Objectives Arthropathies are a common extraintestinal manifestation of IBD, yet population-level data on the risk of inflammatory arthritis (IA) among individuals newly diagnosed with inflammatory bowel disease (IBD) is lacking. We aim to describe the incidence of IA among incident IBD cases. Methods We used population-based health administrative data from Ontario, Canada to identify all incident IBD cases diagnosed between April 1, 2003 and March 31, 2020 using previously validated age-specific algorithms. Among individuals in this inception cohort of IBD patients, we identified individuals diagnosed with IA either before or after their IBD diagnosis. IA diagnosis (rheumatoid arthritis, axial spondylitis, other seronegative spondyloarthropathies, synovitis) required ≥1 hospitalization or emergency department visit or ≥2 physician claims with an IA diagnosis code, with ≥1 claim made by a rheumatologist (adult or pediatric), internal medicine physician, pediatrician, or gastroenterologist. IA diagnoses could occur at any point during data availability (1991-2024). We calculated the time between the diagnoses of IA and IBD, categorizing time into the intervals (>3 years pre-IBD diagnosis to >10-15 years post-IBD diagnosis). Age- and sex-standardized IA incidence rates were calculated within each interval. Analyses were stratified by IBD type, age at IBD diagnosis (<18y, 18 to 64y, ≥65y), and sex. Results We identified 56,776 individuals with incident IBD; 11,814 (20.8%) had an IA diagnosis. The incidence of IA peaked in the 6 months prior to IBD diagnosis (23.1 (95% CI 18.6 to 28.4) per 1000 person-years), then gradually decreased in the time following IBD diagnosis (Figure). This pattern was consistent in all subgroups. Figure. Incidence of IA among incident IBD cases, stratified by sex Conclusion This is the first population-based study to describe the incidence of IA in an inception cohort of people with IBD. The peak in IA diagnosis around the time of IBD diagnosis indicates a need for integrated interprofessional care models to facilitate patient access to both gastroenterology and rheumatology care. Future research will investigate the implications of these co-occurring diagnoses on health services utilization and expenditures.

Background:Immune-mediated extraintestinal manifestations (IM-EIMs) are common in pediatric inflammatory bowel disease (pIBD). This systematic review and meta-analysis aimed to summarize the incidence and prevalence of IM-EIMs in pIBD. Methods:MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov were searched up to May 6, 2024, for studies that included pIBD (2-17 years) patients diagnosed with IM-EIMs. Primary outcomes included the incidence and prevalence of IM-EIMs among pIBD. Meta-analysis included pooled proportions of IM-EIMs using DerSimonian-Laird random-effects model. Results:The pooled proportion of IM-EIMs overall was 10% (95% CI, 8%-12%; I2 = 97.2%) among 65 pIBD studies (35 343 patients). The pooled proportion of IM-EIMs was 10% (95% CI, 7%-13%; I2 = 94.8%) among 37 Crohn's disease (CD) studies (7657 patients), compared to 11% (95% CI, 7%-15%; I2 = 93.3%) among 39 ulcerative colitis (UC) studies (4698 patients). Enthesitis was the highest reported individual IM-EIM (23%, 95% CI, 4%-50%; I2 = 94.7%) in pIBD. Arthritis was the second highest reported individual IM-EIM (8%, 95% CI, 6%-10%; I2 = 96%) in pIBD, followed by primary sclerosing cholangitis (PSC) in UC (5%, 95% CI, 4%-7%; I2 = 81%). Uveitis, pyoderma gangrenosum, autoimmune hepatitis, and PSC in CD were the lowest reported IM-EIMs at 1% or less. The largest difference in proportions between IBD phenotypes was PSC, which was 4% higher in UC than CD. Conclusions:While musculoskeletal manifestations are common, fewer than 5% of pIBD patients experience ophthalmological, dermatological, and liver IM-EIMs. The small number of studies resulted in significant methodological and statistical heterogeneity. Multicenter collaborative efforts are needed to systematically describe the epidemiology of IM-EIMs in pIBD.

Background:Ustekinumab dosing information for pediatric Crohn's disease (CD) is limited. Aims:To examine ustekinumab pharmacokinetic and effectiveness data in a largely bio-naïve cohort, focusing on early (week 8) levels. Methods:Children in the prospective Canadian Children IBD Network initiating intravenous (IV) ustekinumab for CD with a week 8 level were evaluated. Disease activity was assessed by corticosteroid-free clinical remission (CSFR), biochemical CSFR, and mucosal healing (MH) by colonoscopy or fecal calprotectin <150 µg/g beyond 16 weeks. We compared drug levels by weight group (</≥40kg) and outcome, using receiver-operating characteristic (ROC) curves to identify optimal week 8 levels. Results:Amongst 58 children (19 < 40 kg, 81% bio-naïve, median (interquartile range [IQR]) follow-up 11.5 [7.6-16.0] months), the IV loading dose for those <40kg (median 9.1 [8.6-10.2] mg/kg; 253 (239-268) mg/m2) was greater than for those ≥40kg (median 6.1 [5.4-6.5] mg/kg; 218 ([78-237] mg/m2, P < .001). However, week 8 levels were similar (P = .26). This was most striking in those with low albumin. Of 34/58 (59%) without escalation to 4 weekly dosing, 43%, 35%, and 19% exhibited CSFR, biochemical CSFR, and MH, respectively, during established maintenance. Median week 8 levels were roughly 5-6 µg/g vs 7-10 µg/g in patients not achieving vs achieving favorable outcomes, while ROC analysis indicated levels 8-9 µg/mL were associated with improved outcomes. Conclusions:Children <40 kg required more IV ustekinumab (median 9 mg/kg; 250 mg/m2) to achieve similar week 8 levels as children ≥40kg receiving conventional adult 6 mg/kg weight-tiered induction. Higher week 8 levels were associated with favorable later outcomes.

ABSTRACT Impaired linear growth is a common, clinically meaningful complication of paediatric inflammatory bowel disease (IBD), particularly Crohn's disease, arising from the combination of chronic intestinal inflammation, undernutrition, dysfunction of the growth hormone–insulin‐like growth factor‐1 axis, and iatrogenic effects such as glucocorticoid exposure. Up to one in five children exhibit short stature at diagnosis, with higher risk in pre/early‐pubertal onset, small‐bowel involvement, persistent activity, and high cumulative steroid use. Although most patients ultimately achieve adult height close to their genetic potential, preventable height loss still occurs in vulnerable subgroups. Effective control of intestinal inflammation remains central to restoring growth velocity and IGF‐1 bioactivity. Specific nutritional strategies, including exclusive enteral nutrition and the Crohn's Disease Exclusion Diet with partial enteral nutrition, or anti‐TNF therapy are steroid‐sparing options that induce remission and support short‐term weight gain. Individualized energy and protein support, alongside vigilant correction of iron, vitamin D, and zinc deficiencies, is essential, and bone health requires proactive assessment in those with low BMI/height z‐scores or steroid exposure. Routine longitudinal monitoring of height, weight, BMI, and pubertal staging should be embedded as explicit treat‐to‐target outcomes, with early escalation to effective maintenance therapy when growth targets are unmet. Growth hormone therapy has a limited, adjunctive role and should be reserved for exceptional, refractory growth failure after optimization of disease control and nutrition within a multidisciplinary framework. Integrating growth and pubertal progression into standard paediatric IBD care can minimize irreversible deficits and improve lifelong skeletal and psychosocial outcomes.

Despite considerable advancements in the therapeutic landscape of inflammatory bowel disease (IBD) for adults, long delays exist for paediatric IBD (pIBD) approval, with a median delay of >7 years following adult approval. Our aim is to summarise the landscape of pIBD clinical trials through a review of trial registries. We conducted a cross-sectional review of ClinicalTrials.gov and ClinicalTrialsRegister.eu to identify investigational and approved therapeutic agents for the treatment of pIBD. All interventional studies involving pIBD (aged <18 years) from database inception to July 2, 2026, were considered for inclusion. Of 3941 records screened, 123 completed trials (77 randomised controlled trials [RCTs] and 46 non-RCTs) and 90 active trials (55 RCTs and 35 non-RCTs) met the inclusion criteria. A majority of completed trials (71

BACKGROUND:Crohn's disease (CD) is characterized by transmural inflammation, and achieving transmural healing (TH), may lead to improved long-term outcomes. However, evidence supporting this hypothesis is limited. METHODS:Adult patients diagnosed with CD who underwent ileocolonoscopy and cross-sectional imaging within 6 months were included. Long-term outcomes of CD-related surgery and hospitalization in patients with TH, endoscopic healing (EH) alone, radiologic healing (RH) alone, and no healing (NH) were assessed. We used Cox proportional hazards models and modified Poisson regression. RESULTS:Among 180 included patients, 26.7% achieved TH, 21.1% achieved EH, 12.8% achieved RH, and 39.4% were classified as NH. At baseline, 54.4% were on biologics which increased to 81.7% at last follow-up (76-78 months across groups). Cumulative probabilities of surgery were lowest in patients with TH (0%, 2.3%, 7.0% at 1, 3, and 5 years) and highest in patients with NH (13%, 20.5%, and 26.9%, respectively) (P = .03). On Cox proportional hazard regression analysis, TH was associated with a significantly reduced risk of CD-related surgery (hazard ratio, 0.01; 95% confidence interval, 0.00-0.35; P = .009) compared with NH. The probabilities of surgery were lower for patients with RH compared with EH (10% vs 13.2%, 10% vs 18.4%, and 21.2% vs 26.9% at 1, 3, and 5 years) but were not statistically significant (P = .41). Probabilities of CD-related hospitalization were lowest with TH (4.3%, 8.8%, and 13.6% at 1, 3 and 5 years) but were not statistically different than other healing categories (P = .67). CONCLUSIONS:TH was associated with superior long-term outcomes compared with EH or RH alone. Future studies should focus on standardizing its definition and evaluate treat-to-target strategies.

Crohn’s disease (CD) is characterized by transmural inflammation and achieving transmural healing (TH) indicated by absence of inflammation on imaging study or endoscopy may lead to improved long-term outcomes. However, evidence supporting this hypothesis is limited. Adult patients diagnosed with CD who underwent ileocolonoscopy and cross-sectional imaging within 6 months were included. Long-term outcomes of CD-related surgery and hospitalization in patients with TH (definition of both endoscopic healing and radiological healing), endoscopic healing (EH: absence of ulceration on ileocolonoscopy) alone, radiological healing (RH: no sign of active inflammation on imaging study) alone, and no healing (NH: presence of inflammation on both ileocolonoscopy and cross-sectional imaging) were assessed. We used Cox proportional hazards models and modified Poisson regression Among 180 included patients 40.5% were males and the mean disease duration was 12.5 years. Of these patients, 26.7% achieved TH, 21.1% EH, 12.8% RH and 39.4% classified as NH. At baseline, 54.4% were on biologics which increased to 81.7% at last follow-up (76-78 months across groups). Cumulative probabilities of surgery were lowest in patients with TH (0%, 2.3%, 7.0% at 1, 3, and 5yrs) and highest in patients with NH (13%, 20.5%, 26.9%). On Cox proportional hazard regression analysis, TH was associated with a significantly reduced risk of CD-related surgery (HR 0.01, 95%CI [0.00–0.35], p = 0.009) compared to NH. The probabilities of surgery were numerically lower for patients with RH compared to EH (10% vs. 13.2%, 10% vs. 18.4% and 21.2% vs. 26.9% at 1, 3 and 5yrs). Probabilities of CD related hospitalization were lowest with TH (4.3%, 8.8% and 13.6% at 1, 3 and 5yrs) Transmural healing was associated with superior long-term outcomes compared to endoscopic or radiologic healing alone. Future studies should focus on standardizing its definition and evaluate treat-to-target strategies Conflict of interest: Dr. Vuyyuru, Sudheer: Received consulting fee from Alimentiv Inc Goodwin, Shane: None Solitano, Virginia: Speaker’s fees from Pfizer, Takeda, Giuliani, Tillotts Pharma consulting fees from J & J travel grant from Abbvie Ramsewak, Daryl: None Kassam, Zahra: has received consulting fees from Alimentiv Inc and Bayer Inc. Townsend, Cassandra: has received advisory board fees from Celltrion, Pendopharm and Takeda Gregor, James: received speakers fees from AbbVie, Janssen, Takeda, Celltrion, Organon and Ferring Beaton, Melanie: Melanie Beaton has received advisory board or consultancy from AbbVie, Celltrion, Ferring, Janssen, Novo Nordisk, Pfizer, and Takeda. She has participated in clinical trials with AbbVie, Novo Nordisk, Gilead, Takeda, Janssen, Pfizer and Astra Zeneca Crowley, Eileen: Grant: Research grant from Abbvie & Pfizer Personal Fees: Consulting fees from Alimentiv Inc. & Sanofi (Advisory board) Alkhattabi, Maan: None Sey, Michael: has received consultant fees from Medtronic research grants and speaker fees from Pendopharm educational grant from Cook Medical. Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma.

BACKGROUND & AIMS:Tasty&Healthy is an exclusive whole food diet designed to reduce inflammation in Crohn's disease without the need for formula. This TASTI-E randomized-controlled trial compared the effect of Tasty&Healthy versus habitual diet on subclinical inflammation in Crohn's disease. METHODS:Clinically quiescent patients with Crohn's disease, 6 to 40 years of age, with Mucosal Inflammation Noninvasive Index >8 reflecting bowel inflammation, were randomized to an 8-week Tasty&Healthy intervention or to continue their regular diet. Thereafter, the habitual group was offered an 8-week open-label Tasty&Healthy intervention. The primary outcome was >50% decline in calprotectin. The study was terminated early due to COVID-19-related challenges. RESULTS:Of the 46 randomized patients (mean age, 18.2 ± 7.6 years; median disease duration, 9.01 months [interquartile range, 2.9-17.1 months]), 19 were allocated to Tasty&Healthy and 27 to habitual diet. Calprotectin response was greater in the Tasty&Healthy (53%) versus habitual arm (7%; relative risk, 3.23; 95% confidence interval, 1.15-9.01; P = .028). Among 15 patients who crossed over to Tasty&Healthy, the rates of calprotectin <250 μg/g (53% vs 7%, respectively; P = .045) and Mucosal Inflammation Noninvasive Index <8 (93% versus 20%; P = .002) were higher at week 16 versus week 8. Adherence to Tasty&Healthy was 77% based on self-reported questionnaires and 71% by fecal gluten. Micronutrient and macronutrient consumption was similar between the groups, except for higher fiber intake with Tasty&Healthy. The Tasty&Healthy intervention resulted in a unique serum metabolic signature. CONCLUSIONS:The Tasty&Healthy diet may reduce calprotectin levels in patients with Crohn's disease with subclinical inflammation. Its flexible structure, free of formula, likely explains the high adherence among asymptomatic individuals. CLINICALTRIALS:gov, Number: NCT04239248.

The musculoskeletal (MSK) system is the most frequent extraintestinal manifestation (EIM) in Crohn’s disease (CD).[1] One pediatric study has reported on asymptomatic sacroiliitis (SI) in pediatric inflammatory bowel disease (pIBD), detecting this in 15% (5/34).[2] MSK EIMs can have a serious impact on patients’ quality of life and are associated with increased severity of bowel disease activity in pIBD.[3] Given the paucity of literature on this topic, we aim to describe the prevalence of asymptomatic SI and its relationship to clinical characteristics, bowel disease phenotype, intestinal disease activity scores, biomarkers, and other EIMs of disease. In this single-center, retrospective cohort study, data were collected from newly diagnosed (<1 year) pediatric CD patients who had undergone magnetic resonance enterography (MRE) at Children’s Hospital, London Health Sciences Centre over 4 years (2019-2023). Subjects were excluded if the sacroiliac joints were unable to be adequately assessed by the radiologist or if the patient had a previously known diagnosis of spondyloarthritis. Coronal T1, axial T2, and coronal T2W sequences with fat suppression of the MREs were evaluated by an MSK-trained radiologist, with a secondary read by a pediatric-trained MSK radiologist (25% of the cases) to establish inter-rater reliability. Descriptive statistics were used to describe baseline characteristics and group comparisons. Among 135 patients with CD who underwent MRE, 10 patients (7.4%) showed evidence of SI on MRE. Patients were sub-categorized as acute SI (2.2%), chronic SI (3%), and acute on chronic SI (2.2%) (Table 1). Half of the patients with evidence of SI on MRE had evidence of inflammatory MSK manifestations. Patients with SI had higher frequency of arthralgia (p-value 0.033), joint swelling (p-value 0.039), and enthesitis (p-value 0.019). There were no significant differences in symptoms of back pain, neither mechanical nor inflammatory. Patients with SI did have significantly higher Simple Endoscopic Scores-CD at initial scope assessment compared to those without (p-value 0.006). Table 1: Clinical characteristics of pediatric Crohn’s disease patients with magnetic resonance enterography imaging. Among newly diagnosed pediatric CD patients who underwent MRE examination, 7.4% were identified to have SI. Patients with CD and SI were more likely to report other MSK symptoms and had higher CD endoscopic scores. Limitations of this study include the lack of systematic rheumatology assessment of CD patients for MSK signs/symptoms. Further analyses are planned to evaluate the bowel disease outcomes in patients with SI over time. [1.] Ali A. ACR Open Rheumatol 2022;4(6):547-54. [2.] Giani T. Pediatr Rheumatol 2020;18(1):1-6. [3.] Derfalvi B. Pediatr Rheumatol 2022;20(1):1-9.

Musculoskeletal (MSK) manifestations are the most common extraintestinal manifestation (EIM) of Crohn’s disease (CD), which include arthralgias, axial/peripheral arthritis, enthesitis, tenosynovitis and dactylitis. CD is associated with impaired nutritional status which can lead to unintentional loss of skeletal muscle mass, known as sarcopenia. Few studies report on sarcopenia in pediatric CD, but it is estimated to affect up to one-third of patients and may be associated with more treatment-refractory disease and poorer quality of life.[1] This study aims to investigate the prevalence of sarcopenia in pediatric CD patients with MSK EIM compared to CD patients without MSK EIM and to evaluate CD-related clinical outcomes. In this single-center, retrospective cohort study, data were collected from 139 newly diagnosed (< 1 year) pediatric CD patients who had undergone magnetic resonance enterography (MRE) at the Children’s Hospital, London Health Sciences Center over 4 years (2019-2023). Bowel disease activity was assessed by weighted pediatric Crohn’s disease activity index (wPCDAI) scores. Sarcopenia was assessed, by an MSK-trained radiologist, by measuring total psoas muscle area (tPMA) from MRE images and comparing to age and sex-matched reference values.[2] Sarcopenia was defined as a tPMA z-score less than – 2.0. Univariate descriptive statistics were used. 139 patients with CD were included (mean age 13.1 ± 3.1 years, 59% male). Sarcopenia was found in 22 patients (15.8%). Children with sarcopenia had higher wPCDAI scores (p=0.033), higher ESR (p=0.035), lower hemoglobin (Hb) (p<0.001) and a higher number of hospital admissions (p=0.041) compared to children without sarcopenia. Fifty-two children (37.4%) had MSK EIM. Among the 52 patients with CD-MSK EIM, 7 had sarcopenia (13.5%) (Table 1). No statistically significant difference was found in the prevalence of sarcopenia in patients with MSK EIM compared to CD-alone (17.2%) (p=0.555). Only 15.8% (22/139) of the total cohort and 40% (21/52) of the MSK EIM group had seen a rheumatologist. Table 1. Associations between clinical characteristics of pediatric patients with Crohn’s Disease and sarcopenia. Initial findings from our study demonstrate that 13.5% of children with CD who have MSK EIM have sarcopenia. At baseline, patients with CD-related sarcopenia did demonstrate higher bowel disease activity, increased admissions to hospital and more systemic inflammation (higher ESR, lower Hb). Limitations of this study include the lack of systematic rheumatology assessment of CD patients for MSK EIM, resulting in potential under-reporting of MSK EIM. Further analyses are planned to evaluate the impact of sarcopenia on bowel disease outcomes over time in both groups. [1.] Atlan G. J Pediatr Gastroenterol Nutr 2021;72:883-8. [2.] Lurz E. J Cachexia Sarcopenia Muscle 2020;11:1055-65.

Abstract Background Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that frequently coexists with inflammatory bowel disease (IBD). Data comparing the paediatric- and adult-onset PSC-IBD are lacking. We compared disease characteristics and the clinical course of PSC-IBD between Canadian children and adults. Methods This was a multi-center retrospective cohort study including eight paediatric centers from different provinces across Canada including (Ontario, Alberta, Nova Scotia, Manitoba) and four adult centers from the province of Ontario, including patients diagnosed with PSC-IBD from 1985-2023. Patient and disease characteristics and outcome data were extracted from the clinical charts. We compared patient demographics, disease course, laboratory and imaging results, and complications including liver transplant among paediatric- and adult-onset PSC-IBD. Continuous data were reported as median (Q1-Q3) and compared with the Wilcoxon Rank Sum test, and categorical data were reported as number (%) and compared with chi-square or Fisher exact tests. We compared the time to transplant with the log-rank test. Results We included 521 patients (228 children, median follow-up 3.3 (Q1-Q3 1.5-5.8) years; 293 adults, median follow-up 9.8 (Q1-Q3 4.3-16.0) years (Table-1). The interval between PSC and IBD diagnosis was longer in adults. Small duct disease and PSC with autoimmune hepatitis (AIH) features were more common in children, with corresponding higher ALT and more frequently positive autoantibodies. Rates of portal hypertension at PSC diagnosis were similar in both groups. Ulcerative colitis predominated in both groups with more IBD-unclassified in children. Colitis was most severe in the right colon in a third of children and adults. Children were more often treated with ursodeoxycholic acid, vancomycin, corticosteroids and immunomodulators. Adult patients experienced a higher proportion of adverse liver events over the entire follow-up duration, but time to event analysis showed similar rates of progression to liver transplant (log-rank p=0.075; 2- and 5-year survival with native liver in paediatric vs. adult: 97% and 90% vs. 94% and 84%). (Figure-1) Conclusion In this large Canadian multi-center cohort of PSC-IBD, paediatric-onset disease was characterized by more frequent small duct disease and features of AIH. The interval between IBD and PSC diagnosis was far longer in adults. Although a greater proportion of adult-onset patients experienced adverse liver outcomes overall, rates of transplant at 2 and 5 years were similar between groups, suggesting that PSC progression may in fact be similar.

Abstract Aims The burden of arthritis among individuals with inflammatory bowel disease (IBD) is poorly understood. We describe changes over time in the annual prevalence of inflammatory arthritis (IA) and musculoskeletal (MSK)-related physician encounters among individuals with IBD. Methods We conducted a retrospective repeated cross-sectional study using Ontario population-based health administrative data. We used the Ontario Crohn’s and Colitis Cohort which comprises all IBD patients derived from health administrative data using validated age-specific case-identification algorithms. Individuals diagnosed with IBD between April 01, 2003, and March 31, 2020 (population denominator) were followed from their first IBD code (index date) until they died or were lost to follow-up (out-migrated/lost health care coverage), or until the end of available follow-up data (March 31, 2020). We identified the cumulative prevalence of inflammatory arthritis (≥1 hospitalization/ED encounter or ≥2 physician billing claims with IA-related diagnosis codes with ≥1 by a rheumatologist within 365 days). Separately we identified the annual number of individuals with ≥1 hospitalization/ED encounter/physician billing claim with any non-trauma related MSK-specific diagnosis codes. The annual age- and sex-standardized cumulative prevalence of both IA and MSK among individuals living with IBD each year were determined. Results Over the study period, the number of individuals living with IBD increased from 54,283 in 2003 to 108,857 in 2020; the number of children <18yrs increased from 1,547 to 2,667. Among all ages, the age/sex standardized cumulative IA prevalence within the IBD cohort increased from 6.8% (95% CI 6.5-7.2%) in 2003 to 15.2% (95%CI 15.0-15.8%) by 2020 (Figure 1). IA was slightly more common among those with Crohn’s than ulcerative colitis (17.4% vs 13.2%, respectively). By 2020, IA prevalence was 6.8% among children/youth <18yrs, 17.4% among those 18-64yrs, and 23.1% among those ≥65yrs. Overall, crude annual prevalence of an MSK-related encounter remained relatively stable from 30.6% in 2003 to 27.7% in 2020. Conclusions This study is the first to provide population-level estimates of IA and MSK-related conditions in people with IBD. The cumulative prevalence of IA among individuals with IBD has steadily increased over time, particularly among those ≥65years, while MSK-related encounters have not. This may be related to increased physician recognition of IA or increased access to care and diagnosis. These findings have implications for healthcare costs and utilization, given the specialized care and expertise required to manage IA in the context of complex, comorbid conditions like IBD. Funding Agencies CCC

Abstract Background Musculoskeletal (MSK) manifestations are the most common extraintestinal manifestation (EIM) of Crohn’s disease (CD). Features include arthralgias, axial/peripheral arthritis, enthesitis, tenosynovitis and dactylitis. CD is associated with impaired nutritional status which can lead to unintentional loss of skeletal muscle mass, known as sarcopenia. Few studies report on sarcopenia in paediatric CD, but it is estimated to affect up to one-third of patients and may be associated with more treatment refractory disease and poorer quality of life.1 This study aims to investigate the prevalence of sarcopenia in paediatric CD, in paediatric CD with MSK EIM and to assess the impact of sarcopenia on CD related clinical outcomes. Methods In this single centre, retrospective cohort study, data were collected from 139 newly diagnosed (< 1 year) paediatric CD patients who had undergone magnetic resonance enterography (MRE) at the Children’s Hospital, London Health Sciences Center (Ontario, Canada) over four years (2019 – 2023). Bowel disease activity was assessed by weighted paediatric Crohn’s disease activity index (wPCDAI) scores. Sarcopenia was assessed, by an MSK-trained radiologist, by measuring total psoas muscle area (tPMA) from MRE images and comparing to age and sex matched reference values.2 Sarcopenia was defined as a tPMA z-score less than – 2.0. Univariate descriptive statistics were used. Results 139 patients with CD were included (mean age 13.1 ± 3.1 years, 59% male). Sarcopenia was found in 22 patients (15.8%). Children with sarcopenia had lower body surface area (BSA) (p=0.020), higher wPCDAI scores (p=0.033), higher ESR (p=0.035), lower hemoglobin (Hb) (p<0.001) and a higher number of hospital admissions (p=0.041) compared to children without sarcopenia. Of these, 52 children (37.4%) had MSK EIM. Among the 52 patients with CD-MSK EIM, 7 had sarcopenia (13.5%) [Table 1]. No statistically significant difference was found in the prevalence of sarcopenia in patients with CD-MSK EIM compared to CD-alone (17.2%) (p=0.555). Only 15.8% (22/139) of the total cohort and 40% (21/52) of the MSK-EIM group had seen a rheumatologist. Conclusion Initial findings demonstrate that 15.8% of paediatric patients with CD have sarcopenia. Of those with CD-MSK EIM, 13.5% have sarcopenia. At baseline, patients with CD related sarcopenia did demonstrate higher bowel disease activity, increased admissions to hospital and more systemic inflammation (higher ESR, lower Hb). Limitations of this study include the lack of systematic rheumatology assessment of CD patients for MSK EIM, resulting in potential under-reporting of MSK-EIM. Further analyses are planned to evaluate the impact of sarcopenia on bowel disease outcomes over time in both groups. References 1.Atlan L, Cohen S, Shiran S, Sira LB, Pratt LT, Yerushalmy-Feler A. Sarcopenia is a Predictor for Adverse Clinical Outcome in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2021;72(6):883-888. doi:10.1097/MPG.0000000000003091 2.Lurz E, Patel H, Lebovic G, et al. Paediatric reference values for total psoas muscle area. J Cachexia Sarcopenia Muscle. 2020;11(2):405-414. doi:10.1002/jcsm.12514

OBJECTIVES:Exclusive enteral nutrition (EEN) is a first-line treatment for induction of remission in luminal pediatric Crohn disease (pCD). However, as the efficacy of EEN varies from patient to patient, there is a need to distinguish between responders and nonresponding patients. This study had two aims. First, to develop a model to predict EEN-induced clinical remission (weighted pediatric CD activity index [wPCDA] ≤ 12.5) using baseline clinical information. Second, to develop a model to predict corticosteroid-free sustained clinical remission post-EEN induction (wPCDA ≤ 12.5, for ≥36 weeks after EEN). METHODS:We applied machine learning to clinical and laboratory data from a prospectively followed cohort of pCD patients who received EEN as their first treatment for CD (n = 308). This learning algorithm used feature selection and k-fold (internal) cross-validation to systematically find the model with the best combination of features and hyperparameter settings. To estimate the quality of the learned model, we used k-fold (external) cross-validation. RESULTS:Clinical, laboratory, and treatment data were compiled into two different datasets: EEN clinical remission at the end of EEN treatment (mean of 60 days; n = 114) and corticosteroid-free sustained clinical remission post-EEN induction (n = 206). Our resulting models were effective, with external area under the curves of 0.65  ±  0.015 and 0.60  ±  0.018. Moreover, a permutation label test showed that our learning process was stable and significantly different from chance, at p-values of 0.002 and 0.01, respectively. CONCLUSION:Our models, based on accessible clinical features, were able to effectively predict EEN success above chance. This supports the plausibility of building clinical tools to assist precision therapy for pCD patients.

Abstract Background Concurrent immune-mediated extraintestinal manifestations (IM-EIMs; Table 1) are common in paediatric-onset inflammatory bowel disease (pIBD), but the overall epidemiology is unknown. This systematic review and meta-analysis aimed to summarise the prevalence and management of EIMs in pIBD. Methods MEDLINE, EMBASE and CENTRAL, clinicaltrials.gov and conference abstracts were searched up to May 6, 2024, for studies that included pIBD (2-17 years old) with secondarily diagnosed EIMs. The primary outcome included the prevalence of IM-EIMs among pIBD. Secondary outcomes included efficacy and adverse effects of treatment on EIMs. Meta-analysis included pooled proportions with DerSimonian-Laird random-effects analysis. Results The pooled proportion of IM-EIMs among pIBD was 8.4% (95% CI, 6.5-11.0%; I2=97%) among 53 eligible studies. The pooled proportion of IM-EIMs was 10.3% (95% CI, 7.3-13.8%; I2=95%) among 37 Crohn’s disease (CD) studies, compared to 11.3% (95% CI, 7.8-15.3%; I2=93%) among 39 ulcerative colitis (UC) studies. Enthesitis was the highest reported individual IM-EIM (23%, 95% CI, 4-50%; I2=94.7%) in pIBD. Arthritis was the second highest reported individual IM-EIM (8%, 95% CI, 6-10%; I2=96%) in pIBD, followed by primary sclerosing cholangitis (PSC) in UC (5%, 95% CI, 4-7%; I2=81%; Table 2). Uveitis, pyoderma gangrenosum, autoimmune hepatitis, and PSC in CD were the lowest reported IM-EIMs at 1% or less. The largest difference in reported proportions between IBD phenotypes was PSC, which was 4% higher in UC than CD. Only one eligible study described treatment response. Conclusion This meta-analysis identified that while musculoskeletal manifestations are relatively common, fewer than 5% of pIBD patients experience ophthalmological, dermatological, and hepatic IM-EIMs. There was significant methodological and statistical heterogeneity as expected for the relatively small number of individual paediatric studies and likely resulted in the large difference of pooled proportions between individual IM-EIMs. Multicentre collaborative efforts are needed to systematically describe the epidemiology and management outcomes of EIMs in pIBD in the current era of advanced therapies.

INTRODUCTION:Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel disease (IBD) in adults but poorly characterized in pediatric IBD (pIBD). We aimed to primarily investigate the relationship between NLR and pIBD endoscopic disease severity. We also examined whether NLR predicted hospitalization, surgery, and therapy response by 52 weeks. METHODS:We used the Canadian Children IBD Network prospective inception cohort including patients < 18 years old with baseline data from 2013 to 2022. We excluded patients with concurrent diseases affecting NLR. Both Mayo endoscopic score (MES) and simple endoscopic scale for Crohn's disease (SES-CD) were dichotomized as low activity (quiescent-mild) and high activity (moderate-severe). For therapy responses, we examined year-1 steroid- and biologic-free remission. We used logistic regression for binary outcomes. RESULTS:A total of 580 patients with ulcerative colitis and 1,081 patients with CD were included. High NLR was associated with high-activity MES and SES-CD in both univariate and multivariable analyses (odds ratio = 1.45, 95% CI = 1.07-1.97, P value = 0.016; and odds ratio = 1.42, 95% CI = 1.04-1.94, P value = 0.026, respectively). We also calculated the best NLR cutoff point to predict MES (1.90, sensitivity = 68%, specificity = 67%, area under the curve [AUC] = 0.67, AUC 95% CI = 0.59-0.74) and SES-CD (2.50, sensitivity = 63%, specificity = 69%, AUC = 0.66, AUC 95% CI = 0.59-0.75) high activity. NLR did not predict therapy response in either ulcerative colitis or CD. DISCUSSION:Patients with pIBD with high baseline NLR are more probable to have worse endoscopic disease at diagnosis. This highlights NLR potential as a reliable noninvasive biomarker of disease activity. The predictive power of NLR is based mostly on neutrophils and the balance between neutrophils and lymphocytes.

Abstract Background Patients with acute severe ulcerative colitis (ASUC) are at increased risk of colectomy following an episode of acute severe exacerbation. Medical rescue therapy in steroid non-responders has reduced the need for emergency colectomy. However, impact of biologics on longer-term colectomy risk is unclear. Methods A retrospective cohort study of adult patients aged ≥18 years hospitalized with acute exacerbation of UC requiring hospitalization and managed with intravenous corticosteroids between 2010 and 2022 at two regional hospitals in London, Ontario, Canada. Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 264 adults hospitalized with ASUC were included in the analysis (male: 51.1% [n=136], mean age at admission: 40.8±17.8 years). The majority had extensive colitis (71.3% [n=169]) at the time of diagnosis. 46.3% (n=118/255) presented within one year of disease onset and 23% (n=61) had ASUC as their first presentation with UC. 25.7% (n=66/257) of patients had prior purine analogues and 23.3% (60/257) had previous biologics prior to ASUC presentation. After admission, 55.7% (n=147) responded to intravenous corticosteroids. Of the steroid non-responders, 37.5% (n=99) patients were managed with infliximab rescue therapy and only one patient received tofacitinib rescue therapy. Median CRP, stool frequency and Lindgren index score were statistically significant between steroid responders and non-responders (Table 1). A higher proportion of steroid non-responders had prior exposure to biologics or tofacitinib compared to steroid responders (31.9% vs 16.3%, p<0.01). On multivariate analysis for various factors predicting steroid non-response, assessment by Oxford criteria on day 3 was the only factor that was statistically significant (odds ratio 4.70 (95% CI 1.06-20.8), p = 0.04). Oxford criteria on day 3 had a sensitivity, specificity of 58.6% and70.8%, respectively for predicting steroid non-response. 8% (n=21) required colectomy during index admission. An additional 13% (n = 32) underwent colectomy within 12 months of discharge, for which there was no difference between steroid responders and non-responders (12.2% vs 14.7%). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 8% (20/245) and 5.4% (12/223) respectively. Hospitalization with UC exacerbation rate following discharge was 17% (38/223). Conclusion 8% of patients admitted for ASUC require colectomy during the same admission and additional 13% required colectomy within 12 months of discharge. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates remain high.