surface layering (SL), dilated intercellular spaces (DIS), surface epithelial alteration (SEA), dyskeratotic epithelial cells (DEC), and lamina propria fibrosis (LPF).

Of the 64 participants who completed the study, 31 received mepolizumab and 33 received a placebo. Baseline HSS features and total scores were similar between the groups. At month 3, mepolizumab significantly lowered the total HSS grade score (1.2 vs 1.7; P<0.001) and stage score (1.1 vs 1.6; P<0.001) compared with placebo. Eosinophil-related HSS features (EI, EA, SL, SEA) improved for both grade and stage, while non-eosinophil features (BZH, DIS, DEC, LPF) did not change significantly. HSS scores at 3 months moderately correlated with the EREFS for both grade (r=0.45; P<0.001) and stage (r=0.47; P<0.001).

In conclusion, treatment with mepolizumab for 3 months led to significant improvements in histologic severity, specifically in eosinophil-dependent features, compared with placebo.

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   1. Dellon E, et al. Mepolizumab improves histologic severity as measured by the EoE-HSS in adolescents and adults with eosinophilic esophagitis in a multicenter, randomized, double-blind, placebo-controlled clinical trial. Sa1284, DDW 2024, 18–21 May, Washington DC, USA.

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Posted on 11 July 2024