Treatment Of Crohn's Disease Research Articles

Colorectal cAncer and CrohN's DIsease study (CANDID): An international multicentre retrospective audit

AbstractBackgroundInflammatory bowel disease (IBD) affects more than 10 million people worldwide. Men and women are equally affected by Crohn's disease (CD). It has been shown that patients with CD are at an increased risk of a colorectal cancer (CRC) diagnosis and CRC‐related mortality. During the last two decades, biological therapies have revolutionized the treatment of CD. There are no current studies investigating the prevalence of CRC in patients with CD in the era of biological therapy and the possible features of patients with CD who are at high risk of developing CRC.AimWe aim to assess the prevalence of CRC, risk factors and profile of CRC in patients with CD receiving biological treatment compared with those who are not under biological therapy and the impact of CD‐associated colorectal strictures on CRC development. The study hypothesis is that the use of biological therapy in the control of CD activity may decrease the risk of developing CRC.Study design and settingAn international, retrospective, snapshot of the prevalence of CRC in patients with CD, reported according to the SPIRIT guidelines. The study will involve centres that hold regular IBD multidisciplinary team meetings and have both IBD colorectal surgeons and gastroenterologists. Each participating centre will provide a local consultant lead and a local trainee lead. Data will be collected within a 2‐year recruitment period (January 2017–January 2019).Study populationAdult patients who presented with CD during the study period. Patients with an incidental diagnosis of CD during evaluation for CRC will be excluded.Statistical planBaseline patient characteristics will be summarized using the appropriate descriptive statistics. Univariable, multivariable and Cox regression models will be used to identify factors significantly associated with CRC. For noncontinuous variables a comparison between the subgroups will be carried out using the chi‐square test corrected by Fisher's exact test if appropriate. A p‐value of <0.05 will be considered statistically significant.Data storageData will be stored on a secured server, pin‐code protected according to the local data management agreement.

Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review.

Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.

Real-world use of biologics during the first year of treatment for newly diagnosed Crohn's disease in Japan: a claims analysis from 2010 to 2021.

Crohn's disease (CD) leads to bowel damage and disability if suboptimally treated. We investigated firstyear treatment decisions and real-world use of biologics in patients with CD in Japan. In this retrospective observational study (2010-2021) from the JMDC claims database, patients with a new diagnosis of CD (no CD claims record within 12 months before index) who received ≥ 1 pre-defined treatment were grouped by use of biologics and systemic corticosteroids (SCS) within the first year of diagnosis. Of 823 patients included, 470 (57.1%) were prescribed biologics and 353 (42.9%) were not; 77.6% were male, 75.7% had adult-onset CD, and median age was 24 years. Patients prescribed biologics were younger (median: 23 years vs. 28 years) and more had perianal lesions (43.0% vs. 22.9%) than those not prescribed biologics; 64.9% (95% confidence interval, 60.4%-69.2%) received a top-down treatment approach (no SCS before biologics). Factors significantly associated with a top-down treatment approach were male sex, perianal lesions, no use of immunomodulators, and use of anti-tumor necrosis factor therapies. The proportion of patients receiving SCS before biologics (step-up approach) increased after 2018, with a shift from prednisolone to budesonide from 2016. Persistence with first biologics decreased over time, with no differences between biologic types. Use of biologics for treatment of CD within the first year of diagnosis in Japan has remained stable over the past decade. However, there was a shift to a step-up treatment approach, with an increase in use of SCS before biologics over time.

P0753 Early surgery in pediatric-onset ileocecal Crohn’s disease is associated with less unfavourable disease course: a retrospective population-based study

Abstract Background Early surgery in Crohn’s disease (CD) seems to be efficient and safe in recently diagnosed adult ileocecal CD as compared to anti-tumor necrosis factor (anti-TNF) therapy. However, its role in the first-line treatment of paediatric-onset CD remains unknown. We aimed to compare long-term disease course in paediatric-onset CD treated within one year of diagnosis with ileocecal resection (ICR) or anti-TNF therapy. Methods We conducted a retrospective study using a population-based cohort of patients aged of less than 17 years old at the diagnosis of ileocecal CD and treated with ICR or anti-TNF therapy within one year of diagnosis. The primary outcome was unfavourable disease course defined as CD-related hospitalization, major CD-related surgery, systemic corticosteroids or perineal CD. We collected ICR characteristics, post-operative complications and clinical remission (Harvey Bradshaw score < 4 without biologic therapy or new surgery). Cumulative incidence was calculated at 1, 3 and 5 years. We performed a Cox regression model with a propensity score. Results are expressed with 95% confidence intervals. Results From January 1988 and December 2011, 1007 patients were identified. 134 patients with ileocecal involvement at diagnosis were included, 67 patients in the ICR group and 67 in the anti-TNF group. The median follow-up was 6.0 years, IQR (3.2-11.1). Only 19% patients in the anti-TNF group had complicated behaviour as compared to 94% in the ICR group (p<0.001) at diagnosis. The mean length of the surgical specimen was 33.5 cm (IQR: (4-95)) and surgeries were performed in emergency in 20% of the patients.The incidence rate of unfavourable disease course was 80 per 1000 person-years [54-113] in the ICR group, and 270 per 1000 person-years [196-363] in the anti-TNF group with a cumulative incidence of 17%, [7-26], 26% [14-37] and 30% [17-41] respectively at 1, 3 and 5 years in the ICR group, versus 24% [13-33], 54% [40-65] and 71% [55-81] in the anti-TNF group (p <0.0001). When including the propensity score, patients in the ICR group had better disease course than patients in the anti-TNF group with a hazard ratio (HR) of 0.16 [0.08-0.35] over time. Clinical remission was achieved in 83% of patients in the ICR group and 41% in the anti-TNF group (p <0.001) at 5 years. Sixteen patients (23%) experienced an early postoperative complication, including 6 (9%) severe complications (Clavien-Dindo ≥ 3). Only emergency surgery was associated with late complications (HR = 6.9 [2.3-20.6]). Conclusion Early surgery in paediatric-onset ileocecal CD was significantly associated with less unfavourable outcome and seemed safe. These data support the role of early elective surgery in the first-line treatment of paediatric-onset ileocecal CD.

P0972 Higher vedolizumab clearance associates with poor therapeutic outcomes during maintenance therapy of vedolizumab in Crohn’s disease

Abstract Background Drug Clearance (CL) is a better pharmacokinetic (PK) metric compared to trough levels (TL) in associating with therapeutic outcome of infliximab, adalimumab and ustekinumab therapy in Crohn’s disease (CD). However, data regarding vedolizumab (VDZ) are limited. We compared the performances of VDZ CL and TL in associating with therapeutic outcomes in CD. Methods This retrospective analysis included a subset patients from the LOVE-CD trial at Amsterdam UMC. Blood samples were collected at trough during intravenous VDZ maintenance treatment and stored at -80ºC until analysis. VDZ TL were measured using homogenous mobility shift assay and CL was estimated using nonlinear mixed effect models. Therapeutic outcomes consisted of endoscopic remission (Simple Endoscopic Scoring for CD [SES-CD] <3) measured at one-year after starting treatment, and clinical and biochemical remission status (CRP <3 mg/L with CD activity index <150) at each maintenance cycle. Statistical analyses included receiver operating characteristics (ROC) curves, area under the curve (AUC) and logistic regression. Results A total of 50 patients (24 females, mean age 37 years) were evaluated in this analysis. At one year 39 patients had endoscopic data; 17/39 (44%) were in endoscopic remission. In the 50 patients, 38% of cycles (120/312, median 6 per patients) showed clinical and biochemical remission. Median TL and CL were 16.0 µg/mL (IQR: 9.5-23.8 µg/mL) and 0.154 L/day (IQR: 0.125-0.190 L/day) respectively. Anti-drug antibodies to VDZ were negligible in this cohort (2.5%, 8/323 specimens). ROC analysis yielded higher AUC with CL (AUC= 0.824 [95%CI: 0.683-0.964]) than with TL (AUC=0.606 [95%CI: 0.421- 0.790]) (difference= 0.218 95%CI: 0.074- 0.362; p=0.003) in distinguishing endoscopic remission from endoscopic active disease. Similar results were observed with the clinical and biochemical remission outcome (AUC [conc]=0.530 [95%CI: 0.466-0.595] compared to AUC[CL]=0.646 [95%CI: 0.584- 0.709]) (difference: 0.116 95%CI: 0.063- 0.169; p<0.001). Logistic regression revealed that TL were not significantly associated with either of the two outcomes (p>0.28) (Figure). In contrast, higher CL (>0.156 L/day) was associated with 9.0-fold (95%CI: 1.7,44.0) and 2.1-fold (95%CI: 1.3,3.4) lower likelihood of endoscopic and clinical & biochemical remission, respectively (p<0.01) (Table). Conclusion These data support the hypothesis that VDZ CL is better than TL in associating with outcomes of VDZ treatment in CD. Given that there was little immune response to VDZ in this study, the association between higher CL and poor outcome most likely reflects higher inflammatory burden that consumes the drug from the central compartment.

P0175 A new blocker of endothelial dysfunction ameliorates colitis independently of IL-10 by regulating both barrier function and the recruitment of immune cells

Abstract Background Inflammatory bowel diseases (IBDs) like Crohn’s disease (CD) and ulcerative colitis (UC) are chronic gastrointestinal disease with complex pathogenesis, leading to a lack of effective treatments. The efficacy of CU104, a new blocker of endothelial dysfunction,1 in other IBD models with a CD-like phenotype2 and its specific mechanism of action in colitis are still unknown. Methods To evaluate the therapeutic potential of CU104, we induced colitis using dextran sodium sulfate (DSS) in IL-10 knockout mice3 and assessed its effectiveness. Additionally, we used Caco-2, HCT-116, and HT-29 cells to investigate its impact on intestinal barrier function, inflammatory signal pathway, actin dynamics,4 and gene expression through FITC-dextran permeability, trans-epithelial electrical resistance (TEER), reporter gene, gene expression profiling, and immune assays. Results CU104 demonstrated therapeutic efficacy in DSS-induced colitis in IL-10 KO mice by potently suppressing innate immune activation, vascular and intestinal barrier dysfunction, and immune cell recruitment. Mechanistically, CU104 inhibited the activation of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and interferon regulatory factor (IRF),5 as well as the ezrin/radixin/moesin (ERM) signaling pathways6 in vitro and in vivo, which play critical roles in maintaining barrier integrity and regulating immune cell recruitment during inflammation by regulating actin dynamics. Conclusion Our findings suggest that CU104, a pseudo-sugar derivative of cholesterol that regulates actin dynamics and inflammatory signaling, could be a promising new treatment for CD along with UC.

P0898 Comparative Study on the Efficacy of Biologics with Dietary Intervention in Crohn's Disease: Evaluating the Impact of Crohn's Disease Exclusion Diet and partial Entral nutrition Combination with Biologics

Abstract Background Crohn's disease (CD) is a chronic inflammatory condition with significant impact on patient health. While the Crohn's Disease Exclusion Diet (CDED) and partial enteral nutrition (pEN) have shown therapeutic efficacy in CD, real-world study data are limited, and there is a lack of research on the benefits of their combination use with biologic therapies. Methods This retrospective study included CD patients divided into two groups, starting at the initiation of biologics treatment: those receiving biologics alone and those receiving biologics with CDED + pEN for 12 weeks. Clinical outcomes were assessed at baseline, 12, 24, and 48 weeks. Results A total of 51 CD patients were included in the study: 35 received biologics alone, while 16 received biologics with CDED + pEN for 12 weeks. While Crohn’s Disease Activity Index (CDAI) reduction, hemoglobin (Hb) increase, albumin levels, and fecal calprotectin reduction showed no significant differences between groups, notable findings emerged in body weight and C-reactive protein (CRP) levels. The biologics + CDED + pEN group demonstrated a continuous increase in body weight over 48 weeks, whereas the biologics-only group showed a less pronounced trend. Additionally, CRP levels in the CDED + pEN group decreased more rapidly, with significant differences observed by week 12, indicating an early anti-inflammatory effect. Beyond 12 weeks, CRP levels in both groups gradually aligned, but the initial rapid reduction in the combination group highlights the potential of dietary intervention in achieving quicker inflammation control. Despite the discontinuation of CDED + pEN after week 12, the initial benefits in body weight gain and CRP reduction persisted, suggesting lasting effects of the dietary approach when combined with biologics. Conclusion Short-term use of CDED + pEN with biologics may offer early advantages in reducing inflammation and supporting body weight gain in CD treatment.

P1191 Early Clinical, Biological, and Sonographic Response in Ileal Crohn’s Disease Patients Treated with Upadacitinib: A Single-Centre Real-World Experience

Abstract Background Upadacitinib (UPA), a selective JAK1 inhibitor, has shown efficacy in moderate-to-severe Crohn’s disease (CD), even in patients refractory to advanced therapies. This study aimed to evaluate the effectiveness, safety, and durability of UPA in refractory CD in real-world settings, with a focus on early objective assessment using biological markers and intestinal ultrasound (IUS). Methods A retrospective analysis was conducted on 41 CD patients (61% male, median age 40 years [SD: 33–53], mean disease duration 11 years [SD: 6–17]). Disease characteristics and prior treatments, including anti-TNF (100%), ustekinumab (70.7%), vedolizumab (19.5%), and risankizumab (9.8%), were recorded. Clinical (Harvey-Bradshaw Index [HBI]), biological (C-reactive protein [CRP], fecal calprotectin [FCP]), and IUS parameters (wall thickness, affected segment length, Limberg score) were assessed at 1, 2, 3, 6, and 12 months. Median follow-up was 8.2 months (SD: 4.8–12.3). Treatment patterns included standard induction (46.3%), extended induction (29.3%), and sustained high-dose (24.4%). Results Clinical response (≥2-point HBI reduction) was significant from week 4 and sustained throughout follow-up. Baseline CRP was 0.60 mg/dL (SD: 0.28–1.30), decreasing to 0.30 (SD: 0.05–0.80) at 1 month, 0.14 (SD: 0.04–0.64) at 3 months, and 0.10 (SD: 0.04–0.42) at 12 months, showing a non-significant downward trend. FCP dropped from 860 µg/g (SD: 270–1700) to 506 (SD: 186–2343) at 1 month, 260 (SD: 121–1200) at 3 months, and 205 (SD: 120–382) at 12 months, with a similar non-significant trend. Of 31 patients with baseline IUS, 55.6% showed radiological improvement in at least two IUS parameters at 12 months, though not statistically significant. Nine patients (22%) discontinued UPA due to adverse events (7.3%) or lack of response (17%). Non-severe adverse effects were reported in 53.7%, predominantly dermatological, without requiring dose adjustments or discontinuation. No severe infections, thromboembolic events, or cardiovascular complications were observed. Conclusion UPA demonstrated rapid, effective, and safe treatment for refractory CD in clinical practice. Trends toward early clinical, biological, and sonographic improvements were observed, highlighting its potential in real-world management of refractory CD.

P0294 Functional outcomes after primary ileocecal resection for Crohn’s disease

Abstract Background Ileocecal resection (ICR) is a common procedure in Crohn’s disease (CD). Increasing evidence suggests ICR may be considered a first-line treatment for localized ileal CD to maintain long-term remission, rather than starting biologics. However, removal of the ileocecal valve affects bowel transit and disabling symptoms may arise. The aim of our study was to prospectively assess the impact of primary ICR on daily digestive symptoms in CD patients. Methods We included patients who underwent primary ICR at Saint-Antoine Hospital between January 2017 and December 2022. Patients were assessed after a morphological evaluation (endoscopy or MRI) performed between 5 months and 1 year post-ICR. Digestive symptoms were prospectively and systematically collected using a dedicated database. The primary endpoint was the prevalence of a composite outcome, defined as at least 4 soft or liquid stools per day and/or a fecal urgency with inability to delay defecation for more than 15 minutes, and/or moderate to severe daily abdominal pain. Secondary endpoints included other digestive symptoms. Multiple logistic regression analysis was performed to assess predictive factors for the primary outcome. Results One hundred nine patients were included. Indications for ICR were fistulizing disease (n=61, 56%) and stenosis (n=41, 37.6%). Only 7 patients (6.4%) had surgery for uncomplicated inflammatory disease. Thirty-five patients (32.1%) had morphological recurrence, defined as i2b, i3, i4 score, deep ulcers, stenosis, or fistulas on MRI. The primary endpoint was met by 24 patients (22%), with 21.1% having at least 3 liquid stools per day. Diarrhea (soft to liquid stools daily) was observed in 56.9%, fecal urgency in 22.9%, and abdominal pain in 32.1% (Figure 1). The primary endpoint prevalence was 17.6% in patients without morphological recurrence and 31.4% in those with recurrence (p=0.17) (Table 1). Multivariate analysis showed that age >40 years at surgery (OR=3.58 [95%CI 1.06-12.8] p=0.04), disease duration >2 years (OR=5.67 [95%CI 1.69-23.0] p=0.008), sepsis (fever >38.3°C within 7 days before surgery) (OR=8.06 [95%CI 1.68-44.2] p=0.01), and small bowel resection length >40 cm (OR=9.50 [95%CI 2.35-45.8] p=0.003) were associated with poorer digestive quality of life as defined by the primary composite endpoint. Conclusion The prevalence of digestive symptoms after primary ICR for CD is notable, regardless of disease recurrence. Advanced age, long disease duration, sepsis at surgery, and resection length were associated with disabling digestive symptoms. These results suggest that ICR leads to frequent and disabling digestive symptoms for many patients, which should be considered when proposing ICR.

P0384 Applying ChatGPT to Improve Inflammatory Bowel Disease Diagnosis and Evaluation

Abstract Background Chat Generative Pre-Trained Transformer-v4 (ChatGPT-v4) is an unquestionable asset to healthcare professionals. This paper will outline a number of ways in which ChatGPT-v4 can be used to improve the accuracy of its diagnosis and treatment strategies for ulcerative colitis (UC) and Crohn’s disease (CD), in line with the ECCO guidelines. Methods This 102-item questionnaire was designed to assess the accuracy, consistenacy, and inclusiveness of responses to questions about the diagnosis and treatment of UC and CD. The questionnaire was created in the form of true/false and multiple-choice questions and was based on clinical scenarios reflecting real-life situations and the ECCO guidelines. After that, ChatGPT-v4 was shown it, and its reactions were assessed. The responses were evaluated using a Likert scale. The queries were posed to the artificial intelligence at 15-day intervals. Results In 47 responses (92%), ChatGPT adhered to the established guidelines, with deviations observed in 4 instances (8%). Of the 4 responses previously identified as non-compliant, 3 demonstrated no change or improvement following a 15-day reassessment period. The mean values for the accuracy scores were found to differ, with 5.45 for the first set and 5.56 for the second (p = 0.606). The completeness scores showed a similar trend, with the mean value differing by 0.10, with 2.33 for the first set and 2.43 for the second (p = 0.280). The standard deviation trends for the two sets were also comparable. The analysis revealed a significant enhancement in accuracy from the initial to the fifteenth day of assessment (5.49 and 5.56, respectively). A comparable increase was observed in completeness scores, rising from 2.15 to 2.37 between the initial and fifteenth day assessments. The imaging results indicated that more accurate responses were given to questions pertaining to it, although the difference was not statistically significant (p = 0.31). In the context of multiple-choice questions, the performance of the AI model demonstrated enhanced stability and consistency (p = 0.606). The majority of answers were initially correct (90% of the total). Four out of five incorrect answers evolved into correct answers, one incorrect answer persisted, and two correct answers changed to incorrect answers. Conclusion ChatGPT-v4 has demonstrated potential for development as a clinical support tool in the management of inflammatory bowel diseases, including UC and CD. However, performance differed between binary and multiple-choice questions.

P0449 qFIT as a predictor of relapse in quiescent Crohn’s disease – initial results from the Stratifying Crohn’s Using Biomarker Assessment (SCUBA) study

Abstract Background The Stratifying Crohn’s Using Biomarker Assessment (SCUBA) study assessed a number of biomarkers (Faecal Calprotectin (FCP), quantitative faecal immunochemical testing (qFIT), C reactive protein (CRP), plasma and faecal zinc) in their ability to predict relapse in quiescent Crohn’s disease (CD). FCP is widely utilised as a surrogate marker in the monitoring of CD but is labour intensive and expensive. Population qFIT testing is established in colorectal cancer screening and is relatively cheap and simple to analyse. qFIT has been shown to predict relapse in ulcerative colitis1. Here we present a comparison of qFIT and FCP at predicting relapse in quiescent luminal CD. Methods A single centre prospective cohort study was performed. Patients with clinically quiescent CD (Harvey Bradshaw Index ≤3) were identified and provided paired, baseline FCP, qFIT and routine biochemical workup. Patients over 50 years were excluded due to overlay with bowel cancer screening programmes as were those with isolated upper GI or perianal disease. Patients were followed up over 1 year or until relapse defined by need for escalation of CD related treatment, steroids, surgery or hospitalisation for CD. Results 274 patients were recruited with 211 returning paired baseline faecal samples. Median age was 34 years (range 18-49) and 108/211 (51.1%) were female. Median HBI at submission was 1 and median FCP, qFIT and CRP was 61µg/g stool, 9 µg Hb/g and 2 mg/l respectively. 42/211 (19.9%) experienced a relapse during follow up. Both FCP and qFIT showed good ability to predict relapse at 1 year, performing comparably, with the area under the receiver operating characteristic curves (AUROC) 0.80 (95% CI 0.74- 0.85) vs 0.75 (95% CI 0.68-0.80)(p=0.28). Combination biomarker use did not significantly improve performance, AUROC 0.82 (95%CI 0.76- 0.87) p=0.34 and p=0.07 respectively. Optimal threshold for prediction of relapse was >180 µg/g stool for FCP (sensitivity 0.69 and specificity 0.85) and >9 µg Hb/g for qFIT (sensitivity 0.65 and specificity 0.82). Utilising these thresholds (figure 1) patients with both FCP and qFIT above threshold had a probability of relapse free survival of 16.7% (95% CI 0.20%-31.6%) at 1 year vs 95.4% (95% CI 91.7%-99.0%, p<.0001) in patients under threshold. In combination, FCP and qFIT had a positive predictive value of 50.1% and negative predictive value (NPV) of 97.6%. Conclusion qFIT performs well and comparably to FCP in predicting relapse in clinically quiescent luminal CD and may be used in preference to FCP being an easier and cheaper test to undertake. When combined at optimal thresholds, qFIT & FCP show significant discriminatory ability in prediction of CD relapse-free survival with an excellent NPV.

P1070 Comaparison of Effectiveness and Perisitence Anti-TNF drugs on Perianal Fistulizing Crohn’s Disease: A Single Tertiary IBD Referral Center Experience

Abstract Background Perianal Crohn’s disease (CD) is a debilitating and often challenging manifestation of Crohn’s disease that involves the formation of fistulas, abscesses, and other inflammatory lesions around the anus and perineal area. It is associated with significant morbidity, including pain, recurrent infections, and impairment of daily activities. Treatment of perianal CD is complex, requiring a multidisciplinary approach to control disease activity, promote healing, and preserve anal function. Anti-TNF (tumor necrosis factor) biologic agents, such as infliximab and adalimumab, have become a mainstay in the management of perianal Crohn’s disease. However, there is still a debate which anti-TNF agents acts better than other in this subset of patients. Here in this study, we aimed to evaluate the compare the efficacy and persistence of two Anti-TNF agents in perianal Crohn’s disease. Methods This was a single center, retrospective cohort analysis of patients with Crohn’s disease either received adalimumab or infliximab as a first line biologic treatment. A total of 396 patients were included to this analysis. Demographic information such as gender, age, Montreal classification, smoking and prior medications were noted from patients electronic medical records. Weighted Kaplan-Meier and Cox models were used to assess the outcomes. Results Out of 446 Crohn’s disease patients, 128 patients had perianal Crohn’s disease. Gender, smoking, extraintestinal manifestations presence and family history were not different between patients with and without perianal disease. However, in perianal disease group there was more concomitant immunomodulator use than in patients with no perianal involvement (61.5% vs 49.4%, p<0.05). Anti-TNF drug persistence was significantly higher in patients without perianal involvement when compared to patients with with perianal involvement (Figure 1). There was no significant difference in drug persistence rates in perianal Crohn’s disease between infliximab and adalimumab treatment (Figure 2). The concomitant use of immunomodulator drugs did not make any impact. Conclusion In Crohn’s disease patients, anti-TNF medication persistence rates was observed to be significantly lower in those with perianal involvement. However, which anti-TNF agent was chosen as first line biologic did not change medication persistence rates. Concomitant thiopurine use did not make any impact on the results.

P0440 Faecal and plasma zinc as predictors of relapse in quiescent Crohn’s Disease in the Stratifying Crohn’s Using Biomarker Assessment (SCUBA) study

Abstract Background Zinc is an essential trace element playing an important role in immune function, inflammation regulation and intestinal barrier integrity. Deficiency is common in Inflammatory Bowel Disease (IBD). Recent data has shown zinc deficiency is associated with adverse disease specific outcomes in IBD1 and work from our unit has also suggested it a potential predictor of disease course in Crohn’s disease (CD)2. The Stratifying Crohn’s Using Biomarker Assessment (SCUBA) study assessed a number of biomarkers ability to predict relapse in quiescent CD including plasma and faecal zinc. Here we report the performance of these two potential biomarkers. Methods Patients with clinically quiescent CD (Harvey Bradshaw Index ≤3) were recruited prospectively from a single centre over a 2-year period. Faecal calprotectin, quantitative faecal immunochemical test, plasma and faecal zinc were obtained at baseline in addition to routine biochemical work up. Patients over 50 years old were excluded due to overlay with bowel cancer screening programmes as were those with isolated upper gastrointestinal or perianal CD. Patients were followed up for 1 year or until relapse defined by need for escalation of CD related treatment, steroid, surgery or hospitalisation for CD. Results 274 patients were recruited with 216 plasma zinc and 184 faecal zinc samples returned (of which 171 were paired). Median age was 34 years (range 18-49) and123/229 53.7% were female. Median HBI at submission was 1 with median FCP 55µg/g stool and C reactive protein 3mg/l. Median plasma zinc was 11.6 (IQR 10.5-12.6) µmol/L with 54/216 (25.0%) patients deficient at baseline (gender adjusted). Median faecal zinc was 832 (IQR 419-1481) µmol/kg wet weight. 44/229 (19.2%) experienced a relapse during follow up. No association between plasma zinc and faecal zinc was observed (r=0.068, p=0.38). Plasma zinc did not show ability to predict relapse at one year, area under the receiver operating characteristic curve 0.53. Following adjustment for gender, below reference range plasma zinc did not show discriminative value in predicting time to relapse, relative risk (RR) 1.37 (95% CI 0.73-2.56), p=0.33. After adjustment for confounders a RR 0.49 (95% CI 0.21-1.20), p= 0.12 was observed for (log transformed) faecal zinc. Conclusion Previous retrospective studies have reported an association between plasma zinc and time to relapse however this was not observed in our prospective study. Given these finding plasma zinc is unlikely to be of clinical utility with more accurate established biomarkers available. Levels of faecal zinc were noted to be markedly elevated compared to the literature however given the potential for methodological differences further work is required to validate this finding.

P0147 Regulation of Inflammatory Pathways by miR-338-3p and miR-378a-3p: A Novel Approach for Crohn’s Disease Treatment

Abstract Background MicroRNAs (miRNAs), key regulators of gene expression, are promising biomarkers and therapeutic targets in inflammatory bowel disease (IBD) due to their roles in immune response and tissue integrity. This study explores miRNA roles in IBD, focusing on Crohn's disease (CD) pathogenesis and potential therapies. We analyzed epithelial cell-derived miRNA expression in CD patients versus healthy controls and investigated how these miRNAs modulate inflammation in experimental IBD models. Methods Terminal ileum samples were prospectively collected via ileocolonoscopy from non-IBD healthy controls (n=26), CD patients in remission (n=34), and active CD patients (n=42). Clinical remission was defined as a Crohn’s Disease Activity Index score below 150 with endoscopic mucosal healing. For active CD cases, samples were taken from inflamed and non-inflamed regions. miRNA levels were quantified by small-RNA sequencing and validated by qRT-PCR. Based on these results, specific miRNAs were selected, and single-stranded mimics were administered in a 2.5% DSS-induced colitis model to evaluate their effects. Histological grading, immunohistochemistry, flow cytometry, and microbiome analysis using mouse fecal samples were performed. Results Small-RNA sequencing revealed distinct miRNA expression patterns in CD patients, both in remission and in active states (including inflamed and non-inflamed tissues), compared to healthy controls. qRT-PCR validation showed significantly reduced expression of miR-141-3p, miR-338-3p, miR-378a-3p, and miR-200b-3p, along with significantly increased levels of miR-125b-5p, miR-29b-3p, and miR-155-5p in inflamed tissue of active CD patients. Receiver operating characteristic curve indicated diagnostic potential for these miRNAs in relation to disease activity and endoscopic inflammation. In a DSS-induced colitis mouse model, miR-338-3p and miR-378a-3p showed anti-inflammatory effects, reducing body weight loss, colon inflammation, and immune cell markers. Target analyses identified MACC1 and IL-33 as key mRNA targets. Immunohistochemistry indicated an IL-33 pathway-dependent anti-inflammatory response via miR-378-3p, while miR-338-3p appeared to regulate gut inflammation by targeting MACC1 gene expression. In vitro analyses revealed that IL-33 activates MACC1, a process also reduced by miR-378a-3p treatment. Fecal microbiome analysis identified several bacterial species including Akkermansia muciniphilia and certain Bacteroides, associated with beneficial effects in the groups treated with both miRNA mimics. Conclusion This study identifies miR-338-3p and miR-378a-3p as modulators of inflammation in an IL-33-dependent manner in CD patients, underscoring their potential as promising targets for treatment of CD.

P1122 Identification of responder subpopulations in moderately-to-severely active Crohn’s disease patients treated with mirikizumab: Results from the VIVID-1 study

Abstract Background Mirikizumab (MIRI), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile in IBD1. Bowel urgency is common and impactful among patients with Crohn’s disease (CD).2 CD patients show a remarkable heterogeneity in their individual response levels to targeted therapies,3 including MIRI. We explored the existence of subgroups among MIRI-treated, moderate-to-severely active CD patients1 by investigating symptom trajectories and their relationship to treatment outcome. Methods A Growth Mixture Model was used to determine the existence and number of distinct patient clusters based on individual patient daily diary data used to construct Crohn’s Disease Activity Index (CDAI) based response trajectories. Response predictors were assessed with Classification and Regression Trees analysis. Week (W) 12 and 52 clinical endpoints were assessed by trajectory group. Non-responder imputation and modified baseline observation carried forward was used. Results Four response trajectory groups could be statistically separated: Super Responder (N=105; 18.4%), Responder (N=128; 22.4%), Delayed Responder (N=169; 29.5%), and Non/Incomplete Responder (unstable response over time) (N=170; 29.7%) (Figure 1). Patient Reported Outcome (PRO) Response (≥30% decrease in stool frequency and/or abdominal pain and neither score worse than baseline) at W12 was a marker of overall responder group. For patients with a baseline CDAI ≥350, W8 Bowel Urgency Response (≥3-point improvement on 0-10-point Urgency Numeric Ration Scale) was a marker of being a Super Responder. At W12 and W52, efficacy remission endpoints were achieved differentially: Super Responder, Responder, and Delayed Responder groups, respectively: clinical (W12/W52): 62%/80%, 38%/69%, 23%/49% (Table 1); endoscopic: 17%/41%, 20%/30%, 21%/37%; bowel urgency: 52%/72%, 35%/56%, 22%/43%; histologic: 21%/38%, 22%/38%, 24%/32%. Conclusion For MIRI treatment of CD, PRO Response and Bowel Urgency Response are early markers of overall treatment response. The overall response rate was 70.3%. Four symptom response trajectory groups were identified: Super Responder, Responder, Delayed Responder, and Non/Incomplete Responder. Efficacy was robust across all response groups except Non/Incomplete Responders. Super Responders followed by Responders and then Delayed Responders achieved the highest rates of W52 remission endpoints, including endoscopic/histologic, suggesting fast, robust response may lead to higher gains in long-term efficacy. Replication and molecular analysis are needed to investigate whether MIRI differential response kinetics identify CD endophenotypes.

P0846 A patient’s perspective on the use of exclusive enteral nutrition (EEN) for the treatment of paediatric Crohn’s Disease

Abstract Background Crohn’s Disease (CD) is a chronic condition and can result in the inflammation of any part of the gut. If left untreated, children diagnosed with CD are at increased risk of nutrient malabsorption and poor growth. The first-line treatment for CD is a 6-week dietary treatment called Exclusive Enteral Nutrition (EEN). This diet requires patients to stop eating food and switch to taking prescribed nutritional drinks, to achieve outcomes of resolving malabsorption symptoms and improving growth. This treatment is managed exclusively by dietitians. The aim of this study is to acquire an in depth understanding of the paediatric patient experience with EEN; identifying challenges and empowerment strategies that help increase patient adherence to the EEN treatment course. Methods Ethical approval was obtained from the CHI Ethics Committee in October 2023. The design of this study is a mixed-research method that focuses on collecting both qualitative and quantitative data. Participants of the study include patients of both sexes and all ethnicities, between 1-17years old, who were diagnosed with CD and advised to complete their first course of EEN during January 2022 and October 2023. An anonymised survey with 25 questions total was used to gather the information. Results Of the 116 patients who were approached to take part in the study, 47% of participants completed it. Two main themes were identified: (i) barriers to EEN compliance (subthemes included “feelings of isolation, taste/texture/smell of drinks and missing food), (ii) empowerment strategies for EEN (subthemes included drink preparation techniques, eliminating temptation, wide flavour choice, external support and health improvements). Of the 79% of patients who completed a full course of EEN; 55% found it ‘difficult’ and 60% reported that "they would attempt it again if required". Conclusion This study shows that patients find EEN to be a challenging diet which can have physical, emotional, and social impacts on aspects of the child’s life. Empowerment strategies such as external support (from family, friends and dietitians), adequate drink preparation and an awareness of associated health outcomes are imperative to help patients complete EEN. These findings are a valuable addition to the current limited knowledge base in this area.

P1209 Temporal trends in surgery and hospitalization rates for crohn's disease in Brazil: A population-based study

Abstract Background Crohn's Disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, primarily affecting young adults and adolescents. Biological therapies have advanced CD management, reducing hospitalizations and surgeries. Methods This retrospective, population-based study analyzed CD patients treated by the Brazilian Unified Health System (SUS) from 2012 to 2022. Patients were categorized by pharmacological treatment (azathioprine [AZA], infliximab [IFX], adalimumab [ADA]) based on dispensing records. Prevalence data were extracted from the Brazilian Institute of Geography and Statistics. Hospitalizations, surgeries, and prevalence trends were analyzed using TT Disease Explorer® and quantified as annual and average annual percent changes (AAPC). Statistical analysis was conducted in R software. Results From 2012 to 2022, CD prevalence increased 288.07%, from 14.20 to 52.64 cases per 100,000 inhabitants. The proportion of patients treated with AZA decreased from 44.79% to 19.13%, while IFX remained stable and ADA slightly declined (figure 1). In absolute terms, IFX and ADA usage rose by 251.09% and 242.48%, respectively. Hospitalizations dropped by 59.29%, 6.19% to 2.52%, and surgical procedures by 55.08%, 1.09% to 0.49% (figure 2). Conclusion The results indicate that despite the increase in CD prevalence, therapeutic interventions, especially involving biological agents, have been effective in reducing hospitalizations and surgeries. However, the proportional stability in the use of IFX and ADA, despite the absolute increase, suggests challenges in access and implementation of these therapies across Brazil. Additionally, potential coding errors in hospital records may influence data accuracy, possibly underestimating the true burden of hospitalizations and surgeries. Improvements in health record quality are essential to provide more accurate data and promote more efficient public policies.Over 11 years, there was a significant increase in CD prevalence in Brazil, accompanied by a notable reduction in hospitalizations and surgical procedures. Biological therapies have played a crucial role in improving disease management, though the direct relationship between their use and clinical outcomes requires further investigation. Future studies should focus on reference centers to confirm these trends and assist in planning public policies that optimize CD treatment and improve access to effective therapies in Brazil. References Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60(5):571-607. doi:10.1136/gut.2010.2241542. Quaresma AB, Kaplan GG, Kotze PG. The globalization of inflammatory bowel disease: the incidence and prevalence of inflammatory bowel disease in Brazil. Curr Opin Gastroenterol. 2019;35(4):259-264. doi:10.1097/MOG.00000000000005343. Quaresma AB, Damiao AOMC, Coy CSR, et al. Temporal trends in the epidemiology of inflammatory bowel diseases in the public healthcare system in Brazil: A large population-based study. Lancet Reg Health Am. 2022;13:100298. Published 2022 Jun 9. doi:10.1016/j.lana.2022.1002984. Palacio FGM, de Souza LMP, Moreira JPL, Luiz RR, de Souza HSP, Zaltman C. Hospitalization and surgery rates in patients with inflammatory bowel disease in Brazil: a time-trend analysis. BMC Gastroenterol. 2021;21(1):192. Published 2021 Apr 27. doi:10.1186/s12876-021-01781-x Figure 1: Proportion of patients by therapy used in Brazil's Unified Health System from 2012 to 2022. Figure 2: Proportion of surgeries and hospitalizations among Crohn's Disease cases in Brazil's public healthcare system from 2012 to 2022.

Assessment of the Utility of Selected Inflammatory Markers in Correlation with Magnetic Resonance Enterography (MRE) Findings in the Diagnosis of Crohn's Disease.

Crohn's Disease (CD) is a chronic inflammatory bowel disease affecting the gastrointestinal tract. The search continues for new markers for assessing the activity of CD. Among them, pro-inflammatory and anti-inflammatory cytokines appear promising. We performed the analysis of cytokine concentrations in blood serum using the Bio-Plex Multiplex system (Bio-Rad), and their correlations with radiological parameters were assessed by magnetic resonance enterography (MRE), and fecal calprotectin levels were measured quantitatively by ELISA and clinical evaluation according to the Crohn's Disease Activity Index (CDAI). Our study found that measuring cytokine serum concentrations can be a valuable tool in the diagnosis and treatment of CD. Positive correlations were reported between contrast enhancement on DCE-MRE and the concentrations of PDGF-BB and RANTES. Also, a positive correlation was found between the delayed-phase of DCE and IL-10 concentration, a strong negative correlation between the delayed-phase of DCE and IL-12 concentration, and a strong positive correlation between the delayed-phase of DCE and RANTES concentrations. A strong positive correlation was also observed between the thickness of the intestinal wall on T2-weighted images and RANTES concentration. Therefore, concentrations of PDGF-BB, RANTES, IL-10 and IL-12 are promising markers of CD activity. The study also demonstrated significant correlations between the severity of disease activity assessed by the CDAI and the concentrations of IL-5, IL-8 and IL-9, as well as positive correlations between the levels of fecal calprotectin and the concentrations of IL-1RA and VEGF. Therefore, the levels of IL-5, IL-8, IL-9, VEGF and IL-1RA may be useful markers in the diagnosis and clinical assessment of disease activity.

Durable remission after ileocolic resection for Crohn's disease is achievable in selected patients. Long-term results of a prospective multicentric cohort study of the GETAID Chirurgie.

Postoperative recurrence requiring medical treatment intensification or redo-surgery is common after ileocolic resection (ICR) for Crohn's disease (CD). This study aimed to identify a subgroup of CD patients for whom ICR could achieve durable remission. This retrospective follow-up study analyzed 592 CD patients who underwent ICR (2013-2015) in a nationwide prospective cohort. Patients with >36 months follow-up were included. Primary outcome was durable remission, defined as the absence of endoscopic recurrence and/or medical treatment intensification. Uni- and multivariate analyses identified predictive factors for durable remission. Among 268 included patients, 59% had B2 phenotype, 70% had a first ICR and 66% had postoperative medical treatment. After a median follow-up of 85(36-104) months, 52 patients (19%) experienced durable remission, of whom 24 (46%) didn't require medical treatment and 28 (54%) maintained the same postoperative treatment, including anti-TNF in 15/28 patients (54%). Surgery could stabilize the disease course in 112 patients (41.7%), including 22.4% endoscopic recurrence that didn't require CD treatment initiation or intensification. Durable remission rate was significantly increased in B1 phenotype vs. B2/B3 (n=7/18;39% vs n=45/250;18%, p=0.030) and in first ICR vs. redo ICR (n=43/184;23% vs n=9/80;11%, p=0.023). In multivariate analysis, B1 phenotype was the only independent predictive factor for durable remission (OR=3.59, IC95%[1.13-11.37], p=0.030). Surgery for CD achieved durable remission in 20%, rising to 40% in those with a B1 phenotype. These results support surgery as a viable alternative to medical treatment, offering treatment-free durable remission and preserving medical treatment options.

α-Methyl-Tryptophan Inhibits SLC6A14 Expression and Exhibits Immunomodulatory Effects in Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory condition of the intestines with a rising global incidence. Traditional diagnostic and therapeutic methods have limitations, necessitating the exploration of more effective strategies. In this study, we employed the Gene Expression Omnibus database to identify genes that are differentially expressed in CD. RT-PCR and immunohistochemical analysis were used to SLC6A14 RNA and protein expression in the colons of CD mice and CD tissues from patients. The mouse model of CD was induced by dextran sodium sulfate (DSS). Infiltrating immune cells in mouse model were screened by flow cytometry. We discovered that SLC6A14 is significantly overexpressed in CD samples, and its expression is positively correlated with the degree of infiltration by CD4+ and CD8+ T cells. The elevated levels of SLC6A14 RNA and protein were confirmed in clinical CD tissues. The SLC6A14 inhibitor α-methyl-tryptophan (α-MT) significantly decreased the expression of SLC6A14 RNA and protein in the colons of CD mice. The α-MT treatment group also exhibited reduced levels of cytokines involved in T cell differentiation (IFN-γ and TNF-α) and the expression of immune cell surface markers CXCR-3 and LAG-3. Flow cytometry analysis revealed a significant increase in the infiltration of CD4+ and CD8+ T cells in the DSS-treated group compared to the control group. Conversely, the α-MT treatment group showed a significant reduction in CD4+ and CD8+ T cell infiltration and the restoration of intestinal parameters in CD mice. These findings underscore the role of SLC6A14 in regulating intestinal immune cell infiltration during CD progression. Our findings suggest that SLC6A14 could serve as a potential diagnostic biomarker and therapeutic target for CD. Furthermore, α-MT offers a novel approach for the clinical diagnosis and treatment of CD by targeting SLC6A14 for therapeutic intervention.