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

Abstract

Background 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. Methods Treatment naive-patients with ulcerative colitis were included at time of initial diagnosis from 2004–2014, followed by a validation study from 2014–2018. 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. Results We 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. Conclusions The 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.

Clinical Diagnosis and Phar-maceutical Management of Inflammatory Bowel Disease

“…Biologics: In the past twenty years, biological care with monoclonal antibodies targeting TNFα has become a groundwork of managing patients with IBD. Biologics are used routinely and are meant to overcome the limitations of therapies and ensure that individual patients can be treated with optimal drugs that are safe and precisely target IBD [99,100]. Pharmaceutic drug monitoring to guide the use of biologic therapy has widely been reported in AGA guidelines [101,102].…”

Improving prediction of disease outcome for inflammatory bowel disease: progress through systems medicine

“…In addition to serological markers, mucosa derived molecular signatures have also been tested for their disease prognostic value. For example, mucosal TNF-alpha expression combined with histological disease activity scores at the point of diagnosis have been reported to be predictive of a severe outcome in UC with a positive and negative predicate values of 0.89 and 0.87 respectively [40]. However, such parameters are very difficult to implement in routine clinical practice and results are still pending validation in larger, independent patient cohorts.…”