Colitis Activity Index Research Articles

Operating Properties of Disease Activity Indices in Pediatric Inflammatory Bowel Disease: A Systematic Review.

Accurate, reliable, and responsive disease activity indices are important to streamline drug approval and treatment modalities for pediatric inflammatory bowel disease (pIBD). We aimed to identify all scoring indices used in pIBD randomized controlled trials (RCTs) and to evaluate their operating properties. MEDLINE, EMBASE, and CENTRAL were searched on December 6, 2022, to identify studies evaluating clinical, endoscopic, imaging, or patient-reported outcome measures (PROMs) in pIBD including Crohn's disease (CD) and ulcerative colitis (UC). Validity, reliability, responsiveness, and feasibility were summarized. Seventy RCTs evaluating pIBD indices were identified. Forty-one studies reported on the operating properties of 14 eligible indices (n = 9 CD, n = 5 UC). The Pediatric Crohn's Disease Activity Index (PCDAI) varied widely in terms of validity and reliability and was less feasible overall. In contrast, the Mucosal Inflammation Noninvasive Index, which includes fecal calprotectin, had better operating properties than the PCDAI. The Simplified Endoscopic Mucosal Assessment of Crohn's Disease appears more feasible and had similar operating properties than the longer Simple Endoscopic Score for Crohn's Disease. The Pediatric Ulcerative Colitis Activity Index was feasible, valid, and reliable, but responsiveness needs to be evaluated further. The Endoscopic Mayo score and the Ulcerative Colitis Endoscopic Index of Severity were reliable, but validity and responsiveness need to be evaluated further. Imaging and PROMs/quality of life indices need further evaluation. The operating properties of pIBD clinical trial end points varied widely. These results highlight the need for further validation and development of novel indices.

Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

Combination biologic therapy in pediatric inflammatory bowel disease: Safety and efficacy over a minimum 12-month follow-up period.

The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD. Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range[IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ). Clinical remission was achieved in 13 (45%; sevenUCand sixCD) and 12 (41%; sevenUCand fiveCD) Pediatric Weighted Crohn's Disease Activity Index(wPCDAI)/Pediatric Ulcerative Colitis Activity Index(PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nineUCand sevenCD) and 12 (41% sevenUC andfiveCD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UCand fourCD) of patients achieved endoscopic remission. DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD.

Comparison of Fecal Calprotectin and Myeloperoxidase in Predicting Outcomes in Inflammatory Bowel Disease.

Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course. Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months. One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 μg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 μg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course. Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

A268 1 YEAR FOLLOW-UP OF PEDIATRIC ULCERATIVE COLITIS USING INTESTINAL ULTRASOUND

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been previously limited to small samples of patients with no long-term follow up. Aims This project aims to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (pampersand:003C0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (pampersand:003C0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (ampersand:003E250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusions BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity. Funding Agencies TRIANGLE, WCHRI, Stollery Children's Hospital Foundation.

Disordered eating behaviors in pediatric patients with inflammatory bowel disease in remission or mild-moderate disease activity.

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder that affects the gastrointestinal tract. Disordered eating describes irregular eating behaviors that may be a precursor to an eating disorder diagnosis. Higher rates of disordered eating have been described in chronic diseases. Screening for disordered eating is not performed in pediatric patients with IBD. The goal of this longitudinal study was to use the Eating Attitudes Test (EAT-26) to screen pediatric patients with IBD for disordered eating, estimate our population's prevalence, identify potential risk factors, and correlate positive EAT-26 screen results with evaluation in adolescent medicine clinic. Eighty patients with IBD between 10 and 21 years completed the EAT-26 questionnaire during gastroenterology clinic visit. Disease activity was measured using Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI). Patients also rated their own disease activity on a numerical scale. Five patients had a positive EAT-26 screen and were evaluated in the adolescent medicine clinic. One hundred percent of those who screened positive were diagnosed with a concomitant eating disorder once evaluated. Only 20% of those who screened positive had active IBD. Higher weight, body mass index, and patient perception of disease activity were associated with increased EAT-26 score. Pediatric patients with IBD are at risk for disordered eating, with a prevalence of 6% in our population, which is twice the prevalence of disordered eating in the general population. The EAT-26 questionnaire is a feasible tool to screen pediatric IBD patients for disordered eating.

The association between dietary patterns and disease severity in patients with ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease involving the colon and rectum. One of the most modifiable environmental factors affecting UC severity is the patient's dietary pattern. Although the role of dietary patterns on UC aetiology has been investigated previously, its relationship with disease severity has not yet been elucidated. This study examined the association between UC patients' dietary patterns and disease severity. This cross-sectional study was conducted in 340 UC patients. Using an FFQ, food patterns were assessed. Twenty-five food categories were categorised based on the similarity of the nutrient composition of the food using the factor analysis method. A simple clinical colitis activity index was used to determine disease severity. Three dietary patterns were identified based on the factor analysis: healthy, unhealthy and Western dietary pattern. After adjusting for potential confounding factors, patients who were in the highest tertile of healthy dietary pattern compared with the lowest tertile were 92 % less likely to have severe UC (OR: 0·08; 95 % CI: 0·03, 0·22). Also, those in the highest tertile of the Western dietary pattern were 3·86 times more likely to have severe UC than those in the lowest tertile (OR: 3·86; 95 % CI: 1·86, 8·00). Even after controlling for confounding variables, unhealthy dietary pattern did not increase the risk of severe UC. Our data indicate the beneficial role of healthy dietary pattern in amelioration of disease severity in UC patients. To confirm this association, more studies are needed, especially prospective cohort studies.

BREASTFEEDING STATUS AND DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS: AN EXPLORATORY RETROSPECTIVE COHORT STUDY

Abstract OBJECTIVE While the protective effect of being breastfed on the development of ulcerative colitis has been well established, it is not known if being breastfed decreases colectomy rate and disease severity for pediatric patients. This work is designed to better understand the connection between breastfeeding status and disease severity of ulcerative colitis among pediatric patients. METHODS This exploratory retrospective cohort study analyzed the clinical and laboratory data of patients at Boston Children’s Hospital enrolled in a data registry and biorepository since 2012. Data was collected from charts and analyzed to determine if there is a significant difference in colectomy rate, pediatric ulcerative colitis activity index (PUCAI) score, ESR, or CRP, between not breastfed (n=56), breastfed (n=39), and mixed breastfed patients (n=31). Breastfed patients are defined as patients who were exclusively breastfed for greater than or equal to three months. Patients who were never breastfed were considered not breastfed. Patients who were exclusively breastfed for less than three months or received a mix of formula and breastfeeding were considered mixed breastfed. Statistical analysis of the groups was performed using a one-way ANOVA. RESULTS At disease diagnosis, the average PUCAI score of the not breastfed group (32.4) was significantly higher than the exclusively breastfed group (18.4) (p value = 0.0189). No significant difference was detected in the average PUCAI score of the mixed breastfed group (34.1) compared to the not breastfed group (32.4). Significant differences in the colectomy rate between all three groups were not detected, and likewise we did not find significant differences in markers of disease severity including ESR, CRP, and hemoglobin at diagnostic visit between groups. CONCLUSION These results suggest that children with ulcerative colitis who were exclusively breastfed have a lower average PUCAI score at the time of diagnosis than those who were not breastfed. Further investigation with larger data sets may be necessary to determine other benefits of exclusive breastfeeding in pediatric ulcerative colitis patients.

REAL-WORLD SAFETY AND EFFICACY OF USTEKINUMAB AND VEDOLIZUMAB IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract CONTEXT/PURPOSE Ustekinumab and vedolizumab are approved biologicals to treat adults with inflammatory bowel disease (IBD) but currently administered off-label for children. Aims: (1) assess safety and adverse events during treatment with ustekinumab or vedolizumab in pediatric IBD and (2) assess steroid free clinical remission and mucosal healing at 6 months and 1 year. METHODS Retrospective chart review of pediatric patients (&amp;lt;22 years) with IBD treated at an academic hospital and two affiliated practices. Inclusion: Patients with IBD who received either ustekinumab or vedolizumab between January 2015 to June 2022 with minimum of 6 months follow up. Clinical remission assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) &amp;lt; 10 and short Pediatric Crohn’s Disease Activity Index (shPCDAI) &amp;lt;15, and mucosal healing by fecal calprotectin &amp;lt;250 mcg/gram. RESULTS Fifty-eight patients received vedolizumab and 55 patients received ustekinumab. Patients with ulcerative colitis (UC) or IBD unclassified (IBDU) on vedolizumab were more likely to be in remission at 6 months (58% vs. 42%, p = 0.3, Table 1) and significantly higher at achieving 1-year steroid free remission (64% vs. 27%, p = 0.019) compared to ustekinumab. Over two thirds of biologic naïve and about half of biologic exposed patients who received vedolizumab achieved 1-year steroid free remission (78% vs. 58%, Figure 1). All patients who received ustekinumab were biologic exposed. In Crohn’s disease (CD), no significant difference was seen in children receiving vedolizumab compared to ustekinumab at 6 months remission (57% vs. 63%, p = 0.7) or 1-year steroid free remission (70% vs. 70%, p &amp;gt;0.9). All biologic naïve patients and half of biologic exposed patients who received vedolizumab achieved 1 year steroid free remission. Both bionaive and two thirds of biologic exposed patients who received ustekinumab achieved 1-year steroid free remission (100% vs. 67%). When comparing vedolizumab and ustekinumab, no significant difference was observed in 6 month remission (73% vs. 59%, p = 0.2) and 1-year steroid free remission based on calprotectin (61% vs. 66%, p = 0.7). Similar to clinical remission rates, biologic naïve patients tended to have higher remission rates based on calprotectin. Five patients each had minor adverse events with ustekinumab and vedolizumab, and 20 were hospitalized mostly for IBD flare. CONCLUSION Both biologicals were safe and effective in achieving clinical remission at 6 months and 1 year. They were more effective when used in bionaive patients, although numbers were very low for ustekinumab. The superior efficacy of vedolizumab in UC and IBDU at 1-year may be attributed to larger cohort of bionaive patients. Larger multicenter prospective studies are needed to validate these findings regarding efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. Table 1 Remission on Vedolizumab and Ustekinumab Figure 1 Remission on Vedolizumab vs. Ustekinumab Stratified by Biologic Exposure

CLINICAL, BIOCHEMICAL, AND INTESTINAL ULTRASONOGRAPHY RESPONSE TO CURCUMIN-QINGDAI (CURQD) COMBINATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND There are few FDA-approved therapies for pediatric patients with inflammatory bowel disease (IBD). Clinical remission rates plateau at 60%, even with the currently available biologic therapies. Nutraceuticals are novel alternative treatments that can be used as adjunct treatments. AIM In this case series of 8 patients, we aim to present the clinical and radiological response to a novel nutraceutical agent, CurQD, composed of QingDai (Indigo Naturalis) and Curcumin. METHODS Patients included required a baseline pre-treatment clinical assessment and at least a single follow-up examination. Clinical status was evaluated based on the Physician General Assessment (PGA, determined independently from the clinical scoring systems) and the pediatric Crohn’s disease activity index (PCDAI) or the pediatric ulcerative colitis activity index (PUCAI), as appropriate. Baseline biomarkers (Hgb, ESR, CRP, albumin, and calprotectin(FC)) were collected pre and post-treatment when available. When available, intestinal ultrasound (IUS) features were also noted. On the IUS, bowel wall thickness (BWT, in mm) and color Doppler signaling (measured by the modified Limberg score graded 0,1,2, or 3 based on severity) were collected. The longitudinal changes were demonstrated on the most inflamed segment. Considering the small sample size, only descriptive statistics were applied. RESULTS Primary therapies received included anti-TNFα for 3 patients, ustekinumab in 3 patients, 1 on vedolizumab, and mesalamine in 1. Baseline assessment was done at a median time of 1.8 weeks (IQR 0.9-3.6 weeks) before starting the supplement, and the follow-up was 3.9 weeks (IQR 2.8-5.4 weeks) after starting the supplement. Two patients were in clinical remission at baseline but had active disease based on Doppler activity on IUS, 3 patients had mild active disease, and 3 patients had either moderate or severe disease activity. At follow-up, all patients but one were in clinical remission. (Table 1) Median baseline FC decreased from 1047.4 ug/g (IQR 532.4-1107) to 27.1 (IQR 27.5-341.3). Five patients had complete IUS information. When isolating the most inflamed segment on IUS, all patients demonstrated a response to treatment, noted by a decrease in BWT and/or a decrease in Doppler signaling. (Figure 1) No patient had a baseline therapy change after their follow-up. One patient reported abdominal bloating after starting CurQD and discontinued the product after five weeks. CONCLUSION CurQD is a promising nutraceutical that may assist in breaking the therapeutic ceiling of biological therapies in IBD. Based on this small experience, a larger randomized controlled trial in children would be needed to assess the safety and efficacy of this product in this vulnerable patient group. Furthermore, IUS is a practical tool for evaluating response to therapy in a pragmatic clinical setting. Table 1 Change in clinical disease scores in patients receiving CurQD Figure 1 Description of changes in a) bowel wall thickness (BWT) and b) color Doppler signaling (measured by the modified Limberg score) in patients treated with CurQD.

PROTECTIVE ROLE OF SAFFRON TO REDUCE INFLAMMATION AND IMPROVE CLINICAL MANIFESTATIONS IN ULCERATIVE COLITIS PATIENTS

Abstract BACKGROUND We studied saffron as an additional intervention to improve clinical manifestations of Ulcerative colitis (UC) patients. METHODS This is a study at Yazd university where 30 UC patients were randomly assigned to placebo (n=9), low (n=9, 25 mg), or high dose saffron (n=12, 50mg), two times a day for 8 weeks. Hemoglobin, platelet levels, CRP, ESR, and fecal calprotectin along with clinical data Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score, and Hamilton Depression Anxiety Score (HDRS) were recorded at baseline and completion of treatment. For validation, we recruited 3 UC patients at Howard University who received 50mg of Saffron twice daily for 8 weeks, two underwent a wash-out period and received saffron for a second cycle. Inflammatory markers, CRP, stool calprotectin, and the cytokines from PMA/ionomycin stimulated PBMCs, at baseline and 8 weeks Saffron treatment were compared. 16S rDNA analysis was performed on stool DNA for gut microbiome. RESULTS In Yazd study of 30 patients, all participants completed the study successfully. The high dose group showed significant improvement in HDRS score (p=0.001), SCCAI (p=0.04), Partial Mayo score (p=0.01), fecal calprotectin (p=0.009), and CRP (p=0.001) compared to baseline. The low dose group also improved in HDRS score (p=0.01; Table 1, Fig 1). No adverse events were reported. In HU data, saffron improved Partial Mayo Score, health related quality of life and HDRS. Pro-inflammatory cytokines TNFα, INFγ, IL-6, IL-2, IL-17a decreased while anti-inflammatory IL-10, TGF-β increased. Fecal calprotectin levels of 228 μg/g and 169 μg/g decreased to 63 μg/g and 16 μg/g in two individual patients, respectively. After the wash-out period, fecal calprotectin increased. A second saffron treatment cycle reduced it again further validating the causal relationship. Saffron led to a decrease in gamma Proteobacteria, and enrichment in Ruminococcaceae. CONCLUSION This study demonstrates that saffron led to improvements in clinical response including reduction in partial Mayo scores, HDRS scores, and inflammatory markers such as fecal calprotectin and CRP. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with UC. Table 1. Basic characteristics, clinical variables, and laboratory variables among the study participants in three arms of the clinical trial. Figure 1 Effect of Saffron on quality of life and Inflammatory markers.

P890 Usefulness of subcutaneous Infliximab in patients with Inflammatory Bowel Disease in clinical practice: are increased levels associated with clinical benefit?

Abstract Background Switch from intravenous Infliximab (IFXiv) to subcutaneous Infliximab (IFXsc) in Inflammatory Bowel Disease (IBD) has been associated with an increase in trough levels. However, whether this increase is correlated with additional clinical benefit has not thus far been evaluated in clinical practice. Methods Single-center retrospective study of IBD patients who switched from IFXiv to IFXsc (for at least 3 months), between July 2021 and August 2023, due to unfavorable pharmacokinetics (IFX serum levels &amp;lt;3 +/- anti-IFX antibodies). Disease activity was defined as clinically: Simple Clinical Colitis Activity Index (SCCAI) ≥2 for Ulcerative Colitis (UC), Harvey Bradshaw Index (HBI) ≥5 for Crohn´s Disease (CD) or perianal fistulae with active drainage; and biochemical: C-reactive protein (CRP) &amp;gt;5 mg/L and/or fecal calprotectin (FC) &amp;gt;250 µg/g in UC and &amp;gt;150 µg/g in CD. Primary endpoint was to evaluate the effectiveness of IFXsc switch: achieving clinical response (decrease of SCCAI ≥2, IHB ≥3 or ≥50% in fistula drainage) or remission (SCCAI ≤1, IHB ≤4 or absence of active fistula drainage) with biomarkers normalization, or maintenance of remission, in patients with and without previous activity, respectively. Secondary endpoints were to assess IFX levels change and safety of IFXsc switch. Results Twenty-five patients (23 CD, 2 UC) were included (Table 1). Previous IFXiv therapy lasted for a median of 55 (20.6-74.1) months (100% with intensified dose and 48% with combined therapy). Median baseline IFX level was 1.7 (0.4-3) μg/mL, with anti-IFX antibodies in two cases. At baseline, 7 patients were in remission and 18 had active disease: 15/18 clinical or both clinical and biochemical (3/15 luminal, 11/15 perianal or 1/15 both), and 3/18 biochemical only. Median follow-up was 15.2 (10.2-19.2) months. After IFXsc switch, an increase of IFX level was achieved in 96% of cases, with a median final level of 12.4 μg/mL (9.2-18) (Figure 1). None of the patients in remission at the beginning relapsed during follow-up. Of patients with previous clinical activity, 66.6% achieved clinical remission (53.3%) or response (13.3%), which was seen in 50% of patients with luminal and 66.7% with perianal activity, after a median of 79 (75-210) days. CRP and FC normalization was reported in 53.3% of patients with previous biochemical activity. Treatment was discontinued only in one patient due to inefficacy. IFXsc was intensified in 8% and concomitant treatment could be withdrawn in four patients. No adverse events we reported. Conclusion Switching to IFXsc in patients with previous therapy with intensified IFXiv is not only associated with a more favorable pharmacokinetic profile but also with a greater effectiveness.

P1209 Baseline gut microbiota composition and function reflect response to 5-ASA treatment in Ulcerative Colitis

Abstract Background Mesalazine (5-ASA) is a key initial treatment of ulcerative colitis (UC); recent studies have highlighted the role of the gut microbiota in 5-ASA metabolism. There is no established means of predicting treatment outcome. We sought to investigate changes in the gut microbiota and metabolome with 5-ASA treatment, and whether such changes may reflect clinical outcomes. Methods Longitudinal faeces, serum and urine samples were collected from patients with newly diagnosed UC before and after 5-ASA treatment. We documented longitudinal microbiota and metabolome changes with 5-ASA treatment and compared baseline gut microbiota and metabolome in responders (simple clinical colitis activity index (SCCAI) of &amp;lt;4 and faecal calprotectin (FC) of &amp;lt;100 µg/g) and non-responders to 5-ASA. Stool bacterial profiling was performed via 16S rRNA gene sequencing of the V1/V2 hypervariable regions. Host and microbial metabolites in stool, serum and urine were detected and semi-quantitated using liquid chromatography mass spectroscopy (LC-MS) and nuclear magnetic resonance spectroscopy (1H-NMR). Kruskal-Wallis tests and paired analyses using a Wilcoxon rank test were used and p values were adjusted using Benjamini-Hochberg false discovery rate (FDR) correction. Results 37 patients newly diagnosed with UC were recruited. Samples were collected at baseline and a median of 83 days (IQR 22.5 days) later; there were 27 responders and 10 non-responders. Comparing pre- and post- 5-ASA treatment samples demonstrated a reduction in gut microbial α diversity (P=0.01) (Fig 1). Faecal methionine increased with 5-ASA (P=0.04) in all patients, and isovalerate reduced with 5-ASA (P&amp;lt;0.01). Similar reductions after 5-ASA were noted in serum glycoprotein B (GlycB) (P=0.02). At baseline, responders tended to have increased α diversity compared to non-responders, but not statistically significantly (P=0.09). Similarly, there were β diversity differences, although these did not reach significance (P=0.06). At baseline non-responders had a higher relative stool abundance of Bacteroidetes and Firmicutes (P&amp;lt;0.01) compared to responders. Agathobacter, Coprococcus and Blautia genera were enriched in non-responders (P=0.05). At baseline, urinary hippurate was higher in patients going on to respond to 5-ASA compared to non-responders (P=0.04); faecal lysine (P&amp;lt;0.01) and putrescine (P=0.01) levels were also higher in non-responders at baseline. 5-ASA responders had reductions in faecal 2-methylbutyrate and isobutyrate (P=0.02) longitudinally. Conclusion We have shown that baseline relative abundance of certain taxa (such as Blautia), urinary Hippurate and faecal lysine reflect response to 5-ASA. Alterations in the gut microbiome and metabolome are associated with 5-ASA treatment.

P1006 Assessing sexual health care needs in patients with inflammatory bowel disease

Abstract Background Optimal care of inflammatory bowel disease (IBD) should encompass both physical and mental health. Sexual health is often overlooked, despite contributing significantly to patient quality of life. This study aims to further characterise the impacts of IBD on sexual health using an IBD specific scale and assess patient interest in accessing relevant expertise. Methods An electronic survey was emailed to patients with IBD at a tertiary public hospital using REDCap. Assessment of disease severity was based on clinical disease indices: Harvey Bradshaw Index (HBI) for patients with Crohn’s disease (CD); and the Simple Clinical Colitis Activity Index (SCCAI) for patients with ulcerative colitis (UC). The survey also contains de-identified demographic data, basic information about the participant’s IBD and questions derived from both the validated IBD-Specific Female Sexual Dysfunction and IBD-Male Sexual Dysfunction Scales. Comparisons of patient responses from those with clinically active versus inactive disease were made using Fisher’s exact test. Analysis was exploratory and no correction for multiple comparisons was made. Results A total of 101 participants took the survey, including 53 females and 48 males which comprised of 38 patients with UC, 57 with CD, three with indeterminate colitis (and three unsure of diagnosis). Age ranged from 18 to 81 years old with a median of 38; 90% of patients had a disease duration of at least 2 years. Patients with CD recorded a median HBI of five (interquartile range three to nine). Patients with UC recorded a median SCCAI of two (interquartile range one to four). Patients with clinically active CD trended toward more significant sexual dysfunction than those in remission across all domains in the sexual dysfunction scale. Patients with active CD were more likely to report that their disease had prevented engagement in sexual activity in the past year (p=0.04) and more likely to be afraid to participate in sexual activity (p=0.01) compared to those in remission. Patients with active UC were more likely to report that pelvic pain affected sexual activity (p=0.03) compared to those in remission. Regarding seeking additional support, 47% of all patients expressed interest in gaining assistance though only 20% have attempted to seek this advice. 36% of participants would wish to be contacted by their treating team if a sexual health service became available at their hospital. Conclusion Patients with more active IBD were more likely to report that their illness negatively impacts their sexual health. 74% of participants reported interest in accessing expert advice regarding sexual health, highlighting the need for services specifically addressing sexual health for IBD patients.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p &amp;lt;0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P193 Fatigued patients with Inflammatory Bowel Disease exhibit distinct systemic antibody epitope repertoires

Abstract Background Patients with inflammatory bowel diseases (IBD) frequently experience fatigue, affecting up to 80% of those with active disease and approximately 50% with quiescent disease. The exact cause of IBD-associated fatigue is often unknown, making clinical management very challenging. In this study we aimed to explore whether patients with quiescent IBD reporting fatigue exhibit specific systemic antibody responses, which could provide insight into immune reactivities underlying fatigue. Methods Systemic antibody epitope repertoires were profiled in 327 patients with IBD (156 Crohn’s disease [CD]; 171 ulcerative colitis [UC]) leveraging phage-display immunoprecipitation sequencing (PhIP-Seq) against 344,000 rationally selected peptide antigens. Fatigue severity was assessed on a 10-point Likert scale, ranging from 1 (no fatigue) to 10 (highest fatigue severity). Quiescent IBD was defined as clinical (Harvey-Bradshaw Index [HBI] &amp;lt;5 or Simple Clinical Colitis Activity Index [SCCAI] &amp;lt;2.5) and biochemical remission (C-reactive protein [CRP] &amp;lt;5 mg/L) at time of sampling. Multivariable logistic regression analyses, allowing adjustment for potential confounding factors e.g. age, sex, and smoking, were performed to identify associations between fatigue and systemic antibody responses. Results A total of 105 different antibody-bound peptides were associated with fatigue (nominal P-value&amp;lt;0.05), albeit none passed adjustment for multiple comparisons. Among these antibodies, 50 (47.6%) were found to be less frequent in highly fatigued patients (fourth quartile, Q4), while 55 (52.4%) were identified as more frequent in highly fatigued patients compared to those with low fatigue scores (first quartile, Q1). Among highly fatigued patients, antibody responses were primarily directed towards viral antigens, notably several antigens from Epstein-Barr virus (EBV), as well as bacterial antigens, including functional proteins from Streptococcus and Staphylococcus species. Fatigued patients with CD exhibited elevated systemic antibody responses against allergens, Staphylococcus, Pseudomonas aeruginosa, and Shigella spp. Fatigued patients with UC showed higher frequencies of antibody responses against herpes simplex virus (HSV), influenza viruses, and few responses against allergens and Streptococcus bacteria. These results remained materially unchanged when repeating analyses in patients with quiescent IBD. Conclusion This study may suggest a potential role of viral antigens, particularly EBV, in the pathophysiology of fatigue in patients with IBD. However, larger confirmatory studies are needed to validate these findings. PhIP-Seq may represent a valuable strategy to approach the investigation of immune responses underlying complex symptoms such as fatigue.

P910 Salivary calprotectin as a prognostic biomarker in Early Onset Inflammatory Bowel Disease: a cohort study

Abstract Background Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD) affects children in 25% of cases. In Early Onset IBD (EOIBD) oral involvement is common and oral manifestations (OM) are frequently the first presenting sign of disease. This study compared salivary calprotectin (SCp) between EOIBD and healthy controls (HC), differentiating patients based on their history of OM. Furthermore, this report correlated salivary and faecal calprotectin (FCp) in EOIBD and assessed the prognostic accuracy of SCp in predicting disease relapses. Methods A cohort study was conducted; 9 HC and 27 EOIBD (18 UC and 9 CD) were recruited at the University of Naples Federico II. EOIBD were divided in two subgroups based on the history of OM. A sample of stimulated whole saliva was collected by each participant by spitting. The samples were then processed by ELISA for determining SCp. For each patient clinical disease activity was measured through Paediatric Ulcerative Colitis Activity Index (PUCAI) and Paediatric Crohn’s Disease Activity Index (PCDAI), at baseline and during follow-up (4/8/12 weeks). At baseline, patients provided a stool specimen for FCp determination. SCp levels were compared between groups. In EOIBD SCp was correlated to clinical data and to FCp. Results At baseline all the patients were in treatment with immunosuppressive drugs; 19 were in clinical remission (PUCAI/PCDAI &amp;lt;10) and 8 had mild disease (PUCAI/PCDAI&amp;lt;35). 13 EOIBD had an history of OM: 12 suffered from aphthous-like manifestations while 3 reported granulomatous lesions; 10 experienced oral involvement before IBD diagnosis. OM were more prevalent in CD than in UC and were associated to ileocolic, perianal and upper gastrointestinal tract involvement. EOIBD with OM reported significantly higher SCp than EOIBD without OM and HC: 155,79±60,08 pg/mL in EOBD with OM vs 82,95±51,58 pg/mL in EOIBD without OM (P&amp;lt;0,01**) and 98,21±39,67 pg/mL in HC (P=0,21). Despite the systemic therapy and the clinical remission, in 7 EOIBD with OM oral lesions persisted. These patients had higher SCp compared to those who experienced OM remission (P&amp;lt;0,05*). In EOIBD with OM higher SCp was associated to higher FCp (P&amp;lt;0,05*) while in EOIBD without OM this correlation was not described. No correlation was found between SCp values and PUCAI/PCDAI at baseline. EOIBD with OM who reported higher SCp were found to have increased risk of relapse (P&amp;lt;0,05*) while no association was reported in EOIBD without OM. Conclusion In EOIBD with OM SCp is significantly higher, mirrors intestinal inflammation and predicts relapses. Our results suggest the use of SCp as a prognostic biomarker in EOIBD with OM although more studies are needed.

P1132 Fecal incontinence in Inflammatory Bowel Disease (IBD): associated factors and impact on the quality of life of patients in an IBD clinic in Switzerland

Abstract Background Literature on prevalence of fecal incontinence (FI) in inflammatory bowel disease (IBD) and associated factors has not been thoroughly studied. IBD is a chronic disease with high morbidity and significant impact on quality of life. Awareness of prevalence and associated factors of FI would make gastroenterologists more conscious of its burden, leading to targeted clinical assessment and treatment. Methods We conducted a cross-sectional study, looking at risk factors for FI and its impact on quality of life. The study population consisted of IBD patients aged from 16 to 80 years old in an IBD clinic in Switzerland. Patients with a stoma, a J-Pouch and an unspecified IBD were excluded. The survey had 53 questions, with demographics and main clinical variables. The quality of life of patients was assessed using the World Health Organization quality of life scale. Disease severity was measured based on the short Crohn’s disease activity index (SCDAI) for Crohn’s disease (CD) and using the simple clinical colitis activity index (SCCAI) for Ulcerative colitis (UC). Logistic regression was used to calculate crude and adjusted odds ratio (OR), applying 95% confidence intervals (CI). Results 450 questionnaires were randomly distributed. 392 patients met the inclusion criteria. 116 patients (29.5%) reported FI. Factors associated with FI included: age &amp;gt; 50 years old [OR 2.74 (CI: 1.57-3.89)]; one or more vaginal delivery [OR 2.49 (CI: 1.32-4.71)];disease duration &amp;gt; 15 years [OR 2.04 (CI: 1.31-3.16)], abdominal pain [OR 2.56 (CI: 1.60-4.09)], diarrhea [OR 3.70 (CI: 2.26-6.04)], blood in stool [OR 3.33 (1.88-5.89)], more than 3 bowel movements/day [OR 4.50 (CI: 2.79-7.26)],night bowel movements [OR 3.98 (CI: 2.36-6.71)] and an SCCAI ≥ 3 [OR 6.06 (CI: 2.62-14.02)]. There was also a positive association between the presence of one or more extraintestinal manifestation (EIM) [OR 1.64 (CI: 1.03-2.61)] and FI. General well-being [OR 2.61 (CI: 1.65-4.14)] was inversely associated with FI. Similarly, depression and anxiety were associated with FI, respectively; [OR 2.43 (CI: 1.27-4.68) and OR 1.88 (CI: 1.07-3.30)]. Noticeably, 35.3% of patients with FI could not hold their stools for more than 5 minutes, and 14.7% were unable to hold their stools for more than a minute. Conclusion FI was highly prevalent (29.5%) in our survey. Age, vaginal delivery, disease duration &amp;gt;15 years, abdominal pain, diarrhea, blood in stool, &amp;gt;3 bowel movements /day, night bowel movement, SCCAI ≥ 3, ≥ 1 EIM were associated with FI. The quality of life was significantly impacted, and anxiety and depression were associated with FI. These implications highlight the need for interventions aimed at enhancing physical and mental health outcomes among individuals with IBD.

P381 Intestinal ultrasound in newly diagnosed Ulcerative Colitis predicts the need for colectomy

Abstract Background Upon diagnosis of ulcerative colitis (UC), it remains challenging to predict who will have a severe disease course, ultimately necessitating colectomy. Predictive tools capable of risk-stratifying patients and individualize treatment are warranted. The aim of this study was to assess whether Intestinal ultrasound (IUS), performed at the onset of UC, could help predict the need for colectomy within the first year of diagnosis. Methods In a Danish prospective inception cohort, all new-onset adult patients with UC (including unclassified IBD) with left-sided or extensive colitis underwent IUS near the diagnostic endoscopy. The assessment included the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) and the bowel wall thickness (BWT) of the most inflamed segment. Besides IUS, we recorded age, gender, smoking, BMI, the Mayo endoscopic score (MES), the Simple Clinical Colitis Activity Index (SCCAI), and biomarkers hemoglobin (hgb), C-reactive protein (CRP), albumin and fecal calprotectin. Results During inclusion (May 2021 – April 2023), we included 193 UC patients with Montreal classification E2 or E3. In total, 12/193 (6%) underwent colectomy within the first year or during follow-up (min. 6 months). Baseline characteristics are presented in Table 1. Univariable analyses identified high MES, CRP, SCCAI, IBUS-SAS, and BWT, along with low Hgb and albumin, as significantly associated with an increased colectomy risk. Multivariable analysis with stepwise reduction identified only SCCAI (OR: 2.0, CI 1.2–3.3, p&amp;lt;0.005) and BWT (OR: 1.6, CI 1.1–2.3, p=0.01) as independent predictors. Through ROC analysis, BWT presented the highest accuracy (AUC: 0.89), and the optimal cut-off by Youden Index for colectomy prediction was &amp;gt; 6.1 mm. Combining all the significant non-IUS predictors, CRP, MES, SCCAI, hgb, and albumin yielded an AUC of 0.88. The highest accuracy was found by combining SCCAI and BWT, with an AUC of 0.94. Kaplan-Meier curve for colectomy-free survival is presented in Figure 1. Among patients with BWT&amp;gt;6.1mm, 18/21 (86%) started systemic steroids within the first week, compared to 43/125 (34%) of patients with BWT ≤ 6.1, p=0.007. Among patients with BWT &amp;gt; 6.1mm, 11/21 (52%) started biologics within the first 31 days, compared to 5/125 (4%) of patients with BWT≤6.1mm, p&amp;lt;0.001. Despite more aggressive treatment, 8/21 (38%) with BWT&amp;gt;6.1mm had a colectomy compared to 2/125 (2%) with BWT≤6.1mm.Conclusion IUS at UC onset, specifically BWT, is a robust predictor of colectomy risk within the first year of diagnosis. Combining clinical symptom scores with IUS enhances predictive accuracy. It can accurately identify patients at an increased risk of colectomy, guiding early treatment decisions for improved patient outcomes.