Clinical 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.

New trends associated with disease activity in patients with ulcerative colitis

Background/Aim: The severity and extent of ulcerative colitis (UC) guide us in determining the treatment method for each case. It has been suggested in the literature that high neutrophil-lymphocyte and platelet-lymphocyte ratios can serve as markers of active ulcerative colitis. This study retrospectively analyzes the relationship between neutrophil-lymphocyte ratio and platelet-lymphocyte ratio with clinical activity indices and endoscopic activity indices in predicting disease severity in patients with ulcerative colitis. There are few studies in the literature regarding the relationship between platelet-lymphocyte ratio (PLR) and disease activation in ulcerative colitis. This study contributes to the follow-up and outcomes of these patients, as there is a lack of sufficient retrospective studies on the platelet/lymphocyte ratio in patients diagnosed with UC in our country and worldwide. Methods: This study is a population-based, single-center, case-controlled study. It was conducted by retrospectively analyzing the hospital information system for data recorded during the routine diagnosis and treatment of ulcerative colitis patients followed and treated at Celal Bayar University Medical Faculty Gastroenterology Division between January 2014 and December 2021. A total of 135 patients with ulcerative colitis were included in the study. The patients were divided into 2 groups, active disease and disease in remission, based on clinical activity indices and endoscopic activity indices. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (Hb), white blood cell (WBC), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) levels were checked during routine follow-up of patients with ulcerative colitis. These values were recorded at the first presentation to the hospital and 3 months after treatment. Results: Laboratory values at presentation were compared with those at the third month of treatment in a group of 113 patients with UC in remission: NLR (5.529 (3.485) and 4.374 (2.335), [P&lt;0.001]), erythrocyte sedimentation rate (26.81 (20.42) and 21.78 (19.32), [P=0.015]), C-reactive protein (4.087 (6.729) and 1.696 (3.525), [P&lt;0.001]), and white blood cell count (9,864 (3,514) and 8,067 (1,927), [P&lt;0.001]) were found to be lower than the baseline values. As expected, decreases in inflammatory markers were observed in patients in remission. In a group of 22 patients with active disease, values at presentation were compared with those at the third month of treatment: neutrophil count (8,508 (2,908) and 9,646 (3,265), [P=0.037]) and platelet count (289,591 (95,123) and 323,364 (127,647), [P=0.010]) were found to be high. Similarly, ESR (19.63 (15.43) and 27.89 (21.11), [P=0.036]) was found to be high. These values were higher in active disease compared to the time of admission. Conclusion: In our study, neutrophil-lymphocyte ratios and platelet-lymphocyte ratios were significantly higher in patients with active ulcerative colitis. The level of inflammatory markers in ulcerative colitis patients at the time of diagnosis and in the early stages of the disease is helpful in predicting the course of the disease, and this was shown to be related to clinical, endoscopic, and laboratory indices. These inflammatory markers can predict disease activity alone or in combination. However, a threshold value could not be calculated due to the insufficient number of patients, and thus, more comprehensive prospective studies are needed.

A231 EFFECTIVENESS OF DUAL BIOLOGIC THERAPY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE: A MULTICENTRE CANADIAN STUDY

Abstract Background The effectiveness of combining biologics for pediatric inflammatory bowel disease (IBD) is under-investigated. Aims To evaluate the effectiveness of dual biologic therapy in children with IBD. Methods Children and adolescents ampersand:003C 17 years old with IBD enrolled in the Canadian Children IBD Network (CIDsCANN) who received any biologic therapy were included. Patients were classified as cases if they received two biologics simultaneously, and controls if they were switched from one biologic to another. All cases and controls who met inclusion criteria were analyzed. Baseline demographic and disease-specific data were collected. The primary outcome was clinical activity indices at the end of the 1-year period following the start of dual biologic therapy or the switch to a different biologic. The Wilcoxon signed rank test (for continuous variables) and the Fisher exact test (for nominal variables) were used to compare demographic data. A multivariable Cox proportional hazard model was used to infer about disease activity reduction between the two groups. p ampersand:003C 0.05 was used to determine statistical significance. Results Twenty-six cases and 194 controls fulfilled the inclusion criteria. Demographic and disease-specific data are summarized in Table 1. The most common combination was ustekinumab with vedolizumab in 11 (42.3%) patients; while the most common first biologic in the control group was infliximab (104, 54.1%) and the second was ustekinumab (109, 56.2%). The most common indication for the biologic therapy addition or switch was unsatisfactory clinical response. No differences between cases and controls in reductions of disease activity indices were seen at the end of the 1-year period (Figure 1). Conclusions In children with IBD, dual biologic therapy was not more effective than switching from one biologic to another. We are currently investigating the safety of this approach. Baseline data Proportion of patients with 10- and 20-point reduction in clinical activity indices at the end of the 1-year period Funding Agencies None

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.

Window of opportunity in psoriatic arthritis: the earlier the better?

ObjectivesTo investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay.MethodsAll newly diagnosed, disease-modifying...

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.

P1225 The interplay of donor-derived gut microbiota correlates with the efficacy of combination therapy of fecal microbiota transplantation with antibiotics for ulcerative colitis

Abstract Background Our previous reports suggest fecal microbiota transplantation (FMT) following bowel cleansing with amoxicillin, fosfomycin, and metronidazole (Antibiotic FMT: A-FMT) improved its efficacy and the recovery of the Bacteroidota species composition, which is associated with ulcerative colitis (UC) severity. Building upon these previous findings, we considered that manipulating the intestinal microbiome to improve the intestinal immune system seems to be a feasible therapeutic regimen for patients with UC. In this study, we explored the gut microbiota signatures through elucidating donor-derived microbe that colonized the recipients and examined the contributions of these microbe to the efficacy of A-FMT. Methods In this study, 97 patients with active UC were enrolled between March 2014 and October 2019, of whom 49 patients were individually assigned a different donor on a one patient-to-one donor basis. FMT was performed via colonoscopy after a two-weeks oral administration of three antibacterial agents. The Lichtiger’s clinical activity index (CAI) at 4 weeks after A-FMT treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points. Each case contributed three fecal samples (pre A-FMT, post A-FMT, and Donor). 16S rRNA gene sequence analysis was performed on 147 collected fecal samples, and 6,501 Amplicon Sequence Variants (ASV) were identified and characterized. Results In responders, the relative abundance of 6 taxonomies including Alistipes were significantly abundant in both post A-FMT treatment samples and their donors’ samples, while 6 other taxonomies were significantly low. In non-responder, significantly low proportion of donor-derived and significantly high proportions of patients-origin and/or new ASV were observed compared with responders. The similarity of gut microbiota composition between donor and post A-FMT treatment was predominantly higher in responders compared to non-responders (Figure 1). Conclusion This study revealed that the engraftment of specific donor-derived microbes is a major factor in A-FMT outcomes, which may be the foundation for precision FMT. Rational identification of patient and donor characteristics can further advance the development of A-FMT therapy for UC.

P337 Proactive therapeutic drug monitoring of Adalimumab, but not HLADQ*A1 determination, predicts inflammatory bowel disease outcome and persistence of treatment

Abstract Background Anti-TNF drugs have proven effective in managing Inflammatory Bowel Disease (IBD), but a significant percentage of patients exhibit primary or secondary non-response. Therapeutic drug monitoring (TDM) is a valuable tool for optimizing patient management. HLA-DQA1*05 gene has been investigated as a potential marker for immunogenicity and loss of response to anti-TNF therapy.This prospective, multicentric study aimed to assess the clinical impact of determining Adalimumab (ADA) levels and anti-adalimumab antibodies (Abs) in IBD patients and the influence of the HLA-DQA1*05 allele on the response and maintenance of ADA treatment over a 24-month follow-up. Methods Patients initiating ADA treatment between October 2020 and October 2022 were enrolled. Demographic data and IBD characteristics were recorded. Clinical Activity Index, C reactive protein (CRP), faecal calprotectin (FC), endoscopy or radiological activity, Global Physician Assesment (GPA) and PRO (by IBDQ-9) were prospectively collected at baseline and at the same time that ADA levels: week 4, 10, 30 and 12 months. HLA-DQA1*05 was genotyped at baseline. Pearson coefficient was utilized to assess correlations between ADA levels and disease activity. Results We included 170 (age 42±17 years, 54% female) IBD patients (74% Crohn`s Disease, 24% Ulcerative Colitis and 2% Indeterminate colitis) who started ADA (85% naïve to anti-TNF). At baseline, 80% had an active disease (GPA=1); CRP and FC were 10.72 ±17.85 mg/L and 568 ±775 µg/g; PRO at baseline was 63±8.6. HLA was determined in 167 patients, of whom 71 (42%) were HLA-DQA1*05 positives. Median follow up was 17 months. No correlation between HLA and drug levels or Abs was founded. ADA levels at the end of induction was correlated with ADA levels during follow up. ADA serum concentration &amp;gt;7 µg/mL at weeks 4 and 10 correlated with improved clinical response at corresponding time points (p&amp;lt;0.001). Patients with ADA levels &amp;gt;7 µg/mL at week 10 demonstrated better disease control at 12 months. 41 patients stopped ADA. It was associated with active disease, low ADA levels, and adverse clinical and laboratory markers. HLA-DQA1*05 positivity did not correlate with adverse reactions or Abs during the observational period. A significative improvement in PROs in patients who started treatment with ADAL (62.73 at baseline and 69.42 at week 30) (p&amp;lt;0.001) was observed. Conclusion Early Drug level monitoring of Adalimumab may improve the management of IBD patients. PCR, CF and GPA at week 10 may predict treatment failure. ADA levels &amp;gt;7 µg/mL is associated with a better clinical response in short and long-term, independent of HLADQA1*05.

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.

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.

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.

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.

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.

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

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.