Active Colitis Research Articles

BREASTFEEDING STATUS AND DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS: AN EXPLORATORY RETROSPECTIVE COHORT STUDY

Abstract OBJECTIVE While the protective effect of being breastfed on the development of ulcerative colitis has been well established, it is not known if being breastfed decreases colectomy rate and disease severity for pediatric patients. This work is designed to better understand the connection between breastfeeding status and disease severity of ulcerative colitis among pediatric patients. METHODS This exploratory retrospective cohort study analyzed the clinical and laboratory data of patients at Boston Children’s Hospital enrolled in a data registry and biorepository since 2012. Data was collected from charts and analyzed to determine if there is a significant difference in colectomy rate, pediatric ulcerative colitis activity index (PUCAI) score, ESR, or CRP, between not breastfed (n=56), breastfed (n=39), and mixed breastfed patients (n=31). Breastfed patients are defined as patients who were exclusively breastfed for greater than or equal to three months. Patients who were never breastfed were considered not breastfed. Patients who were exclusively breastfed for less than three months or received a mix of formula and breastfeeding were considered mixed breastfed. Statistical analysis of the groups was performed using a one-way ANOVA. RESULTS At disease diagnosis, the average PUCAI score of the not breastfed group (32.4) was significantly higher than the exclusively breastfed group (18.4) (p value = 0.0189). No significant difference was detected in the average PUCAI score of the mixed breastfed group (34.1) compared to the not breastfed group (32.4). Significant differences in the colectomy rate between all three groups were not detected, and likewise we did not find significant differences in markers of disease severity including ESR, CRP, and hemoglobin at diagnostic visit between groups. CONCLUSION These results suggest that children with ulcerative colitis who were exclusively breastfed have a lower average PUCAI score at the time of diagnosis than those who were not breastfed. Further investigation with larger data sets may be necessary to determine other benefits of exclusive breastfeeding in pediatric ulcerative colitis patients.

REAL-WORLD SAFETY AND EFFICACY OF USTEKINUMAB AND VEDOLIZUMAB IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract CONTEXT/PURPOSE Ustekinumab and vedolizumab are approved biologicals to treat adults with inflammatory bowel disease (IBD) but currently administered off-label for children. Aims: (1) assess safety and adverse events during treatment with ustekinumab or vedolizumab in pediatric IBD and (2) assess steroid free clinical remission and mucosal healing at 6 months and 1 year. METHODS Retrospective chart review of pediatric patients (<22 years) with IBD treated at an academic hospital and two affiliated practices. Inclusion: Patients with IBD who received either ustekinumab or vedolizumab between January 2015 to June 2022 with minimum of 6 months follow up. Clinical remission assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) < 10 and short Pediatric Crohn’s Disease Activity Index (shPCDAI) <15, and mucosal healing by fecal calprotectin <250 mcg/gram. RESULTS Fifty-eight patients received vedolizumab and 55 patients received ustekinumab. Patients with ulcerative colitis (UC) or IBD unclassified (IBDU) on vedolizumab were more likely to be in remission at 6 months (58% vs. 42%, p = 0.3, Table 1) and significantly higher at achieving 1-year steroid free remission (64% vs. 27%, p = 0.019) compared to ustekinumab. Over two thirds of biologic naïve and about half of biologic exposed patients who received vedolizumab achieved 1-year steroid free remission (78% vs. 58%, Figure 1). All patients who received ustekinumab were biologic exposed. In Crohn’s disease (CD), no significant difference was seen in children receiving vedolizumab compared to ustekinumab at 6 months remission (57% vs. 63%, p = 0.7) or 1-year steroid free remission (70% vs. 70%, p >0.9). All biologic naïve patients and half of biologic exposed patients who received vedolizumab achieved 1 year steroid free remission. Both bionaive and two thirds of biologic exposed patients who received ustekinumab achieved 1-year steroid free remission (100% vs. 67%). When comparing vedolizumab and ustekinumab, no significant difference was observed in 6 month remission (73% vs. 59%, p = 0.2) and 1-year steroid free remission based on calprotectin (61% vs. 66%, p = 0.7). Similar to clinical remission rates, biologic naïve patients tended to have higher remission rates based on calprotectin. Five patients each had minor adverse events with ustekinumab and vedolizumab, and 20 were hospitalized mostly for IBD flare. CONCLUSION Both biologicals were safe and effective in achieving clinical remission at 6 months and 1 year. They were more effective when used in bionaive patients, although numbers were very low for ustekinumab. The superior efficacy of vedolizumab in UC and IBDU at 1-year may be attributed to larger cohort of bionaive patients. Larger multicenter prospective studies are needed to validate these findings regarding efficacy and safety of vedolizumab and ustekinumab in pediatric IBD. Table 1 Remission on Vedolizumab and Ustekinumab Figure 1 Remission on Vedolizumab vs. Ustekinumab Stratified by Biologic Exposure

CLINICAL, BIOCHEMICAL, AND INTESTINAL ULTRASONOGRAPHY RESPONSE TO CURCUMIN-QINGDAI (CURQD) COMBINATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND There are few FDA-approved therapies for pediatric patients with inflammatory bowel disease (IBD). Clinical remission rates plateau at 60%, even with the currently available biologic therapies. Nutraceuticals are novel alternative treatments that can be used as adjunct treatments. AIM In this case series of 8 patients, we aim to present the clinical and radiological response to a novel nutraceutical agent, CurQD, composed of QingDai (Indigo Naturalis) and Curcumin. METHODS Patients included required a baseline pre-treatment clinical assessment and at least a single follow-up examination. Clinical status was evaluated based on the Physician General Assessment (PGA, determined independently from the clinical scoring systems) and the pediatric Crohn’s disease activity index (PCDAI) or the pediatric ulcerative colitis activity index (PUCAI), as appropriate. Baseline biomarkers (Hgb, ESR, CRP, albumin, and calprotectin(FC)) were collected pre and post-treatment when available. When available, intestinal ultrasound (IUS) features were also noted. On the IUS, bowel wall thickness (BWT, in mm) and color Doppler signaling (measured by the modified Limberg score graded 0,1,2, or 3 based on severity) were collected. The longitudinal changes were demonstrated on the most inflamed segment. Considering the small sample size, only descriptive statistics were applied. RESULTS Primary therapies received included anti-TNFα for 3 patients, ustekinumab in 3 patients, 1 on vedolizumab, and mesalamine in 1. Baseline assessment was done at a median time of 1.8 weeks (IQR 0.9-3.6 weeks) before starting the supplement, and the follow-up was 3.9 weeks (IQR 2.8-5.4 weeks) after starting the supplement. Two patients were in clinical remission at baseline but had active disease based on Doppler activity on IUS, 3 patients had mild active disease, and 3 patients had either moderate or severe disease activity. At follow-up, all patients but one were in clinical remission. (Table 1) Median baseline FC decreased from 1047.4 ug/g (IQR 532.4-1107) to 27.1 (IQR 27.5-341.3). Five patients had complete IUS information. When isolating the most inflamed segment on IUS, all patients demonstrated a response to treatment, noted by a decrease in BWT and/or a decrease in Doppler signaling. (Figure 1) No patient had a baseline therapy change after their follow-up. One patient reported abdominal bloating after starting CurQD and discontinued the product after five weeks. CONCLUSION CurQD is a promising nutraceutical that may assist in breaking the therapeutic ceiling of biological therapies in IBD. Based on this small experience, a larger randomized controlled trial in children would be needed to assess the safety and efficacy of this product in this vulnerable patient group. Furthermore, IUS is a practical tool for evaluating response to therapy in a pragmatic clinical setting. Table 1 Change in clinical disease scores in patients receiving CurQD Figure 1 Description of changes in a) bowel wall thickness (BWT) and b) color Doppler signaling (measured by the modified Limberg score) in patients treated with CurQD.

PROTECTIVE ROLE OF SAFFRON TO REDUCE INFLAMMATION AND IMPROVE CLINICAL MANIFESTATIONS IN ULCERATIVE COLITIS PATIENTS

Abstract BACKGROUND We studied saffron as an additional intervention to improve clinical manifestations of Ulcerative colitis (UC) patients. METHODS This is a study at Yazd university where 30 UC patients were randomly assigned to placebo (n=9), low (n=9, 25 mg), or high dose saffron (n=12, 50mg), two times a day for 8 weeks. Hemoglobin, platelet levels, CRP, ESR, and fecal calprotectin along with clinical data Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score, and Hamilton Depression Anxiety Score (HDRS) were recorded at baseline and completion of treatment. For validation, we recruited 3 UC patients at Howard University who received 50mg of Saffron twice daily for 8 weeks, two underwent a wash-out period and received saffron for a second cycle. Inflammatory markers, CRP, stool calprotectin, and the cytokines from PMA/ionomycin stimulated PBMCs, at baseline and 8 weeks Saffron treatment were compared. 16S rDNA analysis was performed on stool DNA for gut microbiome. RESULTS In Yazd study of 30 patients, all participants completed the study successfully. The high dose group showed significant improvement in HDRS score (p=0.001), SCCAI (p=0.04), Partial Mayo score (p=0.01), fecal calprotectin (p=0.009), and CRP (p=0.001) compared to baseline. The low dose group also improved in HDRS score (p=0.01; Table 1, Fig 1). No adverse events were reported. In HU data, saffron improved Partial Mayo Score, health related quality of life and HDRS. Pro-inflammatory cytokines TNFα, INFγ, IL-6, IL-2, IL-17a decreased while anti-inflammatory IL-10, TGF-β increased. Fecal calprotectin levels of 228 μg/g and 169 μg/g decreased to 63 μg/g and 16 μg/g in two individual patients, respectively. After the wash-out period, fecal calprotectin increased. A second saffron treatment cycle reduced it again further validating the causal relationship. Saffron led to a decrease in gamma Proteobacteria, and enrichment in Ruminococcaceae. CONCLUSION This study demonstrates that saffron led to improvements in clinical response including reduction in partial Mayo scores, HDRS scores, and inflammatory markers such as fecal calprotectin and CRP. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with UC. Table 1. Basic characteristics, clinical variables, and laboratory variables among the study participants in three arms of the clinical trial. Figure 1 Effect of Saffron on quality of life and Inflammatory markers.

P493 Do antiTNF or Ustekinumab trough levels correlate with joint extraintestinal manifestations activity in Inflammatory bowel disease patients?

Abstract Background Inflammatory spondyloarthritis(SpA) are the most common extraintestinal manifestations (EIM) associated to inflammatory bowel disease (IBD), with a prevalence of 20-50% for axial SpA(axSpA) and 5-20% for peripheral(pSpA). AntiTNF is the optimal therapy in axSpA intolerant or refractory to NSAIDs, also effective in pSpA. An optimal trough level has not been yet established in this clinical setting. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients. Methods Prospective, multicenter,cohort study. IBD patients diagnosed with articular EIM under antiTNF or Ustekinumab(UST) for at least 6 months were included. Blood samples were obtained just before administering the drug(trough levels), and a simultaneous evaluation by a rheumatologist and a gastroenterologist, was performed. Definitions: inactive AxSp=ASDAS-CRP<1.3 and BASDAI<2, inactive pSp=arthritis, enthesitis and dactylitis=0, active AxSp=ASDAS-CRP >2.1 and BASDAI>4, active pSp= artritis, entesitis o dactilitis > 0. Aim, to evaluate the correlation between antiTNF and UST trough levels and joint EIM activity in IBD patients. Results A total of 135 patients were included: mean age 51 ± 15, 59 (43.7%)women), 80% CD. 60(44.4%) patients presented axSpA, 50(37%) pSpA and 25(18.5%) mixed. 12(8.9%) had active IBD. Table 1 summarizes the patients' main demographic and clinical characteristics distributed by SpA activity. Fifty-three(39%) were on infliximab (IFX), 61(45.2%), on adalimumab (ADA) and 22 (16.3%) on UST treatment. NSAIDs treatment(12.7% vs 3.1%, p<0.05), higher fecal calprotectin(FC)(486 ± 709 vs 228.2 ± 297, p<0.05), and the prior use of biologics(33.8% vs 17.6%, p<0.05) were more frequent among active vs inactive SpA patients. No differences between IFX(7.05 ± 4.16 vs 5.79± 4.05, p=ns), ADA(7.98 ± 4.20 vs 9.51 ± 6.15 p=ns) and UST levels(3.39 ± 3.47 vs 3.08 ±2.69, p=ns), were found between active and inactive SpA patients, even when were distributed by type of SpA(axSpA/mixed and pSpA). Body mass index(b:-0,29, p=0.01)FC(b:-0,28, p=0.01), and intensified therapy(b:-0,28, p=0.01) were associated to higher IFX levels in the whole SpA cohort. Patients with axSpA or mixed were articular active more frequently than pSpA patients(82% vs 18%, p <0.05). IBD activity was correlated to articular activity only among pSpA patients(2% active IBD in inactive pSpA vs 20% active IBD in active pSpA patients, p=0.03). Conclusion AntiTNF and UST trough levels are not correlated to joint activity in patients with IBD and SpA. In our study more than 80% of patients with active SpA were inactive regarding IBD. Only pSpA patients presented correlation between IBD and articular activities.

P368 Correlation between patient-reported outcome measures in inflammatory bowel disease and other measures of disease activity: a systematic review

Abstract Background The clinical activity of inflammatory bowel disease (IBD) has traditionally been evaluated by healthcare professionals. To allow direct reporting of symptoms by patients, several patient-reported outcome measures (PROMs) have been developed. We evaluated the correlation between IBD-specific PROMs and measures of endoscopic activity. Methods A systematic review of the literature was performed up to June 2022. Searches were conducted in three databases (PubMed, Scopus and Web of Science). The search protocol was registered in PROSPERO (CRD42022383899). Studies reporting the correlation between self-administered, IBD-specific PROMs and endoscopic scores were included. A descriptive analysis was performed by assessing the correlation between PROMs and IBD endoscopic activity. PROMs used in Crohn’s disease (CD) and ulcerative colitis (UC) were considered separately. Results Seventeen PROMs were identified encompassing a series of IBD signs and symptoms, mainly abdominal pain (n=10), stool frequency (n=6) and rectal bleeding (n=4). Twenty-two studies assessed correlations of PROMs with existing clinical measures of disease activity and/or their accuracy in predicting remission. The mainly used endoscopic indices were Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore (MES) (n=11), and clinical indices were Harvey–Bradshaw Index for CD (n=7) and SCCAI for UC (n=7). Most studies used more than one comparator as standard for validation. A marked heterogeneity in the study design and statistical methods was observed. In CD, five studies analysed correlations between PROMs and SES-CD. They generally found weak correlations with PROMs (PRO2, n=2; mobile Health Index [mHI]-CD, n=1) (Figure), except for one which found a negative moderate correlation between PRO2 and SES-CD. The strongest correlation was with the stool frequency item of the Monitor IBD at home (MIAH) questionnaire. In UC, four studies assessed the correlation between PROMs and MES. Positive weak-to-moderate correlations were found with PRO2, MIAH rectal bleeding item and mHI-UC MES in four studies. Conclusion In CD, PROMs poorly correlate with endoscopic activity. However, in UC, rectal bleeding reasonably correlates with endoscopic status. It is well known that IBD symptoms overlap with those of other digestive diseases as functional disorders, especially in CD. In line with this, our data suggest that PROMs cannot substitute endoscopic data to monitor disease activity in IBD, especially in CD patients. Nonetheless, they represent a valuable complementary instrument to comprehensively describe disease control by capturing patient perspective. More studies are needed to better evaluate correlations between PROMs and clinical disease activity measures.

P975 Monitoring Inflammatory Bowel Disease (IBD) by intestinal ultrasound decreases time to treatment change and time to remission in comparison to conventional management: Analysis of patients with IBD on multiple IBD therapies

Abstract Background Intestinal ultrasound (IUS) is a non-invasive, repeatable, and accurate disease monitoring modality that can provide real-time assessment of inflammatory bowel disease (IBD). We previously demonstrated that IUS shortens time to treatment change and time to remission in patients receiving upadacitinib and monitored by IUS compared to conventional management (ACG 2023). Here, we aim to assess the impact of IUS on management and outcomes of our pts with IBD receiving any IBD therapy. Methods We performed a retrospective analysis of patients who completed induction therapy (per individual drug label) but have active disease as measured by SCCAI >2 or HBI >4 between October 2021 and October 2023. We assessed for the time to treatment change (time from a positive clinical index to the time of a medical decision made), and time to clinical remission (time from a positive clinical index to the time of normalization (SCCAI ≤2, HBI ≤4 of the clinical index) and compared those between patients monitored by IUS and those managed with a conventional approach. Patients were matched by their provider and disease type. Active disease by faecal calprotectin (FCP) (FCP >150 mcg/g) and endoscopy (Mayo endoscopic score (MES) >0) were assessed ± a month before a positive clinical index was collected. An abnormal IUS was considered bowel wall thickness (BWT) >3 mm in the colon or terminal ileum and any hyperemia by colour Doppler signal (CDS) (modified Limberg score >0). Chi square analysis was performed, with p<0.10 significance. Results 54 patients (63 encounters) were included in this analysis (33 in the IUS cohort, 30 in the conventional management cohort) from 3 different providers. At inclusion, 9 (27%) pts in the IUS group and 10 (33.3%) in the conventional group had elevated FCP, and 5 (15.2%) pts in the IUS group and 29 (96%) had endoscopic disease. In the IUS group, the average time-to-treatment change was 2.2 (±1.2) days compared to conventional management 25.6 (±14.5), p=0.050. A total of 44 patients achieved clinical remission (22 IUS; 22 conventional management). The average time to remission in the IUS group was 128.1 days (±22.3) vs 230.6 (±38.2) days in the conventional management group, p=0.035). Drug class did not affect time to treatment change or time to remission (Table 1). The most significant reason for delay in the conventional group compared to the IUS group was awaiting endoscopy and FCP results. Conclusion Using IUS to assess disease activity in IBD is associated with earlier treatment changes and shorter time to remission compared to conventional approaches to disease monitoring, independent of therapy choice. Ongoing dissemination and incorporation of IUS in the management of IBD are warranted.

P241 Systemic redox status associates with disease activity and clinical phenotypes in Inflammatory Bowel Disease

Abstract Background Oxidative stress is a key pathophysiological mechanism in inflammatory bowel diseases (IBD). Systemic levels of oxidative stress are reflected by reduced levels of free thiols (FT) in circulating proteins, especially those in albumin, which associates with disease activity in IBD. Yet, clinal value of circulating FT level as biomarkers of disease and therapy response remains largely unexplored. Here we investigated the association between plasma FT levels and clinical parameters, the plasma inflammatory proteome and medication use. Methods Plasma samples from 1,028 patients with IBD (567 Crohn's disease [CD] and 461 ulcerative colitis [UC]), and 500 healthy controls (HCs) participating in the 1000IBD and LifeLines projects were profiled for free thiols (FT), uric acid, bilirubin and 92 inflammation-related proteins (Olink Inflammation panelÒ). All biomarkers were associated with clinical phenotypes using general linear models adjusting for age, sex, body mass index, smoking and medication use. Results Plasma FT levels were significantly lower in IBD compared to HCs (p<0.05) (Figure 1A), with patients with UC showing even lower levels than patients with CD (p<0.05). Patients with UC on induction therapy had lower FT levels compared to patients on maintenance therapy (p<0.05). Furthermore, FT levels of patients with IBD were strongly associated with systemic inflammation (C-reactive protein [CRP], p<0.05) (Figure 1B). In both patients withCD and UC, reduced FT levels were associated with elevated levels of inflammation-, apoptosis-, and growth factor-related proteins, including C-X-C motif chemokine 9 (CXCL9) (Figure 1C-D), CUB domain-containing protein 1 (CDCP1) and caspase-8 (CASP8), proteins previous associated with preclinical IBD1-3. Furthermore, specifically for patients with UC, reduced FT levels were associated with elevated eotaxin-1 (CCL11) (Figure 1C), monocyte chemotactic protein-1 (MCP-1), and several cytokine biomarkers like Interleukine-6 (IL6) and Interleukin-17A (IL17A). Conclusion Systemic FT levels associate with inflammatory disease activity and clinical therapy and may offer potential utility in clinical assessments. This study highlights the intricate involvement of oxidative stress in various inflammatory pathways and components, particularly in innate/adaptive immune balance, cell damage, and apoptosis. These findings contribute to a deeper understanding of the interplay between oxidative stress, inflammation, and IBD. Funding: This study was supported by Janssen Research & Development LLC.

P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases

Abstract Background Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples. Methods Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level. Results The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response. Conclusion Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.

P454 Systemic free thiols associate with clinical and biochemical disease activity in Inflammatory Bowel Disease: a prospective diagnostic validation study

Abstract Background In the pathophysiology of inflammatory bowel diseases (IBD), oxidative stress plays an important role. Lower levels of plasma free thiols (FT) reflect a higher oxidative stress burden and correlate with IBD disease activity. However, their clinical significance as biomarker for disease activity remains unclear. This study aimed to prospectively validate the utility of plasma FT levels as biomarker for clinical, biochemical, and endoscopic disease activity in patients with IBD. Methods In an ongoing prospective diagnostic trial aiming to include 100 IBD patients, we conducted an interim analysis of plasma FT levels in 52 patients with IBD (24 Crohn's disease [CD], 21 ulcerative colitis [UC], and 7 patients with undetermined IBD). Clinical disease activity was quantified by the Harvey-Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Biochemical disease activity was determined by measuring blood C-reactive protein [CRP] and faecal calprotectin [fCal]). Endoscopic disease activity was quantified with the Mayo endoscopic subscore for UC and the Simple Endoscopic Score (SES-CD) for CD. Plasma FT levels were assessed for correlations with disease activity parameters using linear and logistic regressions models. Discriminative capacity of biomarkers was evaluated through calculating receiver operating characteristics (ROC) statistics. Results Plasma FT levels were significantly negatively correlated in clinical parameters, like HBI (r = -0.53, p < 0.05) (Fig. 1A). Other inflammatory biomarkers, like CRP, were also negatively correlated with plasma FT levels and were reduced in patients with active IBD (r = -0.43, p < 0.05) (Fig. 1B). Plasma FT levels accurately discriminated between CD patients with clinically quiescent (HBI < 5) and active disease (HBI ≥ 5) (AUC = 0.80, p = 0.02, Fig. 1C), better than fCal (AUC = 0.55, p = 0.83). Plasma FT were not significantly different for biochemically quiescent (CRP < 5 mg/l) and active (CRP ≥ 5mg/l) disease (AUC = 0.69, p = 0.20, Fig. 1D). Both Mayo and SES-CD scores, after adjusting for confounders, also exhibited a trend towards negative association with plasma FT levels (Fig. 1E). Figure 1 Conclusion Further completion of the trial will reveal whether systemic FT levels will reflect endoscopically observed disease activity, and this interim analysis shows strong correlations FT levels and parameters of clinically and biochemically active disease. Measuring systemic FTs in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity. Funding None

P208 Personalized Machine Learning Algorithm to Predict Ulcerative Colitis Disease Activity from Wearable Data

Abstract Background Due to its ease of use and ability to determine complex information, wearables have been gaining popularity over the last decade. Smart rings such as OuraTM present the ability to track metrics such as sleep quality, resting heart rate, body temperature, and daily activity. This is not only useful for the predicting disease activity in inflammatory bowel disease (IBD), but also to understand behavior changes that can be associated with disease activity. This study aimed to evaluate potential use for wearable data in IBD management. Methods Daily OuraTM ring data of a patient with ulcerative colitis (UC) was collected from OuraTM ring application programming interface from 2019 to 2023. Days were classified as “active disease” or “remission” based on patient symptoms, colonoscopies, and fecal calprotectin levels. Data was collected on the patient’s sleep metrics, activity levels, and daily vitals. Variables with >50% null values were not included in model training. A univariate analysis was conducted to determine features that correlated with flaring periods (p-value <0.3) [ABPM1] [AS2] to be included in model training. An XGBoost classifier was selected with the target variable being flare status. Boosting parameters were then hypertuned to optimize model performance. After hypertuning and kfold cross-validation, the model’s mean accuracy, mean logarithmic loss, and AUC was reported. Further analysis was conducted comparing remission, active disease and pre-diagnosis data. Results 963 days were collected. 444 days were determined to be “flare” based on reported symptoms, 4 fecal calprotectin levels, 2 colonoscopies, and 1 intestinal ultrasound confirming disease activity. Remission was determined by no reported symptoms, 2 normal fecal calprotectin levels and a normal intestinal ultrasound. Generally, worse sleep quality, increased resting heart rate, increased respiratory rate, and deviations in activity levels were positively associated with disease activity. After model training with XGBoost classifier and 10-fold stratified cross-validation, the mean accuracy was 0.92 ± 0.08, mean logarithmic loss of 0.134 ± 0.11, and a mean AUC was 0.94 ± 0.02. The patient’s mean biometric values such as heart rate and respiratory appeared to recover to pre-diagnosis levels with the exception of heart rate. Conclusion Data from the OuraTM ring demonstrated the potential application of wearables in IBD management in a single patient with UC. The high accuracy and AUC of our XGBoost model demonstrates how individualized wearable data can be used to predict IBD flares. Prospective studies with multiple patients could be useful to consider wearables as an additional adjunct disease monitoring device in IBD.

P1031 Intestinal ultrasound for monitoring therapeutic response in patients with ulcerative colitis treated with upadacytynib

Abstract Background Intestinal ultrasound (IUS) is a noninvasive method to assess disease activity in inflammatory bowel disease (IBD) although there are still limited data of usefulness of IUS in ulcerative colitis (UC) compared to Crohn’s disease (CD). The aim of the study was to evaluate usefulness of intestinal ultrasound in comparison to endoscopy in assessment of the efficacy of upadacytynib (UPA) in induction of remission in patients with UC. Methods This was a prospective, two-centers study in which we enrolled 27 patients with a flare of UC (total Mayo score>7) treated with UPA (8 weeks of induction period). IUS, calprotectin level and laboratory tests were conducted in week 0, 4 and 8. Milano ultrasound criteria (MUC) were used to assess the IUS disease activity. Results Among 27 patients 34% achieved clinical remission and 40,6% endoscopic remission already in week 4. After 8 weeks of treatment with UPA clinical remission in 53,1% and endoscopic remission in 56,2% of UC patients were achieved. In IUS the most affected parts of the colon were rectum and sigmoid colon. 100% of the patients had an increased bowel wall thickness (BWT)>3mm in the sigmoid colon and rectum at baseline. In the first 4 weeks of the study, the percentage of patients with an increased BWT in the sigmoid colon and rectum decreased significantly and remained low at week 8. 78% of patients with normalized BWT had endoscopic remission vs 22% without endoscopic remission (p<0.001). There was 74% correlation between MUC and total Mayo score (p=0,013). Conclusion Upadacitinib has demonstrated a positive efficacy during induction of remission in UC patients, shown as improvement in IUS parameters as well as in endoscopy improvement. Our data showed a strong correlation between normalization of BWT and endoscopic remission in patients with UC treated with upadacytynib. IUS seems to be a useful and non-invasive method for monitoring disease course and for assessing treatment response in UC patients.

P288 Fecal leukocyte esterase level can predict endoscopic activity for Inflammatory Bowel Disease patients

Abstract Background The urine leukocyte esterase (LE) strip is widely employed to detect leukocyte presence in human body fluids due to its simplicity, speed, and cost-effectiveness. Our previous study demonstrated that fecal LE (FLE) correlated with fecal calprotectin (FC) which serves as a surrogate marker reflecting disease activity in inflammatory bowel disease (IBD) patients. This study aims to assess the correlation between FLE and endoscopy severity. Methods This prospective study included IBD patients at National Taiwan University Hospital from December 2021 to November 2023. FLE and FC in the same stool sample, which was collected within one month of endoscopy, were analyzed. The correlation between FLC, FC, and endoscopic severity scores was assessed using the Pearson method. Active disease in ulcerative colitis (UC) and Crohn's disease (CD) patients was defined as Mayo endoscopic score (MES) ≥ 2 and simple Endoscopic Score for Crohn's Disease (SESCD) ≥ 8, respectively. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Area Under the Receiver Operating Characteristic curve (AUROC) were analyzed by using SPSS. Results A total of 177 IBD patients (93 with UC, 84 with CD) were included. The correlation between FLE and FC levels was moderately positive (r=0.305, p<0.001). The correlation between FLE and endoscopic severity in UC and CD patients was 0.442 (p<0.001) and 0.293 (p=0.007), respectively. Among UC patients, the area under the receiver operating characteristic curve (AUROC) for predicting MES ≥ 2 by FLE and FC was 0.717 and 0.787 (p=0.241), with an optimal cutoff of 2+ for FLE and 42.5 mg/kg for FC, respectively. At this cutoff point, FLE demonstrated a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for predicting MES ≥ 2 as 52.3%, 81.6%, 71.8%, and 65.6%, respectively. For CD patients, the AUROC for predicting SESCD ≥ 8 by FLE and FC was 0.761 and 0.869 (p=0.203), with an optimal cutoff of 2+ for FLE and 225 mg/kg for FC, respectively. FLE exhibited a sensitivity, specificity, PPV, and NPV of 81.8%, 64.4%, 74.3%, and 95.9% for predicting SESCD ≥8 respectively, at this cutoff. Conclusion Our results demonstrated that FLE can predict endoscopic activity, which is a cheaper and widely available monitoring tool, might be an alternative choice to FC for IBD monitoring.

P1233 Serum insulin is associated with c-reactive protein and gut microbial diversity in inflammatory bowel disease

Abstract Background Obesity, impaired glucose tolerance and unfavorable lipid profile are established risk factors for cardiovascular disease. Patients with inflammatory bowel disease (IBD) may be at increased risk of cardiovascular disease, and new therapies such as JAK inhibitors may further add to this risk. C-reactive protein (CRP) is a marker of systemic inflammation that may increase with active IBD and is correlated with metabolic risk in non-IBD cohorts. Diet, in particular consumption of ultra-processed foods, has been linked to gut dysbiosis and the onset, course, and response to treatment of both IBD and metabolic disease. The aim of this study was to identify metabolic risk in a cohort of individuals with IBD through an analysis of diet, metabolic parameters and stool microbial diversity. Methods This two-week prospective case-control study enrolled non-diabetic individuals with IBD in clinical remission and healthy individuals (HC). Baseline body mass index (BMI), waist circumference (WC) and waist to hip ratio, detailed diet diary, serum metabolic and inflammatory parameters, stool bacterial microbiota and faecal calprotectin (FC) were examined. Results Eighty-one participants; 57 with IBD (26 ulcerative colitis (UC), 31 Crohn’s disease (CD)) and 24 HC participants were recruited. In the IBD group, there was a positive correlation between serum insulin, triglycerides, BMI and WC with CRP and a negative correlation between HDL and CRP (Table 1). There were no associations between measured metabolic risk factors and FC. Stool microbial alpha diversity of the IBD group was lower than that of the HC cohort, with lower species richness (IBD 21.4 v HC 26.8, p<0.01) and Shannon’s diversity index (SDI) (IBD 3.1 v HC 3.4, p=0.03) (Figure 1). In the IBD group, there was a negative association between serum insulin and CRP with stool species evenness (SE) and SDI (insulin: SE r=-0.41, adj-p=0.02, SDI r=-0.39, adj-p=0.02; CRP: SE r=-0.4, p=0.02, SDI r=-0.4, p=0.02) and a negative association between intake of processed meat and stool alpha diversity metrics (SE r=-0.39, adj-p=0.046 and SDI r=-0.42, adj-p=0.02 respectively). There were no significant associations between serum metabolic profile and dietary intake with stool alpha diversity in the HC group. Conclusion Unhealthy diet, higher body weight and suboptimal glucose control were positively associated with CRP in participants with IBD. Gut microbiota with reduced diversity may be a common link between adverse metabolic outcomes and IBD. Serum insulin should be explored as a common biomarker of metabolic and gut microbial health.

P740 Results at 52 weeks of Intravenous Ustekinumab as Maintenance Treatment in Patients with Loss of Response to Subcutaneous Doses: A Multicenter Retrospective Observational Study

Abstract Background Ustekinumab (UST) is indicated for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world,some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous UST. Methods We performed a multicenter observational retrospective study including patients with active IBD on maintenance treatment with IV UST. The study conducted at 2 hospitals in Andalusia.The clinical response and remission was analyzed at week 12 and 52, defined as either Harvey-Bradshaw Index (HBI) ≤4 for CD or partial Mayo Score (pMS) ≤2 for UC. The reduction of objective markers of disease activity, fecal calprotectin (FCal) and C-reactive protein (CRP) was evaluated. Moreover, UST trough levels were measured pre-and post UST IV maintenance, drug persistence at the end of the follow-up and any adverse events were assessed. Results A total of 59 patients were included in the study, with a median age of 41 years [IQR32-52]. 84.7% (50/59) had Crohn's disease (CD). 91.5% (53/59) had previously received at least one biologic or JAK inhibitor treatment. 58.6% (34/59) werepreviously on subcutaneous UST every 4 weeks (Table 1). In patients with CD, the median baseline HBI value was 9 (IQR 6-12), which decreased to 5 (IQR 4-7) at week 12 and 4 (IQR 3-6) at week 52 (p<0.001) (Figure 2A). In patients with ulcerative colitis (UC), the median baseline pMayo value was 8.5 (IQR 6.5-9.0), which decreased to 5.5 (IQR 4.3-6.0) at week 12 and 3 (IQR 2.0-4.8) at week 52 (p=0.017) (Figure 2B). The median baseline FCal was 800.2 μg/g, which decreased to 520 μg/g at week 12 and 220 μg/g at week 52 (p<0.001). Regarding CRP, the median baseline was 7.1 mg/L, which decreased to 4 mg/L at week 12 and 3 mg/L at week 52 (p<0.001). The median UST levels with subcutaneous maintenance treatment were 3.1 mcg/mL (IQR 1.1-7.4) compared to 12 mcg/mL (IQR 9-20) with intravenous treatment (p<0.001) (Figure 2C). Clinical remission at week 12 and 52, was achieved by 47,5% and 64,3% of the patients respectively. At the end of the follow-up, 96.6% of the patients continued with intravenous UST (Figure 2D). No adverse events were recorded in any patient for the duration of the study. Conclusion Intravenous UST for maintenance is able to rescue up to 64% of patients who have failed on subcutaneous doses. 97% of patients continue intravenous UST treatment after one year with an excellent safety profile. UST levels increase fourfold.

N28 Stress and Inflammatory Bowel Disease – are there any differences during flare and remission?

Abstract Background Patients with Inflammatory Bowel Disease (IBD) often experience that stress has a negative effect on the disease. Studies have also shown a possible connection between stress and active IBD. This study aims to investigate the patients´ level of stress (both subjective and objective) in relapse and in remission. With this information we may determine if the levels of stress are higher in active disease compared to remission. Methods Inclusion criteria were having diagnosis with ulcerative colitis or Crohn`s disease, being over 18 years old, and having a flare in IBD. Measurements were made in cortisol in saliva and filling in the questionnaires Short Health Scale (SHS) and Perceived Stress Scale (PSS). All measurements were done at the beginning of the flare and then a second time when the patient was classified as being in remission. Flare and remission were determined by endoscopic examination and fecal calprotectin. Results A total of 20 patients completed the study. Median age was 45 years. A number of 17 (85%) had ulcerative colitis, and 12 (60%) were women. The levels of cortisol showed normal values both in active disease and in remission. Neither the results in PSS showed any differences between active and non-active disease. However, the results showed medium high values of stress in both measurements (table 1). SHS showed improvements in all four questions, but mostly in question 1 concerning symptoms. Conclusion No significant differences could be found in levels of stress when measuring cortisol and experienced stress in flare and in remission. However, the PSS showed that the participants had medium high levels of stress at both measurements. This could indicate a more constant stress in patients with IBD. A weakness in this study is the difficulty in measuring cortisol at the same time in each patient. Another weakness is the small population. There is still a need to examine the connection between stress and IBD. Concerning this study there is a wish to more closely investigate possible differences within each patient.

P1006 Assessing sexual health care needs in patients with inflammatory bowel disease

Abstract Background Optimal care of inflammatory bowel disease (IBD) should encompass both physical and mental health. Sexual health is often overlooked, despite contributing significantly to patient quality of life. This study aims to further characterise the impacts of IBD on sexual health using an IBD specific scale and assess patient interest in accessing relevant expertise. Methods An electronic survey was emailed to patients with IBD at a tertiary public hospital using REDCap. Assessment of disease severity was based on clinical disease indices: Harvey Bradshaw Index (HBI) for patients with Crohn’s disease (CD); and the Simple Clinical Colitis Activity Index (SCCAI) for patients with ulcerative colitis (UC). The survey also contains de-identified demographic data, basic information about the participant’s IBD and questions derived from both the validated IBD-Specific Female Sexual Dysfunction and IBD-Male Sexual Dysfunction Scales. Comparisons of patient responses from those with clinically active versus inactive disease were made using Fisher’s exact test. Analysis was exploratory and no correction for multiple comparisons was made. Results A total of 101 participants took the survey, including 53 females and 48 males which comprised of 38 patients with UC, 57 with CD, three with indeterminate colitis (and three unsure of diagnosis). Age ranged from 18 to 81 years old with a median of 38; 90% of patients had a disease duration of at least 2 years. Patients with CD recorded a median HBI of five (interquartile range three to nine). Patients with UC recorded a median SCCAI of two (interquartile range one to four). Patients with clinically active CD trended toward more significant sexual dysfunction than those in remission across all domains in the sexual dysfunction scale. Patients with active CD were more likely to report that their disease had prevented engagement in sexual activity in the past year (p=0.04) and more likely to be afraid to participate in sexual activity (p=0.01) compared to those in remission. Patients with active UC were more likely to report that pelvic pain affected sexual activity (p=0.03) compared to those in remission. Regarding seeking additional support, 47% of all patients expressed interest in gaining assistance though only 20% have attempted to seek this advice. 36% of participants would wish to be contacted by their treating team if a sexual health service became available at their hospital. Conclusion Patients with more active IBD were more likely to report that their illness negatively impacts their sexual health. 74% of participants reported interest in accessing expert advice regarding sexual health, highlighting the need for services specifically addressing sexual health for IBD patients.

OP04 Endoscopic healing in paediatric IBD perpetuates a persistent signature characterized by pathogenic Th17 cells and tissue-associated molecular and microbial drivers of disease

Abstract Background Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBD) in adults and paediatric patients. However, EH may not represent disease clearance. Hence, risk of relapse remains high and treatment discontinuation after reaching EH often results in disease exacerbation. We aimed to identify persistent cellular, molecular and microbial drivers of IBD under EH and longitudinally collected endoscopic biopsies from paediatric patients for analysis of single T-cell and bulk transcriptomics as well as mucosa-associated microbiota. Methods We followed disease trajectories of paediatric IBD patients treated according to international guidelines and collected mucosal biopsies from the terminal ileum (TI) and sigmoid colon (SC) at baseline (T1) and after approximately 3-12 months (T2) to assess EH. Non-IBD controls showed no macroscopic or histologic signs of inflammation. Host RNA and bacterial DNA were simultaneously extracted from single biopsies for bulk RNA-seq, and 16S rRNA seq. A second biopsy was used for isolation of lamina propria mononuclear cells (LPMCs), followed by CD45+, CD3+ cell sorting and single T-cell analysis (10X Genomics). Data were quality controlled and integrated. Results 217 biopsies (135 simultaneous extraction of host RNA and bacterial DNA; 82 single T-cell analysis) from 32 paediatric IBD patients (mean age 13 ± 3.5 years, 21 Crohn’s disease [CD], 11 ulcerative colitis [UC]; T1 = 32, T2 = 32, T > 2 = 6) and 5 non-IBD controls were analysed. Time between T1 and T2 averages 40 ± 22 weeks. At baseline, 15 patients (14 CD, 1 UC) were newly diagnosed and 31/32 patients had active mucosal inflammation. Twenty-two patients (71%) achieved EH at T2 (SES-CED ≤2 and absence of ulcerations), mostly on anti-TNF therapy. One patient (EH at T1) experienced relapsing disease within 10 weeks after discontinuing medication. In the bulk RNA-seq, we identified 299 differential expressed genes (DEGs; corrected p-value <0.05, FC >2.0), such as DUOX2, SAA2-SAA4, FCGR3B and NOS2, that are associated with active IBD and remained upregulated in EH in contrast to non-IBD controls. In addition single cell analysis revealed an IBD-specific pathogenic Th17 cluster that continued to exist in EH and showed high correlation with top DEGs after data integration. 16S rRNA gene seq highlighted highly individual mucosa-associated bacterial profiles and a reduced α-diversity in active and EH compared to non-IBD controls. Conclusion A persisting IBD signature in EH reflects ongoing cellular, molecular and microbial activity in comparison to non-IBD controls despite EH and mucosal regeneration. These markers may provide targets for future or sequential therapies.

DOP45 Blood-derived neutrophils give rise to differentially activated populations in the mucosa of active Inflammatory Bowel Disease patients

Abstract Background Infiltration of neutrophils is the main histological feature in active inflammatory bowel disease (IBD). Recent data suggests that tissue- and tumour-infiltrating neutrophils can adopt remarkably different phenotypes with potentially different functions. However, the heterogeneity of this population in IBD remains unknown. Methods Single-cell RNA sequencing (scRNA-seq) data was generated from colonic biopsies of 92 individuals including 6 healthy controls (HC), 36 inactive IBD, 19 active Crohn’s disease (CD) and 31 active ulcerative colitis (UC) patients. Neutrophils (6038 cells) found in the inflamed colon of CD and UC patients were analysed using a curated pipeline in Seurat (v4.0.2)1. Posterior analysis included the FindAllMarkers function (differentially expressed genes), Jaccard index similarity and the AddModuleScore function (comparisons with literature-described neutrophils), Monocle3 algorithm (developmental trajectory) and clusterProfiler (v3.0.4; enrichment and pathway analysis). For in vitro stimulation, neutrophils were isolated from the blood of HC donors (n=4) using a double Ficoll gradient 1. Cells and supernatants were analysed for qPCR and ELISA determinations. Results We identified 6 different clusters/states of colonic neutrophils (Figure 1A). In agreement with our previous results1 we found a population of S100A12/S100A8/S100A9 neutrophils (N0), IFN-response neutrophils (N3) and CCL3/CCL4 neutrophils (N2), in addition to N1.1 and N1.2 neutrophils. N3 neutrophils were enriched in the inflamed colon of CD patients compared to UC (17.2% vs 5.8%, p-value= 0.0021; Figure 1C). Comparative analysis with published datasets revealed that N0, N1.2 and N3 resemble populations of neutrophils found in blood2,3. In contrast, N1.1 and N2-like clusters showed some similarity to umbilical cord blood3 and tumour-infiltrating neutrophils4. Trajectory analysis, originating from N0 (peripheral-like) neutrophils, showed two potential branches of differentiation, with N1.2 leading towards N3 (IFN-response) and N1.1 differentiating into N2 (CCL3) neutrophils (Figure 1B). Finally, pathway analysis showed that N2 neutrophils presented enriched gene expression of the TNF signalling pathway, and together with the N1.1 state, an enrichment of the IL1β signalling pathway as well. In vitro experiments revealed that TNF, IL1β and LPS can all induce expression of CCL3 and CCL4, top differentially expressed genes of N2 neutrophils. Conclusion We show that active IBD is associated with a highly heterogeneous population of infiltrating neutrophils. Some of them resemble neutrophils in peripheral blood, while others most likely differentiate in response to inflammatory cues present in the colon of active IBD patients.

P569 Persistence and safety of upadacitinib in Crohn’s disease and ulcerative colitis in real life: results from a Spanish nationwide study

Abstract Background Upadacitinib (UPA) has demonstrated its efficacy in patients with inflammatory bowel disease (IBD) in clinical trials. However, these results may differ from those achieved in clinical practice. Thus, persistence and safety should be analysed in a real-world scenario. Main aim: to evaluate the persistence of UPA in real life, both in Crohn’s disease (CD) and ulcerative colitis (UC). Secondary aims: to assess the effectiveness and safety of UPA. Methods Multicentre, retrospective study of IBD patients who received UPA for IBD in clinical practice. Persistence was calculated from the date of the first dose to the date of the last dose of UPA. For effectiveness assessment, only patients with active IBD at baseline were considered. Active disease was defined as Harvey-Bradshaw index >4 in CD, and partial Mayo score >2 in UC. Negative imputation method was used to deal with missing data. Cox regression and logistic regression analyses were used to identify predictive factors of treatment persistence and effectiveness, respectively. Results One hundred patients from 34 centres were included, 68 with CD and 32 with UC. All patients had been previously exposed to biologics (median 4, IQR 3-4), and 26% to JAK inhibitors (78% in UC); 37% of them were on steroids at baseline. Regarding UPA survival, 81% of patients remained on UPA at month 6, and 66% at month 12 (figure 1). Loss of response was observed in 34% per patient-year of follow-up. Dose intensification was required in 18%, 72% of whom responded clinically. Finally, 23 patients interrupted UPA during the follow-up. Age below 40 at UPA start and CD were associated with higher risk of UPA withdrawal (HR 2.4; 95%CI:1.0-5.7 and HR 3.7; 95%CI:1.0-12.9, respectively). Seventy-eight patients had active disease at baseline and were considered for the effectiveness analysis. Short-term clinical remission was achieved in 51%, 59% and 64% at week 4, 8 and 12; focusing on the type of IBD, clinical remission was achieved in 79% of UC vs. 54% of CD (p=0.03) at week 12. In the long-term, 53% and 42% remained in clinical remission at months 6 and 12. Clinical remission in patients exposed to JAK inhibitors was achieved in 75% and 79% at week 8 and 12, respectively; and in the long-term, in 54% and 55% at months 6 and 12. A total of 41 patients (41%) presented at least one adverse event (Table 1). Conclusion In the largest real-life cohort of IBD patients treated with UPA, the proportion of patients maintaining UPA at 12 months seems relatively high, regardless of prior exposure to JAK inhibitors. UPA seems to be effective in inducing and maintaining clinical remission, both in CD and in UC. The safety profile was similar to that previously described.