Pediatric-onset Crohn's Disease Research Articles

Long-term clinical and endoscopic outcomes of ustekinumab in pediatric Crohn's disease with anti-tumor necrosis factor failure.

Only a few studies have reported the long-term effects of ustekinumab on pediatric Crohn's disease. Therefore, this study aimed to describe the long-term clinical and endoscopic outcomes of ustekinumab and its safety profile in pediatric-onset Crohn's disease with anti-tumor necrosis factor failure. Medical records of patients with pediatric-onset Crohn's disease in whom anti-tumor necrosis factor therapy failed and ustekinumab treatment was initiated from 2017 to 2022 at a Japanese tertiary children's hospital were retrospectively reviewed. The primary outcome was the continuation rates at weeks 8, 52, and 106. The secondary outcomes were the steroid-free remission rates at weeks 8, 52, and 106, changes in the Simple Endoscopic Score for Crohn's Disease, and adverse events during follow-up. Forty-three patients were enrolled. The median ages at diagnosis and ustekinumab introduction were 9.7 (interquartile range: 6.7-13.0) years and 13.6 (interquartile range: 8.0-16.0) years. The median follow-up period was 136 (interquartile range: 102-172) weeks. The continuation rates were 100%, 91%, and 80% at weeks 8, 52, and 106, respectively. The incidence of discontinuation was 6.2% per patient-year of follow-up. The steroid-free remission rates were 44%, 71%, and 80% at weeks 8, 52, and 106, respectively. The Simple Endoscopic Score for Crohn's Disease of patients in clinical remission at the last follow-up significantly decreased (P<0.01), and the safety profile was acceptable. Ustekinumab appeared effective in maintaining long-term clinical remission with endoscopic improvement in pediatric-onset Crohn's disease with anti-tumor necrosis factor failure.

S1489 Polygenic Risk Scores Only Partially Explain the Risk of Pediatric Onset Crohn's Disease

S1489 Polygenic Risk Scores Only Partially Explain the Risk of Pediatric Onset Crohn's Disease

Early predictors of intestinal complications in pediatric-onset Crohn's disease: A long-term cohort study in Taiwan

PurposeIdentifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan. MethodsThis was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications. ResultsAmong 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17–9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively. ConclusionsECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy.

Surgical management of pediatric Crohn's disease

Management of pediatric-onset Crohn's disease uniquely necessitates consideration of growth, pubertal development, psychosocial function and an increased risk for multiple future surgical interventions. Both medical and surgical management are rapidly advancing; therefore, it is increasingly important to define the role of surgery and the breadth of surgical options available for this complex patient population. Particularly, the introduction of biologics has altered the disease course; however, the ultimate need for surgical intervention has remained unchanged. This review defines and evaluates the surgical techniques available for management of the most common phenotypes of pediatric-onset Crohn's disease as well as identifies critical perioperative considerations for optimizing post-surgical outcomes.

P1125 Incidence and Neoplastic Risk Associated with Colonic Stricture in Pediatric-Onset Crohn's Disease: A Population-based Study

Abstract Background The identification of colonic stricture in patients with Crohn's disease (CD) often leads to surgery due to concerns about associated neoplasia. Nevertheless, information regarding the neoplastic risk associated to colonic stricture is still limited. The objective of this study was to assess both the incidence of colonic stricture in pediatric-onset CD and the associated neoplastic risk at the population-based level. Methods All patients diagnosed with CD before age 17 between 1988 and 2011, and included in a population-based registry, were followed until 2013. Colonic stricture was defined as a narrowing of the digestive lumen observed on endoscopic or radiological examination. Excluded were stricture in the ileocaecal valve, anal canal, or low rectum. Univariate risk factors for colonic stricture were explored using Cox proportional hazards models with time-dependent variables, and a multivariable Cox model analysis was performed. Results A total of 1,007 patients diagnosed with CD between 1988 and 2011 were included. Median age at diagnosis was 14.5 years [IQR: 12.0-16.1]. Throughout the follow-up period (median follow-up, 8.8 years [4.6-14.2]), patients were predominantly exposed to 5-aminosalicylates (88.1%), immunosuppressants (70.6%), and biologics (47.9%). Colonic stricture was diagnosed in 52 patients, including 11 at CD diagnosis. The cumulative incidence of colonic stricture in CD was 2.9% [1.8%-4.0%] at 5 years. The overall incidence rate of colonic stricture in CD was 5.4 cases/1000 person-years, 95% CI [4.1-7.1]. In multivariable analysis, an increased risk of colonic stricture was observed during periods of active disease (HR = 2.62, [1.40-4.89], p&amp;lt;0.01). Conversely, the absence of colonic involvement at diagnosis (HR = 0.18, [0.04, 0.80], p&amp;lt;0.05) or treatment with aminosalicylates (HR = 0.39, [0.19-0.79], p&amp;lt;0.05) was associated with a lower risk of colonic stricture. After a median follow-up of 6.4 [2.4-12.7] years, colonic stricture surgical resection was performed in 29 patients (55.8%). Colon adenocarcinoma was detected in one patient (1.9%) within 6 months after the diagnosis of colonic stricture. Conclusion In this population-based study of pediatric-onset Crohn's disease, 52 patients (5%) experienced colonic stricture, with a 2.9% incidence rate observed after 5 years of follow-up. Additionally, one patient (2%) presented with an associated adenocarcinoma.

Amino acid-based enteral nutrition is effective for pediatric Crohn's disease: a multicenter prospective study.

Exclusive enteral nutrition (EEN) therapy effectively induces remission in pediatric Crohn's disease (CD). However, this may depend on the type of enteral formula used. Moreover, data on the efficacy of amino acid-based EEN are limited. Thus, we aimed to prospectively evaluate the efficacy of amino acid-based formulas for EEN in pediatric patients with active CD. Patients with active CD aged between 6 and 17 years were recruited into this prospective study from four hospitals in China between March 2019 and December 2021. Patients received EEN for 8 weeks. Inflammatory and nutrition-associated indices were evaluated at 0, 4, and 8 weeks after treatment. Paired t-tests and Wilcoxon signed-rank tests were used to compare continuous and categorical variables before and after intervention, respectively. Twenty-four patients were included in the analysis. After an 8-week intervention period, the CD activity index significantly decreased (26.3 ± 12.2 vs 7.1 ± 8.3, P < 0.001). Most patients (66.7%) achieved complete clinical remission. Among the 22 patients who had ulcers and erosions diagnosed endoscopically at baseline, 10 (45.5%) achieved complete mucosal healing. The degree of thickening of the intestinal wall was significantly reduced after EEN intervention, with a transmural healing rate of 42.9%. Furthermore, the serum inflammatory markers decreased and there was a significant improvement in the nutrition-related indices (P < 0.05). There were no severe adverse effects. Amino acid-based EEN is effective and safe for treating pediatric-onset CD. Studies with larger sample sizes and mechanistic and follow-up studies are required to further validate these findings.

NOD2 Polymorphisms May Direct a Crohn Disease Phenotype in Patients With Very Early-Onset Inflammatory Bowel Disease.

NOD2/CARD15 was the first susceptibility gene recognized for adult-onset Crohn's (or Crohn) disease (CD). Recessive inheritance of NOD2 polymorphisms has been implicated as a mechanistic driver of pediatric-onset CD. In patients with very early-onset inflammatory bowel disease (VEO-IBD), however, the clinical relevance of NOD2 polymorphisms has not been fully established. Ten VEO-IBD patients with NOD2 polymorphisms ( NOD2 +) were compared to 16 VEO-IBD patients without genetic variants in NOD2 or any other VEO-IBD susceptibility genes ( NOD2 -). The majority of NOD2 + patients exhibited a CD-like phenotype (90%), linear growth impairment (90%), and arthropathy (60%), all of which were significantly more common than in the NOD2 - group ( P = 0.037, P = 0.004, P = 0.026, respectively). We propose that the presence of NOD2 polymorphisms in patients with VEO-IBD might confer a CD-like phenotype, linear growth impairment, and arthropathy. These findings should be validated in larger cohorts and may guide precision medicine for patients with VEO-IBD in the future.

Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study.

Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.

Prediction of Crohn's Disease Stricturing Phenotype Using a NOD2-derived Genomic Biomarker.

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. 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. 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 < 18-years improved performance (HR-3.164, P = 1 × 10-6). Models were modified to include disease location, such as terminal ileal (TI) disease or not. Inclusion of NOD2 risk groups added significant additional utility to prediction models. High-risk group pediatric patients presenting with TI disease had a HR of 4.89 (P = 2.3 × 10-5) compared with the low-risk group patients without TI disease. A NOD2 genomic biomarker predicts stricturing risk, with prognostic power improved in pediatric-onset CD. Implementation into a clinical setting can help personalize management.

Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics: A Population-based Study From The epidemiology group of the Israeli IBD Research Nucleus (epiIIRN).

Both perianal and pediatric-onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult-onset perianal CD and their disease course. We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD-9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease. A total of 12,905 patients were included (2186 [17%] pediatric-onset, 10,719 [83%] adults), with a median follow-up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6-4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1-3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid-dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age. PCD is more common in pediatric-onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.

New Therapeutic Strategies Have Changed the Natural History of Pediatric Crohn’s Disease: A Two-Decade Population-Based Study

We evaluated the impact of immunosuppressants (IS) and anti-tumor necrosis factor (TNF) introduction on Crohn's disease (CD) long-term outcomes in a large population-based, pediatric-onset cohort. All patients included in the EPIMAD registry with a diagnosis of CD occurring when they were younger than age 17 years and between 1988 and 2011 were followed up retrospectively until 2013. Three diagnostic periods were defined: 1988 to 1993 (period [P]1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). Medication exposure and disease outcomes were compared between the 3 diagnostic periods. A total of 1007 patients diagnosed with CD were followed up for a median duration of 8.8 years (interquartile range, 4.6-14.2 y). The IS and anti-TNF exposure rate at 5 years increased over time from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3), respectively. In parallel, the risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P= .0003, Ptrend &lt; .0001), and between the pre-anti-TNF era (P1+ P2, 32%) and the anti-TNF era (P3, 22%) (P= .0007). The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%; P= .11, Ptrend= .041) and between the pre-anti-TNF era (P1+ P2, 28%) and the anti-TNF era (P3, 20%) (P= .040). The risk for a CD flare-related hospitalization at 5 years remained stable over time (P1, 31%; P2, 31%; and P3, 29%; P= .76, Ptrend= .53). In parallel with the increased use of IS and anti-TNF, positive changes in the natural history of pediatric-onset CD were observed at the population level. A decreased risk of both intestinal resections and stricturing complications were observed during the anti-TNF era.

Augmented ustekinumab dosing is needed to achieve clinical response in patients with anti-TNF refractory pediatric Crohn's disease: a retrospective chart review.

Background: Ustekinumab is a monoclonal antibody that inhibits interleukins 12 and 23. It is approved for treatment of Crohn's disease (CD) in adults; however, there is a paucity of data regarding its use in pediatric CD. We describe our experience using ustekinumab in anti-TNF refractory CD pediatric patients. Methods: We performed a retrospective chart review on pediatric patients with CD who were started on ustekinumab from January 2016 to November 2018. We collected patient's clinical history, previous treatment history, surgeries related to CD, disease severity, as measured by abbrPCDAI, and endoscopic severity as recorded by SES-CD before and after ustekinumab. Results: We identified 10 patients with CD who were started on ustekinumab due to non-response to currently approved agents. Seven patients needed augmented maintenance dosing every 4-6 weeks to achieve clinical response or remission. Six of these seven patients had therapeutic drug monitoring during the course of treatment, with five patients showing subtherapeutic drug levels of <4.5 μg/mL while on standard maintenance dosing every 8 weeks, and four patients showing therapeutic drug levels of >4.5 μg/mL on augmented dosing interval. The remaining three patients were on standard maintenance dosing for the duration of treatment. Conclusion: In this retrospective chart review, 7 out of 10 patients with anti-TNF refractory pediatric-onset CD required augmented maintenance doses of ustekinumab to achieve clinical response or remission. A prospective study is needed to define appropriate ustekinumab dosing and interval in management of pediatric CD.

Differences in Biologic Utilization and Surgery Rates in Pediatric and Adult Crohn's Disease: Results From a Large Electronic Medical Record-derived Cohort.

Crohn's disease (CD) is a chronic illness that affects both the pediatric and adult populations with an increasing worldwide prevalence. We aim to identify a large, single-center cohort of patients with CD using natural language processing (NLP) in combination with codified data and extract surgical rates and medication usage from the electronic medical record (EMR). Patients with CD were identified from the entire Cleveland Clinic EMR using ICD codes and CD-specific terms identified by NLP to fit a logistic regression model. Cohorts were developed for pediatric-onset (younger than 18 years) and adult-onset (18 years and older) CD. Surgeries were identified using current procedural terminology (CPT) codes and NLP. Crohn's disease-related medications were extracted using physician orders in the EMR. Patients with pediatric-onset (n = 2060) and adult-onset (n = 4973) CD were identified from 2000 to 2017 with a positive predictive value of 98.5%. Rate of CD-related abdominal surgery over time was significantly higher in adult-onset compared with pediatric-onset CD (10-year surgery rate 49.9% vs 37.7%, respectively; P < 0.001). Treatment with biologics was significantly higher in pediatric vs adult-onset CD cohorts (63.6% vs 49.2%; P < 0.001). The overall rate of CD-related abdominal surgery was significantly higher in those who received <6 months of a biologic compared with ≥6 months of a biologic for both cohorts (pediatric 64.1% vs 39.1%, P ≤ 0.001; adult 69.3% vs 56.5%, P ≤ 0.001). Additionally, 60.9% in pediatric-onset CD and 43.5% in adult-onset CD treated with ≥6 months of biologic therapy have not required abdominal surgery. On multivariable analysis, perianal surgery was a significant risk factor for abdominal surgery in both cohorts. We used a combination of codified and NLP data to establish the largest, North American, single-center EMR cohort of pediatric- and adult-onset CD patients and determined that biologics are associated with lower rates of surgery over time, potentially altering the natural history of the disease.

Oral and Otorhinolaryngological Findings in Adults Who Were Diagnosed With Pediatric Onset Crohn's Disease: A Controlled Study.

Up to 50% of pediatric patients with Crohn's disease (CD) report oral manifestations, but less is known about their oral health when they become adults. Our aim was to provide detailed descriptions of the presence of oral and otorhinolaryngological manifestations in patients with pediatric onset CD once they reached adulthood, to look for predisposing factors and to compare the findings to matched controls. Adult patients diagnosed with CD in childhood at the Children's Hospital, University of Helsinki, Finland, after 2000 were invited for a follow-up appointment in 2016 and 24 were examined by a dentist and otorhinolaryngologist. They were compared with 22 matched controls from the Population Register Centre. The participants completed questionnaires about their general health, any special diets, and their health-related quality of life. Their nutrition was evaluated from food records. Patients with CD had minor oral manifestations at a median of 9 years after their childhood diagnosis and the most common was angular cheilitis, which affected 6 patients and 1 control, but was not statistically significant (P=0.0984). CD with perianal abscessing disease correlated to orofacial findings (P=0.0312). Most of the patients had normal otorhinolaryngological findings. Subjects with oral lesions had lower mean health-related quality of life scores than subjects without oral findings and the differences were clinically but not statistically significant. Oral manifestations were not associated with differences in energy intake. Oral manifestations in adult patients with pediatric onset CD were mild and were not associated with otorhinolaryngological pathology.

Growth failure in pediatric onset inflammatory bowel disease: mechanisms, epidemiology, and management.

Impairment of growth is recognized as one of the most significant complications of inflammatory bowel disease (IBD) in pediatric patients. The reported incidence of growth failure at diagnosis is 15-40% in pediatric onset Crohn's disease (CD) and 3-10% in ulcerative colitis (UC). Growth failure is associated with decreased appetite, abdominal symptoms, malabsorption due to mucosal inflammation, growth hormone (GH) resistance due to inflammation, and even genetic factors. Several population-based studies and cohort studies suggest that patients with pre-pubertal onset CD have a higher risk of growth failure at disease onset. Final adult height is still lower than that of healthy controls; however, its prevalence is generally lower than that at the disease onset. Several IBD treatments were reported to improve patients' growth. In addition to enteral nutrition therapy, treatment with anti-tumor necrosis factor (TNF) agents was reported to have favorable effects on growth of patients with pre-pubertal onset CD. Avoiding corticosteroids (CS) and achieving deep remission seems to be important to maintain optimal growth in patients with pediatric onset IBD.

Su1876 - A Combination of Clinical, Serological and Genetic Factors Predicts Complicated Disease Course in Paediatric-Onset Crohn's Disease: Results from a Population-Based Study

Su1876 - A Combination of Clinical, Serological and Genetic Factors Predicts Complicated Disease Course in Paediatric-Onset Crohn's Disease: Results from a Population-Based Study

Subtherapeutic Infliximab Trough Levels and Complete Mucosal Healing Are Associated With Sustained Clinical Remission After Infliximab Cessation in Paediatric-onset Crohn's Disease Patients Treated With Combined Immunosuppressive Therapy.

We aimed to investigate the outcome in paediatric-onset Crohn's disease patients who had discontinued infliximab after maintaining clinical remission with combined immunosuppression, and to determine factors associated with clinical relapse. We conducted a retrospective observational study of 63 paediatric-onset Crohn's disease patients who had stopped scheduled infliximab during sustained corticosteroid-free clinical remission for at least 1 year with infliximab and azathioprine, and were followed up for at least 1 year thereafter. Cumulative relapse rates and the median time to relapse were estimated statistically. Factors at cessation were also evaluated for their association with clinical relapse. After a median follow-up period of 4.3 years [range, 1-7.5 years], 60.3% [38/63] of patients had experienced clinical relapse. According to Kaplan-Meier survival analysis, the estimated cumulative relapse rates at 1, 4, and 6 years were 19.0%, 62.2%, and 75.2%, respectively, and the median relapse time was 3.3 years from infliximab cessation. According to multivariate Cox proportional hazard regression analysis, infliximab trough levels of ≥2.5 μg/mL and incomplete mucosal healing were associated with clinical relapse (hazard ratio [HR] = 7.199, 95% confidence interval [CI] = 1.641-31.571, p = 0.009 and HR = 3.628, 95% CI = 1.608-8.185, p = 0.002, respectively). Although re-treatment with infliximab was effective in 90.9% [30/33] of patients, 7.9% [3/38] eventually underwent surgery within 1 year of relapse. Considering the high cumulative relapse rates in the long term and cases of severe relapse requiring surgery, discontinuing infliximab in paediatric-onset Crohn's disease patients is currently inadvisable. However, there may be a subgroup of patients who are good candidates for infliximab withdrawal.

The natural history of Crohn's disease in children: a review of population-based studies.

The incidence of Crohn's disease (CD) has been reported to increase. The aim of this review is to perform a comprehensive literature search of population-based studies focused on the natural history of paediatric-onset CD. A literature search of English and non-English language publications listed in the electronic database of MEDLINE (source PUBMED) and EMBASE from 1935 to 2016 was performed. Population-based studies or national cohorts reporting data on the short-term or long-term disease course of paediatric CD were included. Forty-nine paediatric and 15 nonpaediatric studies on CD have been identified. Up to one-third of children with inflammatory behaviour developed bowel complications more than 5 years after diagnosis. From 48 to 88% of children have experienced at least one corticosteroid course irrespective of the period of diagnosis and up to one-third became steroid dependent. Immunosuppressive preparations were used earlier and more frequently in newer than older cohorts (68 vs. 32% at 5 years) and more than one-third of children have received biological treatment early in the disease course. A decline in the surgery rate might be observed in more recent compared with older unselected populations. The relative risk of cancer in childhood-onset CD as well as the risk of death seem to have increased. Childhood-onset CD seems to be an aggressive phenotype of the disease. Compared with older cohorts, a trend towards decreasing surgical rate can be observed in newer cohorts paralleled by an increase in immunomodulator use and biologicals. Nevertheless, the causative role has yet to be investigated.

P125 Rapid increase in pan-treatment refractory Crohn's disease after transition to adult services: a regional cohort study

Background: Inflammatory bowel disease (IBD) presents in childhood in up to 15% of cases. Paediatric onset IBD (PIBD) has a more extensive and dynamically changing phenotype and a faster rising incidence than adult-onset IBD. We aimed to evaluate rates of treatment refractory disease at and then following transition to adult services. Methods: A prospective PIBD database identified a cohort of all patients discharged from our regional service since 01/01/07. A retrospective study of patients graduating from paediatric to adult IBD services through a transition process, transition event (single joint clinic) or transfer until 31/12/13 was conducted with post transfer follow-up (FU) data at a minimum of 1 year to last adult FU (LAFU). Pan-treatment exposure (PTE) was defined as exposure to all of azathioprine (AZA) or mercaptopurine (MP), methotrexate (MTX), infliximab (IFX) and adalimumab (ADA). Pan-treatment refractory (PTR) disease as those refractory (primary non-response [PNR], loss of response [LOR] or intolerance) to all of these therapies. We used the Montreal classification to describe disease location (L) and behaviour (B) phenotypes. Psychological co-morbidity was defined as a formal psychiatric diagnosis, regular psychiatry/psychology input (or intention for this if repeated family refusal), documented anxiety or depression and deliberate self-harm. Results: 138 patients graduated to adult services, 69% (95/138) had Crohn's disease (CD); 59% (56/95) male, 76% (72/95) with extensive disease (L3 or L3+L4) and 22% (21/95) B2 or B3 disease at time of transfer. Median (IQR) age at transfer 17.8 years (17.3, 18.4) and median (IQR) disease duration at transfer 5.4 years (4.6, 7.6). Median (IQR) length of FU post-transfer was 3.3 years (2.1, 5.1). 12% (11/95) had PTE with 4% (4/95) having PTR disease by time of transfer. PTE rates increased significantly to 26% (21/82) p=0.009 at LAFU and PTR disease to 18% (15/82) p=0.003; 13 patients lost to follow-up. 90% (19/21) of those with PTE had extensive disease and 48% (10/21) had B2 or B3 disease by LAFU. 80% (12/15) patients with PTR disease required bowel resection or a defunctioning stoma by LAFU, compared with 37% (30/82) of the whole CD cohort p=0.002. 24% (5/21) of those with PTE had significant psychological co-morbidity by LAFU. Conclusions: Our novel data show that pan-treatment exposure in paediatric-onset CD is already significant by time of transfer to adult services and continues to increase to affect 26% of this regional cohort within a relatively short period of adult follow-up. 18% of paediatric-onset CD patients have failed all medical treatments by LAFU and 71% with PTE require resectional or defunctioning surgery to manage disease.

Surgery in Pediatric Crohn's Disease: Indications, Timing and Post-Operative Management.

Pediatric onset Crohn's disease (CD) tends to have complicated behavior (stricture or penetration) than elderly onset CD at diagnosis. Considering the longer duration of the disease in pediatric patients, the accumulative chance of surgical treatment is higher than in adult onset CD patients. Possible operative indications include perianal CD, intestinal stricture or obstruction, abdominal abscess or fistula, intestinal hemorrhage, neoplastic changes and medically untreatable inflammation. Growth retardation is an operative indication only for pediatric patients. Surgery can affect a patient's clinical course, especially for pediatric CD patient who are growing physically and mentally, so the decision should be made by careful consideration of several factors. The complex and diverse clinical conditions hinder development of a systemized treatment algorithm. Therefore, timing of surgery in pediatric CD patients should be determined with individualized approach by an experienced and well organized multidisciplinary inflammatory bowel disease team. Best long-term outcomes will require proactive post-operative monitoring and therapeutic modifications according to the conditions.