Discovery and validation of mucosal TNF expression combined with histological score - a biomarker for personalized treatment in ulcerative colitis

Jon R Florholmen,Øystein K Moe,Mona D Gundersen,Cecilia Vold,Petter Tandberg,Trine Olsen,Jan-Magnus Kvamme,Renate Meyer,Sveinung W Sørbye,Terje Løitegård,Rasmus Goll,Gabriele Raschpichler,Kay-Martin Johnsen,Knut Johnsen

doi:10.1186/s12876-020-01447-0

Abstract

BackgroundThere are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis.MethodsTreatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004 to 2014, followed by a validation study from 2014 to 2018. Patients were treated according to clinical guidelines following a standard step-up regime. Patients were categorized according to the treatment level necessary to achieve clinical remission: mild, moderate and severe. The biopsies were assessed by Robarts histopathology index (RHI) and TNF gene transcripts.ResultsWe included 66 patients in the calibration cohort and 89 patients in the validation. Mucosal TNF transcripts showed high test reliability for predicting severe outcome in UC. When combined with histological activity (RHI) scores the test improved its diagnostic reliability. Based on the cut-off values of mucosal TNF and RHI scores from the calibration cohort, the combined test had still high reliability in the validation cohort (specificity 0.99, sensitivity 0.44, PPV 0.89, NPV 0.87) and a diagnostic odds-ratio (DOR) of 54.ConclusionsThe combined test using TNF transcript and histological score at debut of UC can predict severe outcome and the need for anti-TNF therapy with a high level of precision. These validated data may be of great clinical utility and contribute to a personalized medical approach with the possibility of top-down treatment for selected patients.

Highlights

There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis
The IBSEN study is one of the most well-known prospective studies on clinical outcomes in Ulcerative colitis (UC), where the patients were divided into 4 predefined patterns of disease [2]
In the severe outcome group, all patients were on anti-tumor necrosis factor (TNF) treatment including one patient that later was in the need of colectomy

Summary

Introduction

There are no accurate markers that can predict clinical outcome in ulcerative colitis at time of diagnosis. The aim of this study was to explore a comprehensive data set to identify and validate predictors of clinical outcome in the first year following diagnosis. Ulcerative colitis (UC) is one of the two main disease entities of inflammatory bowel disease (IBD). Many patients experience severe outcomes of disease with significant reduction in quality of life. Definitions of clinical outcomes and prognosis in IBD are poorly defined, with little agreement on primary and secondary endpoints [4]. The IBSEN study is one of the most well-known prospective studies on clinical outcomes in UC, where the patients were divided into 4 predefined patterns of disease [2]. In a recently published review, the extent of disease and high disease activity were predictors of a more severe progression of disease [5]

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