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Background Crohn’s disease (CD) is highly heterogenous and may be complicated by stricturing behavior. Personalized prediction of stricturing will inform management. We aimed to create a stricturing risk stratification model using genomic/clinical data. Methods Exome sequencing was performed on CD patients, and phenotype data retrieved. Biallelic variants in NOD2 were identified. NOD2 was converted into a per-patient deleteriousness metric (“GenePy”). Using training data, patients were stratified into risk groups for fibrotic stricturing using NOD2. Findings were validated in a testing data set. Models were modified to include disease location at diagnosis. Cox proportional hazards assessed performance. Results Six hundred forty-five patients were included (373 children and 272 adults); 48 patients fulfilled criteria for monogenic NOD2-related disease (7.4%), 24 of whom had strictures. NOD2 GenePy scores stratified patients in training data into 2 risk groups. Within testing data, 30 of 161 patients (18.6%) were classified as high-risk based on the NOD2 biomarker, with stricturing in 17 of 30 (56.7%). In the low-risk group, 28 of 131 (21.4%) had stricturing behavior. Cox proportional hazards using the NOD2 risk groups demonstrated a hazard ratio (HR) of 2.092 (P = 2.4 × 10-5), between risk groups. Limiting analysis to patients diagnosed aged Conclusions A NOD2 genomic biomarker predicts stricturing risk, with prognostic power improved in pediatric-onset CD. Implementation into a clinical setting can help personalize management.

The incidence of paediatric inflammatory bowel disease (IBD) has been increasing over 25 years; however, contemporary trends are not established and the impact of COVID-19 on case rates is unclear.Data from Southampton Children's hospital prospective IBD database were retrieved for 2002-2021. Incidence rates were calculated based on referral area populations and temporal trends analysed. Disease prevalence for those aged18 years was calculated for 2017-2021. Monoclonal prescriptions were reported.In total, 1150 patients were included (mean age at diagnosis 12.63 years, 40.5% female). An estimated 704 patients had Crohn's disease (61.2%), 385 had ulcerative colitis (33.5%), and 61 had IBD unclassified (5.3%). Overall IBD incidence increased, β = 0.843, P = 3 × 10 -6 , driven by Crohn's disease, β = 0.732, P = 0.00024 and ulcerative colitis, β = 0.816, P = 0.000011. There was no change in IBDU incidence, β = 0.230, P = 0.33. From 2002-2021, 51 patients were diagnosed6 years of age, 160 patients aged 6 to10 years and 939 patients aged 10 to18 years of age. Increased incidence was observed in patients aged 10 to18 years of age (β = 0.888, P = 1.8 × 10 -7 ). There was no significant change in incidence of IBD in6 years (β = 0.124, P = 0.57), or 6 to10 years (β = 0.146, P = 0.54). IBD prevalence increased by an average of 1.71%/year from 2017 to 2021, β = 0.979, P = 0.004. The number of new monoclonal prescriptions increased from 6 in 2007 to 111 in 2021.IBD incidence continues to increase in Southern England. Compounding prevalence and increased monoclonal usage has implications for service provision.