P145 Exploring Mucosal Function As a Clinical Endpoint in Ulcerative Colitis

The standard for assessing disease activity, clinical remission and response to therapy in ulcerative colitis (UC) includes evaluation of patient symptoms and signs as well as endoscopic mucosal status. The ultimate goal is reversal of inflammation and its control, including a normalisation of mucosal function (i.e., ion transport and barrier integrity). Here, we hypothesise that mucosal function is a relevant target-to-treat endpoint. In this exploratory study, we studied the mucosal transport properties and compared them to endoscopy and histology findings in quiescent UC. We obtained sigmoid biopsies during colonoscopy from 33 UC patients (mean age 39, 23–75 years., 18 females) in clinical remission and 17 healthy controls (mean age 46, 20–68 years., 9 females). Remission was defined as total Mayo score ≤2 and no subscore >1. Mucosal transport function was assessed by measuring electrogenic ion transport (short-circuit current, SCC). Biopsies were mounted in Ussing-chambers and exposed to various pharmacological interventions: Sodium absorption inhibitor, phosphordiesterase inhibitor, specific COX-1 inhibitor, specific COX-2 inhibitor, and non-specific COX inhibitor were applied in order to stimulate or inhibit ion secretion and absorption, thereby assessing transport properties (see Table). Histology was assessed using Geboes score. All evaluations were blinded and performed by central reading. Most UC patients, 24 (73%), had an endoscopic Mayo subscore of 0 and the remaining 9 (27%) scored 1. Evaluated by Geboes, 11 (33%) had a score of 0–0.2 (no inflammation/deep remission), 15 (46%) a score of 1.1 (mild inflammation), while the remaining seven (21%) scored 1.2 (moderate inflammation). All controls were with normal endoscopic and histological findings. No difference in basal SCC was observed in UC patients vs. controls. Rofecoxib induced a significant decrease in SCC in UC patients vs. controls (see Table). This difference was not correlated to histology. Finally, no differences were observed between patient groups in responses to amiloride, theophylline, SC-560, or indomethacin. UC-patients in clinical and endoscopic remission demonstrate abnormal mucosal ion secretion related to the COX-2 pathway, without correlation to histology. Whether this abnormality carries an increased risk for early and/or increased severity at relapse is unresolved. We propose to further evaluate functional mucosal remission as a potential target-to-treat endpoint.