TBA (25W148)

The Predictive Role of the Glucocorticoid Signalling Machinery in Steroid Non-Responsive Eosinophilic Oesophagitis (EoE)

Author(s)

O Fagan, S N Almeida Cruz, G E Markey, L Crowe, S K Kellett, C Gargan, N Conlon, C L Donohoe, S McKiernan, J C Masterson

Department(s)/Institutions

St James's Hospital, Dublin 8 Allergy Inflammation & Remodeling Research, Maynooth University

Introduction

EoE is a chronic immune mediated disease affecting the oesophagus. Topical corticosteroid/glucocorticoid therapy forms the mainstay treatment. However, steroid-non-responsive (SNR) disease is estimated at 22-69% and there are no reliable predictors of SNR.

Aims/Background

To elucidate a predictive molecular pattern that would distinguish steroid responsive (SR) and SNR EoE using clinical and molecular profiling of glucocorticoid signalling responses.

Method

Over 100 EoE patients were prospectively recruited for paired assessment pre- and post- standard-of-care steroid treatment (oral viscous budesonide OVB, 1mg BD). Oesophageal pinch biopsies and clinical data were collected. Standardised clinical outcomes measurement tools were applied including patient reported symptom scores (ESS), medication-taking scores (MTC), endoscopic scores (EREFS) and histologic activity (eosinophils/hpf). Immunofluorescent (IF) localisation and intensity measures of key glucocorticoid signalling proteins comparing healthy controls (n=9) and paired pre & post-treatment EoE patients with SR and SNR disease was performed. SR (n=12) was defined as symptom improvement, reduction in endoscopic inflammation-score and <15eos/hpf. Partial response (PR; n=4) was defined as some improvement in symptoms/endoscopic inflammation/histologic inflammation not reaching SR criteria. SNR (n=4) was defined as no significant symptom improvement, persistent endoscopic inflammation and persistent histologic activity (>15eos/hpf).

Results

All participants had a high MTC score (≥15), excluding treatment non-compliance as a confounding factor. Distinct glucocorticoid signalling patterns were observed in SNR patients compared to SR comparing pre-treatment biopsies. These were persistent in post-treatment SNR biopsies, indicating a likely prognostic glucocorticoid processing pattern in SNR patients.

Conclusions

Glucocorticoid signalling may play a direct prognostic role in SNR disease.