Active Inflammatory Disease Research Articles

An online mindfulness-based intervention for adults with Inflammatory Bowel Disease & psychological distress: A feasibility randomized controlled trial of the Mind4IBD program

ObjectiveThe bidirectional relationship between disease activity and mental health in inflammatory bowel disease (IBD) has prompted investigations into the efficacy of psychotherapies, such as mindfulness-based interventions (MBI), for improving biopsychosocial outcomes. Therefore, the aim is to examine the feasibility, acceptability, and preliminary efficacy of an online-delivered, self-directed MBI, adapted to individuals with IBD and psychological distress, in comparison to wait-list control (WLC). Methods50 adults with IBD were randomized to WLC (N = 25) or intervention (N = 25) groups. The intervention (MIND4IBD program) consisted of six, weekly, 15-min videos (with guided meditations). Feasibility was examined through recruitment and retention rates, while acceptability was examined through intervention satisfaction ratings and qualitative feedback. Preliminary efficacy was examined using linear mixed models for group differences in outcomes between baseline and post-intervention. ResultsPrimary Outcomes. The retention rate for the WLC group was 92 %, while the retention rate for the intervention group was 48 %. However, 16 % of participants allocated to the intervention group never began the intervention, therefore this resulted in a retention rate of 71 % of participants who began the intervention. Acceptability was high with an average intervention satisfaction rating of 83/100. Secondary Outcomes. When compared with the WLC, the MIND4IBD program improved total mindfulness levels (b = 0.29, 95 %CI [0.11,0.47], p = 0.004) with a large effect size (β = 0.54, b = 0.19, 95 %CI [0.04,0.34], p = 0.014). Themes based on participants' intervention feedback included: 1) beginning of journey with mindfulness, 2) the beneficial impact of mindfulness, 3) why adapting the intervention to IBD is important, 4) views on program delivery, and 5) mixed reactions to AI generated presenters. ConclusionMIND4IBD is feasible and acceptable for individuals with IBD and psychological distress. Participants' total mindfulness levels increased significantly in the intervention group compared to WLC. Most participants provided positive intervention feedback. These findings warrant a full-scale RCT to determine MIND4IBD's efficacy for IBD.

The NLRP3 inflammasome: A central player in multiple sclerosis.

Multiple sclerosis (MS) is a neurological autoimmune condition associated with many symptoms including spasticity, pain, limb numbness and weakness. It is characterised by inflammatory demyelination and axonal degeneration of the brain and spinal cord. A range of disease-modifying therapies (DMTs) are available to suppress inflammatory disease activity in MS, however, there is a pressing need for new therapeutic avenues as DMTs have a limited ability to suppress confirmed disability progression. A body of literature indicates that innate immune inflammation is linked to MS progression. The nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing protein 3 (NLRP3) inflammasome has a well-established function in innate immunity which is closely associated with the pathogenesis of neuroinflammatory conditions. Evidence suggests that the inflammasome may be a therapeutic target in disorders such as MS and at present, inhibitors of the NLRP3 inflammasome are in pre-clinical development. Therefore, this review systematically highlights the pathogenic role of inflammasomes in MS, presenting an overview of research evidence linking inflammasome-related polymorphisms to MS susceptibility, and gathering evidence investigating NLRP3 biomarkers in MS. The role of the NLRP3 inflammasome in murine models of MS is furthermore discussed. Finally, a significant component of this review focuses on evidence that NLRP3 signalling components are novel drug targets in MS. Overall this review defines the role of the inflammasome in MS pathogenesis and identifies inflammasome inhibitor targets that warrant full investigation in MS and related disorders.

Barriers and facilitators to treat-to-target in axial spondyloarthritis in clinical practice: a mixed methods study

This study aimed to explore the perceptions of patients and rheumatologists about a treat-to-target (T2T) strategy in axial spondyloarthritis (axSpA) and identify the barriers and facilitators to its implementation in clinical practice. A mixed methods design was applied. Patients with axSpA who visited the outpatient clinic with active disease (AxSpA Disease Activity Score [ASDAS] ≥ 2.1), but did not receive a treatment adjustment, were identified. These patient cases were discussed in individual semi-structured interviews with the respective treating rheumatologists, and a subgroup of these patients was also interviewed. In parallel, all interviewed participants completed a quantitative survey. Qualitative and quantitative data were analysed thematically and descriptively, respectively. Twenty-three patients were discussed with 11 rheumatologists, and 16 of these patients were interviewed personally. Barriers to T2T included challenges in the measurement of inflammatory disease activity using the ASDAS, and numerous patient-related factors such as concern about treatment adaptations. The limited number of viable treatment options and scarce amount of evidence supporting T2T in axSpA, as well as logistical challenges, were additional obstacles. Facilitators included patients’ broad knowledge about axSpA, rheumatologists’ awareness of T2T recommendations, and positive doctor-patient relationships with the application of shared decision-making. Moreover, a supporting infrastructure, such as one with high accessibility to the outpatient clinic between scheduled visits, was considered necessary for the application of a T2T strategy. In conclusion, numerous barriers and facilitators to the implementation of a T2T strategy in axSpA are present, which need to be considered when applying this treatment approach in clinical practice.

P0660 Comparative Accuracy and Reliability of Handheld versus Cart-Based Ultrasound in assessing Inflammatory Bowel Disease Activity

Abstract Background Bowel wall thickness (BWT) and vascularity are key parameters for assessing inflammatory bowel disease (IBD) activity. Handheld ultrasound devices (HHUS) provide a portable and affordable alternative for incorporating intestinal ultrasound (IUS) into IBD management. However, their diagnostic accuracy and reliability compared to cart-based ultrasound (CBUS) remain uncertain. This study assesses the diagnostic accuracy, reproducibility, and practitioner confidence with HHUS in comparison to CBUS for assessing BWT and vascularity. Methods In this prospective, comparative study, 12 patients with IBD, with body mass index (BMI) <23 kg/m², were assessed. Each patient underwent ultrasound scanning of 2–3 pre-specified bowel segments using five devices: one CBUS device (Samsung™) and four HHUS devices (Clarius™ L15 HD3, GE™ Vscan Air CL, Mindray™ TE Air, and Philips™ Lumify L12-4). Linear probes were used for all devices except Mindray™, which employs a phased array probe optimised for cardiac imaging. Scans were conducted by two to three gastroenterologists accredited by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), who were blinded to each other’s findings to reduce bias. BWT and Doppler vascularity, as well as other standard IUS parameters, were assessed for each segment. Diagnostic accuracy and inter-/intra-expert agreement were analysed using statistical models. Results Among the 12 patients (42% male; median age: 26 years, IQR: 23–36) with CD (n=6) and UC (n=6), a total of 29 bowel segments were assessed with all devices (Table 1). BWT measurements showed high concordance across devices for active segments (mean BWT: 4.3–4.6 mm, p=0.73). However, significant discrepancies were noted in inactive segments (p<0.001), particularly with the Mindray™ device showing larger deviations from the CBUS measurements. Intraclass Correlation Coefficients (ICC) for intra-expert BWT measurements were good to excellent across devices (ICC 0.79–0.97), while inter-expert agreement was good for all devices (ICC 0.70–0.77) except for Mindray™ (ICC 0.36) (Figure 1B). Significant confidence was noted for BWT, vascularity, stratification, mesenteric fat, and inflamed bowel length across devices, highlighting consistent measurement reliability for these parameters (Table 1). Conclusion The majority of HHUS devices used in this study demonstrate high diagnostic accuracy and reproducibility in assessing IBD activity and are comparable to CBUS for identifying and assessing active disease. This study supports the integration of HHUS into IBD management as a portable and accessible tool while highlighting the importance of recognising device-specific limitations when selecting devices for clinical practice.

P1224 Bidirectional association between sleep pattern and inflammatory bowel disease: a large population-based prospective cohort study

Abstract Background Disturbances in sleep have been associated with systemic inflammation and increased susceptibility to various chronic diseases. However, the specific mechanisms by which sleep influences plasma protein expression and contributes to the increased risk of inflammatory bowel disease (IBD) have not been fully elucidated. Methods We analysed data from 381,228 participants in the UK Biobank. Sleep was scored with chronotype, sleep duration, insomnia, and daytime sleepiness. Adjusted odds ratios (ORs) for prevalent IBD in unhealthy sleep patterns were estimated, as well as adjusted hazard ratios (HRs) for incident IBD by sleep patterns. A subset cohort of 40,392 participants was used for proteomic profiling, with differential expression analysis and weighted gene co-expression network analysis (WGCNA) conducted. A proteomic prognostic risk model was also established using the least absolute shrinkage and selection operator (LASSO)-Cox regression. Results Among the 381,228 participants in the clinical cohort, 100,622 (26.4%) had unhealthy sleep (sleep score 0-2) at baseline. Prevalent IBD was associated with increased odds of unhealthy sleep (OR = 1.250, 95% CI: 1.165-1.340, p < 0.001, Figure 1). Participants with unhealthy sleep had a higher risk of incident IBD (HR = 1.237, 95% CI: 1.136-1.348, p < 0.001). In the proteomic cohort, unhealthy sleep and IBD displayed 182 common differentially expressed proteins. Enrichment analysis revealed significant inflammatory pathways, including positive regulation of cytokine production and immune cell activation. WGCNA identified seven module eigengenes, with unhealthy sleep impacting IBD through cell activation and chemotaxis pathway and amino acid and organic acid metabolism. Incorporating protein biomarkers enhanced the performance of predicted models that achieved an AUC of 0.81 for predicting 2-year IBD onset. Unhealthy sleep participants with high protein scores were at high risk of incident IBD (HR=3.370, 95% CI: 2.300-4.938, p < 0.001), highlighting the importance of monitoring systemic inflammation. Conclusion Unhealthy sleep and IBD are bidirectionally linked, with inflammatory and metabolic proteins mediating the effect of poor sleep on IBD risk. Patients with sleep disturbances should be screened for inflammatory biomarkers to evaluate their IBD risk. Enhancing sleep quality may serve as an effective strategy for preventing and managing IBD. References Sleep disorders and inflammatory disease activity: chicken or the egg? Am J Gastroenterol. 2015 Apr;110(4):484-8.

P0079 Serum calprotectin [cpa9-hne], a biomarker of neutrophil activity, is associated with histological inflammation and fibrosis burden

Abstract Background Infiltration of neutrophils into the intestinal tissue is a crucial component of the inflammatory response in Crohn‘s disease (CD). CPa9-HNE, a calprotectin fragment released by human neutrophil elastase during NETosis, has been shown to strongly correlate with endoscopic disease activity in inflammatory bowel disease (IBD) and serves as an indicator for pharmacodynamic response. Furthermore, emerging data suggests that neutrophil extracellular traps (NETs) significantly contribute to the pathogenesis of fibrosis. For the first time, we investigated the association of CPa9-HNE with histological grading of both inflammation and fibrosis. Methods The cohort included 62 patients with stenotic Crohn‘s disease. Inclusion criterion was the presence of stenotic disease requiring bowel resection, as confirmed by radiographic assessment. Upon surgery, the resected specimens were collected and histologically graded according to transmural fibrosis burden, and inflammation (D'Haens score). Serum was drawn at baseline (before resection). CPa9-HNE was measured, reflecting a human neutrophil elastase-derived fragment of calprotectin. Spearman’s rank correlation was applied. Results CPa9-HNE showed an overall positive correlation to the D'Haens score (ρ=0.279, p<0.005). Significant positive correlation was observed between CPa9-HNE and the presence of neutrophils, both in the epithelium and the lamina propria (ρ=0.309, ρ=0.349, p<0.005 both), as well as with epithelial damage (ρ=0.262, p<0.005). We also observed a positive correlation between CPa9-HNE and transmural fibrosis burden, specifically fibrosis in the submucosa (ρ=0.294, p<0.005) Conclusion This study showed that CPa9-HNE, a biomarker of neutrophil activity, correlated with the presence of neutrophils in the intestinal tissue, as well as epithelial damage. Interestingly, CPa9-HNE also showed association to submucosal fibrosis, emphasizing the importance of considering neutrophil activity when targeting the fibro-inflammatory axis. These findings highlight the potential use of CPa9-HNE as a complementary tool for histological grading of inflammation and fibrosis burden, and could be used to further explore the role of neutrophil extracellular traps in intestinal fibrosis.

P0363 Explore the application value of serum GOLM1 in the diagnosis of Inflammatory Bowel Disease

Abstract Background Current biomarkers used to monitor the disease activity of inflammatory bowel disease (IBD) have several limitations in specificity and sensitivity, and there is an urgent need to identify novel biomarkers. Previously, Golgi membrane protein 1 (GOLM1) has been proven to protect against colitis by modulating the equilibrium of Notch signaling pathway. Therefore, we aimed to explore the possible value of serum GOLM1 in the clinical diagnosis and disease activity assessment of IBD. Methods Collected clinical data, including serum GOLM1 and inflammatory markers (ESR, CRP, and Interleukin-6 [IL-6]), from 60 IBD patients (30 UC and 30 CD) and 30 control subjects (patients with colon polyps) at the First Affiliated Hospital of Zhengzhou University between August 2023 and August 2024. Mayo score and Crohn’s Disease Activity Index (CDAI) were used to evaluate the clinical disease activity of UC and CD, respectively. In UC, endoscopic disease activity was determined by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and in CD, it was measured by the Endoscopic Score for Crohn’s Disease (SES-CD). The level of serum GOLM1 was compared between IBD and the control subjects, as well as among different subgroups of IBD patients. Analysed the correlations between serum GOLM1 level and inflammatory markers, and between serum GOLM1 level and disease activity indices. Results 1. Serum GOLM1 levels were all elevated in IBD patients (p < 0.001), UC patients (p < 0.001), and CD patients (p = 0.050) compared with the control patients, and this trend was more pronounced in UC (Figure 1). Serum GOLM1 levels did not differentiate between UC and CD. Also, there was no significant difference in serum GOLM1 levels between remissive and active IBD patients, whether assessed clinically or endoscopically. 2. The level of serum GOLM1 was positively correlated with ESR (r = 0.491, p < 0.001), CRP (r = 0.397, p = 0.002) and IL-6 (r = 0.493, p < 0.001) in IBD patients. The same trend was also observed in UC. Serum GOLM1 level was also positively correlated with UCEIS in endoscopically active UC patients (UCEIS ≥ 1) (r = 0.489, p = 0.048), but not with Mayo score in clinically active UC patients (Mayo ≥ 3) (Figure 2). In CD, serum GOLM1 level was only positively correlated with ESR (r = 0.437, p = 0.016) and IL-6 (r = 0.377, p = 0.040). In endoscopically active CD patients (SES-CD ≥ 3), serum GOLM1 level was not associated with SES-CD. Similarly, no association was found between serum GOLM1 level and CDAI in clinically active CD patients (CDAI ≥ 150). Conclusion This study revealed a significant increase in the serum GOLM1 level in IBD, especially in UC. GOLM1 may be involved in the inflammatory process of IBD and may serve as a potential biomarker of IBD.

P0380 Mild Hyperemia in the Absence of Bowel Wall Thickening on Intestinal Ultrasound is Associated with Biochemical Disease Activity and Worse Disease Outcomes in Patients with Crohn’s Disease and Ulcerative Colitis

Abstract Background Bowel wall thickness (BWT) and hyperemia measured by intestinal ultrasound (IUS) predict endoscopic disease activity in Inflammatory Bowel Disease (IBD). The clinical significance of mild hyperemia (mLim1) without BWT is unknown. We previously described the short-term predictive value of mLim1 without BWT. Here we compare biochemical disease activity and longer-term outcomes in IBD pts with mLim1 to those with normal IUS. Methods We reviewed index IUS exams of pts with IBD at the University of Chicago from 7/18/2022 to 5/7/2024 and included pts with normal BWT (≤3.0mm) + mLim1 and compared them to pts with normal BWT + no hyperemia (mLim0). We excluded pts with mLim2 or 3, BWT>3mm anywhere on index IUS or pts with mLim1 at surgical anastomoses only. Clinical Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (faecal calprotectin (FCP) or C-reactive protein (CRP)) were assessed at the time of index IUS. Clinical remission was defined as HBI of <5 or SCCAI of ≤2, FCP<150 μg/g, CRP<5 mg/L. Primary analysis was poor disease outcome (PDO) within 12 mo of follow-up, defined as: IBD medication change/escalation, prescription of corticosteroids, IBD-related surgery, or IBD-related hospitalization. Results 45 pts with mLim1 (38 Crohn’s disease (CD), 7 Ulcerative colitis (UC)) and 61 pts with mLim0 (52 CD, 9 UC) at index IUS were included (Table 1). At baseline IUS, mLim1 pts had elevated median FCP but normal median HBI/SCCAI, while mLim0 pts had normal median FCP and HBI/SCCAI (Table 1). Of mLim1 CD pts, 14/38 (36.8%) had a PDO within 3 months (mo), 18/38 (47.4%) within 6 mo, and 18/30 (60%) within 12 mo, with median time to PDO of 37 d (IQR 28.5-112.5). Of the mLim0 CD pts, 5/52 (9.6%) had a PDO within 3 mo, 9/46 (19.6%) within 6 mo, and 14/45 (31.1%) within 12 mo, with median time to PDO of 91 d (IQR 93-184). Rates of PDO between mLim1 and mLim0 in CD pts at 12 mo were statistically significant (stat sig), p = 0.013. Of the mLim1 UC pts, 3/7 (42.9%) had a PDO within 3 mo and 2/3 (66.7%) had a PDO within 12 mo, with a median time to PDO of 139 d (IQR 93-184). Of the mLim0 UC pts, one had a PDO at 3 mo with no further events noted at 6 mo (0/8) or 12 mo (0/4). Rates of PDO between mLim1 and mLim0 in UC pts at 12 mo were not stat sig, (p = 0.270). Conclusion Mild hyperemia without BWT is associated with biochemical disease activity in both CD and UC and predicts PDO in CD. Although PDO in UC was numerically higher in mLim1 compared to mLim0, this was not stat sig likely due to small cohort size. These findings support the consideration of treatment adjustments when this isolated parameter is identified and inform future IUS treat-to-target strategies.

P0019 Investigation of the serum sphingolipid and ceramide profile in patients with Crohn's disease at different stages of the disease

Abstract Background Ceramides and sphingolipids are components of the cell membrane of the intestinal epithelium and contribute to the integrity of the intestinal barrier (1, 2). The expression of specific sphingolipid and ceramide subgroups can vary depending on the inflammatory activity of Inflammatory bowel diseases (IBD) and may influence the course of the disease. A distinct lipid profile was shown for ulcerative colitis compared to healthy subjects and different expression depending on disease activity. Less data is available for Crohn's disease (CD) (3). In this study, patients with MC at different stages of the disease were to be analysed with regard to their sphingolipid and ceramide profile using liquid chromatography tandem mass spectrometry (LC-MS/MS). The aim was to identify biomarkers that correlate with inflammatory activity so that they can be used in diagnostics and therapeutic monitoring. They could also serve as a target for a new therapeutic approach. Methods Patients who were experienced in therapy and had relevant disease activity at the time of blood sampling were included in the study after receiving a positive ethics vote. Patients were considered as treatment-experienced if they had received at least 2 prior biologic therapies. Disease activity was defined by clinical activity indices (Harvey-Bradshaw index >/= 4) and faecal calprotectin (>/= 250 ug/g). Further inclusion criteria were: Age of majority, a >3 month diagnosis of Crohn's disease and written informed consent. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to quantify the sphingolipids in plasma. The analytes were extracted using liquid-liquid extraction and measured using two different LC-MS/MS methods for sphingolipids and ceramides. Results In the comparison between the Crohn's disease and the control cohort, there were significant differences for the ceramides Cer d18:1/16:0 (p=0.009), Cer d 18.1/18:0 (p=0.025) and Cer 18.1/24:0 (p=0.035) showed higher concentrations in the MC group. For the lactosylceramides, there were significant group differences for LacCer 18:1/16:0 (p=0.005) and LacCer 18.1/18:0 (p=0.009). For sphingosine-1-phosphatase, there were significant differences for S1P 16:0 (p<0.001). LacCer and S1P concentrations were also higher in the MC group. Conclusion In the present study, a distinct difference in individual sphingolipid and ceramide concentrations could be determined in patients with Crohn's disease under an advanced therapy line and relevant disease activity compared to a control group. Overall, the concentrations in the MC group were higher in the significantly different parameters. Overall, the data on the role of sphingolipids and ceramides in IBD is not yet conclusive and further research is warranted.

P0651 Evaluating tryptophan as a biomarker for treatment success in Inflammatory Bowel Disease patients undergoing therapy

Abstract Background Patients with inflammatory bowel disease (IBD) display heterogenous responses to different treatment modalities suggesting distinct disease pathomechanisms. Herein, tryptophan (Trp) metabolism is associated with a range of chronic inflammatory disease, but the relevance to guide treatment decision in IBD remains unclear. Here, we sought to evaluate Trp serum level as a biomarker of treatment response in IBD in comparison to established disease biomarkers. Methods We analyzed and compared the serum levels of Trp and C-reactive protein (CRP) from patients with Ulcerative Colitis (UC) (n = 15) and Crohns Disease (CD) (n = 10). Longitudinal analyses of 100 serum Trp measurements were obtained and associated with inflammatory IBD markers during the induction period of various biological agents including TNF-α inhibitors (n=2), interleukin inhibitors (n=11), JAK inhibitors (n= 8), Sphingosine modulators (n=3) and integrin inhibitors (n=1). Results As expected, we found an inverse correlation between CRP and Trp (rs = -0.219, p = 0.045), indication a weak, negative correlation between the two variables across all patients. However, while this effect was predominantly observed in UC (r = - 0.317, p = 0.003), patients with CD showed no significant correlation between CRP and Trp levels (rs = -0.082, p = 0.763). In line with these findings, the observed correlation showed significant correlation in the different treatment modalities. Patients who received either interleukin- or JAK inhibitors displayed a stronger correlation (rs = -0.542, p = 0.001 and rs = - 0.358, p = 0.007 respectively), while patients receiving TNF-α-/ integrin inhibitors or Sphingosine-1-phosphate receptor modulators did not show a significant correlation. Conclusion Highlighting the heterogeneity of responses to different biologics, we observed a correlation between high serum Trp levels and a decline in biomarkers associated with a disease flare. These observations were most pronounced in patients with UC receiving treatment with interleukin- and JAK inhibitors suggesting potential therapeutic relevance in indicating early signs of successful induction treatment. References Wang S, van Schooten FJ, Jin H, Jonkers D, Godschalk R. The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome. Nutrients. 2023 Jun 26;15(13):2886. doi: 10.3390/nu15132886. PMID: 37447212; PMCID: PMC10346271. Ding, Xueyan, Bin, Peng, Wu, Wenwen, Chang, Yajie, Zhu, Guoqiang, Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review, Mediators of Inflammation, 2020, 9706140, 10 pages, 2020. https://doi.org/10.1155/2020/9706140 Susanna Nikolaus, Berenice Schulte, Natalie Al-Massad, Florian Thieme, Dominik M. Schulte, Johannes Bethge, Ateequr Rehman, Florian Tran, Konrad Aden, Robert Häsler, Natalie Moll, Gregor Schütze, Markus J. Schwarz, Georg H. Waetzig, Philip Rosenstiel, Michael Krawczak, Silke Szymczak, Stefan Schreiber,Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases,Gastroenterology,Volume 153, Issue 6,2017,Pages 1504-1516.e2,ISSN 0016-5085,https://doi.org/10.1053/j.gastro.2017.08.028.

P0065 Circulating cell-free DNA and mitochondrial DNA differentiate disease activity in paediatric-onset inflammatory bowel disease: Interim analysis from Scotland-wide Mini-MUSIC study (2020-26)

Abstract Background Mitochondrial dysfunction has been implicated in the pathogenesis of inflammatory bowel disease (IBD) particularly paediatric-onset IBD (PIBD).1,2 Circulating cell-free DNA (cfDNA) and mitochondrial DNA (mtDNA) are damage-associated molecular patterns (DAMPS) released into the bloodstream during tissue damage and cell death and can be detected in peripheral blood samples.3 Recent studies have suggested that levels of cfDNA and mtDNA may correlate with disease activity in adult IBD4 but their utility in paediatric populations remains unexplored. This study aims to present initial data on the potential use of cfDNA and mtDNA as biomarkers in PIBD. Methods Mini-MUSIC and GI-DAMPS are ongoing longitudinal and cross-sectional multi-centre translational research studies in Scotland (2020 – 2026) with a primary aim of investigating the inflammatory mechanisms of IBD with a focus on multi-omics, immune- and microbiome-profiling aligned to prospective clinical follow-up. We measured circulating cfDNA (GAPDH) and mtDNA (ND2), using digital droplet PCR, in the peripheral blood of patients diagnosed under 17 years of age (A1 phenotype) and correlated this with phenotypic data and disease activity scores. Results Sixty-five A1 patients were included (39/65 (60%) male; 51 Crohn’s disease (CD), 6 ulcerative colitis (UC), 1 inflammatory bowel disease unclassified (IBDU) and 7 symptomatic non-IBD controls) with a median (IQR) age at diagnosis of 13 (10.0-15.0) years. mtDNA levels were significantly higher in those with highly active disease compared to those in remission (median [IQR] 145.1 (89.5-673.7 ng/μl) vs 64.4 (24.3-167.5 ng/μl), p=0.008) and compared to non-IBD symptomatic controls (median [IQR] 145.1 (89.5-673.7 ng/μl) vs 28.8 (12.6 – 138.7 ng/μl), p=0.036). Circulating cell-free DNA levels were significantly higher in those with highly active disease than non-IBD controls (4.94 (1.1-9.9 ng/ul) vs median [IQR] 0.53 (0.0-1.4 ng/ul), p=0.017). mtDNA levels were positively correlated with endoscopic disease activity (SES-CD) in Crohn’s disease (Pearson r=0.7619, p=0.004). Conclusion Our initial data from ongoing work, demonstrate that the levels of cfDNA and mtDNA in the blood are potentially valuable biomarkers for differentiating disease activity in PIBD and to identify PIBD-patients where mitochondrial dysfunction is dominant and thereby with the potential to stratify future human mechanistic studies and mitochondrial-targeted therapies.

P0910 Evaluating Tryptophan as a Biomarker for Treatment Success in Ulcerative Colitis Patients Undergoing Mirikizumab Therapy

Abstract Background The treatment of ulcerative colitis (UC) has advanced significantly with the introduction of targeted medications, such as IL-23-Inhibitors. However, treatment success in inflammatory bowel diseases (IBD) varies and requires reliable biomarkers to assess therapeutic efficacy. Tryptophan (Trp), an essential amino acid, plays a central role in gut metabolism and immune modulation. Recent studies have shown that Trp metabolism is associated with inflammatory processes and correlates with IBD activity. Aim of the Study We hypothesized that Trp can serve as a reliable marker for assessing treatment success in patients with UC undergoing Mirikizumab therapy. To test this, Trp levels were correlated with established laboratory parameters (leukocytes, C-reactive protein in serum (CRP), fecal Calprotectin (fCal), as well as clinical parameters (IBD Disc). Methods Laboratory and clinical parameters during induction and maintenance therapy of four patients with UC who were treated with Mirikizumab were analyzed. Using SPSS, the Spearman correlation coefficient was used to examine the correlations between Trp and established markers. Results A significant negative correlation between Trp and CRP (n = 18, rs = −0.75, p < 0.001) suggests that lower Trp levels are associated with increased inflammatory activity. Correlations with leukocyte count (n = 18, rs = 0.27, p = 0.39), fCal (n = 10, rs = −0.33, p = 0.35), and the IBD Disk Score (n = 14, rs = −0.25, p = 0.40) were weak and not significant. Conclusion The significant correlation between Trp and CRP suggests that Trp could serve as a potential monitoring tool for assessing the inflammatory status in UC patients undergoing Mirikizumab therapy. However, Trp appears to have limited value as a standalone marker, and no cut-off levels have been established. Further prospective studies with larger sample sizes are necessary to confirm the clinical relevance of Trp as a biomarker for treatment response to Mirikizumab. References Harris, D. M. M., Szymczak, S., Schuchardt, S., Labrenz, J., Tran, F., Welz, L., Graßhoff, H., Zirpel, H., Sümbül, M., Oumari, M., Engelbogen, N., Junker, R., Conrad, C., Thaçi, D., Frey, N., Franke, A., Weidinger, S., Hoyer, B., Rosenstiel, P., … Aden, K. (2024). Tryptophan degradation as a systems phenomenon in inflammation-an analysis across 13 chronic inflammatory diseases. www.thelancet.com Nikolaus, S., Schulte, B., Al-Massad, N., Thieme, F., Schulte, D. M., Bethge, J., Rehman, A., Tran, F., Aden, K., Häsler, R., Moll, N., Schütze, G., Schwarz, M. J., Waetzig, G. H., Rosenstiel, P., Krawczak, M., Szymczak, S., & Schreiber, S. (2017). Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology, 153(6). https://doi.org/10.1053/j.gastro.2017.08.028

P0319 The Fuction of Serological Biomarkers in Assessing Endoscopic Activity in Inflammatory Bowel Disease

Abstract Background Identifying IBD and evaluating disease activity depend critically on endoscopy. But it is expensive and intrusive, which emphasizes the need for more easily available and non-invasive biomarkers to help in IBD diagnosis and assessment. This work seeks to investigate their correlation with endoscopic activity and assess the diagnostic relevance in IBD. Methods Between January 2022 and September 2024, we registered 365 UC patients, 319 CD patients and 100 control patients at the First Affiliated Hospital of Zhengzhou University. The subsequent biomarkers were examined:WBC, Hb, PLT, N, L, HCT, EOS, ALB, GLB, CRP, ESR, ALB/GLB (AGR), CRP/ALB (CAR), CRP/L (CLR), PLT/ALB (PAR), PLT/L(PLR), N/L (NLR). MES, SES-CD were respectively utilized to evaluate endoscopic activity in UC and CD. Mild endoscopic activity was characterized by MES=1 or SES-CD=3-6, moderate activity by MES=2 or SES-CD=7-15, and severe activity by MES=3 or SES-CD≥16. Biomarker comparions were conducted among UC, CD, and control groups, and between biomarkers and endoscopic activity were examined. Results 1. While Hb, HCT, L, ALB, and AGR were significantly lower (P<0.05) in both UC and CD groups compared with controls, N, PLT, GLB, CRP, ESR, CAR, CLR, PLR, PAR, and NLR were significantly raised (P<0.001). EOS levels in UC group averaged 0.19×109/L while in CD group they averaged 0.14×109/L, with this difference reaching statistical significance (P<0.01). 2. Whereas WBC, PLT, N, CRP, ESR, GLB, CAR, CLR, PLR, PAR, and NLR were significantly increased (P<0.01), Hb, HCT, ALB, and AGR were significantly lowered in those with moderate to severe disease compared to mild group. Significant variations in N, CRP, ESR, ALR, GLB, AGR, CAR, CLR, and PAR were noted among mild, moderate, and severe disease categories for CD patients (P<0.05). 3. ESR (OR=1.09, P=0.0015), CAR (OR=381.71, P=0.0018) and PAR (OR=1.27, P=0.0072) were independent risk factors for UC endoscopic activity. The AUC of their combination (0.87; 95%CI 0.82-0.92) surpassed the individual values of ESR(0.81; 95%CI 0.75-0.87), CAR(0.84; 95%CI 0.79-0.89), and PAR(0.81; 95%CI 0.76-0.87). AGR (OR=0.05, P<0.001) and CAR (OR=1.72, P=0.0117) were independent risk factors for endoscopic activity in CD. The AUC for the combination (0.81; 95%CI 0.75-0.86) was also higher than only AGR (0.80; 95%CI 0.74-0.85) or CAR (0.74; 95%CI 0.68-0.80). Conclusion IBD endoscopic activity was substantially correlated with biomarkers WBC, Hb, HCT, PLT, N, CRP, ESR, ALB, GLB, AGR, CAR, CLR, PLR, PAR, and NLR. While a lower AGR and a higher CAR may indicate more severe endoscopic activity in CD patients, elevated ESR, CAR, and PAR may point to more severe endoscopic activity in UC patients. Their amalgamation can enhance diagnostic efficacy.

P0035 Food compounds associated with disease activity in Inflammatory Bowel Disease: a novel approach

Abstract Background Diet plays a disease modifying role in inflammatory bowel disease (IBD), but specific relevant dietary factors have yet to be identified. Previous studies examining the role of diet in IBD have typically analysed food groups or specific macro- and micronutrients. To enhance our understanding, we conducted multivariate analyses on the intake of an extensive range of food compounds, using dietary data from a Dutch IBD cohort. Methods We used dietary and disease status data from IBD patients at the University Medical Center Utrecht, The Netherlands. Dietary data were previously collected using a Food Frequency Questionnaire at baseline. Intake levels for 768 compounds from 135 patients were calculated (Meima et al., 2024, submitted). Hereto, we applied a previously developed tool to translate dietary data into food compounds intake data (Meima et al., 2023). This tool serves as an integrated database, combining compound concentration data from three sources: the Dutch food compounds database NEVO, and international food compounds databases FooDB, and Phenol-Explorer. Using random forest analyses, we explored associations between compound intakes and IBD activity by comparing patients who experienced flares (n=41) or remained in remission during a median follow-up of 29 months (interquartile range 20-48 months). We assessed the potential biological relevance of the most significant compounds (n=35) by examining existing literature on IBD, gut health or immunomodulation. Results Random forest models performed particularly good in predicting remission, with specificities and negative predictive values NPVs up to 77 and 79%, respectively. The intakes of the 35 top-ranked compounds were primarily positively associated with IBD remission (n=29). Most of these were fatty acids (n=24). Other compounds positively associated with remission were 4-hydroxyproline, ethanol, vanillin, heptadecanoyl carnitine, and heme iron. For 11 of the 35 compounds, effects on IBD or the gut were available in literature, most of which aligned with our findings. Among these was butyrate, a short chain fatty acid that has been frequently reported for its beneficial role in IBD and gut health. However, several compounds showed discrepancies with literature. For 11 compounds, immunomodulatory effects were reported in literature. Conclusion With a novel approach, using an integrated food compounds database, we identified several food compounds that may play a modulatory role in IBD. Further research is needed to clarify associations found in our study and validate their possible biological significance. References Meima, M. Y., Westerhout, J., Bijlsma, S., Meijerink, M., & Houben, G. F. (2023). Coupling food compounds data from FooDB and Phenol-Explorer to the Dutch food coding system NEVO: towards a novel approach to studying the role of food in health and disease. Journal of Food Composition and Analysis, 123, 105550. Meima, M. Y., Westerhout, J., Bijlsma, S., van Schaik, F. D. M., Oldenburg, B., Campmans-Kuijpers, M.J.E., Dijkstra G., Meijerink, M., Houben, G.F. (2024, submitted). Calculation of Compound Intake Levels using Integrated Food Compound Databases and Food Intake Data. Journal of Food Composition and Analysis.

P0768 Ultra Processed Food in Inflammatory Bowel Disease – Friend or Foe? An examination into the contribution of UPFs to nutrient intake in an IBD remission cohort

Abstract Background Ultra-processed foods (UPFs) and their effect on the gut microbiome and their role in the pathogenesis and activity of inflammatory bowel disease (IBD) are attracting increasing interest. Dietary restrictions in Crohn’s Disease (CD) are common, whether self-imposed or result from adherence to advice from health professionals1. Increasing attention in UPFs may lead to further food restrictions and impact on nutrient intake. This study investigated the intake of UPFs of adults with CD during disease remission and explored their contribution to overall macro and micronutrient intake. Methods 195 CD outpatients in clinical remission (HBI <5 and faecal calprotectin <250µg) were recruited from a single UK IBD centre as part of the INTICO 2 observational study. Seven-day food diaries were electronically recorded (Nutritics® Libro) and used to determine dietary adequacy (number of nutrients <LRNI). UPF intake was determined using NOVA Scoring System2 to determine UPF (NOVA 4) intake by two registered dietitians. Product ingredient lists were examined to assign a NOVA score. Consensus on NOVA Scoring was achieved, and a data dictionary was prospectively updated to justify the assigned score. Results Mean Nova 4 score was 39.8 (SD 15.7) per 7 day food diary. Inadequacies of micronutrient intake were common and often multiple, with a mean of 6(SD 4) micronutrients below the LRNI per subject. UPFs contributed significantly to overall macro and micronutrient intake from food with 54% energy, 60% carbohydrates, 55% fat and 50% fibre intake derived from foods categorised as NOVA 4. There was no association between NOVA 4 intake and the degree of nutrient inadequacy as the number of nutrients below RNI in this cohort (Pearson’s Correlation P=0.629). Figure 1 and 2 describe the contribution of each NOVA group to micronutrients and fibre respectively. Conclusion In a CD remission cohort, UPF intake as captured by NOVA score was comparable with what was seen in other reports of healthy adults and other studies of patients with IBD. Eating more UPFs was not associated with a lower intake of micronutrients. Importantly, food categorised as NOVA-4 contributed to a significant proportion of energy, fibre, and micronutrient intake. NOVA scoring does not differentiate between UPFs high in fat, sugar, and salt and those that are not. Advice to "avoid UPFs" must be balanced against the potential consequences of reducing micronutrient intake, especially in those with low or marginal nutrient intakes. A targeted approach to reduce the intake of UPFs that provide little nutritional value is required to maintain nutrient intake. References 1)Holt D.Q., Strauss B.J. & Moore G.T. (2017) Patients with inflammatory bowel disease and their treating clinicians have different views regarding diet. J Hum Nutr Diet. 30, 66–72 doi: 10.1111/jhn.12400 2)SACN statement on processed foods and health. GOV.UK. https://www.gov.uk/government/publications/sacn-statement-on-processed-foods-and-healthOffice. SACN statement on processed foods and health - summary report. GOV.UK. Published July 11, 2023. https://www.gov.uk/government/publications/sacn-statement-on-processed-foods-and-health/sacn-statement-on-processed-foods-and-health-summary-report#results Figure 1: Micronutrient intake characterised by NOVA score Figure 2: Fibre intake characterised by NOVA Score

DOP121 Distinct tryptophan metabotypes associate with disease activity, treatment escalation and future disease progression in Inflammatory Bowel Disease

Abstract Background The kynurenine pathway is upregulated in inflammatory bowel disease (IBD) in a disease-activity induced manner. This route of tryptophan (Trp) degradation leads to a variety of bioactive compounds, including several with anti-inflammatory (e.g., kynurenic acid (Kyna), xanthurenic acid (Xana)) or cytotoxic (quinolinic acid (Quin)) effects. Our aim was to stratify patients with IBD into distinct subgroups based on their Trp metabolic profiles (Trp metabotypes) and to assess their prognostic capacity regarding disease progression. Methods We measured 16 Trp-related metabolites with particular attention to kynurenine pathway metabolites in the serum of a longitudinal German cohort (hypothesis generation) of 82 Ulcerative Colitis (UC) and 52 Crohn’s Disease (CD) patients. We used unsupervised k-means clustering to identify distinct clusters of patients based on their metabolite profiles and employed regression analysis to identify associations between the metabotypes and disease activity and progression. The analysis was expanded to three independent prospective validation cohorts recruited in France (n = 281 UC, 788 CD), the USA (n = 329 controls, 470 UC, 374 CD) and an inception cohort in Norway (n = 179 UC, 340 CD). Results We found four highly stable metabotypes within the discovery cohort (Fig 1A). Strong signals from the anti-inflammatory compounds Kyna and Xana characterized the first two metabotypes (High/Low Kyna metabotypes), which exhibited opposing associations with clinical, biochemical, and endoscopic disease activity. The third is characterized by high Quin levels and increased disease activity, while the fourth is metabolically heterogeneous and has lower disease activity (Fig 1B). These metabotypes were present in both UC and CD, albeit with differing proportions. Associations with disease activity were confirmed in three validation cohorts. Furthermore, we found differential probabilities between the metabotypes regarding future escalation to biologic therapies, requirement for steroid courses, IBD-related hospitalization and surgery. This was particularly evident when comparing individuals in the Low Kyna group with the lower incidence rates observed in the High Kyna group (Fig. 1C). Conclusion A distinct pattern of Trp degradation occurs in a subset of IBD patients that is strongly and consistently linked with disease activity and longitudinal outcomes of disease progression across multiple recruitment sites spanning two continents. Further work will focus on metabolic characterization of the metabotypes to understand the physiological processes driving the differentiation. This work may lead to the design of new therapeutic modalities targeting Trp metabolism in distinct patient groups.

P0218 Dietary Inflammatory Index and disease activity in patients with IBD: is there an association? A Preliminary Analysis

Abstract Background Inflammatory bowel disease (IBD) is increasing in incidence in recently industrialized and developing countries, and this increment is paralleled by Westernization of lifestyle.1 In fact, specific nutrients and additives instigate gut inflammation and increasing evidence demonstrates its impact on developing IBD and disease behavior.2,3 Dietary Inflammatory Index (DII) was developed to assess the inflammatory properties of a diet.4 The aim of this study is to assess the association between higher DII scores and disease activity in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Methods A cross-sectional study was conducted from June to October 2024. Patients undergoing ambulatory treatment at a day care IBD unit were consecutively recruited. A self-applied semiquantitative food frequency questionnaire, validated for the adult Portuguese population, was applied and medical charts reviewed. Blood and feces were collected, and anthropometric parameters measured by a body composition analyzer (Tanita DC-430MA). DII score was calculated according to the Shivappa et al. method, using 30 parameteres.4 The primary outcome was to assess the association between DII scores and 4 disease activity levels defined by clinical and biological activity markers (table 1). Clinical activity was classified according to Mayo Partial score for UC and Harvey-Bradshaw index (HBI) for CD. Biological activity was evaluated through fecal calprotectin. Results A total of 100 IBD patients (37 UC, 61 CD and 2 non-classified) were included; mean age 43.47 ±16.03 years, 41% female. Mean disease duration was 9.72±7.62 years. Baseline characteristics are described at table 2. Mean DII score was 1.49±2.43. The calculated DII score was categorized into quartiles. Comparison of calprotectin, CRP and Mayo Partial score by DII quartile was performed using Kruskal-Wallis test, and HBS using one-way ANOVA. No statistically significant correlations were found. Chi-square test for the association between activity levels and DII quartiles showed no statistically significant differences (p 0.496 DC; p 0.492 UC). Conclusion An association between DII scores and disease activity was not observed. Further studies with larger and more homogeneous samples are needed in the future to clarify the utility of this score in clinical practice. Given the undeniable and growing importance of these tools, other scales should also be studied and validated in IBD population.

P1344 Impaired health-related quality of life is associated with alterations in gut microbiota signatures in patients with Inflammatory Bowel Disease: baseline data from the Australian IBD Microbiome study

Abstract Background Inflammatory Bowel Disease (IBD) activity as well as disease monitoring and management have a substantial impact on the health-related quality of life (HRQoL) of affected patients1. This study investigated the association between HRQoL and gut microbial composition in IBD patients using the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). Methods Paired faecal and oral samples alongside participant demographics, disease characteristics and the IBDQ-32 survey were collected at baseline from patients with Crohn’s disease (CD) or ulcerative colitis (UC) enrolled in the Australian IBD Microbiome (AIM) study2 from June 2019 to November 2023. IBDQ-32 scores range from 32 to 224, with a higher score indicating better HRQoL. Patients were divided into two groups: impaired HRQoL (cumulative score <170) and preserved HRQoL (>170). Faecal and oral samples were self-collected in DNA stabilising buffer, aliquoted and stored at -80oC until extraction. Samples underwent 16S rRNA sequencing with annotation of DNA sequences to operational taxonomic units at the genus level. Differences in alpha diversity (Chao1) between groups were assessed using Mann-Whitney U tests. Linear discriminant analysis was performed between groups to identify significantly enriched bacterial taxa. Beta diversity (weighted UniFrac dissimilarity) in bacterial communities were shown using Principal Coordinate Analysis (PCoA), and significance of variance was tested using ADONIS in R. Results 446 participants (232 CD, 214 UC) returned baseline faecal (n = 403) and/or oral samples (n = 436) and were included in the analysis, with patient and HRQoL characteristics in Table 1. Most CD and UC patients were in clinical remission at baseline (77.4% and 65.2% respectively, Table 1). Despite this, impaired HRQoL was common in both CD (42%) and UC (41%). Patients with impaired HRQoL had lower faecal microbial alpha and beta diversity (Fig 1A,B). There were no differences in alpha or beta diversity in oral samples. Linear discriminant analysis showed 9 and 36 significantly altered genera enrichment in impaired and preserved HRQoL faecal samples respectively (Fig 1C). Conclusion Despite a high proportion of clinical and biochemical remission, impaired HRQoL was common amongst UC and CD patients within the AIM study. Lower faecal but not oral alpha diversity was associated with impaired HRQoL, indicating reduced microbial richness in the gut. A high number of bacterial taxa had differential enrichment according to HRQoL status. Identification of a distinct microbial signature associated with impaired HRQoL may help to identify patients that require both optimisation of disease control and greater psychosocial support.

P0489 The impact of inflammatory bowel disease and disease activity on patients’ sexuality

Abstract Background Sexuality is an integral part of general health and wellbeing. Chronic diseases, such as inflammatory bowel disease (IBD), have an impact on patients’ sexual functioning. The aim of this study was to assess the influence of intestinal disease and its activity on sexuality of individuals with IBD. Methods: Patients and Methods A prospective survey study on male and female individuals with IBD using an anonymous questionnaire including 60 inquiries concerning patients ‘intimate relationship and sexual functioning was performed. The following statistical tests were used: chi-square test of independence, Spearman’s rank correlation coefficient, Wilcoxon and U Mann-Whitneyatests. The significance level of p = 0.05 was assumed as statistically significant. Results The survey involved 110 respondents with IBD (41% with Crohn’s disease and 57% with ulcerative colitis) - 52 women (47%) and 58 men (53%). Most of them were aged between 31 and 40 (45%). Before being diagnosed with IBD, the respondents rated their satisfaction with sex on an average of 4.1 on a 5-point scale; after the diagnosis, the rating was lower and amounted to 3.6. In 34% of respondents, the assessment of satisfaction with sex after diagnosis decreased, in 24% it increased, and in 42% it did not change. The difference between the assessments before and after diagnosis was statistically significant (p = 0.007). Statistically significant correlations were found between IBD clinical activity and the impact of the disease on the sexual desire (p < 0.001), the need for sex after diagnosis (p < 0.001), satisfaction with sex after diagnosis (p = 0.003), and the average number of intercourse (p = 0.004), average duration of intercourse after diagnosis (p = 0.001), feeling guilty in the sexual sphere due to the disease (p = 0.006), assessment of one’s attractiveness since diagnosis (p = 0.032), and change in the partner’s erotic perception after diagnosis ( p < 0.001). Respondents with disease exacerbation were less willing to engage in sexual activity, had less need for intercourse, rated their satisfaction with sex lower, had fewer intercourse, and their duration was shorter. They more often felt sexual guilt due to the disease and assessed their current attractiveness worse. Conclusion Inflammatory bowel disease has negative impact on patents’ sexuality and disease activity strongly affects their sexual functioning. The exacerbation of IBD causes in patients decrease in sexual needs, worse sexual experience and lower assessment of one’s attractiveness.

P0333 Predictive factors for thiopurine treatment failure in anti-TNF naïve IBD patients: Insights from a tertiary care Hepato-Gastroenterology center experience

Abstract Background Chronic Inflammatory Bowel Diseases (IBDs) pose a significant challenge due to their chronic nature and the characteristic pattern of relapse and remission. The maintenance’s goal therapy is to prolong remission as much as possible. Immunosuppressants, particularly thiopurines, are widely employed for this purpose. However, Nearly half of patients on these drugs lose remission or fail to maintain it, with the causes still unclear. This study explores patient-related factors linked to thiopurine failure. Methods This retrospective study, conducted over five years and two months (January 2018 to March 2023), included IBD patients treated with thiopurines who had not previously received anti-TNF therapy. Patients were followed for 1 to 5 years after starting thiopurines, with treatment failure defined as requiring two or more corticosteroid courses in a year, escalation to anti-TNF therapy, or surgical intervention. Data were collected from medical records and analyzed using SPSS software, employing the chi-square test and multivariate logistic regression to assess relationships Results We analyzed 165 patients, including 119 with Crohn’s disease (CD) and 46 with ulcerative colitis (UC), with a median age of 39.05 years and a female predominance (sex ratio 0.81). All patients consumed tea (100%), smoking was present in 15.15%, alcohol consumption in 6%, and NSAID use in 10%. Among UC patients, 13 failed thiopurine treatment, with 3 requiring colectomy and 10 escalating to anti-TNF therapy, all diagnosed with UC E3. For CD patients, 99 experienced treatment failure, including 15 ileocolectomies, 30 ileocecal resections, and 54 cases requiring anti-TNF therapy. Hypoalbuminemia (<35 mg/L) at diagnosis was a significant risk factor for thiopurine failure (p=0.05). Non-smoking UC patients (p=0.06) and UC E3 patients with frequent flares (p=0.09) showed a strong, though not statistically significant, trend towards failure. In CD, smoking (p=0.05), NSAID use (p=0.08), and active inflammatory colonic disease with over two flares annually (p=0.04) increased failure risk. Common factors for both UC and CD included anemia (p=0.001), tea consumption (p=0.003), phytotherapy (p=0.06), and younger age (17–32 years, p=0.09) Conclusion Our findings demonstrate that hypoalbuminemia, anemia, and young age at diagnosis pose an increased risk of thiopurine treatment failure. Moreover, some patients characteristics such as smoking, frequency of flares, NSAID use, and phytotherapy may also serve as predictive factors for thiopurine treatment failure. These factors should be regarded as markers of non-response to thiopurines as monotherapy in patients with moderate to severe colonic CD or UC E3.