Simple Clinical Colitis Activity Index Research Articles

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.

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.

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.

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.

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.

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.

P601 Intestinal ultrasound correlates with clinical, biochemical, endoscopic and histologic biomarkers in patients with Ulcerative Colitis: a cross-sectional study

Abstract Background Intestinal ultrasound (IUS) is emerging as a non-invasive monitoring tool in patients with ulcerative colitis (UC). Our goal was to correlate IUS with clinical, biochemical, endoscopic and histological activity. Methods Cross-sectional multicentric study of patients with left (E2) or extensive (E3) UC. Consecutive patients were included and clinical (Patient-Reported Outcome (PRO2) and Simple Clinical Colitis Activity Index (SCCAI)), biochemical (fecal calprotectin (FCal) and C-reactive protein (CRP)), endoscopic (Mayo endoscopic sub-score (sMayo)) and histological (Nancy score) activity were evaluated. IUS activity was characterized by Milan Ultrasound Criteria (MUC). Clinical, biochemical, ultrasonographic, endoscopic and histologic remission were defined as SCCAI≤2, FCal&amp;lt;250 ug/g, MUC&amp;lt;6.2, sMayo=0 and Nancy=0, respectively. All evaluations were performed within 1 month. Pathologist was blinded to endoscopic and IUS results. In patients in IUS remission, the sigmoid colon was considered for analysis. Results 58 patients with UC were included (55% men, with a mean-age of 38 (+/-17) years, 65% with E2 UC). Clinical, biochemical, ultrasonographic, endoscopic and histologic remission occurred in 53%, 53%, 53%, 31% and 12% of the patients, respectively. The most affected segment by both IUS and endoscopy was the sigmoid colon (34.5% and 41.4%, respectively). In our cohort, IUS activity had a strong correlation with PRO2 (r=0.778, p&amp;lt;0.001), SCCAI (r=0.810, p&amp;lt;0.001) and endoscopic activity (r=0.758, p&amp;lt;0.001), and a moderate correlation with FCal (r=0.517, p&amp;lt;0.001), CRP (r=0.402, p&amp;lt;0.001) and histological activity (r=0.475, p&amp;lt;0.001). We observed a consistent increase in the bowel wall thickness (BWT) and MUC score as the sMayo raised. Accordingly, patients with endoscopic activity presented higher BWT and MUC score, when compared to patients in endoscopic remission (Table 1). On the other hand, patients in IUS remission showed higher rates of clinical (90% vs 10%, p&amp;lt;0.001) biochemical (74% vs 26%, p&amp;lt;0.001) and endoscopic remission (94% vs 6%, p&amp;lt;0.001), with a trend towards higher rates of histologic remission (86% vs 14%, p=0.054). Conclusion In our cohort, IUS activity had a moderate to strong correlation with clinical, biochemical, endoscopic and even histologic activity. Additionally, patients with endoscopic activity presented worse IUS activity, suggesting this method as a reliable non-invasive monitoring tool in UC patients.

P944 Ustekinumab in refractory Ulcerative Colitis: single-center, real-world experience

Abstract Background Ustekinumab, an anti-interleukin 12/23 agent, was approved by the European Medicines Agency in 2019 as a treatment for moderate-to-severe ulcerative colitis (UC). Limited real-world data is available regarding the utilization of ustekinumab in UC, particularly medication persistence and escalation, which are indicators of medication performance in real-world settings. Our aim was to describe our experience with ustekinumab in refractory UC patients. Methods This was an observational single-center study on UC patients who received at least one intravenous dose of ustekinumab 16 weeks before data analysis due to active UC (Simple clinical colitis activity index (SCCAI)&amp;gt;5). Data regarding disease activity prior to and post-induction were analyzed. Patients were followed up until the last ustekinumab administration. Clinical response to therapy was assessed at 16, 24,52 weeks, and the end of follow-up. Response was defined as SCCAI&amp;lt;4, and remission as SCCAI≤2. Dose adjustment or IV maintenance was considered part of the treatment regimen. Patients who discontinued ustekinumab due to lack of therapeutic effect or worsening of UC were considered failures. When available, colonoscopy data was analyzed. Results Forty-seven patients who received ustekinumab for refractory UC were included. Thirty-eight percent were female, and 34% were former smokers. Median age was 46 [37.5-61.5]; 62% had extensive disease, and 15% had perianal disease. Ninety-three percent received at least one biologic before ustekinumab, and 24% had received a JAK inhibitor. Thirty-eight patients required dose escalation, and 11 were on maintenance IV. Clinical response at week 16 was achieved in 74% and remission in 46%. At 24 and 52 weeks, 65% and 61% were in remission, respectively. At the end of follow-up, 59% of patients had endoscopic remission (Endoscopic Mayo score ≤ 1). Sixty percent continued treatment during a mean follow-up of 12 months [6-21]. No variable was associated with risk of discontinuation. No serious adverse events were reported. Discontinuation of treatment was due to treatment failure in all cases. Conclusion Ustekinumab was effective for induction and maintenance in our cohort of UC patients, although a significant proportion required dose escalation. Drug persistence was higher than 50% during the follow-up. The safety profile of ustekinumab was similar to that in controlled studies and other real-world studies.

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.

P1072 Upadacitinib appears effective in inducing clinical, biochemical, endoscopic and histologic improvements in previously treatment refractory Ulcerative Colitis

Abstract Background Upadacitinib is a novel, oral agent which acts by inhibition of JAK signaling. It has proven efficacy in large-scale, randomised trials for the treatment of UC. We report our real-world experience of upadacitinib as induction therapy in a single centre study of UC patients, including patients who were refractory or intolerant of other advanced therapies. Methods We performed a retrospective analysis of outcomes in patients who were commenced on upadacitinib for UC at a tertiary IBD centre between October 2022 to October 2023. The parameters used to assess disease activity were the Simple Clinical Colitis Activity Index (SCCAI), faecal calprotectin (FCP), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Nancy Histological Index (NHI). Clinical response was defined as a reduction of SCCAI of ≥3 points, clinical remission as SCCAI of ≤2, biochemical remission as FC&amp;lt;150ug/g. Endoscopic remission was defined as UCEIS 0-1 and histological remission as NHI 0-1. Medical records were reviewed for patient-reported adverse events. Wilcoxon matched-pairs signed rank test was used to compare pre- and post-treatment continuous variables. Results 42 patients were started on 45mg once daily upadacitinib over this period. 20 were female, the mean age was 39. 31 had left sided disease, 8 had pancolitis. 39 (93%) patients had prior experience of advanced therapy and 22 (52%) had ≥2 prior therapies. At baseline, mean SCCAI was 7 (1-15), and mean FCP 1328 (42-6810) μg/g. Baseline endoscopy demonstrated a mean UCEIS of 5 (3-7) and baseline histology a mean NHI of 3 (1-4). At the 6-week follow up, paired data on clinical and biochemical responses were available in 23 and 27 patients respectively, showing an improvement to a mean SCCAI of 3 (p=0.0004) and mean FCP of 491 μg/g (p=0.002). 16 (70%) achieved clinical response, 14 (61%) were in clinical remission. 15 (56%) had a reduction in FCP to &amp;lt;150 μg/g. Endoscopic reevaluation took place after a minimum of 12 weeks on treatment. Paired endoscopic outcomes in 20 patients demonstrated an improvement of UCEIS to a mean of 1 (p&amp;lt;0.0001), with 16 (80%) patients in endoscopic remission. Week 12 histology showed improvement to a mean NHI of 2 (p&amp;lt;0.0001, n=19), with 9 (47%) patients achieving histological remission. 6 (14%) patients were non-responders. 3 required a colectomy, 2 necessitated a switch in medical therapy, 1 remained on extended induction. 3 patients (7%) reported facial acne as an adverse event, no others were reported. Conclusion Upadacitinib appears effective at inducing significant clinical, biochemical, endoscopic and histological improvements within 12 weeks, amongst a real-world cohort of patients with moderate-to-severe UC that has proved refractory to other advanced therapies.

P046 Real-world data on the treatment with Mirikizumab in a mostly biological-experienced Ulcerative colitis cohort

Abstract Background Mirikizumab was approved for treating Ulcerative colitis (UC) in May 2023. However, real-world data, especially in biological-experienced patients, is scarce. We aimed to determine the treatment efficacy and persistence of Mirikizumab in mostly treatment-experienced UC patients. Methods All patients treated for UC in the Inflammatory Bowel Disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-11/23 were analyzed retrospectively. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)), as well as patient history, were collected. Patients were followed up for at least 12 weeks. Results Seventeen patients with UC were included. Sixteen patients had already received at least one biological agent before starting Mirikizumab. Twelve patients were exposed to ≥ 2 biological agents, and four patients to ≥ 4 biological agents before starting Mirikizumab. One patient received Mirikizumab as a first-line treatment. 4 patients were treated with Ustekinumab before the therapy with Mirikizumab. Nine patients received oral steroids as a concomitant treatment. The median SCCAI at the time of the first infusion/start of induction was 7. We report a reduction in clinical disease activity from 7 to 5 based on the preliminary data of the SCCAI. Biochemical disease activity was assessed with FC levels. The median FC level at the start of the induction was 557.5. At week 8, the median FC level was 513 based on 7 out of 17 patients reached week eight until November 2023. Intravenous induction therapy was extended in 2 of 17 patients. There was no report of adverse events. Conclusion We report preliminary real-world data on the evidence and efficacy of Mirikizumab. In our interim analysis, Mirikizumab is an effective and safe treatment in biological-experienced UC patients.

P691 Intestinal ultrasonography accuracy in the evaluation of patients with moderate to severe ulcerative colitis starting infliximab therapy

Abstract Background The diagnostic accuracy of detecting active ulcerative colitis (UC) by transabdominal intestinal ultrasonography (IUS) is well described. However, the value of repeated IUS measurements in tight monitoring during treatment remains to be established. The aim of the study is to evaluate the utility of IUS for monitoring biologic therapy in UC. Additionally, to establish the correlations between IUS findings and the endoscopic Mayo score (EMS), as well as clinical and biochemical severity indices. Methods In a prospective open-label study, individuals with moderate to severe ulcerative colitis who were initiating infliximab therapy were included, excluding those with proctitis. Patients were evaluated at baseline and after 3 months of biologics induction by means of clinical, biochemical, endoscopic mayo score, and IUS assessments. A Paired Wilcoxon analysis was conducted to compare data before and after therapy induction. The correlation between bowel wall thickness (BWT) and the endoscopic mayo score (EMS), C-reactive protein (CRP), calprotectin, and the Simple Clinical Colitis Activity Index (SCCAI) was analyzed across both visits. Results Thirty-two patients were enrolled and completed baseline evaluations and 21 completed follow-up assessments. The median age was 38 years (IQR 29-60), with 53% male, a median disease duration of 7 years (6-9), 41% having left-sided colitis, and 59% with pancolitis. All patients were treated with infliximab. No significant differences were observed at both time points in terms of BWT, EMS, CRP, and calprotectin (5.5 vs 4.4, p=0.2; 2 (2-3) vs 2 (1-3), p=0.4; 9.4 vs 9.6, p=0.4; 979 vs 394, p= 0.1, respectively). The only significant improvement was in terms of SCCAI (7 (4.8-8) vs 3 (1-5), p=0.009). BWT showed significant correlations with EMS (r= 0.43, p= 0.0015) (figure 1), CRP (r= 0.40, p= 0.007), and SCCAI (r= 0.28, p= 0.03), while no correlation was found with calprotectin (r= 0.19, p= 0.25). Conclusion Intestinal ultrasonography could serve as a substitute for lower endoscopy in evaluating disease activity.

P375 Histological activity predicts the risk of colectomy after biological treatment in biological-naive patients with Ulcerative Colitis

Abstract Background Treatment failure with biological agents is common in patients with ulcerative colitis (UC), but the impact of baseline histological disease activity is unknown. We aimed to investigate the predictive role of histopathological findings for biological treatment failure in UC patients. Methods This is a sub-study of the Danish IBD Biobank Project. Adult bio-naïve patients with UC (n=129) were followed prospectively while undergoing biological treatment. Histological activity was assessed using the Nancy Index and the Geboes score in intestinal biopsies sampled before treatment. Endoscopic activity was assessed using the Mayo Endoscopic Subscore, and clinical activity was measured using the Simple Clinical Colitis Activity Index (SCCAI). Associations between histological activity and treatment outcomes were assessed in multivariable models which incorporated the following fixed covariates: age, gender, disease duration, body mass index &amp;gt;30, disease extent, the SCCAI, and the Mayo Endoscopic Subscore. Correlations between histological, endoscopic, clinical, and biochemical activity were assessed using Spearman’s rank correlation. Results Colectomy was needed in 17.1% (n=22) of UC patients during follow-up (Table 1). Histological activity at baseline measured using the Nancy Index was the only significant predictor of the risk of colectomy during follow-up (Nancy 2 vs. 4: HR 0.14, 95% CI 0.02-0.84, p=0.03; Nancy 3 vs. 4: HR 0.11, 95% CI 0.02-0.53, p=0.01) beside baseline haemoglobin concentration (HR 0.32, 95% CI 0.16-0.64, p&amp;lt;0.01. Figure 1). The risk of colectomy was also significantly predicted by a Geboes grade above 5.0 at baseline (HR 2.72, 95% CI 1.14-6.50, p=0.02). In contrast, endoscopic and clinical activity did not predict the risk of colectomy. At baseline, the Nancy Index and the Geboes score were moderately correlated to endoscopic activity, and weakly, but significantly correlated to biochemical markers haemoglobin, albumin, and C-reactive protein. Meanwhile, poor correlations were found between histological activity and clinical activity. Conclusion The risk of colectomy during biological treatment in bio-naïve UC patients was significantly predicted by histological disease activity, but not endoscopic or clinical disease activity. Our study suggests that histological assessment before initiating biological treatment should be encouraged in UC patients. Funding This study is funded by a restricted grant from Takeda A/S, Louis-Hansen Fonden, and a public fund hosted by Hvidovre Hospital.

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.

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.

P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation study

Abstract Background In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD. Methods In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics. Results Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p &amp;lt; 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p &amp;lt; 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI &amp;lt; 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP &amp;lt; 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E). Figure 1 Conclusion Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Funding None

P465 Upadacitinib is effective and safe for the treatment of ulcerative colitis and Crohn’s disease: 1-year prospective real-world experience

Abstract Background Upadacitinib (UPA) is a novel selective Janus kinase 1 inhibitor that has shown efficacy and received approval for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). We previously reported a large real-world experience of UPA induction in UC and CD (Friedberg, CGH. 2023). Here we report our 1-year real-world experience. Methods This is a prospectively collected study of clinical outcomes of UPA treatment in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, 8, then every 3 months until week 52 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and faecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. Results 110 patients were initiated on UPA and followed for a one-year period (CD=57, UC=44, IBDU=5, pouchitis=4). 109/110 (99%) were biologic exposed and 31/110 (28.2 %) were tofacitinib exposed. 99/110 (90%) were initiated on UPA for luminal disease (Table 1). 54 patients remained on UPA therapy at 1 year. In UC: week 8 clinical response and remission was 24/47 (51.1%), 39/47 (83%), respectively; week 26 clinical response and remission was 20/34 (58.8%), 24/34 (70.6%), respectively; 52 week clinical response and remission was 17/30 (56.7%), 29/30 (96.7%), respectively. In CD: week 8 clinical response and remission was 14/32 (43.8%), 25/32 (78.1%%), respectively; week 26 clinical response and remission was 9/22 (40.9%), 15/22 (68.2%), respectively; 52 week clinical response and remission was 10/17 (58.8%), 13/17 (76.5%), respectively. 56 patients discontinued UPA prior to the 1 year follow-up, 13 were due to adverse events[DR1] . The most commonly experienced AEs leading to discontinuation was dermatological side effects (CD=2, UC=2). One instance of shingles occurred leading to discontinuation. No other serious infections or serious adverse events including VTE, MACE, or malignancies occurred. Conclusion In this large 1-year real-world experience in medically resistant patients with UC or CD, we report that UPA is both effective and safe, including in those who had prior exposure to tofacitinib.

P797 Assessment of pharmacokinetics and clinical response in patients transitioning from intravenous to subcutaneous vedolizumab

Abstract Background Vedolizumab is a humanized monoclonal antibody directed against α4β7 integrin used in inflammatory bowel disease (IBS) patients1. The usual dosage of Vedolizumab is 300 mg intravenously (iv). Recently the subcutaneous (sc) formulation (108 mg every 2 weeks) has been approved, which provides more independence for the patient, avoiding visits to the hospital and possible inconveniences associated with it2. Methods The aim of the study is to evaluate the clinical and biochemical response of IBS patients treated with vedolizumab, 16 weeks after transitioning from iv to sc. An observational, prospective, single-center cohort study was performed. Patients with IBS and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. Clinical index as Harvey-Bradshaw Index (HBI)/Simple Clinical Colitis Activity Index (SCCAI) and questionaries (IBDQ-9 and TSQM) were performed on each visit. Results 43 patients were included, 12 of them (27.9%) chose to transition to sc formulation. Baseline characteristics of both groups are shown in Table 1. 34 (79.1%) patients were prescribed vedolizumab due to previous biologic failure, 7 (16.3%) in first line due to comorbidities and 2 (4.7%) because of adverse effects in prior treatment. All included patients remained in remission during follow-up. At week 16 (w16), no significant differences were found in calprotectin levels in patients on iv treatment (mean 146.6 ± SD 45.9) vs sc (159.26 ± 53.9) (p 0.9). Vedolizumab serum levels at w16 were higher in the sc group (22364.3 ± 5141.6) vs. iv (11425.9 ± 1514.2), with statistically significant differences (p 0.009). At w16, 9 (75%) of the patients in the SC group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. 1 patient (8.3%) in the sc group returned to iv treatment. 4 patients (12.9%) in iv and 2 (16.6%) in sc treatment presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. Conclusion In our experience, vedolizumab sc is a safe and convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation. 1. Smith, Michael A et al. "Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases." The Annals of pharmacotherapy vol. 48,12 (2014): 1629-35. 2. Vermeire, Séverine et al. "Efficacy and Safety of Subcutaneous Vedolizumab in Patients With Moderately to Severely Active Crohn's Disease: Results From the VISIBLE 2 Randomised Trial." Journal of Crohn's &amp; colitis vol. 16,1 (2022): 27-38.

P796 Comparative Effectiveness of First-Line Infliximab and Vedolizumab in Patients with Early Ulcerative Colitis

Abstract Background Despite the increasing armamentarium of advanced therapies for the treatment of ulcerative colitis (UC), data comparing the effectiveness of biologics in early disease are scarce. We aimed to categorize selection of patients and assess the effectiveness, therapeutic persistence and safety of biologics used to treat early UC in a bio-naïve patient cohort. Methods This single-center, retrospective study included all bio-naïve UC patients who commenced advanced therapy within two years of diagnosis between 2012-2023. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index; clinical response was defined as a decrease of ≥ 3 points from baseline and clinical remission defined as an SCCAI of ≤2 Results Out of the 1117 patients with UC who were treated at our center during the study period, 46 bio-naïve patients (mean age 36.7 years (±17)) were treated with either infliximab (IFX) or vedolizumab (VDZ), within 2 years from diagnosis. IFX was the first biologic in 19 (41%) patients and VDZ in 27 (58%) patients. At therapy initiation, 38 (82%) patients were receiving corticosteroids and 7 (15%) concomitant immunomodulators (Table 1). Patients treated with IFX had significantly lower hemoglobin (10.4 (IQR 8.5-11.3) vs 12.1 (IQR 10.8-13.9) g/dL, p=0.007) and albumin (3 (IQR 2.8-3.8) vs. 3.8 (IQR 3.4-4.2) g/dL, p=0.01) and significantly higher C-reactive protein (CRP) (48.5 (IQR 9-119) vs. 2.5 (IQR 2-3) mg/L, p&amp;lt;0.001) compared with patients starting VDZ. Following induction (week 14) clinical response and remission rates were similar in both treatment groups (IFX: 73% and 63%; VDZ: 74% and 67%, respectively; p=0.75). At week 52, clinical response and remission rates were similar in both treatment groups (IFX: 50% for both; VDZ: 50% for both, p=n/s). Corticosteroid (CS)-free remission rates amongst patients receiving CS at baseline (17 patients IFX and 21 patient VDZ) at week 52 were similar in both groups (IFX: 58% vs VDZ 57%, p=n/s). Treatment persistence over 2 years of follow-up was similar between IFX and VDZ (Figure 1). Safety profiles were similar in both treatment groups with no new signals noted. Conclusion In these real-world data in patients with early and bio-naïve UC, first line IFX was used in more severe baseline disease as highlighted by lower albumin and hemoglobin levels and higher CRP at baseline. Despite this, IFX showed equal effectiveness in induction and long-term maintenance and showed similar treatment persistence compared with VDZ.