Cohort Of Inflammatory Bowel Disease Patients Research Articles

Effectiveness and safety of GLP-1 agonist in obese patients with inflammatory bowel disease.

Obesity affects many patients with inflammatory bowel disease (IBD). Glucagon-like peptide (GLP)-1 agonists are a promising therapy for obese patients. However, there is a lack of evidence of the use of these drugs in IBD populations. We investigated the efficacy and safety of GLP-1 agonists in a cohort of obese patients with IBD. We analyzed a cohort of consecutive IBD patients who received GLP-1 agonists indicated for treating obesity between 2019 and 2021. The GLP-1 agonists included were semaglutide 1.0 mg or liraglutide 3.0 mg. The coprimary endpoints were the percentage of change in body weight from baseline to 6 months and a weight reduction of 5% or more at 6 months. In addition, we reviewed the safety profile of GLP-1 agonist therapy and its impact on the IBD course. We included 16 obese patients with IBD (9 CD and 7 UC). The median body mass index at baseline was 35 (32-37). The percentage of change in body weight was -6.2% (-3.4-(-8.5)) at 6 months, and a 5% or more weight reduction was achieved in 58.3% (7/12) of patients at 6 months. The most common side effect was nausea (13.3%), and one patient withdrew for diarrhea. IBD activity score did not change significantly during follow-up. Our results showed that GLP-1 agonists were effective and had a good safety profile in IBD patients. Most adverse effects were mild, and the IBD activity had no significant changes.

Epstein-Barr virus seroprevalence among inflammatory bowel disease patients in Saudi Arabia.

Seroprevalence of Epstein-Barr virus (EBV) in patients with inflammatory bowel disease (IBD) is variable based on geographic distribution. There are no published data on the seroprevalence of EBV in patients with IBD in Saudi Arabia. This study aims to assess the seroprevalence of EBV in patients with IBD in a tertiary center in Saudi Arabia. This is a retrospective chart review of patients ≥14 years of age with a confirmed diagnosis of IBD and known EBV status at our institution from January 1, 2018, to January 1, 2023. The primary outcome was the seroprevalence of EBV in IBD. Secondary outcomes included factors associated with EBV seropositivity and rates of EBV seroconversion in originally negative patients. A total of 150 patients were included (74.7% with Crohn's disease, median age 28 years [interquartile range 21-36.3]). EBV non-exposure was noted in 16.8% ( n = 25). The mean age was significantly lower in the EBV-naïve group at 26 ± 8.5 years compared to the EBV-exposed group at 31.2 ± 12.9 years ( P = 0.02). Seroprevalence of EBV was highest in patients >40 years of age (92.9%) and lowest in patients 14-25 years of age (78.2%). The rate of seroconversion in EBV-naïve patients was 16.7% after a mean follow-up time of 47.9 ± 46.3 months. In our cohort of IBD patients, 16.8% were naïve to EBV, and young age was a significant predictor of EBV non-exposure. Our data supports the practice of assessing EBV before initiating thiopurine therapy since EBV seroprevalence is not universal in our population.

A252 DRUG DISCONTINUATION AND PERSISTENT SYMPTOMS AMONG THE USERS OF BIOSIMILAR AND LEGACY ANTI-TNF DRUGS IN A REAL-WORLD CANADIAN IBD COHORT

Abstract Background Biosimilars and their reference originator drugs are increasingly used for inducing and maintaining remission in Inflammatory Bowel Diseases (IBD). Persistent symptoms, such as fatigue and joint pain, have been reported among individuals with IBD in remission. However, there is limited data on the persistence of symptoms among long-term users of biological therapy. Aims We report on drug discontinuation and persistent symptoms among a multicentre cohort of IBD patients 12 months after initiating anti-TNF originators or biosimilars. Methods We enrolled and followed individuals with IBD (ampersand:003E18 years) who initiated therapy with infliximab or adalimumab, bio-originators/biosimilars, between January 2019 and March 2023. We determined the rate of discontinuation of therapy, persistent symptoms, and quality of life (QoL) after 12 months. Difference in effect estimates (proportions and means) between the two groups (originators versus biosimilars) was determined. Results 181 individuals with IBD (CD = 58%, female = 46%, Caucasian = 85%) were enrolled. 62% were biologic-naïve at initiation. Of the 119 participants who completed a 12-month follow-up visit, about 19% (n = 34) discontinued drug use (all were infliximab users). Insufficient disease control was the most common reason for drug discontinuation (18.2%, n = 33). There was a significant reduction in the number of corticosteroid users at follow-up in both originator (rate ratio: 0.33, 95% confidence interval (CI): 0.16-0.49) and biosimilar users (rate ratio: 0.22, 95% CI: 0.14-0.30). With our limited power, we were unable to detect significant reductions in ER visits and hospitalizations in the first year after initiation of anti-TNF agents compared to that in the preceding year. The severity of pain/discomfort anywhere and the frequency of fatigue and anxiety/depression was not significantly reduced at 12 months in either of the groups. The percentage of those reporting moderate/severe abdominal pain was reduced among biosimilar users (46% to 20%; rate ratio of 0.26, 95% CI: 0.15-0.38), and originator users (28% to 13%, rate ratio 0.16, 95% CI: -0.02, 0.33). The proportion of those reporting rectal urgency at least some of the time was also reduced among both originators (30% at baseline to 9% at follow-up) and biosimilar users (33% to 17%). There was a significant improvement in QoL scores among both originator users (mean difference (MD) 13.0, 95% CI: 6.00-22.0) and biosimilar users (MD 10.0, 95% CI: 6.00-14.0) on the SIBDQ. This improvement was replicated on the EQ-5D only among biosimilar users. Conclusions Our study results suggest that even though the use of anti-TNF drugs leads to improvement in QoL, there may be no reduction in some symptoms, such as fatigue, anxiety, depression. Funding Agencies CIHR

A242 EPIDEMIOLOGICAL ASPECTS, RISK FACTORS, AND CUMULATIVE PREVALENCE OF EXTRAINTESTINAL MANIFESTATIONS IN INFLAMMATORY BOWEL DISEASE: RESULTS FROM A 7,150 PATIENTS’ COHORT IN A TERTIARY CARE CENTER

Abstract Background Canada is among the countries with a high burden of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) incorporate a spectrum of systemic IBD-accompanying conditions that are associated with a poorer quality of life, higher disease activity, and increased need for IBD-related surgery and treatment escalation. Aims We aimed to establish the all-time and cumulative prevalence of EIMs in a large cohort of IBD patients and assess the risk factors associated with EIMs in IBD. Methods We conducted a retrospective cohort study of 7,150 IBD patients followed at the Division of Gastroenterology, University of Alberta, diagnosed between 1954–2022, with 159,026 person-years follow-up. Data were obtained via manual chart review, from electronic medical records and administrative reporting systems. The EIMs included ophthalmological, musculoskeletal, urogenital, hepatobiliary, dermatological, and pulmonary. Univariate and multivariate logistic regression models and cumulative prevalence curves with the Kaplan-Meier analysis were used. Results Data of 3,910 CD and 3,240 UC patients (50.3% females, median age 48.0 (range 17-98 y.o.)) were analyzed. Over one-third of IBD patients (34.0%) had at least one EIM. The EIMs prevalence did not differ significantly between CD and UC (34.8% vs. 33.0%; p=0.112). In CD patients, the most common EIM was scleritis/episcleritis (10.9%), followed by nephrolithiasis (10.1%) and axial spondyloarthritis (7.3%). The UC patients most frequently had scleritis/episcleritis (10.3%), primary sclerosing cholangitis (8.4%) and nephrolithiasis (7.8%). In CD patients, age at diagnosis ≥40 y.o. (OR 1.77, 95%CI 1.33-2.37), disease duration ≥20 years (OR 2.28, 95%CI 1.62-3.21) and C-reactive protein≥8.0 mg/L (OR 1.46, 95%CI 1.01-2.12) were independent risk factors for EIMs (Fig.1a). Among UC patients, the following EIM risk factors were identified: disease duration ≥20 years (OR 1.63, 95%CI 1.19-2.22), obesity (OR 1.40, 95%CI 1.04-1.89), vitamin B12 deficiency (OR 1.64, 95%CI 1.12-2.40), and need for IBD surgery (OR 1.63, 95%CI 1.13-2.34) (Fig.1b). Cumulative probability of EIMs in CD vs. UC was 8% vs. 12%, at 10 years, 27% vs. 38% at 20 years, and 51% vs. 59% at 30 years since diagnosis (Log-rank, pampersand:003C0.001) (Fig.1c). Conclusions Over one-third of IBD patients have at least one EIM and their pattern and cumulative prevalence varies substantially between CD and UC. It is important to be aware of the EIMs’ risk factors to recognize them early and provide adequate management aiming to decrease morbidity and mortality and improve the quality of life of IBD patients. Fig. 1a. Associations between demographic, phenotypic and clinical IBD features and EIMs among CD patients - results of the multivariate logistic regression analysis. Fig. 1b. Associations between demographic, phenotypic and clinical IBD features and EIMs among UC patients - results of the multivariate logistic regression analysis. Fig 1c. Cumulative prevalence of EIMs in CD (grey line) vs. UC (pink line). Funding Agencies None

P1135 Increased prevalence of migraine in women with inflammatory bowel disease: a cross-sectional study

Abstract Background Data on a possible comorbidity between migraine and inflammatory bowel disease (IBD) are controversial. Our aim was to determine the prevalence of migraine in a cohort of IBD patients. Methods We performed a cross-sectional study in a cohort of IBD patients at our IBD Unit. After informed consent, consecutive IBD patients aged 18-64 years were interviewed. Those who admitted a history of headache in the last year were asked to answer the three questions of the id-Migraine validated questionnaire. Those who answered "yes" to the three of them were classified as "definite" migraine and those who answered "yes" to two were classified as "probable" migraine. For all patients we collected demographic data, IBD subtype, disease duration, hospitalizations or surgeries and medical treatments. Migraine prevalence data of IBD patients were compared with reported local migraine prevalence data at 18-65 years of age (Cephalalgia 2011; 31: 463-70). Statistical analysis was done with SPSS®. Results We interviewed 283 consecutive IBD patients aged 20-65 years. Main characteristics of this population are described in table 1. Headache was present in 176 (62.2%) patients. Of those, 59 (20.8%; 95% CI 16.1-25.5%) met migraine criteria either definite (n= 33; 11.7%; 95% CI 8-15.4%) or probable (n=26; 9.2%; 95% CI 5.8-12.5). When divided by gender, 12 men (9.6%; 95% CI 4.4-14.) and 47 women (29.8%; 95% CI 22.7-36.9%) met migraine criteria. The prevalence of migraine was significantly increased in IBD patients (20.8%) versus that reported for our general population (12.6%; p= 0.0001). By sex, these differences remained significant in women (29.8% in IBD versus 17.2% in our general population; p=0.0001), but not in men (9.6% in IBD vs 8.0%; p=0.45) (Figure 1). By IBD subtypes, there were no significant differences between CD and UC in migraine prevalence (20.7% vs 19.6% respectively; p=0.58). Regarding IBD characteristics, men with total migraine had higher biologic treatment (66.7% vs 44% p=0.032), and immune mediated inflammatory diseases or extraintestinal manifestations of IBD (33.3% vs 9.6% p=0.0016), but the number of men with migraine was low (12). These associations were not significant for women, nor overall population (p>0.05). Additionally, we did not find any significant association in total migraine patients in the use of mesalazine, disease duration, immunomodulators, surgeries or hospitalizations, neither in total number of patients nor stratified by sex. Conclusion Migraine prevalence is higher in patients with IBD than general population, which is a further example of the bidirectional gut-brain interaction. The fact that this association was stronger for women suggests an influence of sex-related factors. ISCIII PI20/01358 and FEDER.

P360 Prevalence and risk factors for fatigue in patients with inflammatory bowel disease and endoscopic healing

Abstract Background Fatigue is a frequent symptom among patients with inflammatory bowel disease (IBD). While the recent STRIDE II international guidelines consider disability-free and normal quality of life as therapeutic targets, the degree of endoscopic healing required to limit fatigue is unknown. The aim of this study was to investigate the prevalence of fatigue and its determinants in a cohort of IBD patients with endoscopic healing. Methods We conducted a single-center cross-sectional study between January 2019 and June 2023. All consecutive IBD patients with endoscopic healing Crohn's disease (CD, CDEIS <4) and ulcerative colitis (UC, Mayo ≤ 1) were assessed for disability (IBD-disk) the day of the colonoscopy. Fatigue and severe fatigue were defined by an IBD-Disk energy subscore >5 and >7, respectively. Results 166 patients were included, of whom 64% (107/166) had CD. The majority of patients were treated with anti-TNF (91/166, 55%), half of them in combination therapy (44/166). The prevalence of fatigue and severe fatigue were 39% (65/166) and 23.5% (39/166) respectively, with no significant difference between CD and UC (p=0.59). The prevalence of fatigue in patient with partial endoscopic healing (Mayo 1 and CDEIS>0 and <4)) and with complete healing (Mayo 0, CDEIS 0) was 44.4% (24/54) and 36.6% (41/112) p =0.424.In multivariate analysis, factors associated with fatigue were female gender (OR=4.2, [1.1; 16.5], p= 0.040), presence of joint pain (OR=4.36, [1.0; 18.2], p= 0.04), sleep disturbance (OR =26.2, [5.5; 124.4], p <0.0001). Younger age (OR=0.95, [0.9; 0.99], p= 0.023) was associated with a significantly lower risk of fatigue. In multivariate analysis, severe fatigue was associated with female gender (OR=3.2, [1.1; 9.2], p= 0.026), the presence of joint pain (OR=2.9, [1.1; 8.1], p= 0.037) or sleep disorders (OR =11.3, [3.6; 35.9], p <0.0001). Conclusion One third of IBD patients with endoscopic healing suffer from fatigue. Female gender, arthralgia and especially sleep disorders are risk factors for fatigue. These results argue in favor of a holistic management of IBD patients.

P1133 Relative survival and cause-specific mortality of a Chilean Inflammatory Bowel Disease cohort

Abstract Background In the past two decades, multiple studies have shown an improvement in outcomes of inflammatory bowel disease (IBD) patients including a decreasing mortality associated with new treatments, surveillance, and healthcare support. There are no large studies in Latin-American countries addressing survival and death causes in IBD patients. We aimed to assess relative survival (RS) and causes of death in Chilean IBD patients. Methods IBD patients treated in a tertiary reference centre (Pontificia Universidad Católica of Chile, Santiago, Chile) since January 1990 were included in a local database. Death certificates were analysed to obtain the date and specific cause of death. The recorded time started on the date of definitive diagnosis and lasted until death or censoring on December 31st, 2020. The survival of IBD patients was compared with the life expectancy of the Chilean general population based on official life tables collected in the Human Mortality Database (www.mortality.org). The RS was computed using the Ederer II method implemented in the RELSURV package of the R software. A RS greater than 1.0 indicates that the analysed cohort has a higher survival than the expected survival of the reference population for the same age, sex and date at which age was coded. Inclusion of 1.0 within 95% CI indicates no difference between observed and expected survival. Data were also expressed graphically as the observed cumulative survival curves over time and the 95% confidence interval (CI) and compared to the reference population. Results We included 1,289 IBD patients with a media age at diagnosis of 35.9±14 years, 40.9% males and a follow-up of 22,525 patients-year. Ulcerative Colitis, Crohn’s disease and IBD unclassified patients comprised 50.2%, 43.1% and 6.7% of the cohort, respectively. A total of 106 patients (8.9%) died during the study period. Compared with the general population, the survival of IBD patients was higher (RS = 1.04; 95% CI: 1.02-1.07) at 20 years of follow-up (Table and Figure). This higher RS in IBD patients was observed in males and females, as well as CD patients and IBD patients older than 40-year-old (Table). The main causes of death in IBD patients were cancer (34%), infections (27.7%) and cardiovascular diseases (21.3%). Conclusion Compared to the general population, a higher long-term survival was observed in this large cohort of Chilean IBD patients. These findings may be due to a closer surveillance of this group of patients. Causes of death mirrored those in previously reported cohorts; therefore, a special care should be pay on their prevention in Latin-American countries as well.

P062 Characterization of UC1 and UC2 patients: towards personalized medicine in Ulcerative Colitis

Abstract Background Ulcerative colitis (UC) is a highly heterogeneous chronic inflammatory bowel disease (IBD) that primarily affects the colon. Although there are some available classifications, mostly based on clinical parameters, the lack of a molecular stratification prevents full comprehension of the diagnostic and prognostic heterogeneity of patients, and thus from correctly predicting their response to available treatments. We have recently developed an unbiased stratification of UC patients (UC1/UC2) based on their transcriptomic profiles (Czarnewski P; et al. Nature Communications, 2019), which holds great potential for the design of personalized medicine in IBD. However, further characterization is necessary to validate it and consolidate its clinical application. Methods To achieve this goal, we used bulk and single-cell RNA sequencing (sc-RNAseq) datasets from a prospective cohort of Swedish IBD patients to understand whether UC1 and UC2 are different diseases or states of the same disease, and to deeply characterize the cellular composition of UC1 and UC2 patients. In addition, we took advantage of murine spatial transcriptomics datasets of colonic tissues at steady state or during mucosal healing, to get insights into the spatiotemporal dynamics of UC1/UC2 transcriptional profiles. Results A longitudinal analysis of UC1/UC2 transcriptomic profiles as well as gene module analysis revealed that UC1 and UC2 profiles are fluctuant during the course of disease, eventually representing different stages of the same disease. scRNAseq analysis allowed us to identify specific cell types characterizing UC2 patients.[FC1] Finally, while genes defining UC2 patients distributed homogenously within the murine mouse colon at steady state and during mucosal healing, UC1 genes primarily mapped within damage/regeneration regions. Conclusion This study details the differences in immune cell composition and molecular pathways in UC1 and UC2 patients, contributing to a more comprehensive understanding of the new molecular stratification system we have developed for ulcerative colitis patients.

N09 Transition Success Score as a valid quantitative measure to evaluate the effect of transitional care in IBD patients

Abstract Background Transition programs are designed to prepare adolescent patients with inflammatory bowel disease (IBD) for their new role in adult care. The outcome of these programs is often assessed in a qualitative way (patient satisfaction, quality of life, disease burden). However, there is no quantitative measure to evaluate the effect of a transition program. The aim of this study was to develop and validate a Transition Success Score (TSS) by the identified key components of successful transition. Methods The TSS was developed through an international Delphi consensus study, with the expert panel of pediatric and adult healthcare providers and patients. The top 10 key outcome items associated with success of transition were collated into one questionnaire. In every round, the minimum response rate required was 80%, and a consensus of more than 80% was necessary for each item. After four rounds of discussion, a consensus was reached on the initial version of the TSS. This score included seven items for adult healthcare providers to evaluate the patient's disease management behavior, including shared decision making, therapy adherence, and appointment attendance. Additionally, two items concern patient and parent experience concerning the transition period. The TSS was subsequently employed and validated in a prospective multicenter cohort of young adult IBD patients, who made the transfer 9-15 months ago, in the Netherlands. Results In seven hospitals, 160 IBD patients (median age 19.05, male 48.8%, Crohn's disease 56%, median age at diagnose 13.97) completed the TSS, at 9-15 months after transfer to adult care. Hypothesis testing for construct validation revealed significant association of characteristics related to transition care such as knowledge (RTT), independence (TRAQ), and quality of life (IBDQ) (p=<0.005). In addition, Rasch analysis for structural validation showed that the TSS was discriminating at lower levels of transition success (Figure 1). Internal consistency, as measured by Cronbach alpha, was acceptable at 0.64. TSS was significantly lower in patients with high disease burden, exacerbation within the first year after transfer and parental dependency. Also, TSS was lower in certain patient profile types, characterized as either "laid back, nonchalant" or "worried and uncertain". Conclusion The Transition Success Score (TSS) can serve as a quantitative measure to help identify IBD patients who did not have successful transition to adult care. TSS can be utilized for identifying factors that impact successful transition and for measuring the effect of various transition programs in IBD.

P632 Isolation of a novel metalloproteinases transcriptional signature with robust anti-TNF therapy predictive power in patients with Ulcerative Colitis

Abstract Background Anti-TNF agents were the only biologic for Inflammatory Bowel Disease (IBD) patients. However, new drugs targeting α4β7 integrin, IL-12/IL-23, and janus kinases were added to the IBD therapeutic armamentarium. Anti-TNFs are first-line biological agents in our country, and for that reason, the discrimination of patients who will be refractory of those therapies before treatment is relevant to prevent IBD patients from the exposition to multiple therapeutic failures. Therefore, we wanted to isolate robust and reproducible transcriptional markers able to specifically predict the response to anti-TNF therapy, which will contribute to targeted prevention, improve individual outcomes and decrease therapy expenditures. Methods We analysed publicly available microarray and RNAseq datasets of colon biopsies (GSE12251, GSE16879 and GSE73661) and whole blood cells from different cohorts of patients with Ulcerative Colitis (UC) (GSE191328). R package was used to perform the differential expression analyses and calculation of receiver operating characteristic (ROC). Cytoscape software and Morpheus (broadinstitute.org) was used to perform network data integration and visualization. Also, we used our local cohort of UC patients to further validate our results by RT-qPCR (n=21). Results We isolated a transcriptional signature composed of eight metalloproteases (MMPs) with high association with disease activity. Most of the transcripts of that signature were significantly upregulated in colon biopsies of non-responder patients to anti-TNFs before treatment in three different microarray datasets, but not in vedolizumab-treated patients. ROC curves of the different MMPs showed variability in the correlation to anti-TNF response among the different datasets analysed. Only three out of eight MMPs were still showing robust predictive power with an area under the curve around of 80% when all dataset were combined. Interestingly, PBMCs isolated from our local cohort of IBD patients presented increased expression of those MMPs in refractory patients to anti-TNF therapy, confirming that these three MMPs have the highest predictive power both in colon tissue and in peripheral mononuclear cells. Conclusion Overall, our study revealed a novel and robust MMP-transcriptional signature associated with anti-TNF but not vedolizumab therapy response. Nevertheless, our results should be corroborated in independent cohorts of patients with UC to test their efficacy and sensitivity in the clinical setting. Our data definitively contribute to the change from a reactive approach to predictive, preventive and personalised medicine.

P189 Lifestyle and psychosocial factors in IBD; prevalence and patients’ perspective

Abstract Background Lifestyle and psychosocial factors impact mucosal inflammation and subjective well-being in Inflammatory Bowel Disease (IBD) patients. Better understanding of the relevancy of these factors within the IBD population, including prevalence and patients' perspective, may enhance systematic implementation of lifestyle interventions in regular care. This collaborative study with the Dutch patient organisation aimed to estimate the prevalence and patients’ perspectives on lifestyle and psychosocial factors in an outpatient cohort of IBD patients. Methods A multicentre cross-sectional study was conducted, enrolling IBD patients who utilized the remote monitoring platform myIBDcoach in 2022. Patients reported on clinical disease activity, lifestyle and psychosocial factors on this platform. A nationwide online survey was distributed by the Dutch patient organisation for IBD in April 2022 to assess patients’ perspectives regarding the impact of lifestyle and psychosocial factors on intestinal complaints, motivation to make changes, and need for and satisfaction with support in this regard from the hospital. Results In the multicentre myIBDcoach cohort (n=460), 16.3% adhered to a specific diet (Table 1). Two third (67.4%) did not comply with the Dutch healthy exercise norm and smoking was prevalent in 9.3%. About one-third experienced at least regularly poor sleep (33.8%), at least occasionally emotional distress (33.9%), and high perceived stress (36.7%). In the nationwide survey (n=1148), most (58.3-75.7%) patients believed that stress, unhealthy food, poor sleep, minimal or no exercise, and symptoms of anxiety and depression could lead to intestinal complaints (Fig. 1A). Around 70% of patients were taking action or were motivated to do so regarding their diet, stress, and physical activity (Fig. 1B). About 30% had no intention of addressing social support, and 22.8% were unwilling to change their alcohol use. Less than one-fifth received support from the hospital regarding these various factors (Fig. 1C). When support was received, most patients expressed satisfaction. Although desired, approximately 20% lacked support concerning stress, physical activity, diet, and sleep. Conclusion There is considerable scope for improvement in lifestyle and psychosocial factors among individuals with IBD, highlighting the need for systematic integration of these factors into clinical care. From the patient's viewpoint, widespread recognition of the impact of these factors emerged, with most expressing openness to initiating changes across various areas. These insights emphasize the potential for implementing targeted interventions, particularly in areas where patients indicated a need for additional support.

P903 Persistence, efficacy and tolerance of subcutaneous Infliximab after switch from intravenous infliximab in IBD patients in remission: one-year results from a multicenter prospective cohort

Abstract Background Prospective data after switch from intravenous infliximab (IV-IFX) to subcutaneous (SC-IFX) in Inflammatory Bowel Disease (IBD) is needed. The aim of this prospective multicenter cohort was to describe SC-IFX persistence, efficacy and tolerance after switch from IV-IFX. Methods IBD patients in steroid-free clinical remission (defined by a Harvey Bradshaw index (HBI) ≤ 4 for Crohn’s disease (CD), and partial Mayo Score (PMS) ≤ 2 with no subscore >1 for ulcerative colitis UC)) for at least 6 months on IV-IFX, were enrolled in this prospective cohort if they switched to SC-IFX. Clinical (HBI, PMS), biological (CRP, fecal calprotectin (FC)) and pharmacokinetic evaluations were performed at 3, 6, 12 and 24 months from switch. In case of clinical or biological relapse, as per physicians’ judgement, SC-IFX dose could be increased, or drug changed. Primary endpoint was SC-IFX persistence at week 48 (W48). Secondary endpoints comprised steroid-free clinical remission at W48, proportion of patients who switched back to IV-IFX, HBI and PMS changes and FC, CRP and infliximab serum level changes. Statistical comparisons were performed using Fisher’s exact test. Survival without treatment discontinuation was analysed using a Kaplan-Meyer curve. Results 426 patients were included (72.4% CD, 45.1% female, median age 37 years), with a median time from diagnosis of 143 months in CD, 154 months in UC. At baseline, 74% were on IV-IFX standard dose (5mg/kg every 8-week) and 68 (16%) received combination therapy with an immunosuppressant. Among patients with complete data until W48, SC-IFX persistence was 95.3% (CI, 93.2-97.5). 319/367 (89.9%) were on steroid-free clinical remission. From baseline to W48, median HBI and PMS scores were 0, CRP did not change significantly, median FC rate decreased significantly from 52µg/g to 36 µg/g (p=0.015). Mean Infliximab trough level at inclusion was 7.97µg/mL, while it reached 17.96µg/mL at W48 (p<0.0001). 23 (5.4%) patients had an increase of SC-IFX dose and 22 (5.2%) stopped SC-IFX, of which 6 patients switched back to IV-IFX. SC-IFX persistence was significantly higher among patients treated with SC-IFX monotherapy (98.8%) as compared to those on combination therapy (90.0%) (HR=0.14 [0.04-0.53]). Adverse events were reported in 181/426 patients (42.4%), 12 led to treatment discontinuation. Nine severe adverse events (2%) were reported. Three patients (0.7%) had IBD-related surgery and 8 (1.9%) IBD-related hospitalization. Conclusion In this large multicenter prospective cohort of IBD patients in remission, one-year persistence of SC-IFX after switch from IV-IFX was 95.3%, supporting excellent efficacy and tolerance of SC-IFX.

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.

P883 Impaired long-term quantitative cellular response to SARS-COV-2 vaccine in thiopurine-treated IBD patients

Abstract Background SARS-CoV-2 mRNA vaccine induces a robust immune response in most patients with inflammatory bowel disease (IBD). However, humoral short-term response appears to be reduced in patients receiving anti-TNF agents or tofacitinib, even after booster doses. Data on long-term immune response is limited. We aimed to assess short and long-term humoral and T-cell response to SARS-CoV-2 mRNA vaccine in IBD patients receiving anti-TNF and/or thiopurines. Methods A prospective, longitudinal study was carried out in IBD patients receiving thiopurines, anti-TNF mono, or combo therapy. Patients had received between 2 and 4 doses of mRNA SARS-CoV-2 vaccine. Cellular and humoral response to the vaccine was assessed by serum interferon-gamma release assay (IGRA) and antibody SARS-CoV-2, respectively. We defined short-term response as humoral and T-cell response six weeks after the second vaccine and long-term response 6 to 12 months after that. Primary outcome was to determine if T-cell immune response differs in IBD patients receiving anti-TNF versus thiopurines. Results We recruited 148 IBD patients, 57 treated with anti-TNF monotherapy, 53 with anti-TNF combo, and 38 with thiopurines. Short-term T-cell and humoral responses were similar between the three groups. However, long-term T-cell concentration was reduced in thiopurine-treated (median 0.7 UI/mL [0.26-2.35]; p<0.05) and anti-TNF-combo-treated patients (median 0.4 UI/mL [0.22-1.13]; p<0.01) when compared to anti-TNF monotherapy (median 2.2 UI/mL [1-4.15]). Multivariate analysis showed that anti-TNF monotherapy (-0.93, p<0.05) and decreased time between vaccination and T-cell response measurement (0.04 [.00005-.078] p=0.05) were associated with increased T-cell concentration long-term when compared to the other groups of patients. Conclusion We found a diminished long-term quantitative cellular response in our cohort of IBD patients vaccinated for SARS-CoV-2 treated with thiopurines or combo therapy compared with anti-TNF monotherapy. These findings highlight the recommendation to receive booster doses in IBD patients, specially those receiving thiopurines.

P921 Maintenance of clinical, biochemical and transmural remission in inflammatory bowel disease patients switching from intravenous to subcutaneous infliximab

Abstract Background Subcutaneous (SC) infliximab (IFX) effectively maintains biochemical, clinical and endoscopic remission in inflammatory bowel disease (IBD) with a comparable safety profile to intravenous (IV) formulation. Transmural healing is considered a desirable long-term treatment endpoint in IBD, especially in Crohn’s disease (CD). Whether switching from intravenous to SC-IFX effectively maintains transmural remission in IBD is still unknown. Methods This is a preliminary report from a prospective multicentre cohort study on IBD patients in clinical and endoscopic remission on IV-IFX treatment switched to SC-IFX. Enrolled patients were followed-up for 12 months, with fecal calprotectin (FC), C-reactive protein (CRP), infliximab trough levels and anti-drug antibodies (ADAs) measured at baseline, at 3, 6 and 12 months. Intestinal ultrasound (IUS) was performed at baseline and every six months. At month 12 a full colonoscopy was performed for mucosal healing assessment. Remission rates and safety profile were subsequently recorded. T-Test and ANOVA for mean comparisons and Kaplan-Meier estimates were used for survival curves. Results 43 IBD patients (69% males) were enrolled, 58% with CD, of whom 52% reported a history of perianal disease. Median disease duration and IFX therapy were 6 (IQR 3-12) and 5 (IQR 2-9) years, respectively. During a median follow-up of 311 (range 122-489) days, clinical remission rate was 98% (Harvey-Bradshaw Index <5 and Mayo score <2). No reactivation of perianal disease was reported. FC and CRP remained stable at each time point (p> 0.05). The median baseline infliximab level was 10.02 ( range 0.1- 41.84) ug/ml. Undetectable infliximab levels (<1 ug/ml) and positive ADAs were found in 6 and 14 patients, respectively; at 3 months, a significant increase in infliximab levels (mean increase 27.5 ng/ml; ± 12.5 SD; p< 0.001) and a progressive decrease of ADAs titer were observed, despite unchanged SC-IFX dose. At baseline, all patients had normal bowel wall thickness (i.e. ileum ≤ 3mm, colon≤4 mm) and a Limberg score ≤1at IUS; reactive lymphadenopathies were reported in 5 patients and a mild abdominal effusion in 1. No significant changes were shown during follow-up. Mild endoscopic activity was found in 2 out 30 patients who performed follow-up endoscopy. Regarding safety profile 12 mild infectious events, 2 mild cutaneous injection site reaction and 1 non-IBD related hospital admission were observed. Conclusion Switching from IV to SC infliximab in a selected cohort of IBD patients confirmed to be safe and effective in maintaining clinical, biochemical, and transmural remission. IUS is a useful, non-invasive and low-cost tool for periodic disease assessment in this subset of patients.

P160 Integrative transcriptional analysis to identify predictive biomarkers for IBD severity and subtyping

Abstract Background Conventional diagnostic strategies for Inflammatory Bowel Diseases (IBD) heavily rely on invasive biopsy procedures and subjective questionnaires, thereby introducing intrinsic limitations in the context of precision medicine. By understanding the molecular mechanisms behind IBD disease biology, we aim to identify certain signalling pathways relevant for epithelial tissue regeneration under chronic inflammation conditions. Methods To address these limitations, we compared gene expression in a large cohort of IBD patients, utilizing the IBD Plexus database (Crohn’s & Colitis Foundation, US) as well as other publicly available datasets. We further validated our results derived from the transcriptional programs by using patient derived advanced 3D-organoid models (Hospital of Nottingham, UK). These models, derived from ulcerated and normal tissue regions of IBD patients, serve as a sophisticated platform for robust validation, bridging the gap between molecular insights and clinical applications. Results Our primary objective was to discern putative biomarkers that are capable of effectively stratifying IBD subtypes. We further identified the genes that were upregulated exclusively in each subtypes and the gene signature that is elevated in inflamed samples compared to non-inflamed samples. We found that either the chemokine and interleukin (IL-17) signalling pathways which have known roles in recruitment of immune cells thereby perpetuating chronic inflammation and several key chemokines influence the integrity of the epithelial barrier function and regeneration. We are also analysing non-invasive biomarkers by using samples such as blood, plasma and stool and employ machine learning methods to correlate with established clinical indicators such as sCDAI, PRO2, PRO3, and MAYO categories. Conclusion Hence, in identifying specific targets we can introduce novel therapeutic strategies to mitigate inflammation and restore integrity of the gut epithelial barrier. With this research we aim to improve the current IBD diagnostics landscape as well propels it towards precision medicine by offering precise subtyping and predictive markers for disease severity, ultimately contributing to more personalised and effective therapeutics interventions.

Heterologous expression of the human wild-type and variant NaV 1.8 (A1073V) in rat sensory neurons.

Silent inflammatory bowel disease (IBD) is a condition in which individuals with the active disease experience minor to no pain. Voltage-gated Na+ (NaV ) channels expressed in sensory neurons play a major role in pain perception. Previously, we reported that a NaV 1.8 genetic polymorphism (A1073V, rs6795970) was more common in a cohort of silent IBD patients. The expression of this variant (1073V) in rat sympathetic neurons activated at more depolarized potentials when compared to the more common variant (1073A). In this study, we investigated whether expression of either NaV 1.8 variant in rat sensory neurons would exhibit different biophysical characteristics than previously observed in sympathetic neurons. Endogenous NaV 1.8 channels were first silenced in DRG neurons and then either 1073A or 1073V human NaV 1.8 cDNA constructs were transfected. NaV 1.8 currents were recorded with the whole-cell patch-clamp technique. The results indicate that 1073A and 1073V NaV 1.8 channels exhibited similar activation values. However, the slope factor (k) for activation determined for this same group of neurons decreased by 5 mV, suggesting an increase in voltage sensitivity. Comparison of inactivation parameters indicated that 1073V channels were shifted to more depolarized potentials than 1073A-expressing neurons, imparting a proexcitatory characteristic. These findings differ from previous observations in other expression models and underscore the challenges with heterologous expression systems. Therefore, the use of human sensory neurons derived from induced pluripotent stem cells may help address these inconsistencies and better determine the effect of the polymorphism present in IBD patients.

Switching from intravenous to subcutaneous infliximab and vedolizumab in patients with inflammatory bowel disease: impact on trough levels, day hospital visits, and medical expenses

Objective Subcutaneous (SC) infliximab (IFX) and vedolizumab (VDZ) have recently become available. We aimed to examine the impact of switching from intravenous (IV) to SC IFX and VDZ in patients with inflammatory bowel disease (IBD) on costs, the day hospital burden, trough levels, and clinical outcomes. Methods Our study comprised the cohort of IBD patients receiving IV IFX or VDZ at our hospital in 2022. We evaluated costs, day hospital visits, trough levels, biochemical markers, relapse rates, and self-report outcomes until Jun 30th 2023. Results Of 114 patients, 18 continued IV therapy, 80 were switched to SC therapy, and 16 were inductions. Eighty-eight (90%) remained in steroid-free remission with no difference between the IV or SC groups. The mean IFX trough level changed from 8.2 ± 4.5 µg/ml to 14.5 ± 5.9 µg/ml, p < 0.001, and the VDZ trough level from 14.7 ± 7.1 mg/ml to 26.5 ± 13.8 mg/ml, p < 0.001. The average yearly costs of infusions and injections per patient were 2 580 € and 7 482 € for IFX and 15 990 € and 13 101 € for VDZ. The annual reduction of day hospital visits was 6,9 per patient. Conclusions IV and SC IFX and VDZ are equally effective in maintaining remission in IBD, but SC administration reduces day hospital visits and results in higher trough levels. SC VDZ is less and SC IFX more expensive than IV therapy. Further studies are needed to assess optimal dosing and separate trough levels for SC therapy.

Knowledge, attitude, and practice of patients living with inflammatory bowel disease: A cross-sectional study

BACKGROUND Patients with inflammatory bowel diseases (IBDs) generally have poor knowledge, attitude, and practice of their disease, while the data from China are lacking. AIM To address this knowledge disparity among Chinese patients with IBD. METHODS This web-based, cross-sectional study was conducted on a cohort of IBD patients who visited the Second Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Their socio-demographic information and the knowledge, attitude, and practice scores were collected and estimated using a self-designed questionnaire. Pearson’s correlation analysis was used to determine the pairwise correlations among knowledge, attitude, and practice scores. A multivariate logistic regression analysis was further performed to determine the independent factors associated with their knowledge, attitude, and practice scores. RESULTS A total of 353 patients (224 males) with IBD completed the questionnaires. The mean knowledge, attitude, and practice scores were 10.05 ± 3.46 (possible range: 0-14), 41.58 ± 5.23 (possible range: 0-56), 44.20 ± 7.39 (possible range: 0-56), respectively, indicating good knowledge, positive attitude, and proactive practice toward IBD. Pearson’s correlation analysis showed that the knowledge score had significant positive correlations with the attitude score (r = 0.371, P &lt; 0.001) and practice score (r = 0.100, P &lt; 0.001). The attitude score had a significant positive correlation with the practice score (r = 0.452, P &lt; 0.001). Moreover, multivariate logistic regression analysis showed that aged 30-40 years [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.04-15.82, P = 0.043], middle school education (OR = 3.98, 95%CI: 1.29-12.33, P = 0.017), high school/technical secondary school education (OR = 14.06, 95%CI: 3.92-50.38, P &lt; 0.001), and junior college/bachelor’s degree and above education (OR = 15.20, 95%CI: 4.15-55.650, P &lt; 0.001) were independently associated with good knowledge. The higher knowledge score was independently associated with a positive attitude (OR = 1.23, 95%CI: 1.11-1.36, P &lt; 0.001). The higher attitude score was independently associated with proactive practice (OR = 1.20, 95%CI: 1.11-1.30, P &lt; 0.001). CONCLUSION Chinese patients with IBD might have good knowledge, a positive attitude, and proactive practice toward their disease. However, a small number of specific items require education.

Are Depression and Anxiety Underdiagnosed in Socially Vulnerable Patients With Inflammatory Bowel Disease?

Depression and anxiety are highly prevalent among individuals with inflammatory bowel disease (IBD); however, little is understood about how social determinants of health (SDOH) may impact mental health diagnoses in this population. The social vulnerability index (SVI) is a publicly available tool that can be used to study SDOH in IBD patients. Home addresses from a retrospective cohort of IBD patients at a single center were used to geocode patients to their individual census tract and corresponding SVI. We used multivariable logistic regression to examine the relationship between SVI and comorbid mental health diagnoses in patients with IBD. Secondarily, data from standardized health questionnaires were then used to determine if patients were adequately screened for depression and anxiety. In all, 9644 patients were included; 18% had a diagnosis of depression, 21% anxiety, and 32% had a composite of "any mental health diagnosis." Depression (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.02-1.56) but not anxiety (OR, 0.87; 95% CI, 0.71-1.06) nor "any mental health diagnosis" (OR, 1.09; 95% CI, 0.92-1.30) was associated with higher levels of social vulnerability. However, overall rates of screening for depression and anxiety were low (15% and 8%, respectively), with the lowest screening rates among the most socially vulnerable (depression 8.2%, anxiety 6.3%). Disparities in the diagnoses of depression and anxiety for socially vulnerable patients with IBD exist. Awareness of these inequities is the first step toward developing interventions to improve mental health screening, eliminate barriers and bias, and promote referrals for appropriate mental health management.