Introduction：The first–line agent for the treatment of ulcerative colitis is 5–ASA (5–aminosalicylic acid). About 10% of patients taking 5–ASA are deemed to develop a condition called “5–ASA intolerance,” in which they have difficulty taking 5–ASA continuously due to adverse effects. The incidence of 5–ASA intolerance seems to be on the rise. We can provide safer treatment if we can identify patients at high risk of developing 5–ASA intolerance, but there are few prediction models for the 5–ASA intolerance.Objective：The purpose of this study was to develop and internally validate a prediction model for the 5–ASA intolerance among Japanese ulcerative colitis patients using real–world data.Methods：We analyzed data from January 2005 to March 2023 using the payer database held by JMDC Inc. Japanese patients aged 15 years and older who were diagnosed with ulcerative colitis and prescribed oral 5–ASA were included in the analysis. Index date was defined as the date 5–ASA was first dispensed. A prediction model was developed using a Cox proportional hazards model with the number of days from the index date to the occurrence of an event (5–ASA intolerance) as the outcome. Predictors were selected based on expert opinions and the results of Cox regression. Internal validity of the model was assessed from two points; 1) The model’s discriminative ability by optimism–corrected c–index with bootstrapping, 2) The model’s accuracy by a calibration plot.Results：The sample size was 9,520 with 931 events. The selected predictors were gender, age, oral 5–ASA brands, oral 5–ASA prescription dose, and the presence of a diagnosis of a certain disease (i.e. intestinal infection, influenza or pneumonia, iron–deficiency anemia, gastro esophageal reflux disease, gastric ulcer, and acute pancreatitis) within the past 1 year of the Index date. The optimism–corrected c–index was 0.5934. The calibration plot shows adequate fit.Conclusion：With the developed prediction model, we could identify patients with ulcerative colitis who are at high risk for 5–ASA intolerance.

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.