Management Of Inflammatory Bowel Disease Patients Research Articles

Causal association of inflammatory bowel disease with sarcoidosis and the mediating role of primary biliary cholangitis.

Previous observational epidemiological studies have identified a potential association between inflammatory bowel disease (IBD) and sarcoidosis. Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between IBD with genetic susceptibility to sarcoidosis, as well as to explore the potential mediating role. The genetic associations were obtained from publicly available genome-wide association studies (GWASs) of European ancestry. The IBD dataset has 31,665 cases and 33,977 controls, consisting of 13,768 individuals with ulcerative colitis (UC) and 17,897 individuals with Crohn's disease (CD). The genetic associations of sarcoidosis with 4,854 cases and 446,523 controls. A bidirectional causality between IBD and sarcoidosis was implemented to be determined by a two-sample MR approach. The inverse variance weighted (IVW) method was utilized as the main statistical method, and a series of sensitivity analyses were performed to detect heterogeneity and horizontal pleiotropy. A two-step MR approach was used to investigate whether the mediating pathway from IBD to sarcoidosis was mediated by PBC. The forward MR analysis indicated that genetic predisposition to IBD was significantly linked to an increased risk of sarcoidosis (OR = 1.088, 95% CI: 1.023-1.158, pIBD-sar = 7.498e-03). Similar causal associations were observed in CD (OR = 1.082, 95% CI: 1.028-1.138, pCD-sar = 2.397e-03) and UC (OR = 1.079, 95% CI: 1.006-1.158, pUC-sar = 0.034). Reverse MR analysis revealed that genetic susceptibility to sarcoidosis was correlated with an augmented risk of CD (OR = 1.306, 95% CI: 1.110-1.537, psar-CD = 1.290e-03) but not IBD or UC. The mediation analysis via two-step MR showed that the causal influence of IBD and CD on sarcoidosis effects was partly mediated by PBC, and the mediating effect was 0.018 (95% CI: 0.005-0.031, p = 7.596e-03) with a mediated proportion of 21.397% in IBD, and 0.014 (95% CI: 0.004-0.024, p = 7.800e-03) with a mediated proportion of 17.737% in CD. The MR analysis provided evidence substantiating the causal effect of IBD (CD and UC) on an increased risk of sarcoidosis, with PBC playing a mediating role in IBD and CD. However, sarcoidosis only enhances the risk of developing CD, but not IBD or UC. These findings illuminate the etiology of sarcoidosis and contribute to the management of IBD patients.

P507 Can systematic upper gastrointestinal endoscopy benefit patients with Inflammatory Bowel Disease?

Abstract Background In the context of Inflammatory Bowel Disease (IBD), a comprehensive understanding of disease extent and related complications is essential for effective clinical care. While Crohn’s disease (CD) can affect the digestive tract from mouth to anus, ulcerative colitis (UC) is limited to the rectum and colon. This study investigates the potential utility of systemic gastroscopy in IBD management. Methods We conducted a retrospective cohort study using data from our gastroenterology department. Patients diagnosed with IBD who underwent systematic upper gastro-intestinal endoscopy (UGE) were included. Clinical, endoscopic, and histopathological data were gathered and analyzed. Results 141 CD and 61 UC patients were included. The mean age was 40,7 years, and the female to male ratio was 1,33. 95.5% of these patients had no upper gastrointestinal symptoms prior to undergoing UGE. Among the symptomatic participants, the most frequent complaints were dyspepsia and pyrosis. In 73.9% of asymptomatic patients, UGE showed a normal mucosa, the abnormalities found in these patients were: non-specific gastro-duodenal erosions and ulcerations (8.5% of cases), mild esophagitis (4% of cases), aphthoid ulcerations (2% of cases) and duodenal stenosis (0.5% of cases). In symptomatic participants, UGE was normal in 4 cases, it showed atrophy of the fundus mucosa in 1 case, esophageal hernia in 2 cases, and esophageal aphthoid ulcerations in 1 case. Gastro-duodenal biopsies were consistently undertaken, among asymptomatic patients, histopathological abnormalities included: lymphoplasmacytic Infiltrate (47,7%) and helicobacter pylori (HP)(38,1 %), nonspecific duodenitis (44,7%), gastric metaplasia, focal gastritis, atrophic villi and crypt hyperplasia were objectified in 3,5%, 3%, 1,5% and 0,5% of cases. Granulomas were noted in only 1% of cases, and Cryptitis and crypt abscess in 0,5%. In symptomatic participants, histologic abnormalities included metaplasia in the fundus (0.5%), lymphoplasmacytic infiltrate (2.5%), HP (2,4%), atrophic villi in the duodenum (0.5%) and glandular atrophy (0.5%). Our analysis did not reveal any significant associations between endoscopic lesions and UC (p=0.36) or CD (p=0.09) nor the presence of symptoms (p=0.08), however, a significant association was identified between male gender and the presence of endoscopic lesions (p=0.033). Conclusion Although IBD patients might be asymptomatic, UGE and histopathological examination may reveal upper gastrointestinal abnormalities and aid to a better assessment and management of IBD patients.

P499 Anorectal Motility Disorders In Inflammatory Bowel Disease Patients

Abstract Background In spite of prolonged disease remission of IBD patients, induced by the new biological molecules, a significant number of them suffer from persistent debilitating symptoms with major impact on the quality of life. Frequently, these symptoms are due to post-inflammatory motility changes and misinterpreted as functional disorders. Our aim is to identify and characterize the anorectal motility dysfunction in IBD patients. Methods We are conducting an ongoing prospective study started in August 2019, which includes the IBD patients admitted in a Tertiary Gastroenterology Centre in Bucharest, with specific symptoms (anorectal pain, incontinence, difficult defecation). We perform high resolution anorectal manometry using Sandhill Scientific systems, the parameters being analysed using InSIGHT software. The manometric testing comprise measurements of anorectal pressure at rest, during squeeze, simulated evacuation, rectoanal inhibitory reflex (RAIR) and rectal sensory testing, in compliance with International Anorectal Physiology Working Group protocol Results We studied 30 patients (18 patients with Ulcerative Colitis and 12 patients with Crohn’s Disease, 18 females and 12 males, mean age 40 (±12.85) years. Only 33% (10 patients) had rectal active involvement. Symptoms were reported by 87% (26) patients: anal incontinence (85%), difficult evacuation (35%) and urgency (46%); rectal inflammation was not correlated with the presence of symptoms in our study group (p=0.28). Perianal surgical interventions didn’t represent a risk factor for fecal incontinence (p=0.18), or for dyssinergic defecation (p=0.1). Modified manometric parameters were found in 23 patients (79%). Low resting pressures were registered in 48% of patients; 55% of them presented low squeeze pressures; during push maneuvers, 34% of patients had insufficient rectal propulsive force, presenting low rectal pressures and 59% of them lacked anal canal relaxation. We performed sensibility testing on 18 patients: 9 patients presented criteria for hypersensitivity, hence reduced rectal compliance; 7 patients presented rectal hyposensitivity, while only 2 patients had normal rectal sensation. Recto-anal inhibitory reflex (RAIR) was present only in 28% of the patients, reflecting the dysfunction of the enteric neural system. Conclusion Patients with inflammatory bowel disease (IBD) have significantly higher rates of functional anorectal disease. Therefore, pelvic floor investigation is an essential tool in the investigation and management of IBD patients with ongoing symptoms not thought to be related to an IBD flare.

P418 Lipopolysaccharide-Binding Protein (LBP) in Crohn's Disease (CD) Patients: A Promising Non-Invasive Biomarker Monitoring Disease Activity

Abstract Background Current biomarkers of inflammatory bowel disease (IBD) monitoring (serum C-reactive protein (CRP) and faecal calprotectin (FC)) have limitations in terms of specificity (SP) and sensitivity (SE), especially for Crohn’s disease (CD) patients. Lipopolysaccharide-binding protein (LBP) is a soluble acute-phase protein and is thought to partly reflect intestinal permeability by binding to bacterial lipopolysaccharides. The search for new biomarkers to monitor disease activity would improve the management of IBD patients. Methods This is a retrospective study including 69 IBD patients (43 CD and 26 ulcerative colitis (UC)) and 21 healthy controls (HC). Serum LBP levels were measured by enzyme-linked immunosorbent assay. Clinical, biological and endoscopic parameters were analysed for IBD patients. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP. Results Demographics and baseline data of the overall cohort is presented in Table 1. IBD patients displayed a significantly higher LBP median (29.6 µg/mL [19.8-38.8] in CD and 22.8 [13.7-38.8] in UC) than HC (5.5 [4.4-6.5], P < 0.001) with no overlapping distributions, a finding supported by an AUC of 0.997 and 0.989, respectively for CD and UC patients (Figures 1A). In CD patients, LBP levels gradually increased with endoscopic severity, demonstrating a 1.7-fold rise in active patients compared to remitter patients (P=0.02) (Figure 1B). LBP levels were higher in Montreal B1 compared to B2 and B3 CD patients (P < 0.001) (Figure 1C). Overall, a robust correlation was observed between LBP and CRP (ρ=0.75, P < 0.001). The correlation increased upon the exclusion of cases with normal CRP levels but active endoscopic disease (ρ=0.79, P < 0.001). In those endoscopically active patients with normal CRP, LBP level was higher than in remitter patients (34.3 [29.4-37.6] vs 19.1 [10-24.7], P=0.01) with a discriminative cut-off of 25 µg/mL (SE of 100%, SP of 89%). Likewise, LBP level exhibited a positive correlation with FC (ρ=0.42, P < 0.01) which was further strengthened after excluding cases where FC measurements did not align with endoscopic activity (ρ=0.53, P < 0.01). The median LBP for those patients was 25.6 [18.5-31.5], reflecting again the interest of LBP measurement to evaluate CD activity when FC lacks sensibility. Conclusion Our study suggests that LBP might be a promising non-invasive biomarker for monitoring disease activity, especially in CD patients. Furthermore, in clinical situations where current biomarkers (CRP and FC) lack sensitivity for assessing disease activity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.

P502 Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4 T cells as predictors for response to integrin alpha4 beta7-blocking therapy in patients with Inflammatory Bowel Disease

Abstract Background Despite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors. Methods Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response. Results Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4+ memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients. Conclusion Our study provides a comprehensive framework for assessing therapy response and understanding the mechanisms underlying resistance in chronic immune-mediated inflammatory diseases such as IBD. Identifying personalized treatment strategies based on individual patient characteristics, as exemplified by our "stratify to target" approach, can significantly improve IBD management.

P337 Proactive therapeutic drug monitoring of Adalimumab, but not HLADQ*A1 determination, predicts inflammatory bowel disease outcome and persistence of treatment

Abstract Background Anti-TNF drugs have proven effective in managing Inflammatory Bowel Disease (IBD), but a significant percentage of patients exhibit primary or secondary non-response. Therapeutic drug monitoring (TDM) is a valuable tool for optimizing patient management. HLA-DQA1*05 gene has been investigated as a potential marker for immunogenicity and loss of response to anti-TNF therapy.This prospective, multicentric study aimed to assess the clinical impact of determining Adalimumab (ADA) levels and anti-adalimumab antibodies (Abs) in IBD patients and the influence of the HLA-DQA1*05 allele on the response and maintenance of ADA treatment over a 24-month follow-up. Methods Patients initiating ADA treatment between October 2020 and October 2022 were enrolled. Demographic data and IBD characteristics were recorded. Clinical Activity Index, C reactive protein (CRP), faecal calprotectin (FC), endoscopy or radiological activity, Global Physician Assesment (GPA) and PRO (by IBDQ-9) were prospectively collected at baseline and at the same time that ADA levels: week 4, 10, 30 and 12 months. HLA-DQA1*05 was genotyped at baseline. Pearson coefficient was utilized to assess correlations between ADA levels and disease activity. Results We included 170 (age 42±17 years, 54% female) IBD patients (74% Crohn`s Disease, 24% Ulcerative Colitis and 2% Indeterminate colitis) who started ADA (85% naïve to anti-TNF). At baseline, 80% had an active disease (GPA=1); CRP and FC were 10.72 ±17.85 mg/L and 568 ±775 µg/g; PRO at baseline was 63±8.6. HLA was determined in 167 patients, of whom 71 (42%) were HLA-DQA1*05 positives. Median follow up was 17 months. No correlation between HLA and drug levels or Abs was founded. ADA levels at the end of induction was correlated with ADA levels during follow up. ADA serum concentration >7 µg/mL at weeks 4 and 10 correlated with improved clinical response at corresponding time points (p<0.001). Patients with ADA levels >7 µg/mL at week 10 demonstrated better disease control at 12 months. 41 patients stopped ADA. It was associated with active disease, low ADA levels, and adverse clinical and laboratory markers. HLA-DQA1*05 positivity did not correlate with adverse reactions or Abs during the observational period. A significative improvement in PROs in patients who started treatment with ADAL (62.73 at baseline and 69.42 at week 30) (p<0.001) was observed. Conclusion Early Drug level monitoring of Adalimumab may improve the management of IBD patients. PCR, CF and GPA at week 10 may predict treatment failure. ADA levels >7 µg/mL is associated with a better clinical response in short and long-term, independent of HLADQA1*05.

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

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

Transcriptome analysis identifies genetic risk markers and explores the pathogenesis for inflammatory bowel disease

Inflammatory bowel disease (IBD) is an incurable and disabling bowel disease driven by multiple risk factors that severely limit patients' quality of life. We integrated the RNA-sequencing data of 1238 IBD patients, and investigated the pathogenesis of IBD by combining transcriptional element prediction analysis and immune-related analysis. Here, we first determined that KIAA1109 is inhibited in IBD patients. The expression of KIAA1109 and NOD2, the key receptor of NOD-like receptors, showed a negative correlation. The NOD-like receptor signaling pathway is activated and exerts transcriptional regulation on the chemokines CXCL1 and CXCL2 through the activation of the transcription factors NFκB and AP1. Analysis of immune infiltration revealed that the expression of chemokines CXCL1 and CXCL2 may regulate the inflammatory response induced by immune cells. These findings suggest that the KIAA1109-NOD2-NFκB/AP1-CXCL1/CXCL2 regulatory axis is the molecular mechanism of IBD pathogenesis, which will provide a new perspective for the diagnosis, treatment and management of IBD patients.

Офтальмологические проявления воспалительных заболеваний кишечника

The article presents up-to-date data on the pathogenesis, classification and frequency of ophthalmic extraintestinal manifestations (OEM) of inflammatory bowel diseases (IBD). Early detection of OEM is an important aspect of the management of IBD patients, since timely and effective therapy of combined immuno-inflammatory pathology has a positive effect on the prognosis of the disease and reduces the disability of IBD patients. The article provides information on methods of diagnostic of ophthalmic manifestations of IBD and treatment of patients with combined immuno-inflammatory pathology. The close interaction of gastroenterologists and ophthalmologists is an important link in the implementation of multidisciplinary management of patients with IBD and autoimmune uveitis. The use of genetically engineered biological drugs helps to control the course of IBD and ophthalmic manifestations, which prevents the development of complications and improves the quality of life of patients

Iranian Consensus Guideline for Pharmacotherapy with Biologics and Small Molecules Drugs in Adults with Inflammatory Bowel Diseases.

Background: Pharmacotherapy with biologics and small molecules, as the more effective therapies for moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), is complex. Choosing the best methods for their utilization in order to induce and maintain remission are critical for practicing gastroenterologists. We aimed to develop an Iranian consensus on the management of inflammatory bowel disease (IBD) patients with biologics and small molecules. Methods: A Delphi consensus was undertaken by experts who performed a literature summary and voting process. Quality of evidence was assessed using the Grading and Recommendations Assessment, Development, and Evaluation; and an additional risk of bias-protocol. Results: Following an extensive search of the literature, 219 studies were used to determine the quality of the evidence. After three rounds of voting, consensus (defined as≥80% agreement) was reached for 87 statements. Conclusion: We considered different aspects of pharmacotherapy in this consensus. This guideline, along with clinical judgment, can be used to optimize management of IBD patients.

Mental Illnesses in Inflammatory Bowel Diseases: mens sana in corpore sano.

Background and aims: Inflammatory bowel diseases (IBD) are chronic disorders associated with a reduced quality of life, and patients often also suffer from psychiatric comorbidities. Overall, both mood and cognitive disorders are prevalent in chronic organic diseases, especially in the case of a strong immune component, such as rheumatoid arthritis, multiple sclerosis, and cancer. Divergent data regarding the true incidence and prevalence of mental disorders in patients with IBD are available. We aimed to review the current evidence on the topic and the burden of mental illness in IBD patients, the role of the brain-gut axis in their co-existence, and its implication in an integrated clinical management. Methods: PubMed was searched to identify relevant studies investigating the gut-brain interactions and the incidence and prevalence of psychiatric disorders, especially of depression, anxiety, and cognitive dysfunction in the IBD population. Results: Among IBD patients, there is a high prevalence of psychiatric comorbidities, especially of anxiety and depression. Approximately 20-30% of IBD patients are affected by mood disorders and/or present with anxiety symptoms. Furthermore, it has been observed that the prevalence of mental illnesses increases in patients with active intestinal disease. Psychiatric comorbidities continue to be under-diagnosed in IBD patients and remain an unresolved issue in the management of these patients. Conclusions: Psychiatric illnesses co-occurring in IBD patients deserve acknowledgment from IBD specialists. These comorbidities highly impact the management of IBD patients and should be studied as an adjunctive therapeutic target.

The Optimal Management of Inflammatory Bowel Disease in Patients with Cancer.

Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.

STANDARDIZATION ISSUES FOR FECAL CALPROTECTIN MEASUREMENT IN INFLAMMATORY BOWEL DISEASE

Fecal calprotectin (FC) is a non-invasive marker of intestinal inflammation that is often used to guide therapeutic decisions in patients with inflammatory bowel disease (IBD). Each step in FC measurement can influence the results, leading to misinterpretation and potentially affecting the management of patients with IBD. To date, FC measurements are highly heterogeneous, and none of the existing methods is generally accepted as a standard. <b>Aim:</b> to provide a clear position on the preanalytical and analytical steps of FC measurement and to minimize the risk of misinterpretation. <b>Materials and methods.</b> A systematic search of the scientific literature was carried out in the PubMed/MEDLINE, EMBASE and Cochrane databases until June 2021 to identify all studies reporting data on FC measurement (for the key phrases "fecal markers of inflammation", "calprotectin", "inflammatory bowel diseases"). <b>Results.</b> Based on available data, quantitative tests should be preferred to measure FC; FC measurements should always be performed using the same method, and factors affecting his levels should be taken into account when interpreting results. <b>Conclusion.</b> FC concentrations determine treatment decisions by physicians. Although FC is playing an increasingly important role in the management of IBD patients, large multicenter studies should be conducted to determine the reproducibility and to confirm the diagnostic accuracy of the available FC tests.

Causal Association of Inflammatory Bowel Disease on Anorexia Nervosa: a Two-Sample Mendelian Randomization Study

Anorexia nervosa (AN) is a severe and complex psychiatric disorder with the highest mortality rate of all psychiatric disorders. Previous observational studies indicated inconclusive association between inflammatory bowel disease (IBD) and AN, and the causal effect remains unclear. We aimed to test the hypothesis that a causal relationship exists between IBD and the risk of AN using the bi-directional two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was employed as the primary analysis. Furthermore, various sensitivity analyses were conducted to assess the robustness of our results. Notably, IVW analysis of univariable MR revealed that genetically predicted IBD were significantly casually associated with AN risk. In subgroups, consistent positive causal associations with AN might show in ulcerative colitis (UC) and Crohn’s disease (CD). Besides, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. Our study identifies that genetic susceptibility to IBD (NSNP = 12, odds ratio [OR]: 1.143, 95% CI: 1.032–1.266, P = 0.01), including UC (NSNP = 6, OR: 1.153, 95% CI: 1.022–1.301, P = 0.021) and CD (NSNP = 4, OR: 1.153, 95% CI: 1.008–1.319, P = 0.037), could be causally associated with an increased risk of AN. No evidence was observed on the causal effect of AN on IBD, including UC and CD. Our findings may have clinical benefits for early detection of AN and clinical decisions on management of IBD patients.

Molecular characterization of visible low-grade dysplastic lesions in patients with inflammatory bowel disease

We studied pathogenic gene mutations and tumor mutation burden (TMB) in visible low-grade dysplastic lesions in patients with inflammatory bowel disease (IBD). The dysplastic lesions with histologically normal mucosa in the background (group 1) were compared with dysplastic lesions occurring either in a background of chronic active colitis (group 2) or associated with synchronous carcinomas regardless of the status of the background mucosa (group 3). The TMB in group 3 was consistently higher in comparison to the group 1 and group 2 lesions, although the difference was not statistically significant. There also seemto be different mutation profiles between the groups, indicating different pathways of tumor pathogenesis. More frequent APC mutations were seen in group 1 as compared to other groups and TP53 mutations were seen in groups 2 and 3, but none in group 1. Molecular characterization could potentially be used as an ancillary prognostic marker in challenging cases to guide the further management of IBD patients with visible dysplastic lesions.

P437 Early therapeutic drug monitoring of Adalimumab, but not HLADQ*A1 determination, predicts inflammatory bowel disease outcome

Abstract Background Anti-TNF drugs are effective treatments for the management of Inflammatory Bowel Disease (IBD), yet treatment failure is common. Monitoring drug levels and their antibodies (ATIs) can be useful to optimize the management of patients. In addition, the HLA-DQA1*05 gene has been recently related as a possible marker of immunogenicity and loss of response to anti-TNF therapy.The aim of this study was to evaluate the clinical impact of determining adalimumab (ADA) levels and anti-adalimumab ATIs in patients with IBD, and the influence of the HLA-DQA1*05 allele on the response and maintenance of adalimumab treatment in this population. Methods This observational, multicentric and prospective study enrolled patients who started treatment with ADA from October 2020 to October 2022. Demographic data and IBD characteristics were recorded. Clinical Activity Index (Harvey Index and Parcial Mayo Score) and C reactive protein(CRP), faecal calprotectin (FC), endoscopy or radiological activity, Global Physician Assesment (GPA) and PRO (by IBDQ-9) were prospectively collected at baseline and at the same time that ADA levels: week 4, 10, 30 and 12 months. HLA-DQA1*05 was genotyped at baseline. Pearson coefficient was used to assess the correlation between ADA levels and activity disease at different points Results We included 131 (age 42±17 years, 56% female) IBD patients (78% Crohn`s Disease, 21% Ulcerative Colitis and 1% Indeterminate colitis) who started treatment with ADA (80% were naïve to anti-TNF and 57% started ADA combined with immunomodulator treatment). At baseline, 81% had an active disease (Global Physician Assesment=1), 49% had CRP >5 mg/L and 77% had FC > 150 mg/kg. PRO at baseline was 63±9.1. HLA was determined in 99 patients, of whom 42 (42%) were HLA-DQA1*05 positives. We found a positive correlation between PRO score and Hb levels and albumin, meanwhile a negative correlation with FC and CRP at week 0. No correlation with ADA levels or ATIs was established. Patients HLA-DQA1*05 positive had not more adverse reaction or ATIs during the observational period. Patients with ADA serum concentration >7µg/mL at week 4 had CRP <5mg/dL at week 4 (p=0.04) and at week 10 (p=0.01). Patients with ADA serum concentration >7µg/mL at week 10 had more stable disease (PGA =0) and CRP <5mg/L, FC <150 mg/kg at week 10 (p<0.05), CRP <5mg/L at week 30 (p<0.05) and FC <150 mg/kg at 12 months. Conclusion Early Drug level monitoring of Adalimumab (after induction) may improve the management of IBD patients. Our study shows that ADA levels >7 µg/mL is associated with a better clinical response in short and long-term, independent of HLADQA1*05.

MANAGEMENT STRATEGIES FOR OBESITY VARY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Abstract INTRODUCTION Obesity among patients with inflammatory bowel disease (IBD) is increasing with prevalence of 15-40%. Studies have shown that obesity may have poor prognostic implications on IBD treatment and outcomes. There is lack of data focused on the management of obesity in IBD patients. This study’s primary aim was to evaluate whether patients with obesity and IBD have similar rates of obesity management compared to non-IBD obese patients with and without nonalcoholic fatty liver disease (NAFLD). METHODS This is a single-center retrospective study of 400 obese (body mass index > 30 kg/m2) adult patients seen in a primary care clinic between March 2019 and August 2021. Four cohorts, each with 100 patients, were studied. The 4-level cohort analysis included patients with ulcerative colitis and obesity (UC-O), Crohn’s disease and obesity (CD-O), NAFLD and obesity (NAFLD-O), and a control group of patients with obesity only. The 3-level cohort analysis combined UC-O and CD-O and compared this cohort to the NAFLD-O and obesity-only cohorts. Obesity management data collected included: if obesity was documented (OD) in the medical record’s problem list, dietician referral, pharmacologic therapy, and bariatric surgery referral. One-way ANOVA was used to compare numeric variables and chi-squared was used for categorical variables. Logistic regression models were used for primary outcomes. RESULTS Baseline characteristics of BMI, age, gender, and race were similar among patients in the 4-level and 3-level cohort analyses (Tables 1 and 2). Across both analyses, NAFLD-O patients had the highest prevalence of OD (79% p<0.001) and 2.61 higher odds of OD than the control (p =0.003). NAFLD-O patients also had the highest prevalence of dietician referrals (69%, p=0.01). CD-O patients had the highest prevalence of pharmacologic intervention (17%, p=0.01). UC-O patients were less likely to be referred to a dietician (OR=0.55, p=0.03) while CD-O patients were more likely to have pharmacologic management (OR=3.21, p=0.02). Secondary outcomes of comparisons of IBD-specific variables between UC-O and CD-O revealed significant differences as well (Table 3). DISCUSSION This is the first study investigating differences in treatments offered for obesity in IBD. With emerging evidence that obesity likely plays a role in IBD pathogenesis, timely identification and treatment is crucial. Significant differences in management of IBD patients with obesity highlight the need for increased awareness among healthcare providers. Our findings that CD-O patients had a higher rate of corticosteroid, immunomodulator, anti-TNF, anti-interleukin use, and IBD surgery compared to UC-O patients suggests that obesity may contribute to the pathogenesis of CD more so than UC. Further studies are needed to determine which obesity therapies are most effective in the IBD population.

Telenutrition for the management of inflammatory bowel disease: Benefits, limits, and future perspectives.

Patients with inflammatory bowel disease (IBD) require lifelong and personalized care by a multidisciplinary healthcare team. However, the traditional medical model is not ideal for patients who require continuous close monitoring and whose symptoms may dramatically worsen between regularly scheduled visits. Additionally, close dietary follow-up and monitoring of IBD in a traditional setting are challenging because of the disease complexity, high pressure on outpatient clinics with a small number of IBD specialist dietitians, and rising incidence. Given the significant burden of IBD, there is a need to develop effective dietary management strategies. The coronavirus disease 2019 pandemic caused an unprecedented shift from in-person care to delivering health care via technological remote devices. Traditional nutrition therapy and consultation can be provided by telenutrition through remote electronic communication applications that could greatly benefit patient care. Telenutrition might be useful, safe, and cost-effective compared with standard care. It is likely that virtual care for chronic diseases including IBD will continue in some form into the future. This review article summarizes the evidence about telenutrition applications in the management of IBD patients, and we gave an overview of the acceptance and impact of these interventions on health outcomes.

Dietary Habits and Nutrient Deficiencies in a Cohort of European Crohn's Disease Adult Patients.

Wrong dietary habits, such as the Western-style diet, are considered important risk factors for the development of Inflammatory Bowel Diseases (IBDs). Nevertheless, the role of dietary patterns in the clinical management of IBD patients has not been fully investigated yet. Fifty-four patients diagnosed with active Crohn's disease (CD) were enrolled and subjected to nutritional intake analysis through a weekly food diary. Nutritional patterns were analyzed, and nutrient intake was compared with those of 30 healthy subjects (HS). Blood levels of cholesterol, folic acid, minerals (K, Mg, Fe) and amino acids, were measured in CD patients to assess the presence of nutritional deficiencies. CD patients, with respect to HS, consumed significantly lower amounts of fiber, vitamins (A, E, C, B6, folic acid) and β-carotene. Their calcium, potassium, phosphorus, iron, magnesium, copper and iodine intake were also found to be significantly lower. In blood, CD patients had significantly lower concentrations of total cholesterol, potassium, iron, and amino acids. Active CD patient diet was significantly different from those of HS and may contribute to the establishment of nutritional deficiencies. Intestinal malabsorption was evidenced in these patients. Correction of the diet with specific nutritional plans is a necessary therapeutic step for these patients. ClinicalTrials.gov: NCT02580864.

Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide. The increasing disease burden worldwide, lack of response to current biologic therapeutics, and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy. Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics. Sphingosine-1-phosphate (S1P) receptor (S1PR) modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement. S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival, differentiation, migration, proliferation, immune response, and lymphocyte trafficking. T lymphocytes play an important role in regulating inflammatory responses. In inflamed IBD tissue, an imbalance between T helper (Th) and regulatory T lymphocytes and Th cytokine levels was found. The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD. S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking, lymphocyte number, lymphocyte activity, cytokine production, and contributing to gut barrier function.