OP014 Histological remission is predictive of improved clinical outcomes in patients with ulcerative colitis: results from the TOUCHSTONE open-label extension.

Background: Histological remission (HR) has been reported as a positive prognostic indicator of clinical activity in ulcerative colitis (UC). The TOUCHSTONE open-label extension (OLE) is an oppor-tunity to examine the impact of histologic remission on UC activity during a long-term evaluation of efficacy and safety of ozanimod 1 mg. TOUCHSTONE was a randomized, double-blind, placebo-controlled phase 2 trial designed to assess the efficacy and safety of ozanimod 0.5 mg and 1 mg versus placebo during induction and maintenance in patients with moderate to severe UC [1], and estab-lished that ozanimod induced and maintained clinical response, clinical remission (CR), endoscopic mucosal healing, and HR through weeks 8 and 32. Methods: A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod at 0.5 mg, 1 mg, or placebo in TOUCHSTONE. Of the Background: The optimal therapeutic approach to ileocecal Crohn’s disease (CD) remains unclear. The objective of the study was to com-pare infliximab with laparoscopic ileocecal resection in patients with thiopurine or steroid refractory recurrent CD of the terminal ileum, with respect to quality of life (QoL) and cost-effectiveness. Methods: A multicentre randomised controlled, open-label trial was performed in 33 centres in The Netherlands and the UK. Adult patients with CD of the terminal ileum who failed > 3 months of thiopurine treatment or steroids without signs of a critical stricture were randomly allocated to either infliximab or laparoscopic ileocecal resection. Patients Background: Microscopic colitis (MC) is a chronic inflammatory bowel disease and includes two distinct histological forms: lympho-cytic colitis (LyC) and collagenous colitis (CC). The etiology of MC is probably multifactorial, secondary to an abnormal immune reac-tion in predisposed individuals, triggered by luminal factors (such as infection, drugs or bile acids). Bile acid (BA) malabsorption has been described in approximately 44% of MC patients, which often respond to cholestyramine, a BA-binding resin. Farnesoid X receptor (FXR) is the main BA receptor and is expressed at high levels in the intestine, especially in the terminal ileum (TI) and proximal colon. FXR-mediated mechanisms prevent the noxious effects of BA accu-mulation, preserving the integrity of the intestinal epithelial barrier and preventing chemically induced intestinal inflammation. Reduced FXR activation has been implicated in the pathophysiology of inflammatory bowel disease. Our aim was to explore the expression of FXR in patients with MC. Methods: Archival formalin-fixed paraffin-embedded (FFPE) samples (from the TI, right colon-RC and left colon-LC) were obtained from patients with MC and age and gender-matched healthy controls. Immunohistochemistry was performed using a mouse anti-human FXR monoclonal antibody (Perseus Proteomics, Tokyo, Japan). Nuclear FXR expression was scored in a semi-quantitative way by one experienced gastrointestinal pathologist, who was blinded to the clinicopathological information and biopsy location. Results: 140 FFPE samples (24 from the TI, 54 from the RC and 62 from the LC) from 34 patients with MC (26 LyC and 8 CC) and 31 controls were retrieved. There was a non-significant reduction of FXR expression in the ileum of patients with MC versus controls (moderate-high FXR expression: 76.9% vs 90.9%; p=NS). There was a significant reduction of FXR expression in patients with MC versus controls both in the right colon (moderate-high FXR expression: 23.1% vs 64.3%; p=0.003) and left colon (moderate-high FXR expression: 12.1% vs 44.8%; p=0.027). We found no difference in FXR expression between the two types of MC. Conclusions: Patients with MC present a significantly lower expression of FXR in the colon. This could render colonic epithelial cells more susceptible to the deleterious effects of BA, contributing to disease pathogenesis and symptoms in MC. These results open the possibility of exploring FXR agonists in the treatment of steroid-refractory MC.