IBD Patients Research Articles

REAL WORLD EFFECTIVENESS OF JAK INHIBITOR UPADACITINIB IN ULCERATIVE COLITIS VERSUS CROHN’S DISEASE IN AN IBD TERTIARY CARE CENTER

Abstract BACKGROUND Upadacitinib is a selective Janus kinase inhibitor approved for the management of Crohn’s Disease (CD) and Ulcerative Colitis (UC). AIMS To compare response to upadacitinib between patients with UC and CD in a real world tertiary care center. METHODS Retrospective cohort study of adult patients with CD vs UC seen at UCSF Colitis and Crohn’s Disease Center from 2019-2023. The primary outcome was endoscopic remission as noted in post-induction staging scope. Endoscopic remission was assessed using SES-CD and Mayo scores for CD and UC, respectively. Outcomes were assessed at 3 or 6 months after starting upadacitinib for UC and CD, respectively. Failure was considered failure to meet remission criteria, change in medications shortly after induction, or surgery. RESULTS A total of 60 patients were reviewed, 26 with Crohn’s Disease and 34 with Ulcerative Colitis, who had taken Upadacitinib and had post-induction follow up data in EHR review. 10 patients with CD achieved remission (38.5%) compared to 17 patients with UC (50%). This difference was found to be nonsignificant (P=0.38). CONCLUSION In this real-world cohort of IBD patients seen at a tertiary care center, there was no significant difference in response between patients with CD or UC.

INFLIXIMAB AND ITS BIOSIMILARS FOR INFLAMMATORY BOWEL DISEASE: ANALYSIS OF MEDICARE PART D CLAIMS AND COSTS

Abstract INTRODUCTION Inflammatory Bowel Disease (IBD) presents a multifaceted healthcare challenge, and biologics have emerged as crucial in its management. The introduction of biosimilars, designed to enhance cost-efficiency and access, has garnered significant attention. This analysis of the Medicare Part D database assesses trends in total drug claims and costs for infliximab and its biosimilars, specifically, infliximab-dyyb (FDA approved in 2016) and infliximab-abda (FDA approved in 2017). This study aims to comprehensively evaluate the influence of biosimilars on the utilization and cost trends of infliximab in the context of IBD. METHODS We used Python to extract all instances of infliximab, infliximab-dyyb, and infliximab-abda prescriptions, occurring at least once between 2013-2021 in each state from the Medicare Part D prescribers database. Univariate regressions were performed independently for each state to identify the slope and significance of the change in total drug claims and costs over time. The Pearson correlation coefficient (R) was calculated for each state, and we examined national trends to determine if a consistent pattern emerged. Two study periods, 2013-2017 and 2017-2021, were used to represent infliximab trends before and after the introduction of biosimilars, respectively. North Dakota and South Dakota were excluded from the study due to data limitations, while the Virgin Islands were included. RESULTS Our analysis revealed varied shifts in the utilization of infliximab across states following the introduction of biosimilars (Figure 1). At the national level, biosimilars exhibited increased utilization. In contrast, both the utilization and cost of infliximab continued to rise; however, the rate of increase decelerated (Table 1). This deceleration suggests that the introduction of biosimilars has influenced prescribing patterns. DISCUSSION Our findings underscore transformations in the landscape of biologic utilization for IBD, subsequent to the introduction of biosimilars. The ascension of biosimilars, marked by their increased utilization, signals their acceptance due to cost-effectiveness. Meanwhile, the utilization of infliximab appears to plateau, potentially reflecting the influence of biosimilars on prescribing patterns. Given the high cost of biologics, sustained efforts are imperative to address the overall cost of therapy and management for IBD patients. While promising trends are evident with increased biosimilar utilization and cost savings, ongoing initiatives are essential to optimize the cost-effectiveness of biologic treatments, ensuring accessible care for IBD patients without compromising outcomes. Figure 1 State trends in total infliximab claims from 2017-2021 in the Medicare Part D database. Negative Pearson correlation coefficients indicate an overall decrease in infliximab claims from 2017-2021, while positive values indicate an overall increase in claims. Table 1 US national trends in total Medicare Part D claims and costs for infliximab and its biosimilars from 2013-2021.

SARCOPENIA AT INITIAL DIAGNOSIS OF PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Inflammatory bowel disease (IBD) can impact patients’ nutritional status. Poor oral intake, poor nutrient absorption, stool protein loss, and increased energy requirement all contribute. Poor nutritional status can manifest as inadequate growth, reduced weight gain, and sarcopenia, defined as decreased muscle mass and strength. Studies demonstrate decreased muscle mass in pediatric IBD patients leads to higher rates of therapy escalation, surgery, and post-operative complications. We sought to obtain the muscle mass at IBD diagnosis via cross-sectional imaging, compare to pediatric age- and sex-specific psoas muscle reference values for pediatric norms, and analyze muscle mass comparison between IBD subtypes and correlations with anthropometrics at diagnosis. METHODS Patients with new diagnosis of IBD [Crohn’s disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC)] aged 6-16 at diagnosis during 1/01/2016 through 12/31/2019 at our tertiary care facility were included in this retrospective study. Those with chronic medical conditions and lack of cross-sectional imaging within 3 months of diagnosis were excluded. Demographic and anthropometric data at diagnosis of IBD were obtained. The psoas muscle area in mm2 was measured on cross-sectional imaging at lumbar level 3-4 (L3-4) and 4-5 (L4-5) bilaterally to obtain total psoas muscle area (TPMA) at each level and compared to pediatric reference values. Statistical analysis included analysis of variance and Spearman correlations, performed using SAS v9.4. RESULTS Cross-sectional imaging from 162 patients with newly diagnosed IBD were reviewed. Average age was 12.1 years, with male predominance of 93 patients (57.4%). Most patients were diagnosed with CD (n=119, 73.5%), followed by UC (n=39, 24.1%), and IC (n=4, 2.5%) (Table 1). Measures of sarcopenia at both lumbar levels for TPMA and both lumbar levels z-score showed significant difference across IBD subtypes (Table 2). CONCLUSIONS Negative mean TPMA z-score < -1 was noted in all patients at both L3-4 and L4-5 levels, with a statistically significant difference between IBD types and mean TPMA at L3-4, TPMA at L4-5, mean z-score at L3-4, and mean z-score at L4-5. In a subgroup analysis, UC patients were significantly different from CD patients on all four measures, suggesting a higher rate of sarcopenia in CD patients at diagnosis. We plan to expand analysis to compare sarcopenia with disease location, medical therapy, hospitalization rate, need for surgical intervention, and anthropometrics over time. We hope to underscore importance of sarcopenia as measure of nutritional status at diagnosis, particularly when patients present with normal anthropometrics. Table 1 Table 2 SUBGROUP COMPARISONS Ulcerative Colitis patients were significantly different from Crohn’s Disease patients on all 4 measures. Indeterminate Colitis patients were significantly different from Ulcerative Colitis patient on the 2 Total Psoas Muscle Area Measures.

N-ECCO Grant Spiritual needs of patients with inflammatory bowel disease and their caregivers: a European cross-sectional nursing study

Abstract Aims Spirituality is the search for meaning or purpose in life (Delgado, 2005), not strictly from a religious perspective. Spiritual well-being is positively connected with physical and psychic well-being, and achieving the first is likely to help to maintain the latter (Bożek et al., 2020). Individuals with chronic disorders or experiencing a life-changing condition (e.g. Inflammatory Bowel Disease - IBD), may have gone through a spiritual quest of some sort that can produce spiritual anguish or 'spiritual distress', interpreting the disease as a punishment, feeling as a victim of 'superior injustice', losing faith in prayer (Klimasiński et al., 2022), but data on the spiritual needs (SpNs) of IBD patients are lacking. The main objective of this project is to describe the SpNs of IBD patients to provide information to IBD nurses on how to address these needs. Methods A multilingual cross-sectional electronic survey will be carried on assessing the SpNs of patients using the Spiritual Needs Questionnaire (SpNQ). The tool is made up of items assessing the importance attributed by patients to SpNs using a 4-point Likert scale (Büssing et al., 2010), and is available in ten European languages, but it could be translated and validated in other European languages inside the project in case of anticipated participation by a country that need the questionnaire available in the local language if a collaboration with IBD clinicians and patients in that country will be possible. Anticipated Impact The findings of such a study can provide better consideration of SpNs in the treatment of IBD patients, emphasizing the importance of addressing SpNs for IBD nurses in managing IBD patients, adopting the tools to screen patients for these needs; furthermore, the results of this project can provide additional evidence of the importance of nursing in IBD patients’ care.

N08 Awareness of Inflammatory Bowel Disease-associated Colorectal Cancer risk and its management in patients with Inflammatory Bowel Disease: a systematic review

Abstract Background Inflammatory bowel disease (IBD) increases the risk of colorectal cancer (CRC). Although literature exists on patients’ general IBD knowledge, little is known about IBD patients’ awareness of CRC risk. This systematic review aimed to explore the literature on IBD patients’ knowledge, attitudes, and awareness of CRC risk and its management. Methods Medline, EMBASE, and PubMed databases were searched from inception to November 2023. All study designs and publication types were included. Non-English articles and those assessing general IBD knowledge were excluded. Cochrane’s ‘checklist of items to consider in data extraction’ was adapted for data extraction and the appraisal tool for cross-sectional studies (AXIS) was used to appraise the quality of included studies. All data relevant to the review question were extracted from the included studies and were thematically analysed for main themes. Results Twenty-three studies (17 full papers and 6 conference abstracts), including 4674 participants (2481 Ulcerative Colitis, 53.5% females) were included (PRISMA diagram Figure 1). The quality of included studies ranged from moderate to low. Overall, 18 studies reported CRC risk knowledge, 3 studies reported patients’ knowledge of CRC symptoms and risk factors, 7 reported attitudes towards cancer screening and 8 reported patient knowledge or attitude towards colectomy for dysplasia. The review found that IBD patients were moderately aware of the CRC risk, poorly aware of the symptoms and risk factors for CRC, and moderately feared this complication of IBD. Most overestimated their own risk of CRC and wanted more discussion with health professionals. Although the role of colonoscopy in cancer screening and diagnosis was well known, patients expressed mixed attitudes towards it due to the unpleasantness of bowel preparation, discomfort, or fear of colonoscopy complications. Low awareness of screening initiation time and varied willingness to undergo colectomy for dysplasia, irrespective of the extent of risk, was reported. Surgery was reported to be a last resort. Conclusion Limited literature exists on IBD patients’ awareness of CRC risk and its management to confidently infer the level of awareness and extent of educational needs of IBD patients. More research is needed to establish patients’ understanding of CRC risk and to optimise management.

P139 A potential protective rule of Mannose Binding lectin (MBL) against SARS-COV2 infection in IBD patients

Abstract Background Since the beginning of the COVID-19 pandemic, IBD patients have appeared to be less susceptible to a severe form of the disease, despite undergoing immunosuppressive treatments. Mannose binding lectin (MBL) is a humoral fluid-phase pattern recognition molecule (PRM) crucial for activating the lectin complement pathway. It is capable of binding to the spike protein and blocking SARS-CoV-2 infection. Low MBL expression has been linked to poor outcomes in both SARS and SARS- CoV-2 infections. In IBD patients, the role of MBL is controversial; low concentrations seem to predispose individuals to the development of IBD, while high concentrations have been observed in severe forms of Crohn's disease. Methods Since April 2020, 104 IBD patients have been enrolled, with 20% treated with mesalazine, 50% with Anti-TNFa, 20% with Vedolizumab, and 20% receiving no treatment. Additionally, 45 healthy controls (HC) from North Italy were included. Serum samples and colon biopsies from inflamed and non- inflamed mucosa were collected. Serum samples underwent an ELISA test to quantify circulating MBL concentration, and MBL gene expression in biopsies was analyzed using qPCR. Results Both Crohn's disease and Ulcerative Colitis patients exhibited significantly higher circulating MBL levels than HC (411.6 ± 45.5 ng/ml vs. 160.9 ± 35.3 ng/ml, p < 0.05). Patients treated with Anti-TNFa showed significantly higher circulating MBL levels compared to those not undergoing therapy (530.1 ± 76.5 ng/ml vs. 225.4 ± 61.6 ng/ml, p < 0.05) and patients receiving Vedolizumab (530.1 ± 76.5 ng/ml vs. 155.3 ± 32.1 ng/ml, p < 0.05). MBL intestinal gene expression is higher in IBD patients than HC (5.55 ± 0.9 vs. 2.36 ± 0.6; p=0.591) and tended to be elevated at similar levels in inflamed and non-inflamed mucosa (5.14 ± 1.4 vs. 5.79 ± 1.1; p=0.337), suggesting a prevalent genetic determination of MBL concentration regardless of the inflammatory background. Conclusion MBL appears to play a key role in SARS-CoV-2 infection. We demonstrate that IBD patients have, on average, higher circulating MBL levels than HC independently of their inflammatory status. The highest MBL levels were observed in patients treated with Anti-TNFa. These findings contribute to understanding the reported low mortality and hospitalization for COVID-19 among IBD patients treated with Anti-TNFa.

P579 Dietary beliefs, barriers, and acceptability of diet in IBD patients – a multi-centre survey from the Asia-Pacific region

Abstract Background Dietary beliefs and behaviors in IBD patients may affect both clinical outcome and psychosocial aspect of patients’ lives. New emerging studies have shown varying efficacy of different diets in inducing and maintaining remission in IBD patients. This study aims to investigate the dietary beliefs, barriers, and acceptability of diet among IBD patients in the Asia-Pacific region. Methods A multi-centre survey was conducted across 4 countries in Asia-Pacific. An anonymized online electronic survey was disseminated at 10 participating IBD centres. Patients were asked to rank acceptability of IBD-related diets on a Likert scale of 1 to 5, with 1 being strongly unacceptable and 5 being strongly acceptable. The survey is currently still ongoing and preliminary results from the initial 3 months are reported below. Results A total of 402 responses were recorded. Patient demographics and disease characteristics are shown in Table1. Most patients received dietary advice from their doctor (n=279,69.4%) and social media (n=150,37.3%). 168 (41.7%) patients believe that diet plays a role in the development of IBD. Conversely, 107(26.6%) did not believe so, and 128(31.8%) were unsure. Most patients (n=336,83.6%) patients would avoid certain foods during a flare. Diet modifications were attempted by 188 (46.8%) patients and the most common dietary modifications were the low fibre diet (n=106, 56.4%), followed by the Exclusion diet (n=69, 36.7%), and gluten free diet (n=54,28.7%). 100 (24.9%) patients are currently on an IBD-related diet. The barriers to the acceptance of IBD-related diet were identified and the two most common reasons cited were difficulty in meal preparation (n=196,48.8%) and interference of social life (n=176,43.8%). Acceptance of IBD-related diets would increase if the diet is effective in inducing remission or reducing symptoms (n=315, 78.4%) and easy to prepare (n=284,70.6%). Patients were most accepting of the low fibre diet (n=260, 64.7%) and Mediterranean diet (n=189,7.1%). Exclusive enteral nutrition (n=71,17.7%) and low FODMAP diet (n=109,27.1%) were the least acceptable. Type of IBD, duration of disease, current use of steroids and small molecules were not associated with previous dietary modification. Use of biologics, current use of more than one medication, the belief that diet can induce remission and reduce flare were independently associated with previous attempted dietary modification (p< 0.05). Conclusion Exclusive enteral nutrition has the lowest acceptance despite its role in inducing remission. Future IBD-related diet studies should consider the aforementioned barriers to make it more widely acceptable among IBD patients.

N02 Inflammatory bowel disease patients with impaired quality of life on biologic therapy benefit from the support of an IBD nurse specialist: Results of a randomized controlled trial in Germany (IBDBIO-ASSIST study) - The IBD nurses perspective

Abstract Background IBD nurses play an important role in the Multidisciplinary Team of managing patients with IBD. IBDBIO-ASSIST was a randomised controlled trial assessing the efficacy of care provided by an IBD nurse specialist in improving health-related quality of life (QoL) in IBD patients on biologic therapy in an outpatient setting in Germany. Methods In total, 1086 IBD patients on biologic therapy were randomly assigned to either a control group (CG) receiving usual IBD care or an intervention group (IG) receiving additional care from an IBD nurse. Two IBD nurses per site received an extra study specific IBD training before including patients. The primary outcome was disease-specific QoL (sIBDQ) assessed at months (M) 6, 12, and 18. In addition, IBD nurses provided a final assessment of various aspects of their work in the context of the study at M6 (T0) and M15 (T1), and patients were asked about their satisfaction level with the IBD nurses. Results The analysis of patients with impaired QoL at baseline (EQ-VAS < 75 [median]), showed an improvement in sIBDQ over 6 M that became significant at M12 and remained significant through M18 (baseline: IG 4.24; CG 4.31; M18: IG 5.02; CG 4.76; P= .017) (Table 1). Regarding the 5 aspects of fun, usefulness, successful discussions in consultations with patients, successful support of patients, and appreciation by patients, the nurses expressed positive assessments (“completely” and “rather”) at both measurement points, with values of more than 90% (Fig. 1). About 20% to 30% of the nurses reported being rather dissatisfied with two aspects of their jobs: time and space resources for discussions and recognition by physicians. 94% of patients in the IG felt that the additional care provided by the IBD nurses was highly beneficial. Conclusion IBD patients with impaired QoL derived a significant benefit from the additional care provided by an IBD nurse specialist, leading to meaningful improvements in sIBDQ over the long term. The survey results from the IBD nurses and patients in the IG revealed a very positive perception of the new form of care. It is noteworthy that an improvement in care provision was reported both by the nurses and the participating patients. Some physicians also experienced benefits from the intervention as they were relieved of certain time-consuming tasks by the IBD nurses. It should be noted that more than 20% of the IBD nurses did not feel sufficiently appreciated by physicians, and about 30% criticised the lack of time and space resources. When introducing the IBD nurse-led care concept into usual practice, these aspects should be considered.

P096 Human extrachromosomal circular DNA is an emerging biomarker in Inflammatory Bowel Disease

Abstract Background Inflammatory Bowel Diseases (IBD) are chronic multifactorial disorders, which affect the gastrointestinal tract, including Ulcerative Colitis (UC) and Crohn’s Disease (CD). The existence of extrachromosomal circular DNA fragments (eccDNA) is well established, and it arises from all parts of the genome. eccDNA has mainly been studied in the context of cancer and not in relation to other diseases, and it has become a promising diagnostic and prognostic biomarker for different types of cancer. Herein, we investigate for the first time the role of eccDNA in IBD. Methods Forty consecutive IBD patients (19 CD, 21 UC) and 13 HC were enrolled, who underwent screening colonoscopy were prospectively enrolled at our center in this observational, case-controlled study. In IBD patients, disease activity was assessed using PMS and MES for UC, and HBI and SES-CD for CD. Colonic biopsies were collected from both inflamed and healthy mucosa in IBD patients and from HC. eccDNA was enriched, sequenced, and identified with Circle Finder from intestinal biopsies. Results Colonic mucosal samples from IBD patients showed increased average of eccDNAs, across all chromosomes than samples from HC. Furthermore, there was a slight yet significant tendency for larger eccDNAs in IBDs compared to HCs. Focusing on eccDNA coming from genic elements ("genic eccDNAs"), approximately 60% were fragments from protein coding genes, 32% from non-coding RNAs and 8% from pseudogenes. IBD patients had, on average, significantly more genic eccDNAs in their intestines as compared to HC. Moreover, IBD in remission had fewer eccDNAs in their intestines than active disease, although not statistically significant. eccDNAs from phosphodiesterase genes and genes involved in lipid metabolism were enriched in patients with active IBD than patients in remission. eccDNA from inflamed mucosa (both in UC and in CD) show an enrichment of genes related to inflammatory and immune pathways, such as MAPK, mTOR, ErB, Rap-1 and cGMP (SPOKE3, GRID2, DLEU1, ITGA8, NRG1). Conclusion We are the first to uncover an IBD-specific pattern of eccDNA production. Furthermore, we identified genic hotspots which characterize active vs. inactive disease and inflamed vs. healthy colonic tissue. We propose that eccDNA identification could be a promising new diagnostic marker for IBD patients.

P780 Persistence of Health-related Quality of life decline in IBD patients after the COVID-19 outbreak

Abstract Background Inflammatory bowel disease (IBD) affects many aspects of a patient’s life and impairs their health-related quality of life (HRQoL). We previously showed that there was a negative impact of the COVID-19 outbreak on the HRQoL of IBD patients in remission. This study aimed to assess if IBD patients in stable, clinical remission could recover their pre-outbreak HRQoL once the global emergency for COVID-19 ended. We also compared their self-perceived stress scores during and after the outbreak. Methods We carried out a prospective, observational study on IBD patients with biological treatment and stable clinical remission who had participated in the previous study. Patients filled in the IBDQ9 and the Perceived Stress Scale (PSS) electronically. The results of the IBDQ9 pre-, during, and post-COVID-19 outbreak were compared to determine any changes. PSS scores during and after the outbreak were also compared. Results Ninety-three patients in clinical remission were included, with a median age of 43 years; 40% were female, and 78% had Crohn’s disease. Median pre-COVID-19 IBDQ9 was 54 (50-59) and decreased to 50 (46-58) during the outbreak, and post-outbreak was 49 (44-56) (p<0.01). PSS score improved after the outbreak, with a median value of 10 (8-18) during the outbreak and a score of 14 (9-19) after the pandemic. There was a significant negative correlation between the PSS (during the outbreak) and post-outbreak IBDQ9 (r=-0.76, p<0.001). Regression analysis showed that the PSS score during the outbreak was independently associated with a lower post-outbreak IBDQ-9 (p<0.05). Conclusion During the COVID-19 pandemic, there was a negative impact on the HRQoL of IBD patients in remission that persists after the outbreak, with higher self-perceived stress scores during the pandemic associated with a lower post-outbreak QoL. The results of this study underscore the long-term impact that unexpected situations can have on IBD patient's HRQoL. Unforeseen circumstances are mostly non-predictable, as the COVID-19 outbreak has shown, and measures to provide high-quality health care, including access to mental care, will hopefully be implemented for IBD patient care.

P714 Immunogenicity and safety of adjuvated recombinant zoster vaccine in IBD patients on different immunosuppressive therapies

Abstract Background Aberrant immune regulation and the use of immunosuppressive therapy make IBD patients more susceptible to complications of primary Varicella Zoster Virus (VZV) infection and significantly increase the risk of Herpes Zoster (HZ). HZ can be prevented by vaccination and RZV is the first HZ vaccine approved for immunocompromised persons. Limited data on immunogenicity and safety of RZV in immunosuppressed IBD patients are available. We investigated humoral and cell-mediated response and safety of RVZ vaccination in IBD patients under different immunosoppressive therapies. Methods In this prospective single centre study, adult IBD patients were enrolled and vaccinated with 2 doses of RZV between May and July 2022. Different immunosuppressive regimens (anti-metabolites, anti-TNF mono and combination therapy; ustekinumab and vedolizumab monotherapy; mofetyl mycofenolate/steroid combination therapy) were not discontinued and the administration schedule maintained. Immunogenicity was evaluated by quantitative detection of serum IgG anti-VZV antibodies and anti-VZV glycoprotein E (gE) antibodies before and 1 month after vaccination completion using ELISA. Reactogenicity was evaluated by diary cards reporting adverse events for 7 days after each dose. Events were graded from 1 (mild, not interfering with everyday activities) to 3 (severe, preventing normal everyday activities). Disease activity was assessed by SCCAI and HBI before vaccination, 7 and 30 days after each dose. Results Vaccination was completed in 104 (98.1%) out of 106 enrolled patients (median age 49.7 years, 59.4% male; 55.7% UC, 44.3% CD). Humoral response was observed in all patients, with a significant increase of anti-VZV antibodies (median UTI 23.8; IQR: 20.2-26.2 vs median UTI 419; IQR: 20.2-26.2, 376-458, p<0.001, median 17.8 fold increase, figure 1) and anti-gE antibody concentration compared to baseline (median OD 0.24; IQR: 0.21-0.26 vs OD 0.53; IQR:0.4-0.6, median 2.3 fold increase, p<0.001, figure 1). Imunosuppressive agents, either in mono or combination therapy, did not influence anti-VZV titre, anti-gE concentration and CMI response. Local and systemic solicited reactions after any dose were reported in 96.2% (grade 3=24.8%) and 88.6% (grade 3=33.3%) of patients respectively, with higher grade of intensity after the second dose. No severe adverse events related to vaccination were observed; 2 patients (1.9%) reported a disease flare. Conclusion RZV vaccine is able to induce a robust gE-specific humoral immune response. The type and intensity of immunosuppressive regimens did not influence humoral immunogenicity. RZV vaccination was safe and well tolerated in terms of both reactogenicity and exacerbation of disease.

P692 An IBD nurse-led educational programme on safety and efficacy of adjuvated recombinant zoster vaccine can improve vaccine uptake in IBD patients on immunosuppressive treatment

Abstract Background Herpes Zoster (HZ) represents one of the most frequent opportunistic infections in IBD patients under immunosoppressive treatment and can be prevented by vaccination. Adjuvated recombinant zoster vaccine (RZV) is the first HZ vaccine approved for immunocompromised persons. IBD patients are less likely to receive appropriate vaccinations compared to the general population. IBD nurses operate as the primary point of contact for patients and this unique position provides a suitable opportunity to positively impact patient care and encourage vaccination. We aimed to improve RZV vaccination rates by a nurse-led education intervention within an on-site RZV vaccination programme. Methods IBD patients on immunosuppressive therapies were actively recruited by phone contact, mail and during outpatient clinic or infusion centre attendance. Prior immunization to VZV was collected from medical records. Patients were randomly assigned to receive either standard explanation on the importance of HZ vaccination by the IBD attending physician (group P) or additional education by an IBD nurse (group N). Patients in group N were referred to an IBD nurse for an individual 15 minutes nurse–patient interview. During the interview, disease activity and current treatment, previous immunization to VZV and history of HZ were reviewed; the importance, benefits and safety of HZ vaccination with RZV were discussed with the patient. Patients were then referred to dedicated on-site vaccination clinics where vaccine administration was provided by the IBD nurses running the infusion centre. Reasons for vaccine refusal was also recorded. Results From February to April 2022, 164 (80%) out of 205 eligible patients were enrolled (median age 48.5 years, 54.1% male; 48.7% UC, 51.3% CD); 65 patients (39.6%) were randomized to group P and 99 patients (60.4%) to group N. Six months after randomization, 112 (68.2%) had received at least 1 RZV vaccine dose whereas vaccination was completed in 110 patients (67%). Vaccination rate was significantly higher in the nurse-led education intervention group compared to standard clinical care (group N 75.7% vs group P 56.9%,p<0.05). Most common reasons for vaccine hesitancy were concerns about side effects (40.9%), fear of vaccine aggravating the disease (14.7%), considering themselves not at risk (13.3%) and objection to the administration of vaccine (10.1%). Conclusion Vaccination recommendations should be responsibility of the IBD patient care team and efforts should be made to reduce vaccine hesitancy. We showed that a simple nurse-led educational intervention on vaccine safety and efficacy was able to improve RVZ vaccination rates in IBD patients on immunosuppressive treatment.

P284 Sex-specific aspects in IBD: a multidimensional view

Abstract Background Inflammatory bowel diseases (IBD), including Ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal disorders characterised by varied intestinal symptoms and a negative impact on the patients` quality of life. Increasing evidence demonstrates sex differences regarding the prevalence, pathophysiology, clinical presentation and treatment outcome of IBD. While for some factors evidence is rather good, for others data are conflicting – thus a deeper understanding of sex related differences in IBD courses is still needed. Methods In this monocentric, cross-sectional study 221 IBD patients were stratified into 2 groups according to gender/biological sex (male [n=106]; female [n=113]). We evaluated patients personal and medical data including disease-specific quality of life (IBDQ) as well as clinical (HBI, PMS) and biochemical (CRP, fecal calprotectin) parameters of disease activity. Furthermore, we isolated and stimulated PBMCs with various pathogens to test ex vivo cytokine responses of this heterogeneous IBD cohort. Results Binary logistic regression analysis suggested an independent association of diagnostic delay (p= 0.039), IBD entity (p= 0.001), IBDQ (p= 0.001), and vitamin D3-25-OH serum level (p= 0.035) with disease activity for female IBD patients, while for male IBD patients an independent association was only suggested for IBD entity (p= 0.004) and IBDQ (p= 0.001) (figure 1). Next, we tested the association between the number of ADT (Advanced Therapies) taken during the overall course of the disease with both disease activity and diagnostic delay. We found a significant association between ADT and disease activity in both sexes (male-p = 0.015, female-p=0.037), but ADT was only significantly associated with diagnostic delay in female IBD patients (p=0.044) (figure 2). Regarding the frequency of therapies used in both sexes, we found that male patients are more frequently subscribed prednisolone (Mann-Whitney-U, p= 0.009) as well as 5-ASA (p= 0.004) (figure 3). Cytokine responses upon PBMC stimulations with various pathogens showed a significant trend in Interferon gamma levels in male CD patients (p< 0.05) (figure 5A). A significant negative correlation between Interferon gamma levels and CD activity has only been found in male CD patients, but not in female CD patients (figure 5B). Conclusion In this analysis of a cross-sectional study, we are able to illustrate sex-specific aspects of not only clinical courses in IBD patients but also within specific immunological responses – highlighting the importance to closely take the IBD patients sex into consideration in the upcoming era of personalized medicine.

P064 Investigating the genotoxic effect of reduced glutathione, n-acetylcysteine, human umbilical cord-derived mesenchymal stem cell exosomes and let-7 miRNA mimics in human lymphocytes and EpiIntestinal cells

Abstract Background The current treatments for IBD frequently do not provide sufficient control over the disease, warranting the investigation of alternative therapeutic options with minimal risk of side effects. In IBD, the overgeneration and insufficient removal of reactive oxygen species (ROS) leads to oxidative stress. Reduced glutathione (GSH) and n-acetylcysteine (NAC) are antioxidants which may possess therapeutic potential in IBD, by modulating endogenous mechanisms that decrease ROS production or increase antioxidant enzymes. Additonally, exosomes from human umbilical cord blood derived mesenchymal stem cells (hucMSCs-exo) may be used to treat IBD. These are a subset of extracellular nanosized membrane vesicles which participate in intercellular communication by delivering their contents, such as functional miRNAs to recipient cells, thereby influencing the physiological and pathological processes in various diseases. The therapeutic potential of exosomes can be enhanced through the overexpression of the let-7 family of miRNAs. Methods The EpiIntestinal tissue model is a physiologically relevant predictor of drug-induced GI toxicity. EpiIntestinal cells and lymphocytes from 3 IBD patients were transfected with 50 μL miRNA mimics and inhibitors, and treated with 50μL hucMSC-exo, and 50 μL 1mM GSH and NAC. Next, in comparison to negative controls, single-stranded DNA damage was assessed in peripheral blood mononuclear cells (PBMCs) from IBD patients using the fast microplate DNA damage assay, and double-stranded DNA damage was assessed in EpiIntestinal cells using the alkaline Comet assay. In addition, the viability of healthy and IBD lymphocytes was assessed following treatment with selected concentrations of hucMSC-exo, GSH and NAC. Results Double-stranded DNA damage was significantly reduced in EpiIntestinal cells compared to the negative control following treatment with hucMSC-exo, GSH, NAC, and miRNA mimics for let-7a-5p, -7b-5p, -7c-3p, -7d-3p and -7d-5p. In addition, single-stranded DNA damage was reduced in IBD PBMCs compared to the negative control following treatment with hucMSC-exo, and let-7b-5p and -7c-3p mimics, but was increased following treatment with inhibitors for let-7b-5p, -7c-5p and two novel miRNAs. Additionally, GSH, NAC and hucMSC-exo increased cell viability in treated versus untreated lymphocytes from healthy individuals and IBD patients. Conclusion Selected concentrations of HucMSC-exo, GSH, NAC and/or let-7 miRNA mimics reduced DNA damage and increased cell viability in treated versus untreated cells which may reduce the risk of colorectal cancer in IBD patients. Acknowledgements Our gratitude goes to the MatTek Team for generously granting us a SMI-100-FT EpiIntestinal kit in support of this research.

P899 Inflammatory Bowel Disease Patients Show More Recognizable Digestive Symptoms of COVID-19: A Questionnaire Study

Abstract Background It's important to manage IBD patients in the era of coronavirus pandemic (COVID-19). However, there is few studies on the clinical symptoms and prognosis of COVID-19 in IBD patients. Methods A web-based survey concerning symptoms of COVID-19 in people with or without IBD was designed. A pilot-test was carried out to ensure the feasibility of the questionnaire. Propensity score matching (PSM) was used to compensate for differences in baseline characteristics. Wilcoxon rank-sum test and Chi-square test were used to compare the clinical and prognosis differences between two groups. Results A total of 1274 individuals (including 631 with IBD) completed the questionnaire. After the use of PSM, 786 cases including 393 of IBD and non-IBD individuals respectively were included in the analysis. Fever and nasal congestion were the most common clinical manifestations of COVID-19 in our study. As for gastrointestinal (GI) symptoms, more IBD patients presented with new-onset abdominal pain (26.7% vs. 12.7%, p<0.001), diarrhea (22.4% vs. 14.5%, p<0.005) and altered bowel habits (38.7% vs. 24.9%, p<0.001). Conclusion COVID-19-related GI symptoms are more common in IBD patients. It is important to rule out COVID-19 infection in patients experiencing recurrence or exacerbation of GI symptoms.

P309 Impact of EBV Status on decision making for advanced therapies in IBD Patients

Abstract Background The CESAME study suggested that Thiopurines confer increased risk of lymphomas in IBD patients who are naïve to Epstein - Barr virus (EBV) particularly in young males. European Crohn’s and Colitis Organisation (ECCO) guidelines recommend considering EBV screening in individuals prior to initiating immunomodulator therapy. The impact of EBV serology status on decision-making processes regarding advanced therapies in IBD patients is not studied before. Methods Consecutive patients initiated on advanced therapies (biologics or small molecules). EBV nuclear and vca IgG status were recorded. The first advanced therapy of the positive and negative patients were compared. Proportion of the negative patients who seroconverted and the time to seroconversion were analysed. Results We included 491 patients (M: F 1:14). Median age of patients who had EBV serology done prior to initiating on advanced therapies was 31.5 years (range 5-84 years) .In 41 (8.35%) patients, neither nuclear nor vca IgG antibody were detected at initial screening. The median age of EBV negative patients was 26 years (range 13-51 years).30 of the EBV negative patients were males. Azathioprine/6MP was not initiated in 37 (90.24%) of the EBV negative patients. Re-testing of EBV negative patients were done at a median interval of 28 months (range 3-90 months). 5 of these retested patients (12.2%), seroconverted and in three of this patients Azathioprine was used following seroconversion. Conclusion A significant minority of IBD patients are EBV negative when tested as part of pre biologic screening, including in male patients above the age of 25. Thiopurine therapy was avoided in these patients. Only a fraction of EBV negative patient seroconverted on re-testing. The impact of EBV testing in treatment decision, as well as the attributable costs needs to be evaluated further.

P1155 Impact of COVID19 pandemic and vaccination among IBD patients: a multinational cross sectional survey

Abstract Background The aim of current study is to evaluate impact of COVID19 pandemic and vaccination against it on the course and symptoms of IBD. Methods During a six months’ period, all of the IBD cases who attend in outpatient clinics of nine referral centers in 6 countries include and request to fill a questionnaire about their demographic characters and pattern of IBD, any history of involvement with COVID19 and their vaccination history. Results overall 812 cases from 16 countries included (52.4% male) with average age of 36.8 y (range 7 – 76). 68.5% of participants diagnosed as UC and 29.5% as CD. 80% of participants have vaccinated against COVID19 (average 2.3 times, range 1 – 5). Among those who vaccinated (group A) 31.6% experienced side effects and complication without any mortality. The most common complications of vaccination include fever (24%), fatigue (20.1%) and anorexia 8.6%. The most common reasons for vaccination refusal (group B) were fear of vaccine complication (55.5%), no believe in vaccine protection (29.6%) and fear of immunocompromised condition (17.9%). In group A overall 61% of participants involved with COVID 19 (36.2% after vaccination) in comparison with 48.1% in group B (P = 0.0052). Most of the involvements in both groups were not sever and just a minority of patients admitted to hospital (10% in group A and 6.4% in group B). Following COVID involvement, 45.1% of cases suffered with GI symptoms (mostly diarrhea (72.5%) and abdominal pain (64.5%)). In group A, 37.3% of involvements have happened before vaccination. Conclusion Vaccination against COVID19 is safe and effective among IBD patients and following vaccination, most of complications are minor and negligible. In case of COVID involvement, it would not be serious and there is no need to hold the medications. Among IBD patients, the most common reason for vaccination refusal is fear of vaccine side effect.

P324 Urine metabolite profile characterizes clinical activity and disease extent in patients with inflammatory bowel disease

Abstract Background Inflammatory Bowel Disease (IBD), which comprises Crohn's Disease (CD) and Ulcerative Colitis (UC), is a disorder in which complex interactions between genetic, environmental, and microbial factors trigger alterations in the immune intestinal response. On the other hand, nutrient catabolism from the diet carried out by the microbiota results in the formation of metabolites that also impact immune responses on the intestinal mucosa. Considering that IBD patients have altered microbiota compared to healthy controls (HC) and that the urinary metabolic profile of an individual is the result of a combination of genetic, dietary, and microbial components, we propose the hypothesis that the urinary metabolic profile distinguishes IBD patients from HC. The aim of the study was to compare metabolomic analysis of urine samples from HC and IBD patients. Methods 27 patients were included [HC (n=10), UC (n=10), and CD (n=7)]. Clinical IBD activity was evaluated with partial Mayo score (UC) and Harvey-Bradshaw index (CD). Metabolites in urine were measured using gas chromatography-mass spectrometry (GC-MS). Metabolomic analysis and machine learning were performed using the MetaboAnalyst software. PLS-DA was used for multivariate analysis, and clustering separation was performed using hierarchical clustering. To identify and interpret patterns of metabolite concentration changes in a biologically meaningful way we perform Over Representation Analysis. Results In total, 62 organic acids were detected. Comparing UC and HC revealed 11 significantly altered metabolites (9 increased and 2 decreased). Main increased metabolites comprised lactic acid (p=0.0015), pyroglutamic acid (p=0.0147), isocitric acid (p=0.0325), and phosphoric acid (p=0.0091). Interestingly, the value of adipic and suberic acids were higher in remission vs. active patients. Furthermore, adipic acid was higher in UC patients with proctitis compared to left-side colitis/extensive colitis. Comparing CD and HC revealed only 2 significantly altered metabolites, glycolic acid (p=0.0214), and lactic acid (p=0.0111). Oxalic acid was more concentrated in CD patient with perianal disease. Finally, propionic and phosphoric acid were able to discriminate UC from CD patients. The most affected metabolic pathways were related to energy metabolism and oxidative stress, including the Warburg effect (p=0.0016), gluconeogenesis (p=0.0106), pyruvate metabolism (p=0.0197) and glutathione metabolism (p=0.0039) (Fig.1). Conclusion We found that the urinary metabolic profile of IBD patients differs from the HC, particularly for UC patients. These metabolites profile could be used to improve diagnosis and monitoring in patients with IBD.

P186 Comparative Analysis of Clinical Phenotypes and Pathogenic Features between Late-Onset and Infantile-Onset Monogenic Inflammatory Bowel Disease

Abstract Background Previous research on monogenic IBD (m-IBD) has mainly focused on very-early-onset IBD (VEO-IBD) and Montreal classification A1 type IBD patients. In non-A1 type (age > 16y) late-onset IBD patients, some individuals also exhibit IBD manifestations due to monogenic mutations. Here we systematically review the literature, using infantile-onset monogenic IBD patients as a control, to explore the genetic characteristics, clinical presentations, and treatment strategies of late-onset monogenic IBD. Methods Based on the onset age of IBD, m-IBD was categorized into infantile-onset (IO, <2 years) and late-onset (LO, >16 years as non-A1 type based on Montreal classification) groups. A systematic review was conducted to analyze the gastrointestinal (GI) clinical features of detailed cases published from January 1990 to June 2023 and to summarize the correlation between genetic pathogenesis and onset ages. Results 512 m-IBD cases (398 IO and 114 LO) associated with 87 genes were included. Of these genes, 25 out of 87 genes were found to cause both IO and LO conditions. Crohn’s disease (CD) was the predominant type of IBD, account for 42.2% of IO and 44.7% of LO cases. Difficult-to-treat IBD patients showed similar rates (17.4% for IO and 13.0% for LO). However, infantile-onset cases were predominantly associated with complex perianal disease (13.5%), while late-onset cases were linked to postoperative recurrence following surgical resections (10.6%). Anti-inflammatory medicine and biologics were the main strategies, but in infantile-onset (IO) cases, immunosuppressants (57.9%), parenteral nutrition (26.8%), gastroenterostomy (20.2%), and HSCT (24.6%) were more frequently utilized compared to late-onset (LO) cases, where intestinal resection (37.8%) was more prevalent. Homozygosity was the predominant zygosity type (39.9% in IO and 39.3% in LO), while heterozygosity was more prevalent in LO cases (28.9%) compared to IO cases (13.3%) (p<0.05). Most of the genes associated with median onset ages of IBD before 2 years were causative genes for primary immunodeficiency (PID), whereas significantly lower rate of PID genes mutation was found in LO cases (26/27, 96.3% vs. 6/11, 54.5%, p= 0.005). Conclusion m-IBD patients predominantly present with CD, ulceration and atypical pathology, colon involvement, and difficult to treat regardless of onset ages, but vary in terms of family history, GI symptoms, location of the lesion, polyps and villous atrophy, type of complications, treatment options, and type of Difficult-to- treat IBD.

P215 Mir-135b, an Early Biomarker of Sporadic and IBD-Related Colorectal Carcinogenetic Progression

Abstract Background Although the rates of IBD-related-CRC are decreasing over time, CRC is still a leading cause of mortality and reason for colectomy in patients with IBD. Among the different cancer biomarkers, microRNAs (miRs) have emerged as noninvasive tools for diagnosis, monitoring, and prognosis in tissues and biofluids of patients with IBD. Therefore, we aimed to investigate the role of miRs in the development and natural course of IBD-related CRC, in order to identify potential early biomarkers for IBD-related CRC screening and progression. Methods The cases were retrospectively collected from the archives of the Surgical Pathology and Cytopathology Unit at the University of Padua. We analysed 9 miRs in colonic tissue specimens of IBD patients with adenoma or dysplasia, with IBD related-CRC, other than 2 control groups of patients with sporadic CRC and of healthy subjects (HC). In addition, we included tissue samples from a colonoscopy that patients with IBD with adenoma or dysplasia underwent some years before the development of mucosal lesions (from 2 to 5 years before), therefore without evidence of adenoma or dysplasia. Results were analyzed with ThermoFisher Connected™ Software and a p-value < 0.05 was considered significant. Results Compared to HC, all nine analysed miRs were significantly up-regulated in patients with sCRC, with IBD-related CRC and in IBD patients with adenoma. While, only 3 miRs (miR-135b, mir-21, miR-224) were significantly upregulated in IBD patients with dysplasia (and in their own controls) compared to HC (p<0.0001). Notably, no differences in miRs expression levels were found in patients with IBD-related CRC compared to those found in patients with sCRC. Among all miRs analyzed, only miR-135b and miR-21 resulted significantly up-regulated in patients with IBD. Considering the levels of miR-135b in the tissue samples of IBD patients, we observed an evident increasing trend going from tissue specimens without lesions to those with adenoma or dysplasia and then to those with neoplastic lesions. miR-21 was significantly upregulated in patients with IBD-related CRC compared to both IBD patients with adenoma and their own control samples from a previous negative colonoscopy (p=0.003 and p=0.006, respectively). Likewise, a significant difference in miR-21 levels was observed between patients with IBD-related CRC and those with dysplasia (p=0.02). Conclusion miR-21 and miR-135b are involved in the carcinogenesis process of patients with IBD. They could be potential candidate biomarkers for diagnostic purpose, prognostic and predictive stratification of patients.