Discovery and validation of mucosal TNF expression combined with histological score-a biomarker for personalized treatment in ulcerative colitis
AuthorFlorholmen, Jon; Johnsen, Kay-Martin; Meyer, Renate; Olsen, Trine; Moe, Øystein Kittel; Tandberg, Petter; Gundersen, Mona Dixon; Kvamme, Jan-Magnus; Johnsen, Knut; Løitegård, Terje; Raschpichler, Gabriele; Vold, Cecilia; Sørbye, Sveinung; Goll, Rasmus
Methods - Treatment 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.
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.