Adult Crohn's Disease Research Articles

Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.

Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs). This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined. Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors. We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.

Assessment of outcomes in Crohn's disease: A systematic review of randomized clinical trials to inform a multiple outcome framework.

Longstanding disease control in Crohn's disease (CD) is challenging and requires understanding treatment efficacy and outcomes assessment. With multiple novel therapeutic options, rigorous evaluation of outcomes in randomized controlled trials (RCTs) is crucial to inform clinical practice. This study systematically reviewed RCTs focusing on CD outcomes to elucidate the breadth and depth of reported outcomes and measurement instruments. A systematic search was conducted on MEDLINE and Scopus for RCTs published from 1 January 2000 to 31 January 2023. Eligible studies included full-text articles with at least 50 adult CD patients. Primary and secondary outcomes, along with their measurement instruments, were categorized according to the Outcome Measures in Rheumatology Filter 2.1 framework. From 88 included studies, 393 outcomes were analyzed. Clinical outcomes, such as clinical remission and response, were the most prevalent (50.6%); biomarkers (11.5%) and patient-reported outcomes (10.2%) were also assessed. Other outcomes included disease behavior and complications (2%), endoscopy (10.4%), histology (0.5%), radiology (1.3%), healthcare utilization (3.8%), and therapy-related safety (6.9%). Composite outcomes showed an increasing trend, reflecting a shift toward comprehensive evaluations. Coprimary endpoints, including clinical symptoms and mucosal inflammation, were reported in 21 of 88 studies. This review highlights the evolving landscape of outcome assessment in CD RCTs, emphasizing the increasing complexity of outcomes. The prominence of composite outcomes underscores efforts to capture the multidimensional nature of CD. These findings will inform the second stage of a two-round e-Delphi aimed at prioritizing key domains and outcomes for developing a multiple-component outcome for RCTs in CD research.

Assessing the impact of dietary interventions on nutritional adequacy in adult Crohn's disease patients: preliminary results

Assessing the impact of dietary interventions on nutritional adequacy in adult Crohn's disease patients: preliminary results

Real-World Ustekinumab Experience in Ileum-Dominant Versus Colonic Crohn’s Disease

Abstract Background Crohn’s disease (CD) presents with diverse phenotypes. It remains unclear if CD location affects therapy efficacy. The aim of this study was to compare the real-world performance of ustekinumab in ileum-dominant and colonic CD. Methods We performed a single-center, IRB-approved, retrospective review of all adult CD patients who received ustekinumab. We stratified patients by ileal involvement: ileum-dominant (ileal and ileocolonic) and colonic CD. The primary outcome was the absence of ulcers on follow-up colonoscopy. The secondary outcomes included CRP, calprotectin, surgery, and hospitalization. Chi-square tests (or Fisher’s exact test) and 2-sample t-tests (or Wilcoxon’s rank-sum test) were used to compare categorical and numeric variables between groups, respectively; analyses were performed using R Computing Software versions 3.6.1. Results Eighty-four patients with ileum-dominant CD and 27 patients with colonic CD were treated with ustekinumab. The median time to follow-up endoscopy was 13 months. Follow-up colonoscopy after ustekinumab therapy was ulcer-free in 45% of ileum-dominant CD and 76% of colonic CD (P = .02). Of patients with ulcers prior to starting ustekinumab, 24% of ileum-dominant CD and 67% of colonic CD were ulcer-free (P = .01). There were similar rates of hospitalizations and surgery and no significant differences in mean calprotectin and CRP between the two groups on follow-up after ustekinumab therapy. Conclusions This real-world experience of ustekinumab demonstrates higher rates of endoscopic healing among colonic CD when compared to ileum-dominant CD. Disease location may predict endoscopic healing by ustekinumab. Further studies are necessary to expand our understanding of ustekinumab responsiveness to different CD phenotypes.

Crohn’s Patients and Healthy Infants Share Immunodominant B Cell Response to Commensal Flagellin Peptide Epitopes

Inflammatory bowel disease (IBD) is a chronic manifestation of dysregulated immune response to the gut microbiota in genetically predisposed hosts. Nearly half of patients with Crohn's disease (CD) develop selective serum immunoglobulin (Ig)G response to flagellin proteins expressed by bacteria in the Lachnospiraceae family. This study aimed to identify the binding epitopes of these IgG antibodies and assess their relevance in CD and in homeostasis. Sera from an adult CD cohort, a treatment-naïve pediatric CD cohort, and 3 independent non-IBD infant cohorts were analyzed using novel techniques including a flagellin peptide microarray and a flagellin peptide cytometric bead array. A dominant B cell peptide epitope in patients with CD was identified, located in the highly conserved "hinge region" between the D0 and D1 domains at the amino-terminus of Lachnospiraceae flagellins. Elevated serum IgG reactivity to the hinge peptide was strongly associated with incidence of CD and the development of disease complications in children with CD up to 5 years in advance. Notably, high levels of serum IgG to the hinge epitope were also found in most infants from 3 different geographic regions (Uganda, Sweden, and the United States) at 1 year of age, which decrements rapidly afterward. These findings identified a distinct subset of patients with CD, united by a shared reactivity to a dominant commensal bacterial flagellin epitope, that may represent failure of a homeostatic response to the gut microbiota beginning in infancy.

CROHN'S DISEASE AND OSTEOPOROSIS: RISK FACTORS, DIAGNOSIS AND CLINICAL TREATMENT

Crohn's disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract. Osteoporosis, in turn, is a skeletal disease characterized by decreased bone mass and deterioration of bone microarchitecture, increasing the risk of fractures. The association between these two diseases has been increasingly investigated, with evidence suggesting that patients with CD are at increased risk of developing osteoporosis. This comorbidity can be attributed to several factors, including corticosteroid use, nutrient malabsorption, chronic inflammation, and hormonal dysfunction. Objective: The objective of this systematic review was to identify and synthesize the available scientific evidence on the relationship between Crohn's disease and osteoporosis, focusing on risk factors, diagnosis, and clinical treatment. Methodology: A systematic review of the literature was performed, following the recommendations of the PRISMA statement. The PubMed, Scielo and Web of Science databases were searched using the following descriptors: “Crohn’s disease”, “Osteoporosis”, “Risk factors”, “Diagnosis” and “Treatment”. Original articles published in the last 10 years, in Portuguese or English, that investigated the association between CD and osteoporosis in adults were included. Case studies, narrative reviews and articles that did not address the relationship between the two diseases were excluded. Results: The results of the review demonstrated that osteoporosis is a frequent complication in patients with CD. Several risk factors were identified, including the use of corticosteroids, malabsorption of calcium and vitamin D, chronic inflammation and hormonal dysfunction. The diagnosis of osteoporosis in patients with CD can be challenging due to the presence of other factors that can affect bone mineral density, such as malnutrition and immobilization. Treatment of osteoporosis in patients with CD should be individualized and may include pharmacological and non-pharmacological measures, such as calcium and vitamin D supplementation, regular physical activity, and reduced tobacco and alcohol consumption. Conclusion: Crohn's disease represents a significant risk factor for the development of osteoporosis. The association between these two diseases is complex and multifactorial, involving several pathogenic mechanisms. Early diagnosis and appropriate treatment of osteoporosis in patients with CD are essential to prevent fractures and improve the quality of life of these patients. It is essential that health professionals are aware of this comorbidity and offer integrated clinical management for these patients.

Early Biological Therapy Within 12 Months of Diagnosis Leads to Higher Transmural Healing Rates in Crohn’s Disease

Transmural healing (TH) is emerging as a potential Crohn´s Disease (CD) treatment target. Early biological treatment seems to be associated with improved disease outcomes, but its impact on TH remains unclear. We aimed to assess the impact of early biological treatment initiation on TH and its influence on CD prognosis. This multicenter retrospective study included adult CD patients starting biological therapy. TH was assessed using magnetic resonance enterography (MRE) at 12±6 months post-therapy initiation, with radiological examinations reviewed by blinded expert radiologists. TH was defined as complete normalization of all MRE parameters. Timing of biological therapy initiation was analyzed as a continuous variable, with optimal cut-off determined using the Youden index and clinical relevance. Logistic regression with propensity score-adjusted analysis was used to assess the association between early biological therapy initiation and TH. Long-term outcomes (bowel damage progression, CD-related surgery, CD-flare hospitalization, and therapy escalation) were evaluated. Among 154 CD patients, early biological therapy initiation within 12 months of diagnosis was associated with significantly higher TH rates (aOR 3.23, 95% CI 1.36-7.70, p<0.01), which persisted after adjusting for previous biological therapy use (aOR 2.82, 95% CI 1.13-7.06, p=0.03). Time-to-event analysis demonstrated that TH was significantly associated with reduced time until bowel damage progression (aHR 0.28, 95% CI 0.10-0.79, p=0.02), CD-related surgery (aHR 0.21, 95% CI 0.05-0.88, p=0.03) and therapy escalation (aHR 0.35, 95%CI 0.14-0.88, p=0.02), independently of early biological therapy. Early initiation of biological therapy within 12 months of diagnosis significantly increases TH rates, leading to improved long-term outcomes in CD patients.

A Comparison of Clinical Outcomes of Colectomies for Pediatric and Adult Patients With Inflammatory Bowel Disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are prevalent in adult and pediatric populations, but their differences are not well studied using national data. We compared the clinical outcomes of these patients using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases.Methods: Colectomy cases for CD and UC, the 2 major forms of inflammatory bowel disease (IBD), were compared between adult and pediatric patients using the 2017-2019 ACS NSQIP databases. Various clinical factors were analyzed, with postoperative complications being the primary outcome of interest.Results: We identified 542 pediatric and 5174 adult CD patients and 360 pediatric and 1292 adult UC patients. Adults with CD or UC were more likely to be on steroids preoperatively (CD: 60.15% vs 24.54%; UC: 65.63% vs 51.39%). Children with IBD were more likely to have preoperative transfusions (CD: 1.48% vs .33%; UC: 8.33% vs .62%), systemic inflammatory response syndrome (CD: 3.51% vs .93%; UC: 12.78% vs 3.10%), or sepsis (CD: 1.85% vs .66%; UC: 1.39% vs .31%). Unplanned reoperations were more common among pediatric patients in both disease states compared to adults (CD: 6.27% vs 4.10%; UC: 11.11% vs 4.26%), with P-values for all factors described as ≤.02. Multivariate logistic regression found pediatric age to be associated with higher odds of needing a reoperation among UC patients but not CD patients.Conclusion: Pediatric patients were sicker at the time of surgery, and those with either disease were more likely to require a reoperation within 30days.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Are Internet Information Sources Helpful for Adult Crohn's Disease Patients Regarding Nutritional Advice?

Background: Adult patients suffering from Crohn's disease (CD) are often dissatisfied with the information they receive from their physicians about nutrition and its impact on CD inflammation activity. Only a few publications are available about patients' internet research on nutrition in CD. The study aim is to elucidate the internet information sources of adult CD patients regarding nutritional advice via a questionnaire. Methods: A questionnaire with 28 (general and specific) questions for outpatients at our tertiary center with CD was created and used for an analysis of their information sources about nutrition in CD. Four CD and/or nutritional medicine experts examined the 21 most relevant websites referring to nutritional advice for CD patients. Results: One hundred and fifty CD patients reported their Internet research behavior for nutritional advice and their dietary habits. Many CD patients prefer to consult the Internet instead of asking their general practitioner (GP) for nutritional recommendations. Most of the websites providing nutritional advice for CD patients are of very poor quality and cannot be recommended. We found significant correlations between (a) nutritional habits of CD patients, (b) their information sources and several demographic or CD-related factors. There is a lack of websites which provide high-quality, good nutritional advice to CD patients. Conclusions: The majority of the examined websites did not provide sufficient information according to the CD guidelines and nutritional medicine guidelines. A higher quality level of website content (e.g., on social media or on university/center websites) provided by experienced physicians is required to secure trustworthy and reliable nutritional information in CD.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Risk Factors for Complications and Disease Recurrence after Ileocecal Resection for Crohn's Disease in Children and Adults.

This study reports the complication and disease recurrence rates for ileocecal resection for pediatric and adult Crohn's disease (CD) and identifies perioperative risk factors for these adverse outcomes in the two groups. Patients who underwent ileocecal resection for CD in a tertiary hospital in Italy (2010-2021) were included. Risk factors for postoperative complications and clinical and surgical disease recurrences were investigated with multivariate models. A total of 96 patients were included (children, 25%). There were no intraoperative complications. Thirty-one (32.3%) patients experienced 35 (36.5%) postoperative complications, and five (5.2%) were severe (Clavien-Dindo III-IV-V), with no intergroup difference for either overall postoperative complication rate (p = 0.257) or severe postoperative complication rate (p = 0.097). Most of these (77.1%) occurred within 30 days after surgery, especially in adults (p = 0.013). The multivariate analysis did not show risk factors for postoperative complications. Clinical and surgical recurrence rates after 5 years were 46.8% and 14.6%, respectively, with no intergroup rate differences. Clinical disease recurrence was positively correlated with previous abdominal surgery (p = 0.047) and negatively correlated with preoperative Hb levels (p = 0.046). A positive correlation was found between perianal disease and both clinical (p = 0.045) and surgical disease recurrences (p = 0.045). Urgent surgery was positively associated with surgical disease recurrence (p = 0.045). Notably, no children underwent urgent surgery in this study. In conclusion, the risk of postoperative complications among CD patients receiving ileocecal resection remains high, but most of them are nonserious. Some factors, such as urgent surgery, may increase the risk of disease recurrences.

A Short-Term Enteral Nutrition Protocol for Management of Adult Crohn's Disease-A Pilot Trial.

Crohn's disease (CD) is often treated with either exclusive or supplemental enteral nutrition (EN) in pediatrics, but adult practice guidelines primarily focus on medications. Here, we demonstrate the feasibility of a 4-week semi-elemental-formula-based oral nutrition delivery program for managing adult CD (n = 4). Patients consumed ~66% of calories from the formula, a finding that might provide an improved calorie target for future trials. We identified Flavinofractor as the only differentially abundant genus, distinguishing post-intervention samples from pre-intervention samples. Findings from this pilot trial demonstrate the feasibility of a partial enteral nutrition protocol in adult CD management and contribute to the growing body of literature on the potential role of EN therapy in adults with CD.

The association between hemoglobin level and sarcopenia in Chinese patients with Crohn’s disease

Sarcopenia and anemia are common complications in patients with Crohn’s Disease (CD). However, few studies have shown the association between sarcopenia and hemoglobin levels in CD patients. This retrospective study aimed to explore such association in Chinese patients with CD. Two hundred and twelve adult CD inpatients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) examinations from July 2019 to December 2021 were included in the study. Sarcopenia was defined according to the cutoff value of skeletal muscle index of lumbar spine 3 (SMI-L3) (< 44.77cm2/m2 for males and < 32.5cm2/m2 for females). The CD patients were divided into two groups based on the presence or absence of sarcopenia. Clinical data, hemoglobin levels, and other laboratory data were retrospectively collected. The association between hemoglobin levels and sarcopenia was analyzed by univariable and multivariable logistic regression analysis. Sarcopenia occurred in 114 CD patients (53.8%). Compared to patients without sarcopenia, patients with sarcopenia had a lower proportion of L1 (30.7% vs. 45.8%, p = 0.032) and B1 classification (58.8% vs. 72.4%, p = 0.037). Patients with sarcopenia had significantly lower levels of hemoglobin (Hb) (116.5 ± 22.8 vs. 128.1 ± 21.0, p < 0.001). The prevalence of sarcopenia increased with the decrease in hemoglobin level (p for trend < 0.05). Linear regression analysis showed that hemoglobin levels were associated with SMI-L3 (β = 0.091, p = 0.001). Multivariable logistic regression analysis found that higher hemoglobin levels (OR:0.944; 95% CI: 0.947,0.998; p = 0.036) were independent protective factors for sarcopenia. Lower hemoglobin levels are independently associated factors of sarcopenia in adult Chinese patients with CD.

Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology, and several have been implicated in the pathogenesis of adult CD. However, there is a dearth of large-scale miRNA studies for pediatric CD. We hypothesized that specific miRNAs uniquely mark pediatric CD. We performed small RNA-Seq of patient-matched colon and ileum biopsies from treatment-naive pediatric patients with CD (n = 169) and a control cohort (n = 108). Comprehensive miRNA analysis revealed 58 miRNAs altered in pediatric CD. Notably, multinomial logistic regression analysis revealed that index levels of ileal miR-29 are strongly predictive of severe inflammation and stricturing. Transcriptomic analyses of transgenic mice overexpressing miR-29 show a significant reduction of the tight junction protein gene Pmp22 and classic Paneth cell markers. The dramatic loss of Paneth cells was confirmed by histologic assays. Moreover, we found that pediatric patients with CD with elevated miR-29 exhibit significantly lower Paneth cell counts, increased inflammation scores, and reduced levels of PMP22. These findings strongly indicate that miR-29 upregulation is a distinguishing feature of pediatric CD, highly predictive of severe phenotypes, and associated with inflammation and Paneth cell loss.

MRI AND BLOOD-BASED BIOMARKERS ASSOCIATED WITH SURGICAL MANAGEMENT IN CHILDREN AND ADULTS WITH SMALL BOWEL CROHN'S DISEASE

Abstract BACKGROUND Despite advances in medical therapy, many children and adults with ileal Crohn’s Disease (CD) progress to fibrostenosis requiring surgery. Prior studies have identified circulating and imaging biomarkers associated with strictures, although their associations with need for surgery are not well-established. PURPOSE We aimed to identify MRI and circulating biomarkers associated with the need for surgical management in chidlren and adults with ileal CD. METHODS This prospective, multi-center study included pediatric and adult CD cases undergoing ileal resection (n=50), and CD controls receiving medical therapy (n=83). Noncontrast research MRI examinations measured bowel wall three-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA) (Figure 1). Circulating biomarkers included CD64, ECM1, and GM-CSF autoantibodies (Ab). Clinical variables, including demographics, anthropometrics, and routine clinical laboratory data (e.g., CRP, fecal calprotectin), also were obtained at the research visit. Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS Mean participant age was 23.9±13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR]=2.87; p=0.0009), normalized 3D MTR (OR=1.05; p=0.002), log MOLLI T1 (OR=0.01; p=0.02), log IVIM perfusion fraction (f) (OR=0.38; p=0.04), and IVIM apparent diffusion coefficient (ADC) (OR=0.3; p=0.001). MRI and circulating biomarker Tukey box plots are presented in Figure 2. The multivariable model for surgery based upon AICc criteria included age (OR=1.03; p=0.29), BMI (OR=0.91; p=0.09), log GM-CSF Ab (OR=3.37; p=0.01), normalized 3D MTR (OR=1.07; p=0.007), sMaRIA (OR=1.14; p=0.61), luminal narrowing (OR=10.19; p=0.003), log CRP (normalized) (OR=2.75; p=0.10), and hematocrit (OR=0.90; p=0.13). CONCLUSION After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with need for surgery in ileal CD. GM-CSF autoantibodies and MRI biomarker sequences may be useful for guiding management decisions in CD patients. Figure 1 Research MRI images from a surgical Crohn’s disease patient with stricturing behavior involving the terminal ileum. A and B. Coronal and axial fat-saturated T2-weighted single-shot fast spin-echo (SSFSE) images show wall thickening and luminal narrowing of the terminal ileum (arrows) with more proximal bowel dilation measuring greater than 3 cm. C. Axial 3D magnetization transfer images – MT pulse on (bottom image, arrow), MT pulse off (top image, arrow). D. Axial modified Look-Locker inversion recovery (MOLLI) T1 relaxation image (arrow). E. Representative axial intravoxel incoherent motion diffusion-weighted images with increasing b-values (left to right, arrows). Figure 2 Variation in circulating and imaging biomarkers in Crohn’s disease patients with medical and surgical management. Ctrl: non-IBD healthy controls; Med: CD patients with nonsurgical medical management; Surg: CD patients with surgical management.

P1207 Microbiome composition determines sustained remission after the Crohn’s Disease Exclusion Diet (CDED) with or without Partial Enteral Nutrition in adults with mild-moderate Crohn’s disease; Results from the CDED-AD Pilot Randomized Controlled Trial

Abstract Background The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we can determine sustained clinical remission (SCR) from the baseline microbiome composition and examine the effect of CDED on microbiome composition in adult CD. Methods This was an open-label, prospective, randomized, controlled pilot trial involving patients with mild-to-moderate CD and evidence of active inflammation. Patients were randomly assigned to receive CDED with partial Enteral Nutrition (PEN) or CDED alone, both for 24 weeks. The V4V5 region of the 16S rRNA gene was amplified and sequenced, and reads were processed using QIIME2 and the SILVA database. Relationships between the microbiome, SCR, and Fecal Calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, paired T-Tests and subsampling ranking forward selection. Results Clinical remission (CR) at weeks 6, 12 and 24 was achieved in 62.5%, 52.5%, and 50% of patients, respectively. Week 0, 6, 12 and 24 stool samples were available for 35,32,30 and 26 patients, respectively. In patients with SCR, defined as remission at both weeks 12 and 24, the baseline microbiome revealed lower alpha diversity compared to those without SCR (p=0.018), and differing Microbiome principal components (PC) scores (p &amp;lt; 0.01). PC1 and PC3, characterized mainly by Alistipes, Faecalibacterium and UCG-002 predicted SCR (P&amp;lt;0.01). PC2 predicted elevated FC&amp;gt;250 µg/g at week 12 (p=0.004). Baseline abundance of Haemophilus was associated with decreased SCR probability (p&amp;lt;0.01). At week 6 in the entire cohort, there was a significant decrease in Actinobacteriota (p=0.035) and a significant increase in Bacteroidota (p=0.003). Additionally, there was a significant increase in several genera, including beneficial Alistipes and Oscillibacter (p&amp;lt;0.02) in those who achieved CR after 6, 12, or 24 weeks. Higher Firmicutes at week 6 were associated with FC&amp;lt;250 at week 12 (p=0.031). An uncultured genus from the Oscillospiraceae family was significantly associated with a decrease in the probability of SCR (p&amp;lt;0.01) and was significantly increased at week 6 in patients who did not attain CR (p&amp;lt;0.05). Conclusion The baseline microbiome composition was associated with SCR and FC&amp;lt;250 at week 12 in adult patients treated with CDED (with or without PEN) over 24 weeks. This suggests that the microbiome could be useful tool to identify patients who would benefit from long-term dietary intervention.

P719 Vitamin and micronutrient excess in patients with Crohn’s disease under oral ambulatory exclusive enteral nutrition

Abstract Background Exclusive enteral nutrition (EEN) is recommended for preoperative nutritional optimization (PNO) in adult Crohn's disease (CD) patients. However, during ambulatory oral EEN, a lack of routine monitoring for vitamins may occur, with a potential risk of hypervitaminosis-related toxicity, which remains unexplored. This study aims to assess the serum levels of vitamins and micronutrients in CD patients undergoing EEN and to examine its potential impact. Methods Complicated phenotype CD patients followed at a University Tertiary Hospital who were started on oral EEN June 2021 - June 2023 were prospectively included. EEN composition was determined and modified by an IBD nutritionist according to patients’ nutritional status and needs and laboratory values. Compliance was monitored daily, both for in- and outpatients. Patients’ weight and serum values (albumin, C-reactive protein [CRP], iron, folic acid, and vitamins B1, B6, B12, A, D, E and K) were monitored weekly. Results Nine patients (median age 29 years, 55.6% female) received a median of 24 (IQR 14.5-25.0) days of EEN, for PNO of symptomatic stricturing (7, 77.8%) or abdominal penetrating disease (2, 22.2%). All patients were discharged while on EEN, which was maintained until elective surgery (4, 44.4%) or the planned start of advanced medical therapy (5, 55.6%), with EEN successfully avoiding emergent surgeries. Patients were started on a combination of hypercaloric-hyperproteic and hypercaloric-normoproteic ready-to-drink concentrated polymeric formulas, providing 30 kcal/kg/d and 1.2-1.5g/kg/d of protein. EEN daily volume ranged from 1000 to 1400mL. Compliance was 100%, requiring flavour adjustments for tolerance. Table 1 illustrates changes over time in patients' weight and serum levels of interest. Resolution of anaemia and hypoalbuminemia was achieved, while weight was maintained . Hypervitaminosis cases were remarkably detected: 5 (55.6%) for vitamin B1, 4 (44.4%) for A, 2 (22.2%) for E, and 3 (33.3%) for K, with increasing trends over time. However, no symptoms related to hypervitaminosis were reported. Conclusion Our study on PNO EEN in CD uncovered a gap in routine monitoring for essential vitamins during EEN. While achieving significant clinical improvement, our findings revealed subtle and asymptomatic cases of hypervitaminosis in short-term EEN courses. These results underscore that vitamin monitoring is advisable during EEN, especially in prolonged EEN protocols due to possible hypervitaminosis-related toxicity.

P592 Higher predictive power of epigenetic signatures for response to vedolizumab and ustekinumab in anti-TNF naïve patients with active Crohn’s disease

Abstract Background Despite the significant progress in IBD care with biological therapies, the current 'trial-and-error' method remains suboptimal. Previous results from our EPIC-CD study demonstrated that two distinct epigenetic panels of 25 and 68 DNA methylation markers, respectively, were associated with (non-)response to vedolizumab (VDZ) and ustekinumab (USTE) in active Crohn’s disease (CD)1. Data from clinical trials have demonstrated that response rates in patients naïve to biological treatment are higher. We therefore aimed to evaluate the performance of our models in bionaive and anti-TNF exposed subpopulations. Methods We prospectively measured peripheral blood DNA methylation profiles from 184 adult CD patients prior to treatment with VDZ or USTE in a discovery (n=126) and independent validation (n=58) cohort using the Illumina EPIC BeadChip array. Between 26 and 52 weeks, patients were categorized as responders or non-responders based on a combination of endoscopic response (≥50% reduction in SES-CD score), steroid-free clinical response (≥3-point drop in Harvey-Bradshaw Index (HBI) or HBI ≤4 AND no systemic steroids), and/or biochemical response (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin or a CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Epigenetic biomarker identification and classification analyses were conducted through stability selection gradient boosting on the discovery cohort. Subsequently, the performance of the identified epigenetic biomarkers was assessed independently on the validation cohort, with patients stratified by prior anti-TNF exposure. Results Out of the 58 patients in the validation cohort, 25 received treatment with VDZ, and 33 with USTE, with 52% (n=13) and 36% (n=12) respectively naïve to anti-TNF treatment. Baseline characteristics between anti-TNF naive and anti-TNF exposed patients showed no significant differences, despite a slight significant age difference in the vedolizumab group, where anti-TNF exposed patients were significantly younger (table 1). In the overall independent validation cohort, the prediction models demonstrated an AUC of 0.75 for both VDZ and USTE. However, after stratification by prior anti-TNF exposure, we observed increased performance of our models among anti-TNF naive patients for both VDZ (AUCnon-exposed=0.85 versus AUCexposed=0.66) and USTE (AUCnon-exposed=0.97 versus AUCexposed=0.63 (figure 1). Conclusion Our findings demonstrate that prior anti-TNF exposure leads to somewhat reduced predictive power of our epigenetic models for Vedolizumab and Ustekinumab response. The predictive models may therefore find its optimal application in bio-naive patients, although they remain significant in anti-TNF exposed patients.

P827 Has opioid use increased among adults with Crohn’s disease? A Swedish Nationwide cohort Study 2008-2020

Abstract Background Chronic opioid use has turned into a global health challenge. Crohn’s disease (CD) patients may experience severe pain requiring opioids which could exacerbate CD symptoms and pose a risk of chronic use. The use of opioids among CD patients has not been explored on a national level. We compared the secular trends of opioid use among prevalent CD patients and matched reference individuals in Sweden. Methods This nationwide cohort study included adults with a prevalent CD diagnosis who lived in Sweden for at least 12 consecutive months at some point between 1 January 2008 and 31 December 2020. For each patient, up to 10 reference individuals from the general population were matched on birth year, sex, calendar year, and place of residence. We retrieved the data on dispensed opioid prescriptions (opioid use) from the National Prescribed Drug Register. We defined opioid use as ≥1 filled prescription per calendar year. We also estimated the annual prevalence of ≥1 dispensation of weak (codeine combinations, tramadol, and Dextropropoxifen) and/or strong opioids (Oxycodone, Morphine, Hydromorphone, Fentanyl, Buprenorphine, Tapentadol, and Petidin). Results We identified 43,155 adult CD patients and 418,218 reference individuals (Table 1). The prevalence of opioid use was stable from 2008-2016. However, between 2017 and 2020 it decreased from 19.7% (95% CI: 19.2, 20.2) to 16.9% (95% CI: 16.2, 17.7) and from 8.5% (95% CI: 8.4, 8.7) to 6.9% (95% CI: 6.7, 7.1) among CD patients and reference individuals, respectively (Figure 1a). However, between 2008 and 2020, the prescription of strong opioids more than doubled among both CD patients (increasing from 4.3% [95% CI: 4.1, 4.6] to 11.5% [95% CI: 11.1, 11.8]), and reference individuals (increasing from 1.3% [95% CI: 1.3, 1.4] to 5.4% [95% CI: 5.3, 5.5]) (Figure 1b). In 2020, the last year of the observation, compared with males, both female CD patients (20.3% [19.7, 20.8] vs 9.3% [9.2, 9.5]) and their matched reference individuals (15.3% [14.8, 15.9] vs 7.1% [6.9, 7.2]) had a higher prevalence of annual opioid use. The secular trends of overall opioid use and increasing use of strong opioids were similar for males and females (data not shown). Conclusion Annual opioid use among prevalent CD patients in Sweden, a country with publicly-funded healthcare and access to modern CD treatment, was two-fold higher than in the general population in the last 13 years. The annual opioid use remained stable from 2008-2016 and slightly decreased from 2017-2020 for CD patients and reference individuals. During the same period, the use of strong opioids more than doubled for CD patients and the general population.