Inflammatory Bowel Disease Population Research Articles

P896 You Can Lead a Horse to Water But You Can’t Make it Drink: A Study on Medication Adherence of Inflammatory Bowel Disease Patients in Ireland

Abstract Background Medication adherence is important in ensuring adequate treatment of Inflammatory Bowel Disease (IBD). The High Tech Hub (HTH) is an online system used in Ireland to prescribe and monitor the ordering of High-Tech Medication, specifically oral small molecules and subcutaneously-delivered biologics. We aimed to observe compliance rates of treatment in our centre, observe trends between different medication and identify factors associated with adherence. Methods We extracted prescribing and medication dispensing information from the HTH database for our centre between May and November 2023. We collected information on patient demographics such as age and gender, patient disease subtype, medication class and duration of prescription given against the duration of prescription collected by the patient with an 85% threshold as a marker of compliance to treatment. Statistical analysis was used to compare differences in adherence between subsets of the population and a multivariate regression model was used to identify factors associated with adherence. Results We extracted information from 824 prescriptions from 644 unique patients. The median age was 42 years (IQR 32-52) with 52.2% males. 60.7% (n=391) had Crohn’s Disease, 33.4% (n=215) had Ulcerative Colitis and 3.1% (n=20) had IBD-U. Majority of patients, 77.3% (n=498), were on Anti-TNF medication, followed by 13.2% (n=75) on anti-Interleukins, 6.2% (n=40) on JAK Inhibitors and 3.3% (n=21) Anti-Integrins. 6.5% (n=42) of patients required dose optimization during the 6-month observation and 1.7% (n=11) required a change of medication. 9.5% (n=61) of patients collected prescriptions for steroids. Further analysis demonstrated no significant difference in adherence within gender (Male: 61.0% vs. Female 53.6%, p=0.056), age (<25 years: 66.2%, 25-39 years: 55.0%, 40-54 years: 58.6%, ≥55 years: 54.6%, p=0.346), disease type (Crohn’s: 58.6%, Ulcerative Colitis: 56.7%, IBD-U: 50%, p=0.776), medication class (Anti-TNF: 56.4%, Anti-Interleukin: 65.9%, Anti-Integrin: 57.1%, JAK Inhibitor: 52.5%, p=0.378). However, we found significant lower adherence rates in patients who required dose optimization (21.4% vs. 60.0%, p<0.001) and those who required a change in medication (18.2% vs. 58.1%, p=0.008) in the observation window. There was also a lower rate of adherence noted in those who received prescriptions for steroids (45.9% vs 58.9%, p=0.051). Conclusion There was a high rate of non-adherence noted in our IBD population, worse in those who ended up requiring dose optimization or change in therapy. Addressing compliance by monitoring the online dispensing of medication may be a useful way to ensure adequate treatment and avoid unnecessary treatment escalation.

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.

N34 Transition of Inflammatory Bowel Disease patients from pediatric to adult Care: A single-center ten-years experience

Abstract Background Transition of adolescents with inflammatory bowel disease (IBD) to adult care is a challenge for patients, families, and healthcare providers. Considering that ~ 25% of IBD patients are diagnosed before the age of 16 years, and that these patients are at higher risk for poorer clinical disease outcomes. interest in the transition of care has been increasing considerably in the last decade.To assess the main clinical and epidemiological features of peadiatric IBD patients in a single pediatric center in Sardinia, Italy, at diagnosis and at the time of transition to the adult center Methods From January 2014 to June 2023 we performed a multicenter, observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit. Results Sixty-five IBD patients were enrolled (UC 40, CD 25, M 32, F 33). Median age at diagnosis was 13 years (IQR 2-18). After a median disease duration of 8 years (IQR: 1-25), no UC patients experienced proximal estension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1-84)] and CD patients [4,5 months (IQR: 1-48)]. At the transition visit, overall, twenty-nine patients (44,6%) were exposed to one biologic agent (vs 3% at baseline; p<0.02); 0 patients (0%) were exposed to two biologic agents. 4,6% of patients (3/ 65) underwent surgery Conclusion Our results provide important insights into the clinical and epidemiological features of pediatric IBD population, and while waiting for a nation Italian registry, present eligible data on the IBD population in Sardinia

P462 The burden of mental health disease in people with inflammatory bowel disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background The impact of Inflammatory Bowel Disease (IBD) on individuals’ quality of life is well reported. Recent studies have shown that depression or anxiety affect almost 1 in 5 people with IBD and may be a predictor of active disease. We aimed to explore the burden of MHI in the Australasian IBD population and examine the real-world variation in screening and care across different sites and care settings Methods Crohn’s Colitis Care’s (CCCare) clinical quality registry (CQR) is created by deidentified data flowing across from routine care encounters. Data in the CQR for all individuals with a clinical encounter since August 2018 were interrogated in April 2023. Mental health data were collected from documentation during routine care or through patient consumer completion of embedded questionnaires, namely Depression Anxiety and Stress Scale 21 [DASS-21] and Kessler Psychological Distress Scale [K10] Results The CQR contained 6614 people with IBD with a mean age of 44.4 (SD +/- 22.09) and even gender distribution (50.9% female). 79.5% of people were from Australia and 20.5% from New Zealand. 57.1% of people had Crohn’s disease (CD), 40.4% ulcerative colitis (UC) and 2.5% IBDU with a mean disease duration of 13.3 years (SD +/-23.0). Anxiety was the 4th most listed comorbidity affecting 17.8% of individuals, depression 7th affecting 13.7% of people and both depression and anxiety 13th affecting 9.1% of people with IBD. In total 40.8% or 2 in 5 people with IBD in Australasia had received a formal diagnosis of a MHI. 2,928 consumers had been invited to complete the DASS-21 and 2,340 the K10 (44% & 35% respectively). Of the questionnaires sent, 32% of DASS-21s and 33% of K10s were completed. Rates of both invitation and completion varied significantly between centres. Invitation rates varied from 11% - 90% (p<0.001) while questionnaire completion rates varied from 26% to 46.8% (p<0.001). The mean DASS-21 score for all people with IBD was 8.1 for depression (7-10 indicating moderate disease), 6.6 for anxiety (6-7 suggests moderate disease) and 11.2 for stress (10-12 indicates moderate disease). Individuals with current fistulising CD (representing severe IBD phenotype) mean DASS-21 scores were higher than the wider IBD population, averaging 9.9 for depression (p<0.001), 7.4 for anxiety (p<0.001) & 12.9 for stress (p<0.001) Conclusion Individuals with IBD suffer from high rates of MHIs, with those suffering more severe disease phenotypes scoring worse on mental health assessment tools. Despite the availability of screening and monitoring tools, healthcare providers use these variably and insufficiently. This may result in unmet care needs. Standardisation of care addressing the psychosocial care needs of people with IBD is needed

P1157 Burden of herpes zoster in patients with inflammatory bowel disease treated with immunosuppressive agents

Abstract Background Patients with inflammatory bowel disease (IBD) are at increased risk of infections such as herpes zoster (HZ) due to immunosuppressive (IS) therapy. We conducted a targeted literature review to identify the burden of HZ in patients with IBD treated with IS agents. Methods We conducted a PubMed search to collate publications reporting on HZ in patients with IBD receiving IS treatment (from 01/01/2013 to 01/11/2023; excluding preclinical studies, narrative reviews and case reports). Findings were supplemented with a second PubMed search specific to paediatric patients with IBD (aged ≤18 years). Additional publications were included based on authors’ expertise as well as relevant abstracts presented at ECCO and DDW in 2022 and 2023. Results Overall, 178 publications were identified and 77 were included, along with ten recent congress abstracts. The most common IS treatments were Janus kinase inhibitors (JAKi), including tofacitinib and upadacitinib, followed by tumour necrosis factor inhibitors (TNFi). Additional treatments included anti-interleukin (IL)-23 agents (risankizumab, ustekinumab, mirikizumab) and sphingosine-1-phosphate (S1P) receptor modulators (etrasimod, ozanimod). HZ incidence rates are typically higher in patients with IBD compared with non-IBD populations (7.02–18.34 vs 3.22–11.29 per 1000 patient years, respectively). In paediatric patients, incidence rates are as high as 8.49/1000 patient years, with a standardised incidence ratio of 3.38 compared with the general population. Two studies reported a significant association between IBD and risk of hospitalisation for HZ in children and adolescents. Patients with IBD aged <50 years may have higher incidence of HZ compared with those aged >60 years without IBD. Risk factors for HZ in IBD patients include older age, lower weight, geographic region, prior TNFi failure and use, dose, and combination of IS medications. Increased incidence of HZ is associated with IS medication, particularly JAKis. Limited data exists on novel anti IL-23 agents and S1P receptor modulators, with some studies reporting a similar risk of HZ in treated patients compared with placebo, and others reporting an increased risk. HZ-related discontinuation is rare. Vaccination can reduce the risk of HZ in treated IBD populations, and studies have identified areas to improve vaccination adherence. Conclusion Patients with IBD of all ages, but specifically those aged <50 years, are at higher risk of HZ compared with non-IBD cohorts, and IS medications contribute to this risk. Vaccination against HZ prior to initiating IS treatment could benefit patients with IBD.

P729 Prospective observational study evaluating the effects of GLP1-RA on Inflammatory Bowel Disease (IBD) in patients with Type 2 Diabetes Mellitus (TDM2)

Abstract Background GLP-1 RA are antidiabetic drugs approved for treatment of TDM2 as second-choice therapy for long-term treatment in patients with TMD2 without previous cardiovascular events or as first-choice therapy in patients with previous cardiovascular events and without heart failure (SID/AMD guidelines). Their beneficial effect is not only associated with glycol-metabolic control, but also with a systemic anti-inflammatory action. In view of this anti-inflammatory action, we wanted to assess whether GLP1-RA could have a possible beneficial effect on IBD in terms of laboratory and clinical parameters. Moreover, these drugs have proven to improve liver function and histology, therefore, liver wellbeing may also be included as a cross-sectional element of evaluation in the possible benefits of these therapies. Methods Through the evaluation of 981 medical records of IBD patients followed in the gastroenterology department of the Hospital San Giovanni Antica Sede (SGAS), 71 TDM2 patients were identified. Among these, 21 were recruited for the study. The recruited patients were scheduled for a diabetological examination: GLP-1 RA treatment could then be introduced where indicated. At a 3-month follow-up interval, both the GLP-1 RA treatment group and the subjects that did not have any changes in therapy (control group) underwent re-evaluation of the parameters of interest. All patients in the study were offered the possibility to receive a FibroScan to measure liver stiffness at the start of the study and at the 3-months follow-up. Results A prevalence in the IBD population of TDM2 was found to be 7.2% (vs. Piedmont population prevalence 6.2%, p = 0.31). Out of the 21 patients recruited, 6 received GLP-1 RA treatment. At 3 months, an analysis of the results through the Wilcoxon test showed that the GLP-1 RA treated patients had a reduction in faecal calprotectin levels, an improvement in disease scores, an improvement in glycemic balance and a reduction in CAP and FIB4 when compared to the control group; these results did not reach statistical significance. In contrast, the reduction in BMI reached statistical significance. A comparison of the deltas for the variables under analysis between the two groups was also carried out using the Mann-Whitney test. Concordant and positive trends were observed in the GLP-1 RA-treated group: in this case the reduction in HbA1c reached statistical significance. Conclusion Treatment with GLP-1 RA in patients with TDM2 and IBD appears safe and seems to show benefits from an intestinal, metabolic and hepatic viewpoint. Studies with a larger number of subjects are certainly needed to effectively confirm the benefit of GLP-1 RA in this specific category of patients.

P897 The association of HLA-DQA1*05 carriage with immunogenicity to anti-tumour necrosis factor therapy and drug persistence in Asian patients with inflammatory bowel disease

Abstract Background HLA-DQA1*05 carriage increases anti-tumour necrosis factor (TNF) immunogenicity and lowers drug persistence in European inflammatory bowel disease (IBD) patients. There is a paucity of data for Asian patients. We hypothesize that the HLA-DQA1*05 allele is present in our local IBD population and may be associated with similar clinical and pharmacokinetic outcomes as European cohorts. Methods A single-centre retrospective study of consecutive IBD patients on Infliximab (IFX) or Adalimumab (ADM) was performed. HLA-DQA1*05 carriage was tested with Sanger sequencing. Serum anti-drug antibody (ADA) levels were analysed at each IFX infusion and per physician discretion for ADM. Concomitant immunomodulator (IM) therapy with Azathioprine or Methotrexate was recorded. Primary outcome was immunogenicity to IFX or ADM, defined as ADA concentration ≥10 AU/ml at any time point. Secondary outcomes were loss of response (LOR), defined as IBD symptom-related treatment intensification, and persistence, defined as anti-TNF continuation at end of follow-up. The effects of HLA-DQA1*05 carriage on outcomes and predictors of persistence were analysed. Results 39 patients (28 Crohn’s disease, 11 ulcerative colitis) were included (mean age 39 years, median disease duration 10 years). 24 patients had IFX as first anti-TNF agent (21 with IM, 3 as monotherapy), 7 of whom had second-line ADM with IM. 15 patients had ADM as first anti-TNF agent (13 with IM, 2 as monotherapy), 2 of whom had second-line IFX (1 with IM). 15/39 (38.5%) patients were positive for HLA-DQA1*05. 42/48 (87.5%) of anti-TNF exposures were on IM. In HLA-DQA1*05 carriers compared to non-carriers, development of ADA (61.1% vs 47.8%, p=0.397) and LOR (42.1% vs 31.0%, p=0.433) was numerically higher but not statistically different. Persistence of first anti-TNF agent was similar between carriers and non-carriers at the end of follow-up (median 28.0 months vs 21.5 months, p=0.364) (Figure 1). ADA development was not associated with LOR (p=0.07) or persistence (p=0.29). 19/48 (39.6%) of anti-TNF exposures discontinued treatment at the end of follow-up, 13 of whom experienced LOR. 10/13 (76.9%) of patients with LOR were female. Female sex was significantly associated with anti-TNF non-persistence on univariable (OR 4.82, 95% CI 1.38-16.75, p=0.01) and multivariable logistic regression (OR 7.24, 95% CI 1.35-38.90, p=0.02), after adjusting for HLADQA1*05 carriage, presence of ADA and anti-TNF order (first versus second-line) (Table 1). Conclusion In Asian IBD patients, HLA-DQA1*05 carriage may not affect immunogenicity nor treatment persistence, especially with proactive therapeutic drug monitoring and concurrent IM. Female sex negatively affects persistence. Larger prospective studies are needed.

P1116 Risk of fractures in children and adults with inflammatory bowel disease: A report from the epi-IIRN

Abstract Background Both adult and pediatric patients with inflammatory bowel disease (IBD) are at risk of osteopenia and osteoporosis, nevertheless, whether patients with IBD are subjected to a higher risk for bone fractures is debated. Thus, we aimed to assess the risk for bone fractures, osteopenia and osteoporosis in IBD vs non-IBD patients, using the epi-Israeli IBD Research Nucleus (IIRN) data. Methods Data of patients with IBD and non-IBD matched controls (approximately 3 non-IBD controls per case) were retrieved from the epi-IIRN cohort (January 2005- June 2020) that maintain data on all patients with IBD from the four Israeli HMOs. Data included demographics, osteoporosis medications, fracture data and IBD related characteristics. Patients were stratified by age group (0-17,18-49, and ≥50). Patients with known osteopenia or osteoporosis before IBD diagnosis were excluded. Results We included 32,263 patients with IBD and 89,423 non-IBD controls [48% female, 56% Crohn’s disease (CD)]. Time to first fracture was significantly shorter in female pediatric patients (p=0.01), in both female (p=0.0004) and male (p=0.003) adult and elderly patients (p<0.0001) (Figure 1). Time to diagnosis of osteopenia/osteoporosis in patients with IBD was significantly shorter in all age groups and genders. Rate of fractures was significantly higher in patients with IBD versus controls for all groups, and rate of osteopenia/osteoporosis was also higher in patients with IBD in all groups (Table 1). In a subgroup analysis, fracture rate did not significantly differ between CD and ulcerative colitis (UC) for all age groups, but osteopenia and osteoporosis were significantly higher in CD compared to UC in all age groups. The hazard ratio for fractures in the pediatric IBD population was 1.02 (0.88-1.16) for males and 1.17(0.95-1.44) for females, in adults 1.08 (0.99-1.16) for males and 1.12 (1.02-1.21) for females, and in the elderly 1.2 (1.08-1.32) for males and 1.19 (1.08-1.31) for females. Arthritis was significantly associated with fracture risk [HR: children 1.47 (1.15-1.88); adults 1.3 (1.17-1.44); elderly 1.19 (1.07-1.30)]. In adults and elderly, older age at diagnosis, chronic obstructive pulmonary disease, diabetes and long-term proton pump inhibitors usage were also associated with a significant increase in fracture risk. Conclusion In this large nationwide cohort, patients with IBD had significantly higher risk for bone fractures than matched controls in almost all age groups, with no difference between CD and UC. Additionally, the rate of osteopenia and osteoporosis was higher in patients with IBD, suggesting that further efforts need to be invested in bone health of this at-risk population.

N25 "I Felt So Alone” Exploration of experience of being newly diagnosed with inflammatory bowel disease: a phenomenological study

Abstract Background Individuals recently diagnosed with Inflammatory bowel Disease (IBD) often have unmet informational and psychological needs, leading to distress and anxiety. This lack of support negatively affects their quality of life, mental health, social functioning, and physical outcomes. Additionally, the absence of counselling and peer support isolates many people and places an emotional burden on them. Delayed diagnosis or misdiagnoses due to symptoms being dismissed by health professionals exacerbate the problem. Acknowledging these unmet needs and adverse outcomes, this study aims to shed light on patients' experiences to inform improvements in clinical practice, support services, and workplace policies, particularly during the immediate diagnosis phase. Aim The aim of this study is to explore the experience of people newly diagnosed with IBD and their need for support. Methods The study employed interpretive phenomenology semi-structured interviews following a topic guide and analysed the data using Braun & Clark's (2023) thematic analysis method and Nvivo software. Crohn's and Colitis UK (CCUK) charity acted as the gatekeeper for access to participants. Participants were purposively selected on specific criteria: IBD diagnosis ≤1 year, aged 16 or older, English language proficiency and diversity of demographic and clinical variables. Results Of 49 volunteers who responded to the research advertisement, 15 were selected based on eligibility criteria. Participant characteristics are shown in Table 1. Four themes emerged (Fig 1), with 12 subthemes. Participants expressed extreme dissatisfaction, either due to misdiagnosis or diagnostic delays, indicating the need for timely streamlined diagnosis. Additionally, IBD diagnosis itself triggered distress and anxiety. Participants reported the need for continuous psychological counselling and peer support. Due to symptoms like blood loss and diarrhoea, IBD profoundly affects physical health, emotional wellbeing, social interactions, and work-life balance, hence challenging patients' sense of normalcy. However, patients demonstrated resilience via lifestyle adjustments, social support networks, and coping strategies. Conclusion This qualitative study sheds light on the profound impact of an IBD diagnosis. It reveals emotional struggles and the need for streamlined diagnosis and psychological support. Lifestyle disruptions affect physical and mental health, but participants adapt through support and coping. These insights have practical implications for improving care, mental health services, workplace adjustments, social support, and coping resources for the newly diagnosed IBD population. Future research should expand to larger, diverse patient samples. Table 1:

P151 Characterization of platelet activation profile in Inflammatory Bowel Disease

Abstract Background Platelet-related markers associated with a procoagulant state have been described for Immune-mediated Inflammatory Diseases (IMIDs), but a broader profiling of these abnormalities in Inflammatory Bowel Disease (IBD) is lacking. Methods Cross-sectional study to describe and compare platelet biomarkers of IBD outpatients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC), vs healthy controls (HC). Patients over 18 years old with a diagnosis of CD or UC according to the European Crohn’s and Colitis Organization (ECCO) criteria were included. Fecal calproctectin (Fcal) >=150ug/g was used as a cutoff level for active disease. Exclusion criteria for IBD patients are listed under Table 1. Fibrinogen (FBG) receptor on platelet’s surface was determined with anti-CD41 and anti-CD61 monoclonal antibodies (mAbs); and von Willebrand factor receptor with anti-CD42a and anti-CD42b mAbs. Platelet activation markers [TRAP and ADP-induced activation of fibrinogen (FBG) receptor, and P-selectin (Psel) and CD63 exposure] were determined, respectively, through binding of PAC1, anti-P-selectin and anti-CD63 (mAbs). All variables were determined by flow cytometry. Results 55 patients (27 CD, 28 UC) and 75 HC have been included. 43 IBD patients had active disease (21 CD, 22 UC). Complete baseline characteristics of the IBD population are described in Table 1. Basal Psel (% of positive cells) was increased in CD vs UC (median [IQR]: 5.64 [4,4-10,4] vs 2,9 [1,8-6,8], p=0,02) and vs HC (3,5 [1,4-6,8], p=0,008). ADP-induced Psel was increased in CD vs HC (mean, SD: 49.92, SD 12.75 vs 41.943, SD13.15, p=0,007). Basal CD63 (% of positive cells) was significantly higher in active IBD vs HC (W = 1143, p = 0.02) and inactive IBD vs HC (W = 528, p= 0.006). CD42a (% of positive cells) was decreased in IBD vs HC (W = 1128.00, p=0.007) and CD vs HC (W = 777.00, p =0.04). CD42b (% of positive cells) was also decreased in IBD vs HC (mean, SD: 106.9 SD, 17.32 vs 115.7, SD 28.42, p=0,01) and CD vs HC (104.06 SD 14.49, p=0,03). No differences in basal or TRAP/ADP induced PAC binding, and in CD41 or CD61 expression were observed among groups. Multiple linear regression showed association of Fcal with basal Psel in IBD patients (p=0,02); and Spearman’s correlation showed negative moderate correlation between Fcal and basal Psel (r=0,3; p=0,003) Conclusion Features of platelets in IBD suggest increased platelet degranulation and reduced vWF receptor with regards to healthy controls, specially in CD, but no differences in FBG-related receptors. Inverse moderate correlation between Fcal and Psel in IBD patients suggests depletion of intra-platelet granules at higher levels of gut inflammation.

Performance of ASCVD Risk Prediction Models in Individuals With Inflammatory Bowel Disease: A UK Biobank Study.

Lay Summary This study suggests that the current atherosclerotic cardiovascular disease risk prediction models used in clinical practice performed better in the non–inflammatory bowel disease (IBD) cohort compared with IBD, highlighting the need for a more specific risk prediction model tailored to the IBD population.

Safety and Effectiveness of Vedolizumab and Ustekinumab in Elderly Patients with Inflammatory Bowel Disease: A Real-Life Multicentric Cohort Study.

Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.

Economic impact of inflammatory bowel disease in Catalonia: a population-based analysis.

Inflammatory bowel disease (IBD) has a major economic impact on healthcare costs. The aim of this study was to evaluate the current healthcare expenditure associated with IBD in a population-wide study in Catalonia. Retrospective observational study. All patients with IBD included in the Catalan Health Surveillance System (CHSS) were considered eligible. The CHSS compiles data on more than 7 million individuals in 2020 (34,823 with IBD). Data on the use of healthcare resources and its economic impact were extracted applying the International Classification of Diseases, 10th revision, Clinical Modification codes (ICD-10-CM codes). Health expenditure, comorbidities, and hospitalization were calculated according to the standard costs of each service provided by the Department of Health of the Catalan government. The data on the IBD population were compared with non-IBD population adjusted for age, sex, and income level. IBD costs were recorded separately for Crohn's disease (CD) and ulcerative colitis (UC). Prevalence of comorbidities was higher in patients with IBD than in those without. The risk of hospitalization was twice as high in the IBD population. The overall healthcare expenditure on IBD patients amounted to 164M€. The pharmacy cost represents the 60%. The average annual per capita expenditure on IBD patients was more than 3.4-fold higher (IBD 4200€, non-IBD 1200€). Average costs of UC were 3400€ and 5700€ for CD. The risk of comorbidities was twice as high in patients with IBD and their use of healthcare resources was also higher than that of their non-IBD counterparts. Per capita healthcare expenditure was approximately 3.4 times higher in the population with IBD. The study was not previously registered.

Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease.

Inflammatory bowel disease (IBD) is often associated with complex extraintestinal manifestations. The incidence of nonalcoholic fatty liver disease (NAFLD) in IBD populations is increasing yearly. However, the mechanism of interaction between NAFLD and IBD is not clear. Consequently, this study aimed to explore the common genetic characteristics of IBD and NAFLD and identify potential therapeutic targets. Gene chip datasets for IBD and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules in those datasets related to IBD and NAFLD. ClueGO was used for biological analysis of the shared genes between IBD and NAFLD. Based on the Human MicroRNA Disease Database (HMDD), microRNAs (miRNAs) common to NAFLD and IBD were obtained. Potential target genes for the miRNAs were predicted using the miRTarbase, miRDB, and TargetScan databases. Two-sample Mendelian randomization (MR) and two-way MR were used to explore the causal relationship between Interleukin-17 (IL-17) and the risk of IBD and NAFLD using data from GWAS retrieved from an open database. Through WGCNA, gene modules of interest were identified. GO enrichment analysis using ClueGO suggested that the abnormal secretion of chemokines may be a common pathophysiological feature of IBD and NAFLD, and that the IL-17-related pathway may be a common key pathway for the pathological changes that occur in IBD and NAFLD. The core differentially expressed genes (DEGs) in IBD and NAFLD were identified and included COL1A1, LUM, CCL22, CCL2, THBS2, COL1A2, MMP9, and CXCL8. Another cohort was used for validation. Finally, analysis of the miRNAs identified potential therapeutic targets. The MR results suggested that although there was no causal relationship between IBD and NAFLD, there were causal relationships between IL-17 and IBD and NAFLD. We established a comorbid model to explain the potential mechanism of IBD with NAFLD and identified the chemokine-related pathway mediated by cytokine IL-17 as the core pathway in IBD with NAFLD, in which miRNA also plays a role and thus provides potential therapeutic targets.

Impact of inflammatory bowel disease on women's reproductive life: a questionnaire-based study.

Inflammatory bowel diseases (IBDs) have a peak incidence between the second and fourth decades of life and can affect women's reproductive life. Our study aimed to assess the impact of IBD on the reproductive life of female patients with this condition. Cross-sectional study. Women with IBD followed at our IBD Unit and a group of healthy controls were enrolled. Data on reproductive life were collected using a dedicated questionnaire. The study included 457 women, of whom 228 had IBD, and 229 age-matched healthy controls. No differences were found in the use of contraceptives, infertility, and endometriosis. The risk of spontaneous and voluntary abortions was significantly higher in IBD patients than in healthy controls [odds ratio (OR) 2 and 3.62, respectively]. The risk of obstetrical complications in the IBD population was more than six times higher in patients who experienced disease reactivations during pregnancy than in those with persistent remission [OR 6.9, 95% confidence interval (CI) 1.51-31.28]. Finally, we found that the chances of breastfeeding were 66% lower in patients with IBD than in controls (OR 0.44, 95% CI 0.22-0.91). Our study underlines the negative impact of IBD on women's reproductive life, supporting the need for proactive preconception counseling.

The Impact of Obesity on Inflammatory Bowel Disease.

Obesity is prevalent in the inflammatory bowel disease (IBD) population, particularly in newly developed countries where both IBD and obesity in the general population are on the rise. The role of obesity in the pathogenesis of IBD was entertained but results from available studies are conflicting. It does, however, appear to negatively influence disease course whilst impacting on our medical and surgical therapies. The pro-inflammatory profile of the visceral adipose tissue might play a role in the pathogenesis and course of Crohn's Disease (CD). Interestingly, isolating the mesentery from the surgical anastomosis using a KONO-S technique significantly decreases anastomotic recurrence rate. Anti-obesity therapy is not widely used in IBD but was suggested as an adjunctive therapy in those patients. In this review, we aimed to highlight the epidemiology of obesity in IBD and to describe its influence on disease course and outcomes.

Assessing vitamin D as a biomarker in inflammatory bowel disease.

A reliable serum biomarker for inflammatory bowel disease (IBD) activity is needed. Vitamin D is involved in inflammation and has been demonstrated to be low in IBD patients with active disease. It is routinely measured in IBD patients. Therefore, vitamin D may have a role as a serum biomarker in IBD. This study aims to investigate whether serum vitamin D may be useful as a biomarker in IBD in a real-world IBD population. Patients were identified by review of fecal calprotectin (FCP) results, and those who had a clinical review, vitamin D test, and FCP performed within 3 months were included. Clinical scores were calculated from chart review. Nonparametric tests were used to investigate vitamin D and FCP levels, serum biomarkers, and clinical scores. Of 616 patients identified, 325 episodes of matched vitamin D level and biomarker data were obtained. A statistically significant correlation was found between vitamin D levels and FCP levels for all patients (r = -0.19 [s -0.29 to -0.080], P < 0.001]. This remained true when patients were divided into IBD subsets. Low vitamin D was associated with partial Mayo scores and C-reactive protein (CRP) to albumin ratio in ulcerative colitis, and CRP and CRP/albumin ratio in Crohn's disease. Vitamin D level is negatively correlated with FCP and it may be considered as an adjunct biomarker at this stage. A prospective study would be beneficial to investigate further correlations between vitamin D and existing biomarkers of inflammation in IBD.

Factors that influence infliximab biosimilar trough levels in the pediatric inflammatory bowel disease population

ABSTRACT Background The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly investigated. The aim of this study was to investigate factors predicting IFX-BioS trough levels (TLs). Research design and methods IBD children with an indication to start IFX-BioS were included in this prospective observational study (January 2021-June 2022). TLs were measured at the 4th and 6th infusions and correlated with several covariates. Results A total of 110 TLs in 55 children were included. The multivariate linear regression model at the 4th infusion found a positive correlation between TLs and age at diagnosis (B:1.950, 95% CI: [0.019, 3.882], p = 0.048) and IFX-BioS dose/kg (B:1.962, 95% CI: [0.238, 3.687], p = 0.029), and a negative correlation with clinical scores (B:-0.401, 95% CI: [-0.738, -0.064], p = 0.023). At the 6th infusion, female gender (B:6.887, 95% CI: [0.861, 12.913], p = 0.029), hemoglobin (B:1.853, 95% CI: [0.501, 3.204], p = 0.011), and IFX-BioS dose/kg (B:1.792, 95% CI: [0.979, 2.605], p < 0.001) were found to be positively correlated to TLs. No association between combined clinical and biochemical remission and TLs was found. Conclusions This study discovered some predictors for IFX-BioS TLs in IBD children. Knowledge of predictive factors could help physicians choose the best dosing regimen.

Investigation of optimal hernia repair techniques in patients with inflammatory bowel disease.

Multiple laparotomies, immunosuppressive therapy, wound infection, and malnutrition are risk factors for incisional hernia development, which places inflammatory bowel disease (IBD) patients at high risk. With advances in minimally invasive techniques, this study assesses incisional hernia repair techniques and complications in the IBD population. A single-center, retrospective review of adults with IBD who underwent incisional hernia repair from 2008 to 2022. Complications relative to operative approach and mesh placement location were assessed using descriptive and univariate statistics. Eighty-eight IBD patients underwent incisional hernia repair. Fifty-two (59.1%) were on immunomodulators and 30 (34.1%) were repaired primarily. Thirty-five (39.7%) hernias recurred, of whom 19 (33%) had mesh placed. Three (30%) occurred in onlay repairs and 16 (33%) occurred in underlay repairs. Subdivision of underlay repairs into intraperitoneal, preperitoneal and retrorectus mesh placement revealed recurrence rates of 35.1%, 50%, and 14.3%, respectively. Patients with open repair were more likely to have intraoperative bowel injury (28.6% vs 9.7%, p = 0.041) and develop postoperative seromas/abscesses (12.5% vs 0%, p = 0.001) and wound complications (17.9% vs 0%, p = 0.012) compared to laparoscopic. Seromas/abscesses developed more frequently in onlay repairs compared to underlay (40% vs 2.13%, p = 0.001). Twelve (13.6%) patients presented with postoperative small bowel obstruction (SBO), 7 (58.3%) of whom had mesh placed, and 6 (85.7%) were underlay. All SBO after underlay repair had intraperitoneally placed mesh. When comparing surgeons, hernias were more likely to recur performed by colorectal surgeons compared to hernia surgeons (63.3% vs 21.3%, p < 0.001). In IBD patients, minimally invasive approaches lead to fewer perioperative complications compared to open. Underlay mesh placement demonstrated decreased incidence of seroma/abscess formation compared to onlay. When sub-grouped, underlay placements were similar in terms of complications. Retrorectus placement, however, had fewer recurrences and no readmissions for SBO. This suggests a minimally invasive approach or placement of retrorectus mesh may provide the optimal repair in this patient population.

Characterizing the pre-clinical phase of inflammatory bowel disease

Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor modification, but this pre-clinical phase of disease remains poorly characterized. Using measurements from 17 hematological and biochemical parameters taken up to 10 years before diagnosis in over 20,000 IBD patients and population controls, we address this at massive scale. We observe widespread significant changes in multiple biochemical and hematological parameters that occur up to 8 years before diagnosis of Crohn's disease (CD) and up to 3 years before diagnosis of ulcerative colitis. These changes far exceed previous expectations regarding the length of this pre-diagnosticphase, revealing an opportunity for earlier intervention, especially in CD. In summary, using a nationwide, case-control dataset-obtained from the Danish registers-we provide a comprehensive characterization of the hematological and biochemical changes that occur in the pre-clinical phase of IBD.