Unclassified Inflammatory Bowel Disease Research Articles

The need for surgery in pediatric patients with inflammatory bowel disease treated with biologicals

PurposeInflammatory bowel disease (IBD) in childhood often presents with a more extensive and more aggressive disease course than adult-onset disease. We aimed to evaluate if biological treatment started in childhood decreases the need for intestinal surgery over time.MethodsThis was a retrospective, single-center, cohort study. All pediatric patients with IBD initiated to biological therapy at the Children’s Hospital, were included in the study and followed up to the first surgical procedure or re-operation in their adulthood or until 31.12.2021 when ≥ 18 of age. Data were collected from the pediatric registry of IBD patients with biologicals and medical charts.ResultsA total of 207 pediatric IBD patients were identified [150 with Crohn´s disease (CD), 31 with ulcerative colitis (UC), 26 with IBD unclassified (IBDU)] of which 32.9% (n = 68; CD 49, UC 13, IBDU 6) underwent intestinal surgery. At the end of a median follow-up of 9.0 years (range 2.0-25.9), patients reached a median age of 21.4 years (range 18–36). Patients who had intestinal surgery in childhood were more likely to have IBD-related surgery also in early adulthood. The duration of the disease at induction of the first biological treatment emerged as the only risk factor, with a longer duration in the surgical group than in patients with no surgery.ConclusionDespite initiation of biological treatment, the risk of intestinal surgery remains high in pediatric IBD patients and often the need for surgery emerges after the transition to adult IBD clinics.

Clinical features of inflammatory bowel disease unclassified: a case-control study

BackgroundApproximately 10-15% of inflammatory bowel disease (IBD) patients with overlapping features of ulcerative colitis (UC) and Crohn’s disease (CD) are termed as inflammatory bowel disease unclassified (IBDU). This study aimed to describe the clinical features of IBDU and evaluate the potential associated factors of reclassification.MethodsThe clinical data of 37 IBDU patients were retrospectively analyzed from November 2012 to November 2020. 74 UC and 74 CD patients were randomly selected and age- and sex-matched with the 37 IBDU patients. Clinical characteristics were compared between the three patient groups. Potential factors associated with the IBDU reclassification were evaluated.Results60% of IBDU patients displayed rectal-sparing disease, and 70% of them displayed segmental disease. In comparison to UC and CD, the IBDU group demonstrated higher rates of gastrointestinal bleeding (32.4%), intestinal perforation (13.5%), spontaneous blood on endoscopy (51.4%), and progression (56.8%). The inflammation proceeded relatively slowly, manifesting as chronic alterations like pseudopolyps (78.4%) and haustra blunt or disappearance (56.8%). 60% of IBDU patients exhibited crypt abscess, and 16.7% of them exhibited fissuring ulcers or transmural lymphoid inflammation. The proportions of IBDU patients receiving immunosuppressants, surgery, and infliximab were basically the same as those of CD patients. During the 79 (66, 91) months of follow-up, 24.3% of IBDU patients were reclassified as UC, while 21.6% were reclassified as CD. The presence of intestinal hemorrhaging was associated with CD reclassification, while hypoalbuminemia was associated with UC reclassification.ConclusionsIBDU may evolve into UC or CD during follow-up, and hemorrhage was associated with CD reclassification. Different from the other two groups, IBDU exhibited a more acute onset and a gradual progression. When an IBD patient presents with transmural inflammation or crypt abscess but lacks transmural lymphoid aggregates or fissuring ulcers, the diagnosis of IBDU should be considered.

Short noncoding RNAs as predictive biomarkers for the development from inflammatory bowel disease unclassified to Crohn's disease or ulcerative colitis.

Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60-97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

Comparison of endoscopic healing and durability between infliximab originator and CT-P13 in pediatric patients with inflammatory bowel disease.

Favourable clinical data were published on the efficacy of CT-P13, the first biosimilar of infliximab (IFX), in pediatric inflammatory bowel disease (IBD); however, few studies have compared the effect on endoscopic healing (EH) and drug retention rate between the IFX originator and CT-P13. Therefore, we aimed to compare EH and the drug retention rate between the IFX originator and CT-P13. Children with Crohn's disease (CD) and ulcerative colitis (UC)/IBD-unclassified (IBD-U) at 22 medical centers were enrolled, with a retrospective review conducted at 1-year and last follow-up. Clinical remission, EH and drug retention rate were evaluated. We studied 416 pediatric patients with IBD: 77.4% had CD and 22.6% had UC/IBD-U. Among them, 255 (61.3%) received the IFX originator and 161 (38.7%) received CT-P13. No statistically significant differences were found between the IFX originator and CT-P13 in terms of corticosteroid-free remission and adverse events. At 1-year follow-up, EH rates were comparable between them (CD: P=0.902, UC: P=0.860). The estimated cumulative cessation rates were not significantly different between the two groups. In patients with CD, the drug retention rates were 66.1% in the IFX originator and 71.6% in the CT-P13 group at the maximum follow-up period (P >0.05). In patients with UC, the drug retention rates were 49.8% in the IFX originator and 56.3% in the CT-P13 group at the maximum follow-up period (P >0.05). The IFX originator and CT-P13 demonstrated comparable therapeutic response including EH, clinical remission, drug retention rate and safety in pediatric IBD.

Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn’s Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.

Familial Mediterranean fever in Armenian children with inflammatory bowel disease.

Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) are inflammatory diseases with complex interactions among genetic, immune, and environmental factors. FMF is a monogenic autoinflammatory disease, characterized by recurrent febrile attacks and polyserositis, and is manifested mainly in childhood. FMF is widespread in Armenia. There are reports on the concurrent occurrence of FMF and IBD. MEFV gene mutations may have a disease-modifying effect on IBD. We have investigated the frequency of MEFV mutations and FMF in Armenian children with IBD and their influence on the clinical course. A total of 69 untreated IBD patients under 18 years of age were enrolled: 52.1% (36) had ulcerative colitis (UC), 21.7% (15) had Crohn's disease (CD), and 26.0% (18) had unclassified colitis (IBD-U). The frequency of FMF among them was 36.2% (25/69), and MEFV mutations were identified in 53.6% (37/69). The highest rate of MEFV mutations and FMF was in UC patients (61.1% and 41.6% respectively). In all, 56.7% (21/37) of IBD patients with MEFV mutations had M694V mutated alleles, mainly in compound heterozygous and heterozygous states. There were no associations in the group of IBD patients with coexisting FMF (25), either between any MEFV mutation and type of IBD or coexistence of FMF. Overall, 36.0% (9/25) of them developed VEO IBD and carried mainly the M694V mutation. We concluded that the carrier frequency of MEFV mutations among Armenian pediatric IBD patients was rather high (53.6%), especially for UC. It was suggested that the MEFV gene is not necessarily a susceptibility gene but most likely modifies the course of IBD. MEFV genetic testing was recommended for Armenian pediatric IBD patients, especially for VEO UC and IBD-U, atypical IBD course, or resistance to the conventional treatment. They should also be asked for isolated febrile attacks, recurrent arthritis, and family history, even in the absence of FMF typical symptoms, to rule out FMF and its complications.

SHORT NONCODING RNAS AS PREDICTIVE BIOMARKERS FOR THE DEVELOPMENT FROM INFLAMMATORY BOWEL DISEASE UNCLASSIFIED TO CROHN’S DISEASE OR ULCERATIVE COLITIS

Abstract BACKGROUND Numerous pathogenic processes are mediated by short noncoding RNAs (ncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether short ncRNAs can predict CD or UC among IBDU patients. METHODS Of 35 IBDU patients initially diagnosed with IBDU, 12, 15, and eight were reclassified into CD(IBDU-CD), UC(IBDU-UC), or remained as IBDU(IBDU-IBDU) respectively. Eight IBD patients, were included as references. Short ncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. RESULTS Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95 % CI: 60 - 97) in discriminating IBDU-CD from IBDU-UC. CONCLUSIONS Based on the three-short ncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

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

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

INFLIXIMAB AND VEDOLIZUMAB HAVE SIMILAR CLINICAL AND SAFETY OUTCOMES AMONG BIOLOGIC-NAÏVE PATIENTS WITH MILD TO MODERATE PEDIATRIC INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Infliximab (IFX) is the only FDA-approved intravenous therapy for the treatment of pediatric inflammatory bowel disease (IBD). The gut-selective anti-integrin vedolizumab (VDZ) has been increasingly used as second-line therapy. However, the comparative effectiveness of IFX vs. VDZ to treat biologic-naïve children with IBD is currently unknown. AIMS 1. Compare the real-world effectiveness of IFX vs. VDZ in bio-naïve pediatric patients with IBD at 12 months. 2. Study the safety of IFX and VDZ in the pediatric population. METHODS A single-center retrospective cohort study was conducted at an academic children’s hospital between February 2015 and August 2023. We included bio-naive mild-moderate IBD patients, <23 years old, who started IFX or VDZ as their first advanced therapy. Patients with a confirmed diagnosis of IBD based on Porto criteria with baseline and at least 6-month follow-up data were included. Exclusion criteria were designed to limit the study population to patients who would typically be eligible for vedolizumab treatment according to the current standard of care, including: prior biologic use; steroid-refractory acute-severe colitis; stricturing or penetrating Crohn’s disease (CD); or perianal disease; and extraintestinal manifestations. The primary outcome was steroid-free clinical remission (SFCR) at 12 months, defined by the PUCAI <10 or ShPCDAI <10 and off corticosteroids. Biochemical remission (BR) was defined as fecal calprotectin (FCP) <250 μg/g. Descriptive statistics included the Chi-square and the Mann-Whitney U test. RESULTS Among the 100 included patients, 73 in IFX group vs. 27 in VDZ group, the mean age was 13 ± 4 years old, males were 68% (IFX) vs. 41% (VDZ) (P = 0.01). 49% had CD, 48% had UC, and 3% had unclassified IBD (IBDU). IFX- and VDZ-treated patients had similar Paris classifications. Baseline albumin levels (3.7 vs. 4.2 g/L, P<0.01) and steroid use (58% vs. 74%, P = 0.13) were lower in IFX vs. VDZ-treated patients. 12-month SFCR was 72% (49/68) and 71% (15/21) in IFX- and VDZ-treated patients, respectively (NS). Among SFCR at 12 months, BR was 59.62% (IFX) vs. 76.47% (VDZ), P = 0.21. Adverse events were rated as mild to moderate and occurred rarely in 8.22% (6/73) of IFX patients and in 7.41% (2/27) of VDZ patients (P = 0.89). These included an infusion reaction (1 in each group), elevated liver enzymes (1 in each group), infection (1), folliculitis (1), eczema (1), , and psoriasis (1). CONCLUSION We found both IFX and VDZ to have similar effectiveness in achieving SFCR and BR at 12 months when used as first-line agents for patients with uncomplicated mild-moderately active IBD. Prospective, larger head-to-head studies are needed for further validation. IFX group vs. VDZ group at the baseline. IFX group vs. VDZ group for Steroid Free Clinical Remission Patients at 12 months.

P1174 The disease course of elderly patients with Inflammatory Bowel Disease two years prior to their death

Abstract Background The number of elderly patients with inflammatory bowel disease (IBD) is increasing. Hence, more patients will be dying with their IBD. Limited research has examined the disease course of IBD in the aging body, particularly in the period preceding their death. The purpose of this study was to investigate the disease course of elderly IBD patients leading up to the end of their lives. Methods This was a nationwide population-based study using the national Danish registries. We used a validated algorithm to identify patients that were diagnosed with Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) in a period between 1976-2018 from the Danish National Patient Registry. This information was linked with other national Danish registers which provided data on dates of death, cancer, hospitalisations, and corticosteroid usage. We included 6,183 IBD patients aged 65 and above at death, with no cancer or palliative treatment at the time of death. We analysed IBD-related hospitalisations, corticosteroid usage, and disease relapses (defined as a combined endpoint of corticosteroid prescription and/or hospitalisation, or both), in the two-year period before death. Results We analysed CD, UC and IBDU patients separately, and observed a noticeable spike in hospitalisations, prescription rates of corticosteroids and disease relapses in the last two months before the IBD patients’ death. Out of 6,183 IBD patients, 954 (15.43%) were hospitalised in the last two years before their death (see Table 1 for key characteristics). In the last two months, hospitalisation rates were 139 (28.66%) for CD patients, 155 (23.96%) for UC patients and 83 (34.87%) for IBDU patients. Corticosteroids were prescribed to 1,054 (17.05%) out of 6,183 IBD patients, and in the last two months 90 (20.45%) CD patients, 149 (20.13%) UC patients, and 67 (19.36%) IBDU patients received a corticosteroid treatment. Overall, 1,652 (26.72%) IBD patients experienced a disease relapse two years preceding their death, and during the last two months, 553 (22.45%) CD patients, 194 (24.01%) UC patients and 228 (20.25%) IBDU patients experienced relapses. Conclusion During the two-year period prior to death, we observed that hospitalisation, prescription, and relapse rates were highest during the final two months of life. For better understanding of the disease course of elderly IBD patients, further research should investigate the cause of death and differences between early- and late disease-onset patients as well as establish a cohort for comparison.

P652 Transitioning Inflammatory Bowel Disease patients from an intravenous to a subcutaneous infliximab protocol: a single centre experience and patient satisfaction survey

Abstract Background Infliximab is used for the treatment of Ulcerative colitis (UC) and Crohn's disease (CD). Subcutenanous (SC) infliximab (CT-P13) received regulatory approval from the European Medicines Agency for Inflammatory Bowel Disease (IBD) in July 2020. Our study aim was to assess the efficacy and safety of SC infliximab in our patient cohort at University Hospital Lewisham as well as gain patient feedback on their experience of subcutaneous infliximab compared to intravenous infliximab. Methods We retrospectively analysed the records of all patients receiving infliximab treatment from May 2022 to May 2023 for age, gender, diagnosis, clinical response, faecal calprotectin levels and side-effects. We designed a patient questionnaire for patients who were switched from IV to SC infliximab to assess patient preferences with regards to route of administration, satisfaction with treatment as well as reported side effects. Results 60 patients (M:F ratio 1:1; average age 36.2y) were receiving infliximab during this time frame. 23 patients were switched to SC infliximab whilst 37 patients remained on IV infliximab. 37/60 (61.7%) had CD, 20/60 (33.3%) UC, and 3/60 (5.0%) IBD unclassified (IBD-U). Mean faecal calprotectin (FC) levels during treatment were comparable in both groups (Mean FC 117 in IV group; Mean FC 94 in SC group). No patient in either group required hospital admission or gastrointestinal surgery. 1/23 (4.3%) patients switched to an alternate biologic in SC group due to loss of response, whist 3/37 (8.1%) patients in IV group required a switch of biologic therapy over the same time frame. There were no major side effects reported in either the SC group or IV group. There were 5 minor side-effects recorded in the IV group - 4/37 (10.8%) rash; 1/37 (2.7%) mildly deranged liver function tests. There was 1 minor side effect reported in the SC infliximab group of mild injection site skin reaction 1/23 (4.3%) 18/23 (78.2%) SC infliximab patients completed the patient satisfaction questionnaire. All respondents (18/18, 100%) found the drug more convenient to self-administer than attending the infusion unit for IV infliximab. 1 patient (4.3%) reported mild pain and skin reaction at the injection site. 22/23 (95.7%) of the SC group were satisfied with their treatment and preferred to continue on the SC regimen rather than receive IV infliximab. The one patient who preferred IV infusions reported fear of needles and self-injections as the reason for the IV preference. Conclusion Our study showed that SC infliximab was a safe, well tolerated and efficacious treatment compared to IV infliximab. Our patient satisfaction survey showed that a large majority of patients preferred the SC method of administration and were satisfied with their treatment.

P420 Natural history of intra-abdominal inflammatory masses (phlegmons) in Crohn’s disease

Abstract Background Intra-abdominal inflammatory masses (phlegmons) are a feature of penetrating Crohn’s disease (CD). However, there are few data on the natural history and outcomes of inflammatory masses in CD. We aimed to describe clinical outcomes and predictors of surgery in individuals with CD and intra-abdominal inflammatory masses (IAIM). Methods We conducted a multi-center retrospective cohort study. Patients with a diagnosis of CD or inflammatory bowel disease unclassified (IBD-U) and a finding of phlegmon, phlegmonous change or inflammatory mass on cross-sectional imaging with IV contrast (MR or CT) at two tertiary care centers were included between July 2006 and April 2023. Data collected included demographics, clinical characteristics, Montreal CD classification, treatments at the time of and after IAIM diagnosis, and size and location of the IAIM. Primary outcome was surgery defined as any CD-related resection or surgical drainage. Bivariate comparisons between patients who did or did not undergo surgery were performed. Multivariable logistic regression was performed with backward selection of variables to identify those associated with surgery. Results A total of 100 patients were included, and comparison between those who did or did not undergo surgery is given in Table 1. Most were white (80%), 44% were women, and 12% were current smokers. A majority had ileocolonic disease location (77%) and 50% were on a biologic at time of diagnosis. Mean size of IAIM was 3.4 cm and the majority (72%) were located adjacent to small bowel. Radiologic evidence of intra-abdominal fistula was seen in 40%, and 30% of patients had a stricture adjacent to the IAIM. A large proportion required hospitalization (75%) and received intravenous antibiotics (64%); 13% progressed to an abscess, and the mean (SD) time to abscess was 108 (119.4) days. The majority (65%) underwent surgery, with a mean (SD) time to surgery of 59 (97.8) days. Seven patients developed sepsis, all of whom subsequently required surgery. On multivariable analysis, patients were more likely to require surgery if there was a concomitant stricture (aOR = 3.12, 95% CI 1.01 – 11.9) and less likely to require surgery if treated with steroids (aOR = 0.15, 95% CI 0.03 – 0.61). Antibiotic use was not associated with surgery (aOR 1.22, 95% CI 0.53 – 2.81) nor was IAIM size. Conclusion In this large retrospective cohort, most intra-abdominal inflammatory masses required surgery, particularly if there was a concomitant stricture. Patients treated with steroids were less likely to require surgery though this may be confounded by severity of disease.

P621 Safety and effectiveness of vedolizumab and ustekinumab in inflammatory bowel disease patients after liver transplantation for primary sclerosing cholangitis: results from an ECCO-confer case series

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease often necessitating liver transplantation (LTX). Approximately 70% of PSC patients have a concomitant diagnosis of inflammatory bowel disease (IBD) and could need treatment with biological therapy on top of the immunosuppression to prevent transplant rejection. Vedolizumab (VDZ) and ustekinumab (UST), both agents with a favorable safety profile, are often used in this population despite lack of data concerning safety and effectiveness in the post-LTX setting. Methods A retrospective multicenter case series was performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Primary endpoints were clinical and endoscopic remission at week 52, occurrence of infectious complications, occurrence of malignancy, hospitalizations, and death after liver transplantation. Results In this retrospective study, 58 patients (male n= 34 (59%), median age 42 (interquartile range (IQR) 32-52) were included across 16 participating centers of which 24 (38%) were treated with UST and 40 (63%) with VDZ. Twelve patients (20%) were diagnosed with Crohn’s disease (CD), 44 (76%) with ulcerative colitis (UC), 2 (3%)- with unclassified IBD (IBD-U) and in 12 (20%) patients had an ileal pouch anal anastomosis (IPAA). Median disease duration was 16 years (IQR 13-26) and 33 (56%) had received biological therapy prior to LTX (33% anti-TNF, 11% VDZ, 5% UST). Median disease duration for PSC was 15.5 years (IQR 11-25) and median time since LTX was 6 years (IQR 4-10). Clinical remission, assessed according to physician global assessment, at week 52 was achieved in 44% of VDZ compared to 38% of UST treated patients (p=0.17), while endoscopic remission was seen in 17% of patients in the VDZ group versus 33% in the UST treated patients (p=0.87). Clinical effectiveness was similar across CD (respectively 33% and 20%), UC (33% and 37%) and IPAA patients (36% vs 60%). Infectious complications occurred in 21 patients (29%; 27% VDZ vs 33% UST) post LTX on biological therapy (p=0.66), malignancy occurred in 10 patients (14.1%, 12.8% VDZ vs 16.7% UST, p=0.66), hospitalizations in 32 (45%; 51% VDZ vs 34% UST, p=0.15), and death in 2 patients (3.4%; 2.1% VDZ vs 4.2% UST, p=0.66) (see table). Conclusion In IBD-PSC patients who underwent LTX both UST and VDZ show similar effectiveness with clinical remission rates of respectively 44% and 38% after 1 year. Safety profiles are similar although infectious complications and occurrence of malignancy remains an important concern in this patient group.

P1113 Depressive symptoms in ulcerative colitis and Crohn's disease – differences in improvement at 1 year follow-up

Abstract Background Mental health (MH) has been reported to be poorer among patients with inflammatory bowel disease (IBD) than general population. However, it is not known whether MH is more driven by inflammation itself or related to gastrointestinal (GI) symptoms. Also, the dynamics of MH following IBD diagnosis is not well understood. Methods In the Swedish Inception Cohort of IBD (SIC-IBD), patients with Crohn’s disease (CD), ulcerative colitis (UC) and unclassified IBD (IBD-U) as well as symptomatic controls (SC) and healthy controls (HC) filled in Patient Health Questionnaire-9 (PHQ-9), a validated screening tool for depression. Patients completed PHQ-9 at diagnosis and at one year follow-up while the controls completed it once. Disease outcome was defined at one year based on requirement of advanced treatments/ surgery. Results In total, 286 individuals (16 HC, 89 SC, 62 CD, 104 UC, 15 IBD-U) completed the questionnaire at baseline. HC had significantly lower PHQ-9 score, (fewer depressive symptoms), at baseline compared to all the other groups (p<0.01). The baseline PHQ-9 score was not significantly different between SC and CD, UC and IBD-U patients (p=0.06). At one year follow-up, 38 CD and 53 UC patients completed the PHQ-9. Between baseline and follow-up, UC patients had a significant drop in their PHQ-9 score (p<0.0000001), whereas CD patients did not have any significant change in their PHQ-9 score (p=0.06). Furthermore, UC patients had significantly lower PHQ-9 score compared with CD patients at follow-up (p=0.04, Figure 1). Baseline PHQ-9 score was not correlated with calprotectin at baseline neither in UC nor CD patients (p=0.7 and 0.5 respectively). Also, there was no positive correlation between PHQ-9 score change and calprotectin change in either UC or CD patients, and neither baseline nor follow-up PHQ-9 scores were significantly different in patients with poor or good outcome (p>0.05). When analysed separately by sex, there was still no correlation between baseline PHQ-9 score and outcome in neither CD nor UC patients (p>0.05) Conclusion IBD patients have at the time of diagnosis more depressive symptoms than HC, but not different from SC. Depressive symptoms are more related to GI symptoms than IBD specific inflammation or disease outcome. UC patients show more of an improvement in their depressive symptoms one year after diagnosis than CD patients.

DOP60 Prevalence of undiagnosed inflammatory Bowel Disease in patients with spondyloarthritis: EISER Study

Abstract Background A significant proportion of patients with inflammatory bowel disease (IBD) have concomitant rheumatological manifestations. Patients with spondyloarthritis (SpA) often report gastrointestinal symptoms, some of them being associated to IBD. However, the exact prevalence of this disorder is still controversial, and the optimal approach to its diagnosis remains unknown. Methods Aim: to determine the prevalence of undiagnosed IBD in patients with axial SpA and psoriatic arthritis (PA). EISER is an observational, cross-sectional study carried out in13 Spanish hospitals. Patients ≥18 years-old diagnosed with PA or SpA were selected. Patients receiving biologics or systemic steroids were excluded. Among patients ≥ 50 years, only those without valid colonoscopy in the previous 3 years were included. Rheumatologists performed a baseline visit and collected demographic, clinical data. Fecal calprotectin (FC) was determined by the Quantum Blue rapid test and this was followed by a gastroenterologist consultation. Figure 1 summarizes study protocol. Results A total of 559 patients were included (51% men; mean 52.2 years; mean disease duration of SpA/PA was 12.3 years). The most frequent disease was radiographic SpA (37%), followed by peripheral APs (36%). Tabla 1 shows demographic characteristics of patients. A total of 40% of patients has FC ≥ 80 ug/g. In the multivariate logistic regression analysis factors associated with a greater likelihood of FC ≥ 80 µg/g were disease duration (OR 1.021, 95%CI 1.000 to 1.042, p<0.05) and disease activity by ASDAS-CRP (OR 2.158, 95%CI 0.906 to 5.139, p<0.1), while general health status by EQ-5D-5L was associated with a lower likelihood of FC ≥ 80 µg/g (OR 0.976, 95%CI 0.960 to 0.993, p<0.01). 28 patients were diagnosed of IBD, leading to a prevalence of 5.7%, 22 out of the 248 patients with axial SpA had IBD (8.9%) and 6 out of the 246 patients with PsA (2.4%). 24 were diagnosed with Crohn’s disease (CD), 3 unclassified IBD, and 1 UC. Seven (25.0%) of these IBD patients showed symptoms. The ROC curve for FC and the diagnosis of IBD is presented in Figure 1 (AUC of 0.870 (p<0.001, 95CI% 83.7 to 89.8). The highest sensitivity(S) and specificity (Sp) corresponded to a FC level >147 µg/g (S= 85.7% and a Sp of 75.5%, a PPV of 17.4% (95%CI 14.5 to 20.8) and NPV of 98.9% (95%CI 97.3 to 99.5). Conclusion - 5.7% of SpA patients have undiagnosed IBD. This prevalence was higher among axial SpA than PsA patients. - CD is the most frequent IBD type observed.· - FC is a useful tool to identify patients with SpA and lesions secondary to IBD. - FC has a high NPV to rule out IBD in axial SpA patients. - Disease duration, quality of life and disease activity of SpA are associated with higher levels of FC.

P450 Influence of radon levels at home in the clinical course of inflammatory bowel disease incident patients

Abstract Background Inflammatory Bowel Diseases (IBD) are a group of pathologies of unknown etiology associated with some environmental factors, only partially identified. The role of indoor radon, a radioactive gas, has not been formally studied and it might play a role on the evolution of the disease. The aim of this study is to analyze if residential radon exposure is associated with the evolution and development of flares or hospitalizations of IBD new diagnosed patients in a radon-prone area. Methods An observational prospective study was developed between June 2020 and September 2023, including incident cases with IBD that had been living at least 5 years in the same dwelling, those with a change of address in the last 5 years prior to diagnosis were excluded. All patients were followed-up through one year to assess the evolution of the disease. Hospitalizations related with the disease during the period, and number and severity of flares (measured by Partial Mayo Score and Harvey- Bradshaw) were collected. Radon levels were measured over three months in the participants’ home. Each individual was provided with a residential radon meter (a RSKS trace detector), given and read by the Galician Radon Laboratory, a certified radon laboratory. Radon concentrations were categorized into three groups, 0-99 Bq/m3, 100-299 Bq/m3 and >299 Bq/m3. Results are expressed as Odds Ratios with their 95%CI obtained through logistic regression. Results 136 patients with IBD (78 ulcerative colitis, 52 Crohn’s disease and 6 unclassified colitis) were included and prospectively followed, with a median age of 52 years old (IQR 40 – 59). 50% were females. There were no statistically significant differences in radon levels, taking levels of 0-99 Bq/m3 as reference, between patients hospitalized compared with non-hospitalized (OR 0.8 95%CI 0.3-2.1 for 100-299 Bq/m3, OR 1.7 95%CI 0.6-5.0 for >299 Bq/m3) nor in patients with a flare compared with patients without flares during the follow-up year (OR 0.4 95%CI 0.0-4.5 for 100-299 Bq/m3, OR 5.4 95%CI 0.8-34.3 for >299 Bq/m3). Radon levels were not associated with the number of flares either (OR 0.6 95%CI 0.3-1.7 for 100-299 Bq/m3, OR 1.5 95%CI 0.5-4.5 for >299 Bq/m3). Results are shown in table 1. Stratifying by type of IBD, results do not vary. For Crohn’s disease, OR for flare are 2.5 (95%CI 0.4-16.1) and 4.1 (95%CI 0.6-27.9), and for hospitalization 1 and 6.5 (OR95% (0.2-205-2). For ulcerative colitis, OR for flare are 0.6 (95%CI 0.2-1.8) and 1.8 (95%CI 0.4-7.8) and for hospitalization 0.9 (95%CI 0.1-17.1) and 9.3 (95%CI 0.6-134.0). Conclusion Indoor radon concentration seems to be not associated with an initial worst evolution of IBD patients in terms of hospitalizations or flares.

P1106 Is indoor radon associated with new diagnosis of inflammatory bowel disease patients?

Abstract Background Inflammatory Bowel Diseases (IBD) are a group of pathologies of unknown etiology associated with some environmental factors, only partially identified. The role of indoor radon, a radioactive gas, has not been formally studied and it might play a role on the onset of the disease. The aim of this study is to analyze the role of individual residential radon exposure on the incidence of IBD in a radon-prone area also characterized as a high incidence IBD region. Methods A case-control study was developed in the health area of Santiago de Compostela (Galicia, Spain) between June 2020 and September 2023, including incident cases with IBD. Controls were selected trough a frequency matching based on sex and age and without IBD. All participants had to be living at least 5 years in the same dwelling, those with a change of address in the last 5 years prior to diagnosis were excluded. Endoscopic index, imaging techniques and analytic parameters were collected. Radon levels measured over three months in the participants’ home were compared between cases and controls, and between the different types of IBD. Each individual was provided with a residential radon meter (a RSKS trace detector), given and read by the Galician Radon Laboratory, a certified radon laboratory. Procedure is summarized in Figure 1. Radon concentrations were categorized into three groups, 0-99 Bq/m3, 100-299 Bq/m3 and >299 Bq/m3. Results are expressed as Odds Ratios with their 95%CI obtained through logistic regression. Results 178 incident cases and 178 controls (102 ulcerative colitis, 70 Crohn’s disease and 6 unclassified colitis) were included, with a median age of 51 years old (IQR 40 – 59.5). 51.7% were females. Median radon levels of IBD patients´ homes were 144.5 (IQR 83 – 260) and median radon levels of controls´ homes were 189.5 (IQR 112 – 292.5) (figure 1). Adjusting by age and sex, high radon levels showed a negative association for the development of IBD (taking levels of 0-99 Bq/m3 as reference, OR 100-299 Bq/m3 is 0.5 (95%CI 0.3-0.8), and OR >299 Bq/m3 is 0.5 (95%CI 0.3-0.9). Results are shown in table 1. Analyzing women and men separately, there are no statistically significant differences (p>0.05 in each group). Taking into account the different types of IBD, radon levels show the same negative association but without statistical association. Conclusion High radon levels might be a protective factor for developing IBD overall and its most common types, Crohn’s disease and ulcerative colitis. Further studies in other areas with lower radon concentrations will be necessary to corroborate whether it influences the incidence of IBD.

P1136 Relationship between occupation and Inflammatory Bowel Disease’s activity in newly diagnosed patients

Abstract Background It is well known that occupational activity can affect health. The association between type of work and Inflammatory Bowel Diseases (IBD) has been studied previously, but the studies on the topic are scarce and they do not have studied the relationship with clinical activity of the disease. The aim of this study is to elucidate if the type of work is a risk factor for the disease activity and severity in recently diagnosed IBD patients. Methods An observational prospective study including incident cases of patients with IBD diagnosed between June 2020 and September 2022 in the area of Santiago de Compostela was developed. Type of work, divided into white collar and blue-collar, sedentariness at work divided into high activity, moderate activity and sedentary activity according to the classification of occupational activity categories using accelerometry, and place of work divided into indoor and outdoor, time at work and contact with animals at work was recorded. All cases were followed-up through one year to assess the evolution of the disease. Endoscopic index at one year from the diagnosis, analytic parameters, hospitalizations related with the disease during the period, treatments administered, and number and severity of flares (measured by Partial Mayo Score and Harvey- Bradshaw) were collected. To analyze the results, a logistic regression was used. Results 136 patients were included and followed their activity for a year. 68 (50%) were females. 78 (57.4%) had ulcerative colitis, 52 (38.2%) Crohn’s disease and 6 (4.4%) unclassified colitis. 30 patients (22.1%) had at least one flare during this time (23 had 1 flare, 5 two and 2 three), and 4 patients were primary non responders. 7 patients (5.2%) were hospitalized. Neither the type of job (white or blue collar), time at work (working hours per week), physical activity at work (sedentary work, moderate activity or high activity), working outdoor vs. indoor nor contact with animals at work were associated with hospitalization (all p>0.05). When contact with chemicals, solvents and dusts were analyzed, no statistically significant difference was found (p>0.05). Regarding the appearance of flares, high activity at work and working outside were protective factors of the appearance of a flare, with OR 0.1 (0.0 – 0.7) and 0.2 (0.1 – 0.8) respectively (Table 1).After stratifying results according to type of IBD, there were no statistically significant differences. Conclusion High activity jobs and working outside are protective factors for a flare appearance in patients with recent diagnosis of IBD. Type of job it is not related with risk of hospitalization.

P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort. Methods We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval <8 weeks and/or dosing >5mg/kg. We examined IBD outcomes prior to and 12 months post DE. Results A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml). Faecal calprotectin (FCP) remission rate (FCP <250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p<0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p<0.001) and radiological investigations (243 vs 343; p<0.001). Conclusion Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.

P286 Variation of outcomes in inflammatory bowel disease at ten Australasian centres - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Inflammatory bowel disease (IBD) is a global health issue with Australia having amongst the highest prevalence rates worldwide. Our study examined the quality, safety and equity of care amongst ten Australasian centres using Crohn’s Colitis Care electronic management record. The aim was to describe current care delivery at each centre for a range of performance indicators to provide a baseline from which to engage in a regional care quality benchmarking initiative Methods Deidentified data prospectively entered by clinicians during routine clinical practice throughout 2022 were retrospectively analysed. Only centres with >100 eligible people with IBD and an assessment during the trial period were included. Sites from Australia and New Zealand were a mixture of public and private IBD referral centres Results The cohort included 7172 people with IBD from 10 centres; 58.6% with Crohn’s disease (CD), 39.1% ulcerative colitis (UC) and 2.3% IBD-unclassified (IBDU). Mean age was 44.3 (SD +/- 18.0) with an even gender balance (50.7% female). The number of people with IBD per centre ranged from 201 to 2151 (median 566). In the total cohort, 38.3% were currently on advanced IBD therapy (biologics or new small molecules), with centre variation from 30.8% to 43.5% (p<0.001). Of those on advanced therapy, 42% were on dose escalated therapy which varied between centres substantially from 18% to 64%. Current steroid use ranged from 0.3% to 6.1% (median 1.6%; p<0.001). Documented IBD surgical rates varied from 0.1% to 7.2% (median 2.0; p<0.001). IBD admission rates ranged from 0.1% to 13.6% (median 1.2; p<0.001) while current smokers comprised 1.7% to 12.5% (p<0.001) of the cohort with a mean of 6.0% across all ten centres. A total of 3,379 faecal calprotectin’s (FCP) with an overall remission rate (< 250μg/g) of 71% varying from 63.4% to 83.1% (median 69.1; p=0.001); 2,616 lower endoscopies were performed with an observed remission rate of 56%; this varied between sites from 0% to 69%. Recorded Influenza vaccination rates varied from 6.3% to 54.4% (median 19.8) and Covid vaccination rates from 14% to 78.5% (median 43.4). Skin care check completion rates ranged from 16.3% to 32.3% (median 22.9). The centre with the highest documented healthcare maintenance completion rate across all three domains was private. Conclusion Despite advances in treatment and much literature addressing care guidelines and targets, significant disparity in care documentation and outcomes remains for people with IBD in routine care. CCCare as an IBD-specific EMR supports easy, serial examination of these measures at scale and is therefore a useful tool to measure and drive efforts to improve these deficiencies and reduce unwarranted care variation