Patients In Remission Research Articles

Prediction of long-term drug-free outcomes in ACPA-positive and ACPA-negative rheumatoid arthritis by combined clinical and ultrasound assessment of residual disease: a 5-year prospective study

ObjectiveTo delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission...

Confocal Endomicroscopy Intestinal Epithelial Barrier Abnormalities in Individuals Without Documented Gastro-Intestinal Disease.

Probe-based confocal endomicroscopy (pCLE) allows real-time microscopic visualization of the intestinal mucosa surface layers. Despite remission achieved through anti-tumor necrosis factor or vedolizumab therapy, anomalies in the intestinal epithelial barrier are observed in inflammatory bowel disease (IBD) patients. Our study aimed to assess these abnormalities in non-IBD individuals and compare them with IBD patients in endoscopic remission to identify the associated factors. The study involved 84 patients, 40 with IBD under biologic therapy for over 6months and in endoscopic remission, and 44 without IBD or irritable bowel syndrome (IBS) undergoing colorectal screening colonoscopy. White light endoscopy and probe-based confocal laser endomicroscopy were performed in the ileum, right colon, transverse colon, left colon, and rectum. Demographic, clinical, biological, and morphological factors were examined. pCLE revealed abnormalities in both non-IBD individuals and those with IBD in endoscopic remission, such as fluorescein leakage, blood vessel dilatation, and hypervascularization across all segments, as well as epithelial gaps in the ileum, and crypt dilatation in the colon. Comparing the two groups, IBD patients exhibited slightly more gaps in the ileum, increased fluorescein leakage in the transverse colon, and fewer vessel dilatation in the transverse colon. Abnormalities were more frequent in cases of hypertension (p=0.03), dyslipidemia (p=0.02), female gender (p=0.02), selective serotonin reuptake inhibitor (p=0.03), and family history of IBD (p=0.04) or colorectal cancer (p=0.03). Confocal endomicroscopy abnormalities are present in both non-IBD individuals undergoing colorectal cancer screening colonoscopy as in those with IBD in endoscopic remission. Further research is needed to understand the pathophysiological mechanisms of these abnormalities and their clinical impact.

ALLG APML5: Bioavailability and safety of oral arsenic trioxide assessed during consolidation therapy for APL.

The prognosis for patients with acute promyelocytic leukemia (APL) has improved dramatically since the introduction of all-trans retinoic acid (ATRA) and intravenous arsenic trioxide (ATO). However, ATO administration requires daily infusions over several months, representing an onerous burden for hospitals and patients. We evaluated the bioavailability of a novel encapsulated oral ATO formulation in APL patients in first complete remission during standard-of-care consolidation. After a pilot study exploring the likely oral dose requirement, total arsenic pharmacokinetics were evaluated in 20 patients after both intravenous and oral ATO 0.15 mg/kg/d, with exposure to oral ATO restricted to the first week in 2 of the 4 ATO cycles. The primary endpoint was bioequivalence of area under the curve from 0-24 hours (AUC0-24), with bioequivalence of maximum concentration achieved (Cmax) as the key secondary endpoint. The 90% confidence intervals (CI) around point estimates of the geometric means of the oral/intravenous ratios for AUC0-24 and Cmax were compared with bioequivalence limits specified by the European Medicines Agency (0.80-1.25). The estimated oral/intravenous ratios and 90% CI for AUC0-24 in whole blood and plasma were 0.993 (0.954-1.034) and 1.030 (0.977-1.087) respectively; data for Cmax also satisfied bioequivalence requirements. Exploratory studies of arsenic species in plasma showed bioequivalence for AUC0-24 with As(III) (oral/intravenous ratio 0.966 (0.879-1.063)). The adverse event profiles of oral and intravenous ATO were comparable for cycles commencing with the IV and oral formulations. In conclusion, this novel oral ATO formulation is bioequivalent with intravenous ATO and offers a convenient alternative for patients with APL. Accession Number: ACTRN12616001022459.

Anti-tumor Necrosis Factor Drug Concentration Is Not Associated with Disease Outcomes in Pouchitis: A Retrospective, International Study.

Therapeutic drug monitoring is important for optimizing anti-tumor necrosis factor-α (TNF-α) therapy in inflammatory bowel disease. However, the exposure-response relationship has never been assessed in pouchitis. To explore associations between anti-TNF-α drug concentration and pouchitis disease activity in patients with a background of ulcerative colitis. A retrospective, multicenter, cross-sectional study was conducted in adult patients with pouchitis requiring anti-TNF-α treatment. Rates of clinical and endoscopic remission were calculated, and drug concentrations during maintenance therapy were compared between remission and non-remission cohorts. Sixty-three patients were included: median age, 48years (IQR 36-59) and median time since pouchitis diagnosis, 7years (IQR 2-13). Patients received infliximab, n = 27 (43%), adalimumab, n = 29 (46%), or both n = 7(11%). Thirty-two (51%) patients received concomitant immunomodulation. Median infliximab trough concentrations (mg/ml) were similar between patients in clinical remission (n = 21) vs non-remission (n = 11), 5.3 vs. 4.4, p = 0.73. For adalimumab, median drug concentrations did not significantly differ between remission/non-remission groups based on clinical (n = 18/18), 11.4 vs 7.6, p = 0.32, or endoscopic assessment, (n = 7/29), 9.0 vs. 7.8, p = 0.78. Four patients had positive anti-drug antibodies with undetectable drug concentration. In a cohort of patients with pouchitis, higher anti-TNF-α drug concentrations were not associated with more clinical or endoscopic remission.

Usefulness of Novel Image-Enhanced Endoscopy for Predicting Maintenance of Clinical Remission in Ulcerative Colitis.

The performance of endoscopic evaluation of ulcerative colitis (UC) using conventional scoring, including Mayo endoscopic subscore (MES) and ulcerative colitis endoscopic index of severity (UCEIS), is not satisfactory. Recently, the usefulness of novel image-enhanced endoscopy (IEE) such as texture and color enhancement imaging (TXI) and red dichromatic imaging (RDI) has been reported in the endoscopic evaluation of UC. We evaluated the performance of IEEs in UC, particularly focusing on the correlation with MES and UCEIS, and prediction of relapse. This is a prospective, observational study. UC patients in clinical remission who underwent colonoscopy with evaluation of IEEs and follow-up for > 3months were analyzed. TXI and RDI were evaluated using the previously reported scoring system (TXI 0-2 and RDI 1-4). The IEE scores were compared with the conventional scoring, fecal calprotectin levels, and histological findings using Geboes score, and patient's clinical relapse rate stratified by each IEE score was examined. Both TXI and RDI scores were well-correlated with MES and UCEIS (both p < 0.001), fecal calprotectin levels (p = 0.015 and p = 0.006), and histology evaluated with Geboes score. In the Geboes subscore, the subscore 2B (neutrophil infiltration in lamina propria) was the most correlated with each endoscopic scoring. RDI 3-4 was significantly correlated with subsequent relapse (hazard ratio 3.56, 95% confidence interval 1.13-11.24), but TXI scoring did not predict relapse significantly. The assessment using RDI could be a convenient and useful endoscopic evaluation method for predicting the prognosis of UC.

P1314 Multi-omics analysis of Crohn’s Disease trajectory from active to remission reveals that the altered ileal anti-bacterial epithelial signals and pathogenic microbial composition and metabolomics persist despite normalizing ileal immune signals during remission

Abstract Background Characterizing gut factors that improve or persist during Crohn’s disease (CD) trajectory from active to remission to healthy-normal states is crucial for defining treatment targets and CD cure. Methods Using multi-omics (ileal transcriptomics, microbiome, and metabolomics), we aimed to compare active, mostly treatment naïve newly diagnosed CD to patients in remission, using controls as a reference Results 193 subjects were included (median age 32 years, 60% male); 78 CD in remission, 38 active and mostly (80%) treatment naïve newly diagnosed CD patients, and 77 non-IBD controls (Table 1). Controls and CD remission groups had significantly lower and mostly normal CRP, with significantly lower fecal calprotectin in the remission than in the active group (Table 1). Most patients (79%) in remission were on biologics (58% on anti-TNF and 21% on vedolizumab/Stelara). Ileal transcriptomics (Fig. 1A-B) highlighted a significant reduction of genes and pathways related to adaptive T cell activation in treated patients in remission compared to active treatment naïve patients. This decrease was significantly lower than in controls, suggesting some immune compromise likely secondary to CD therapy. There were no differences between the levels of S1008/9 genes encoding for fecal calprotectin and OSM and TREM1 genes related to the anti-TNF response in patients in remission on treatment, compared to controls. Despite that, patients in remission still showed persistent signals of elevated expression of epithelial antimicrobial pathways and genes, including DUOX2, CEACAM5/6, REG4, and DMBT1, and more novel increased goblet cells and mucin glycosylated genes and signals (Fig. 1A-B). Interestingly, these epithelial antimicrobial signals during remission were coupled with persistent pathogenic gut microbial composition, as indicated by several microbial measurements, including the published Gevers et al index (PMID:24629344), our general health and specific IBD indexes (PMID:35197084), and alpha diversity (Fig. 1C), with significant enrichment of oral bacteria that dislocated to the gut in the CD groups. Similarly, 39 of 43 (91%) of the gut metabolites (Fig. 1D) that were significantly different between CD in remission vs. controls showed similar altered directionally in active treatment naïve CD patients vs. controls, suggesting persistent metabolic alterations during remission Conclusion Multi-omics analysis shows that despite normalizing ileal immune signals and genes encoding calprotectin during remission, the altered anti-bacterial epithelial signal and pathogenic microbiome and metabolome signatures persist. This highlights the need to directly target the epithelia-microbes axis, in addition to immune suppression, to improve CD outcomes.

Residual pain and fatigue are affected by disease perception in rheumatoid arthritis in sustained clinical and ultrasound remission.

Regardless of remission status, residual pain (RP) might persist in rheumatoid arthritis (RA). The aim of this study was to characterize RP, its perception, and patient-dependent features and to evaluate its possible association with residual synovitis in patients with RA in remission. Ninety-seven patients with RA, including 68 in sustained clinical and ultrasound remission (Rem/RA) and 29 in high/moderate DAS28-CRP disease activity (H-Mo/RA) were enrolled in the study. Thirty patients with fibromyalgia were enrolled as a control group(FIBRO). At study entry, demographic, clinical, ultrasound characteristics, and pain dimension assessment (VAS-pain, FACIT, CSI, GHQ, and RAID) were collected for each patient. RA patients underwent synovial tissue biopsy to evaluate the degree of synovitis using the Krenn synovitis score (KSS). Forty-eight percent of Rem/RA still declared unacceptable pain (VAS-Pain > 20) compared to 80% of H-Mo/RA patients (p < 0.0001). Furthermore, Rem/RA patients presented comparable levels of pain dimension assessment regardless of KSS. However, classifying Rem/RA group based on RAID score (< 2 as satisfied SAT-Rem/RA and ≥ 2 as unsatisfied UNSAT-Rem/RA), SAT-Rem/RA group presented a lower grade of VAS-Pain (p < 0.0001), lower percentage of patients with an unacceptable pain (p < 0.0001) and lower grade of fatigue(p < 0.0001) compared to the UNSAT-Rem/RA patients. The percentage of SAT-Rem/RA patients who presented a disease flare did not differ from UNSAT-Rem/RA over the 24months of follow-up. Finally, female Rem/RA patients presented higher VAS-Pain compared to male Rem/RA (p = 0.0119). Moreover,73% satisfied female Rem/Ra patients presented an acceptable pain compared to 23% unsatisfied female Rem/RA patients (p = 0.001). RP in RA patients in remission can represent the way by which the patients communicate their state of non-acceptance of the disease. It can be useful to treat RP with the appropriate treatments. Key Points • Rheumatoid arthritis patients still reported unacceptable residual pain despite sustained clinical and ultrasound remission and despite the low grade/absence of histological synovitis. • Only a small rate of rheumatoid arthritis patients in sustained clinical and ultrasound remission showed residual pain as part of a central sensitivity syndrome or psychiatric disorders. • Rheumatoid arthritis patients in sustained clinical and ultrasound remission complained residual pain and fatigue as part of not acceptance of disease and/or dissatisfaction in the disease management.

P0293 The utility of small bowel capsule endoscopy in Crohn’s Disease – a retrospective cohort study

Abstract Background Small bowel capsule endoscopy (SBCE) has the highest sensitivity and specificity for identifying Crohn’s disease (CD) affecting the small bowel. The recent CURE-CD study demonstrated that proactive treatment optimisation with SBCE monitoring led to improved outcomes. [1] We performed a retrospective cohort study at a tertiary centre in the UK to evaluate the impact of SBCE in the management of Crohn’s disease. Methods We reviewed the capsule database from December 2021 – December 2022. 181 SBCE were performed in this time period. We included patients who were either newly diagnosed with CD following SBCE or patients with known CD undergoing SBCE as part of disease reassessment. All patients included had no/minimal changes on imaging and/or endoscopy to justify treatment initiation/escalation for ongoing symptoms. Data was extracted from their electronic health record. Correlations were analysed using Spearman’s ranked test. Results 96 patients met the inclusion criteria. 67 patients (69.8%) with known CD underwent SBCE as part of disease reassessment and 29 patients (30.2%) were newly diagnosed with CD following SBCE. Their baseline demographics pre-SBCE are illustrated by table 1. Small bowel visualisation was adequate in 93 (96.8%) and the median transit time for a SBCE study was 4hrs and 36 minutes. The median Lewis Score (LS) was 423. 71 (73.9%) patients had active SB Crohn’s disease (defined as a LS &amp;gt;135). Of these, 26 (36.6%) had moderate to severe disease (LS&amp;gt;790). There was a poor correlation between inflammatory biomarkers and symptoms of diarrhoea/abdominal pain with active CD on SBCE with none of these reaching a correlation level greater than 0.3. The impact of SBCE on the management of patients is showed by figure 1. 47 (48.9%) had a repeat SBCE for disease reassessment with a median time of 449 days between the first and second SBCE. The median LS for the repeat SBCE was 112. There was a significant reduction in moderate-to-severe active disease at the follow-up SBCE (baseline 26/96, 27.1% to follow-up 8/47, 17%). Repeat SBCE identified more patients in remission defined as LS &amp;lt;135 (baseline SBCE remission 25/96, 26% vs repeat SBCE remission 27/47, 57.4%, p=0.005). No cases of capsule retention occurred. Conclusion In a large cohort of patients with minimal/no changes on conventional investigative modalities for Crohn’s disease, SBCE led to a change in treatment in 63.5%. Repeat SBCE showed significantly higher proportion of patients in endoscopic remission. Conventional non-invasive markers of inflammation and symptoms correlated poorly with activity on SBCE further highlighting the importance for clinicians to consider SBCE in both the workup and reassessment of disease activity in patients with Crohn’s disease.

P0497 Faecal Incontinence and Urgency in IBD Patients on Biologic Therapy in Remission: Prevalence and Risk Factors

Abstract Background Despite being in clinical remission, patients with inflammatory bowel disease (IBD) on biologic therapy may experience faecal incontinence (FI) and urgency, significantly impacting their quality of life. This study aimed to determine the prevalence of FI and urgency in this population and to identify associated risk factors. Methods A cross-sectional study was conducted in a tertiary referral centre, including IBD patients in remission on biologic therapy (evaluated by partial Mayo score or Harvey-Bradshaw Index). Data on demographic and clinical characteristics were analysed, including age, sex, disease duration, previous biologic therapies, surgical history, and severity indices. FI was defined as a St. Mark’s Vaizey score ≥6, and urgency was assessed using a Visual Analog Scale (VAS) score ≥4. Statistical analysis included chi-squared, Fisher’s exact, and Wilcoxon rank sum tests. Results The study included 124 IBD patients (85 Crohn’s disease, 39 ulcerative colitis). FI was observed in 15% of patients, while urgency (VAS ≥4) was reported by 8%. Notably, 14.1% of Crohn’s disease patients in endoscopic remission (SES-CD ≤2) experienced significant FI. Risk factors significantly associated with FI included advanced age (median 49 years vs. 38 years, p=0.007), gender (male 33% vs. female 63%, p=0.014), and history of surgical interventions (58% vs. 26%, p=0.005). Urgency was more prevalent in patients requiring diapers or pads (30% vs. 5.7%, p&amp;lt;0.001) with no other significant factors identified. CRP and faecal calprotectin levels were not significantly associated with either FI or urgency in this cohort. Conclusion FI and urgency remain prevalent among IBD patients in clinical but also endoscopical remission on biologic therapy, underscoring the need for continued symptom monitoring and management strategies. Advanced age, gender and surgical history are key risk factors. Future studies should explore targeted interventions to mitigate these complications in this patient group.

P0306 Application of 5 different machine-learning approaches to develop an artificial intelligence pathway to predict IBD-associated fatigue: Analysis of 1200 data points in 531 IBD patients.

Abstract Background Fatigue is commonly identified by IBD patients as one of the most important issues that affect their wellbeing1. Despite advanced immune therapies, 50% of patients experienced significant fatigue. The central mechanisms beyond gut inflammation that drives fatigue are not known. Methods We utilized 5 different machine-learning (ML) approaches in a combined prospective and cross-sectional multi-center cohort2 in UK (2020-24) to develop models and identify factors that can predict IBD-associated fatigue. Our ML-modelling involved 531 IBD (260 UC, 246 CD, 25 IBDU) patients, ~100 clinical variables (including CUCQ32-patient reported outcomes, seasonality, BMI, drug treatments, disease phenotype and all hospital-based blood/stool tests) and 1200 data points over time. ML-approaches were gradient boosting, random forests, logistic regression, support vector machines and deep neural networks. We incorporated various methods to identify the relative importance of clinical factors and our ML-performance. We trained our ML-fatigue on overall IBD and on patients in remission. Results Using an IBD CUCQ32 dataset involving 2500 patient responses (Figure 1), we used patient-reported data of significant fatigue experienced in 10 out of 14 days as IBD-fatiguehigh (Figure 1). Through train-validate-test steps, we found that traditional statistics and machine learning performed similarly (Random Forest AUC of 0.75; logistic regression AUC of 0.74 using R). AdaBoost, XGBoost, random forest and logistic regression models performed similarly while support vector classifiers and neural networks performed poorly (Table 1). SHapley Additive exPlanations (SHAP) analysis of the models3, based on game theory, revealed that each model prioritises different variables - the top 3 factors for XGBoost were has_active_symptoms, weight and platelets; whereas logistic regression ranked seasonality variables (autumn and winter) higher. The analysis indicates the potential of ML to integrate non-linear factors in a way that traditional statistics do not capture well. ML performance to predict IBD-fatiguehigh in patients in biochemical remission (CRP&amp;lt;5 and calprotectin &amp;lt;250) was poor, with AUCs of 0.61 for logistic regression and 0.66 for random forest. Conclusion We provide a comprehensive ML-pathway to predict IBD-associated fatigue. Despite integration of multiple clinical factors and use of interpretable ML-approaches, prediction of fatigue in IBD patients, remains suboptimal. Our data suggests a large ‘hidden’ pathobiological component and current work is in progress to integrate deep molecular data and build a clinical-scientific AI model to improve understanding of IBD-associated fatigue.

P0048 Alterations in circulating T-cell subpopulations reflect disease activity in Ulcerative Colitis

Abstract Background Ulcerative colitis (UC) is a chronic condition characterised by dysregulation of the immune response and consequent uncontrolled inflammation. Circulating T cells play a crucial role in maintaining immune balance and their dysfunction contributes to disease progression1. This study aims to evaluate the expression of circulating T-cell subpopulations in UC patients and explore their association with disease activity. Methods Blood samples were collected from UC patients with active disease (partial Mayo score (PMS) &amp;gt; 1), UC patients in clinical remission (PMS 0-1) and healthy controls (HC). A cytofluorimetric analysis using the BD FACSLyric Flow Cytometry system was performed for T-cell subpopulations analysis [table 1]. ANOVA test was used to compare the expression levels of subpopulations across the three groups, while t-tests were conducted for pairwise analysis. Results 21 UC patients (11 in clinical remission and 10 with active disease) and 10 HC were enrolled. Central memory CD4 T cells resulted significantly reduced in active UC compared to UC in remission and HC (p&amp;lt; 0.05), while effector memory and effector CD4 T cells were markedly elevated in active UC compared to UC in remission and HC. Similarly, central memory CD8 T cells were reduced in active UC, while effector memory CD8 T cells and effector CD8 T cells showed significant increase in active patients compared to patients in remission and HC (p&amp;lt; 0.01). Notably, regulatory T cells were significantly higher in remission UC compared to active disease (p&amp;lt; 0.05) [figure 1]. No significant differences were observed among other subpopulations analysed. Conclusion This study demonstrates significant alterations in circulating T-cell subpopulations in UC compared to controls, with distinct differences based on disease activity status. The progression of T cells toward effector phenotypes parallels increased inflammatory activity, linking T-cell differentiation and immune aging to disease progression. These findings underscore the potential of circulating T-cell subpopulations as non-invasive biomarkers for disease activity and as promising therapeutic targets. References Casalegno Garduño R, Däbritz J. New Insights on CD8+ T Cells in Inflammatory Bowel Disease and Therapeutic Approaches. Front Immunol. 2021 Oct 11;12:738762. doi: 10.3389/fimmu.2021.738762. PMID: 34707610; PMCID: PMC8542854.

P0185 Prevalence of IBS-like symptoms in Ulcerative Colitis patients in clinical remission

Abstract Background Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with a higher prevalence in patients with inflammatory bowel disease (IBD) compared to the general population. Ulcerative colitis (UC) patients frequently report symptoms such as abdominal discomfort, bloating, altered bowel habits, and worsening symptoms due to foods or stress, even during clinical remission. This study examines the prevalence of IBS-like symptoms in UC patients at an IBD clinic in a London teaching hospital. Methods A survey among 100 UC patients included those with active disease (flare) and in remission. Remission status was defined by: (1) faecal calprotectin levels ≤250µg/g in the last year, (2) C-reactive protein (CRP) within the normal range in the past six months, and (3) a Mayo score of 0 on a flexible sigmoidoscopy/colonoscopy within 6 months. The IBS information questionnaire was based on WHO criteria1 and included 16 questions. Data collected included disease location, year of diagnosis, gender, and current treatment. Results Among the 100 patients, 34% had active disease and 66% were in remission during time of survey completion and 91% on active drug management. Total symptom scores differed significantly between active and remission groups (p=0.0066), with higher scores in active disease. However, 94% of patients in remission reported 1&amp;lt; symptom and the mean total score was 11.32 (SD ~6.08) indicating persistent symptoms. There is a female preponderance in symptoms scores than males in both active and remission states. In active disease, females had a mean score of 16.67 (SD: 5.91) vs males at 11.53 (SD: 5.66); in remission, females scored 11.77 (SD: 5.96) vs males at 9.59 (SD: 5.56). A statistically significant gender difference was found in active disease (p=0.0144) but not in remission (p=0.129). Table 1 shows symptoms reported in remission. Bloating correlated with constipation (r=0.32, p=0.008), potentially indicating proximal constipation in UC remission. Additionally, loose stools were strongly correlated with bowel urgency (r=0.73, p=&amp;lt;0.0001), suggesting a symptom cluster. Among remission patients, proctitis showed the highest scores, while pancolitis scored the lowest. Disease location was weakly negatively correlated with symptom scores (r=-0.19, p=0.76), as was time since UC diagnosis (r=-0.13, p=0.305). Conclusion This study shows that IBS-like symptoms persist in UC patients during remission, with 94% reporting 1&amp;lt; symptom despite active drug management. Symptom clusters such as loose stools and bowel urgency and gender differences, emphasise the need for tailored, symptom-focused care. Comprehensive strategies are essential to address residual symptoms and improve quality of life for UC patients, even in remission.

P0045 Serologic levels of fatty acids as promising biomarkers for the severity of Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Disease (IBD) is a chronic and autoimmune disease which affects the gastrointestinal tract. Several changes in the metabolomic profile have been described in urine, blood and feces samples of IBD patients. However, little is known regarding the relationship between these metabolic changes and the severity of IBD. Therefore, we aim to characterize the metabolomic profile, specifically the fatty acid profile, in serum from both active and in remission IBD patients. Methods Blood samples from UC active patients (n=20), UC patients in remission (n=20), CD active patients (n=21), CD patients in remission (n=21) and non-IBD controls (n=21) were obtained. UC and CD patients were classified in active or remission according to the Mayo-score and Harvey-Bradshaw Index, respectively. Serum was obtained after centrifugation of the fresh blood. Metabolomic analysis was performed using Liquid Chromatography High-Resolution Mass Spectrometry. Data were expressed as mean±SEM (μg/mL) and compared by a t-test or ANOVA. A p-value&amp;lt;0.05 was considered statistically significant. Results A total of 42 fatty acids were quantified and results are shown in Table 1. 23 of them showed significant differences, either Control vs UC, Control vs CD, or CD vs UC. In addition, 9 fatty acids showed significant differences between active CD vs remission CD patients (FA 15:0, FA 16:1n10, FA 17:0, FA 18:0, FA 18:1n12 + FA 18:1n13 + FA 18:1n9trans, FA 20:0, FA 20:3n9, FA 20:4n6, FA 22:4n6). In case of UC, 24 fatty acids showed significant differences in active vs remission patients, especially those with large and very large chain (FA 14:0, FA 15:0, FA 16:1n10, FA 16:1n9, FA 17:0, FA 18:1n12 + FA 18:1n13 + FA 18:1n9trans, FA 18:1n7trans, FA 18:1n9, FA 18:2n6trans, FA 18:3n6, FA 19:0, FA 20:0, FA 20:1n9, FA 20:2n6, FA 20:3n3 + FA 20:3n6, FA 20:3n9, FA 20:4n6, FA 22:0, FA 22:1n9, FA 22:2n6, FA 22:3n3 + FA 22:3n6 + FA 22:3n9, FA 22:4n6, FA 22:5n6 and FA 24:1n9). Moreover, 4 fatty acids, specifically FA 20:0, FA 22:0, FA 22:1n9 and FA 22:4n6, showed areas under the curve higher than 0.8 in the ROC curves (0.87, 0.84, 0.89 and 0.81 respectively). Conclusion Differences in serum levels of fatty acids were detected between active and remission patients of both CD and UC. The ROC curves of some of them point these fatty acids as potential biomarkers indicating the severity of IBD in these patients. Table 1. Levels of the fatty acids in serum of both non-IBD and IBD patients.

P0573 The Burden of Urgency in Ulcerative Colitis: Impact of Disease Duration and Activity

Abstract Background Urgency is a prevalent and distressing symptom in ulcerative colitis (UC) that significantly impairs quality of life. In longstanding UC, urgency often persists even during remission. This study aims to assess the burden of urgency in UC according to disease duration, and to disease activity. Methods A cross-sectional study was conducted on 96 UC patients in a tertiary care center, divided into two groups based on disease duration: 45 patients with UC for under 5 years and 51 with UC for over 5 years. Additionally, patients were categorized by disease activity, with 48 patients in remission and 48 experiencing active disease. All participants completed a questionnaire evaluating urgency frequency, severity, and its impact on daily life, while quality of life was assessed using validated scales. Statistical analyses compared urgency burden across both duration and activity groups. Results Patients with UC duration over 5 years reported significantly higher urgency severity and greater interference with daily activities, social interactions, and work compared to those with a shorter disease duration (p&amp;lt;0.05). Among all patients in remission, urgency persisted in 45%, with 55% of longstanding patients more likely to report urgency as a significant burden, compared to 39% of patients with more recent disease (under 5 years). Comparatively, urgency was more severe in patients with active disease, but a notable portion of those in remission (particularly in the over-5-year group) continued to experience substantial urgency-related impact. Conclusion Urgency remains a considerable burden in patients with UC, persisting in 45% of those in remission and affecting quality of life more significantly in longstanding disease. This elevated frequency and impact in patients with prolonged disease may be attributed to cumulative bowel damage, chronic inflammation, or altered bowel sensitivity over time, even when the disease is in remission. Addressing urgency early in the course of the disease is essential to improving quality of life and preventing the chronic sequelae seen in longstanding UC.

P1316 Increased ultra-processed food consumption is associated with inflammation-promoting shift of gut microbiota in Inflammatory Bowel Disease

Abstract Background Previous epidemiologic studies have suggested that increased consumption of ultra-processed food (UPF) can increase the risk of developing inflammatory bowel disease (IBD) by exacerbating gut dysbiosis.1 However, studies directly linking UPF to specific microbial shift in IBD patients are limited. Our study explored differences in gut microbiota profile based on UPF intake in patients with IBD. Methods This multi-centre cohort study included 313 IBD patients from three hospitals. Patients were divided into four quartiles (Q1, Q2, Q3, Q4) based on their percentage UPF consumption, evaluated from the Korea National Health and Nutritional Examination Survey. 16S rRNA sequencing was conducted on stool samples to analyse microbial composition. Subgroup analysis was performed based on IBD activity, whereby faecal calprotectin 250 ug/g was used as a cutoff value for defining active and remission state. UPF quartiles were grouped as Q1, Q2 and Q3, Q4 when conducting subgroup analysis to maintain an adequate number of samples for comparison. Age-adjusted analysis was conducted on patients younger than 50 years. Results General characteristics of the study population showed that there were no significant differences in inflammatory markers between quartiles. However, age was significantly different (p=0.001), with the first quartile having the highest median age of 49 years. Microbial analysis showed differences in beta diversity across quartiles (p=0.046), with the abundance of Lachnospiraceae and Faecalibacterium decreasing as UPF consumption increased. Subgroup analysis showed that patients with active inflammation showed no difference in alpha or beta-diversity, but Lactobacillus was more abundant in Q1, Q2 than Q3, Q4. Patients in remission differed in beta-diversity (p=0.012), with a greater abundance of Lachnospiraceae and Faecalibacterium in Q1, Q2 and Escherichia/Shigella and Veillonella in Q3, Q4. Age-adjusted analysis showed that in active IBD, Lactobacillus was more abundant in Q1, Q2 whereas Enterobacteriaceae was more abundant in Q3, Q4. Age-adjusted analysis of patients in remission showed that Lachnospiraeae, Faecalibacterium, Bifidobacterium were more abundant in Q1, Q2 than Q3, Q4. Conclusion This study suggests that increased UPF consumption is associated with an inflammatory-promoting shift in the gut microbiome of IBD patients. Restricting UPF intake may be important for controlling gut inflammation and preventing IBD relapse.

P0723 Lengthening ustekinumab treatment intervals from every 8 to every 12 weeks in IBD patients in stable remission: preliminary results of a prospective observational cohort study

Abstract Background Ustekinumab (UST) is registered as maintenance therapy for patients with inflammatory bowel disease (IBD) in an 8- (Q8W) or 12-weekly interval (Q12W) (1,2). Although Q12W might be associated with less side effects and reduced treatment costs (3), the majority of IBD patients are on Q8W as maintenance therapy (4). This study compares the UST drug-survival between IBD patients in stable remission who lengthen the UST interval from 8 to 12 weeks versus those who continue on 8 weeks. Methods Adult IBD patients who lengthened the UST interval from Q8W to Q12W were included in the prospective nationwide Initiative on Crohn and Colitis (ICC) Registry between July 2022 and May 2024. Patients were screened on clinical and biochemical remission (HBI≤ 4 or SCCAI≤ 2 and CRP≤ 10 Mg/L and FC≤ 250 µg/g) and had to be on a stable Q8W interval for at least six months. The interval was lengthened at the discretion of the treating physician. The control group consisted of patients previously included in the ICC registry (March 2016 - July 2022) who were in clinical and biochemical remission on Q8W at least one year after initiating UST. Inverse Probability of Treatment Weighting was used to adjust for confounding and selection bias. A drug event was defined as escalation of UST interval, IV re-induction or UST stop. Primary outcome was 24 and 52-week cumulative drug survival (4 weeks range). Results In total, 105 Q12W patients and 88 Q8W controls were included (table 1). Currently, 74 Q12W patients completed the follow-up period of 52 weeks. The cumulative drug survival at 24 and 52 weeks was comparable between the Q12W and control group (87.6% vs 90.9% and 64.0% vs 77.3% (p= 0.078), respectively). In the weighted analyses, 52 week drug survival was statistically different (Q12W 63.5% vs control 79.7%; p=0.04). In CD patients, the 52 week drug survival was slightly better than in the total cohort (Q12W 67.8% vs control 77.2%; p=0.32). Out of 34 drug events in the Q12W group, 1 patient stopped UST because of a malignancy (classified as not-drug related), 1 switched to vedolizumab due to an allergic reaction, 2 switched to ozanimod due to loss of response and 30 intensified their UST interval (1 to Q10W, 25 to Q8W, 3 to Q6W and 1 to Q4W). In the Q12W group, 8 patients (7.6%) started oral steroids, all in combination with an UST intensification, compared to 10 (11.4%) in the control group (p = 0.459), where 5 patients initiated steroids without an UST intensification. Conclusion Lengthening the UST interval from every 8 to every 12 weeks is safe and effective in approximately two-thirds of IBD patients in stable remission. Future studies should focus on identifying patients who will benefit the most from lengthening the UST interval.

P0748 Characterisation of Remission Levels in Patients with Ulcerative Colitis Treated with 5-Aminosalicylates: Results of the CARUC-ASA Prospective Multicentre Study

Abstract Background The treatment goals for chronic inflammatory bowel diseases are increasingly ambitious, targeting steroid-free remission, mucosal healing, and biomarker normalisation. In ulcerative colitis (UC), histological remission lowers risks of hospitalisation, cancer, and relapse. This study aims to describe remission levels in UC patients in symptomatic remission on first-line 5-aminosalicylic acid (5-ASA) and factors associated with remission. Methods This national, multicentre, prospective, phase 4 interventional study (ClinicalTrials.gov: NCT05992142) included UC patients in symptomatic remission, defined by a stool frequency score ≤ 1 and no rectal bleeding, on 5-ASA monotherapy (oral and/or rectal) for at least 6 months. Patients on corticosteroids, immunomodulators, biologics, or small molecules were excluded. Assessments included stool frequency, rectal bleeding, urgency, rectosigmoidoscopy (Mayo score, UCEIS), biopsies with the Geboes score assessed by central reading, faecal calprotectin (FCP), and MARS (Medication Adherence Report Scale) questionnaire. The different levels of remission were defined as followed: Complete Symptomatic Remission (CSR: PRO-2 = 0, no urgency), Endoscopic Remission (ER: Mayo 0–1, UCEIS 0–1), Complete Endoscopic Remission (CER: Mayo 0, UCEIS 0–1), Histological Remission (HR: Geboes 0–1), and FCP &amp;lt;150 μg/g; and Deep Remission as combined CCR, CER, and HR. In the absence of CER, physicians completed a questionnaire to investigate the reasons for not altering therapy. Results From December 2022 to February 2024, 198 UC patients (median age 50, 41% female) were enrolled from 14 centres. Montreal classifications were E1 (37%), E2 (44%), and E3 (18%). Treatment included oral 5-ASA (n=134, 68%), rectal 5-ASA (n=19, 9%), and a combination (n=45, 23%) with a median duration of 2.0 years (1.0 - 4.0). The median MARS-5 score was 24. ER was observed in 172/198 patients (87%), CER in 138/198 (70%), and HR in 156/196 (80%). Among those in ER and CER, 151/172 (88%) and 127/137 (93%) also had HR, respectively. Normal FCP was seen in 152/194 (78%) and in 128/153 (83%) of the HR subgroup. Deep remission was achieved in 47/197 (24%) of patients. The main reason for absence of deep remission was the absence of CSR (63%). The main reason for not altering treatment, despite the absence of CER, was physician reluctance in 37% of cases. 5-ASA administration form was significantly associated with ER (p=0.5, OR=2.9, 95%CI 1.1-7.3) for oral against combined. Conclusion In UC patients in clinical remission on 5-ASA, the majority achieved endoscopic and/or histological remission, suggesting that higher remission levels beyond clinical remission alone are attainable in selected, highly adherent patients on first-line therapy.

P1145 Comparison of Clinical Relapse between Tofacitinib and Filgotinib as Maintenance Therapy in Ulcerative Colitis Patients in Clinical Remission: A Retrospective Propensity Score-Matched Cohort Study

Abstract Background Strategies to reduce relapse after induction therapy using JAK inhibitor are controversial in patients with ulcerative colitis (UC). In this study, we aimed to compare relapse rate between tofacitinib (TOF) treatment and filgotinib (FIL) treatment for UC patients in clinical remission. Methods We used the data of UC patients who received TOF 10mg/day or FIL 200mg/day as maintenance therapy between May 2018 and October 2024. We included UC patients in clinical remission at baseline. Clinical remission was defined as follows: partial Mayo score ≤2, each subscore ≤1 and a rectal bleeding subscore of 0. The primary outcome was the time to relapse, defined as the requirement of dose escalation or switching therapy for UC with the worsening of clinical symptoms. The secondary outcome was safety during the observation period. Kaplan-Meier analysis and log-rank test were used in order to assess difference in therapy duration between two groups. A propensity score-matched (PSM) analysis was performed to adjust for potential confounders. Results We enrolled patients with UC who received either TOF 10mg/day (n = 101) or FIL 200mg/day (n = 43) as maintenance therapy. The median age was 39 [IQR 28–50] and 44 [34–55] years, and the median disease duration was 4 [1–11] and 7 [5–16] years, respectively. The number of previous exposures to anti-TNF agent was 52 (51.5%) and 18 (41.9%), respectively. In the TOF group, cumulative relapse rates at 8, 16, 24, and 48 weeks were 0%, 8.8%, 12.7%, and 25.5%, respectively. On the other hand, in the FIL group, cumulative relapse rates at 8, 16, 24, and 48 weeks were 0%, 2.3%, 4.7%, and 7.0%, respectively. After PSM, forty-three patients in both the TOF and FIL groups were isolated. The cumulative clinical relapse rate was significantly higher in the TOF group than in the FIL group (p = 0.039). Adverse events that required treatment discontinuation were reported in 8 patients in the TOF group, but no adverse events leading to discontinuation were observed in the FIL group. Conclusion Our findings suggested that FIL could prevent relapse in UC patients who are in clinical remission more effectively than TOF.

P0543 Impact of disease clearance on the disease course in Ulcerative Colitis patients in clinical remission over a ten-year follow-up

Abstract Background Despite being in clinical remission, ulcerative colitis (UC) patients continue to have a risk of disease flare-ups. Although endoscopic and histological evaluations are considered the gold standard for follow-up, the value of histological inflammation in predicting disease flare-ups in clinically remitted patients is not clearly known. This study aimed to investigate the relationship between histological inflammation and disease flare-ups in UC patients in clinical remission. Methods Adult patients with UC, no history of colectomy, followed up in our outpatient clinic, and in clinical remission were included in the study (total Mayo score &amp;lt; 2). Biopsy reports from colonoscopies performed during clinical remission were examined for histological activity. The follow-up period was defined as 10 years, based on the last clinical remission recorded in the outpatient clinic records. The Nancy histological index (NHI) was used as the histological activity score. Patients with NHI &amp;lt; 2 were considered to be in histological remission. The temporal relationship between histological inflammation and the first clinical flare-up was evaluated using Spearman correlation analysis. Results A total of 53 patients, including 26 women and 27 men, with a diagnosis of UC in clinical remission were included in the study. The mean age of the patients was 51.5 years. While 28 patients were in endoscopic remission, 25 were followed up as endoscopically active. Among the 28 patients in endoscopic remission, 15 were in histological remission, and 13 were histologically active. Flare-ups were observed after a median of 18.0 months in patients with endoscopic remission and 10.0 months in those with endoscopic activity (p=0.07). Flare-ups were observed after a median of 96.0 months in patients with histological remission and 10.5 months in those with histological activity (p&amp;lt;0.05). A negative correlation was found between histological inflammation and disease flare-up (r=-0.381, p&amp;lt;0.05). Conclusion The risk of disease flare-ups is higher in patients who do not achieve disease clearance (i.e., those who are histologically active even in endoscopic remission).

P0169 Relapse of ulcerative colitis on dose reduction of tofacitinib is associated with markers of T-cell activation but not clinical features: a prospective, multicentre observational study

Abstract Background Tofacitinib (TOF) is an effective treatment for ulcerative colitis (UC). A relationship between dose and both response and side-effect profile is recognised for JAK inhibitors. Dose reduction from 10mg bd to 5mg bd is therefore associated with improved safety but also with a risk of relapse. The BRITE study aimed to identify clinical predictors and biomarkers of relapse in a cohort of patients with stable UC undergoing TOF dose reduction. Methods Steroid-free patients with stable UC responding to TOF 10mg bd for at least 8 weeks were followed from dose reduction to time of relapse or for one year. Relapse was defined by worsening modified Mayo score, including an increase in the rectal bleeding and endoscopic subscores of ≥ 1 point. Clinical and endoscopic assessment with biopsy was performed prior to dose reduction (baseline) and at end of trial. PBMCs were isolated at baseline and were cryopreserved. Flow cytometry analysis of phospho-STAT levels of STAT1, STAT3, STAT4 and STAT5 was performed in T cells from unstimulated and cytokine-stimulated baseline PBMC. In addition, CD4 T cells were isolated from PBMC and were stimulated with plate-bound anti-CD3 and anti-CD28 (TCR activation) for 5 days; cell supernatants were analysed for 17 CD4 T-helper (Th) cell effector cytokines using a 17-cytokine Luminex assay. Results 50 patients were enrolled across 3 centres; baseline characteristics are displayed in table 1. 23 (46%) patients relapsed after a median duration of 23 weeks (IQR 9-45). Demographics, disease duration, prior advanced therapy exposure (including duration on TOF), and baseline clinical, biochemical (calprotectin/CRP), and histo-endoscopic disease severity were not associated with risk of relapse. In contrast, molecular differences in CD4 T-cell function were identified in relapsers and non-relapsers. pSTAT5 levels were significantly induced by IFNa in relapse patients (p&amp;lt;0.05), but not in remission patients (Fig 1a), while canonical pSTAT5 activation by IL2 showed no significant differences between the two cohorts of patients. Furthermore, TCR activation of baseline CD4 T cells showed significantly higher expression of IL10 (p=0.01) in remission patients compared to relapse (Fig 1b). Higher levels of resting pSTAT1High expression that was refractory to IFNa stimulation in relapse patients but inducible in remission patients was also identified (p=&amp;lt;0.01). Conclusion In this large prospective study of TOF dose reduction, in contrast to previous studies, no baseline clinical or endoscopic predictors of relapse were found. However, potentially clinically useful association with markers of T cell activation were identified and should be investigated further.