Pediatric Crohn's Disease Activity Index Research Articles

Ustekinumab in pediatric patients with Crohn's disease: safety, and efficacy results from a multicenter retrospective study in China.

Ustekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed. This study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease. This multicenter retrospective study carried out at three tertiary care centers, and identified children who received their first dose of UST at 18 years old or younger and followed up for a minimum of 24 weeks. Data on demographics, disease behavior, location and activity, treatment history were collected. The primary outcomes were clinical remission at weeks 24-32 and weeks 48-56 of UST therapy. Secondary outcomes were clinical response at the same time points, endoscopic remission, changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin and fecal calprotectin, improvement in growth parameters, and rate of adverse events. Sixteen patients were included, and 11/13 (84.6%) continued to receive UST after 1 year. Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was lower than baseline (43.8, IQR: 31.3-51.9 vs.15, IQR: 5.6-25, p < 0.001) and 75% at weeks 48-56 with wPCDAI was lower than baseline (42.5, IQR: 23.8-50 vs. 7.5, IQR: 0-13.8, p = 0.004). Five of eleven children achieved endoscopic remission. No serious adverse events were recorded during the study period. UST is efficacious and safe in pediatric patients with CD. Pediatric patients could benefit from UST as either a primary or secondary biologic therapy for the induction, or maintenance of remission of CD.

Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. gov NCT03508193.

Operating Properties of Disease Activity Indices in Pediatric Inflammatory Bowel Disease: A Systematic Review.

Accurate, reliable, and responsive disease activity indices are important to streamline drug approval and treatment modalities for pediatric inflammatory bowel disease (pIBD). We aimed to identify all scoring indices used in pIBD randomized controlled trials (RCTs) and to evaluate their operating properties. MEDLINE, EMBASE, and CENTRAL were searched on December 6, 2022, to identify studies evaluating clinical, endoscopic, imaging, or patient-reported outcome measures (PROMs) in pIBD including Crohn's disease (CD) and ulcerative colitis (UC). Validity, reliability, responsiveness, and feasibility were summarized. Seventy RCTs evaluating pIBD indices were identified. Forty-one studies reported on the operating properties of 14 eligible indices (n = 9 CD, n = 5 UC). The Pediatric Crohn's Disease Activity Index (PCDAI) varied widely in terms of validity and reliability and was less feasible overall. In contrast, the Mucosal Inflammation Noninvasive Index, which includes fecal calprotectin, had better operating properties than the PCDAI. The Simplified Endoscopic Mucosal Assessment of Crohn's Disease appears more feasible and had similar operating properties than the longer Simple Endoscopic Score for Crohn's Disease. The Pediatric Ulcerative Colitis Activity Index was feasible, valid, and reliable, but responsiveness needs to be evaluated further. The Endoscopic Mayo score and the Ulcerative Colitis Endoscopic Index of Severity were reliable, but validity and responsiveness need to be evaluated further. Imaging and PROMs/quality of life indices need further evaluation. The operating properties of pIBD clinical trial end points varied widely. These results highlight the need for further validation and development of novel indices.

A257 EARLY PROACTIVE THERAPEUTIC DRUG MONITORING WITH USTEKINUMAB THERAPY IN PAEDIATRIC CROHN’S DISEASE

Abstract Background Ustekinumab (UST) is an effective therapy for adults with moderate to severe Crohn’s disease (CD), but data concerning optimal dosing in children are sparse. Aims To examine real-world post-induction PK and efficacy in a prospective multicentre cohort study of paediatric CD (Canadian Children IBD Network (CIDsCaNN)). Methods Children 2-17 years-old with CD were eligible for this analysis if they received IV UST for treatment of luminal CD and had serum UST levels measured at week 8. Median with interquartile range (IQR) UST dose and serum trough levels at weeks 8 and 16 were compared between children ampersand:003C40 kg and ≥40 kg with Mann-Whitney U test. Clinical remission was defined as weighted Pediatric CD Activity Index (wPCDAI) ampersand:003C12.5. UST durability was compared between those with a week 8 serum UST level ampersand:003C5 versus ≥5 µg/mL (log-rank p-value). Results Between 21/04/2017 and 30/04/2023, 39 children were eligible (74% M; median age 13.5 (IQR 11.9-15.6) y; median weight 44.7 (IQR 30.4-55.0) kg, 12 children ampersand:003C40 kg; 84% bio-naïve). Median disease duration at UST start was 4 (IQR 1-17) months; CD location distal ileal ± limited cecal (18%), colonic (26%), ileocolonic (54%). Median follow-up duration was 10.0 (IQR 6.7-12.7) months. All children received UST IV induction (67% 260 mg, 18% 390 mg) followed by 90 mg SC every 8 weeks. Induction doses in mg per kg were higher in those ampersand:003C40 kg (median 9.11 (IQR 8.68-10.08)) compared to those ≥40 kg (5.77 (IQR 5.24-6.45) mg/kg), pampersand:003C0.001. Induction doses in mg per body surface area (BSA) in m2 were similarly higher in those ampersand:003C40 kg (median 251.66 (IQR 244.16-258.99) versus 195.15 (IQR 172.71-224.11) mg/m2, pampersand:003C0.001). Despite higher induction doses, week 8 trough levels were numerically lower in those ampersand:003C40 kg (median 4.32 (IQR 1.33-8.36) versus 6.96 (IQR 5.38-8.90) µg/mL, p=0.29). Week 16 serum UST levels were also numerically lower in ampersand:003C40 kg versus ≥40 kg (median 4.04 (IQR 1.92-6.98) versus 5.50 (IQR 3.17-8.27) µg/mL, p=0.57). Interval shortening during maintenance to every 4 weeks occurred in 7 children prior to week 16, and in 14 children prior to 6 months. By 4 months, 19 of 33 children with available data (56%) achieved clinical remission. Overall, 8/39 (21%) ceased UST. Those who discontinued UST had significantly lower week 8 levels than those who continued UST (median 3.52 (IQR 1.19-6.12) versus 7.15 (IQR 5.09-10.15) µg/mL, p=0.027). In survival analysis, week 8 trough level ampersand:003C5 µg/mL was associated with an increased risk of UST discontinuation (log-rank p=0.032) (Figure 1). Conclusions Higher UST concentration at week 8 is associated with greater drug durability. A higher BSA-based induction for children ampersand:003C40 kg is supported by higher serum drug levels and improved drug durability. Figure 1. Ustekinumab durability by week 8 serum drug level Funding Agencies CIHR

Disordered eating behaviors in pediatric patients with inflammatory bowel disease in remission or mild-moderate disease activity.

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder that affects the gastrointestinal tract. Disordered eating describes irregular eating behaviors that may be a precursor to an eating disorder diagnosis. Higher rates of disordered eating have been described in chronic diseases. Screening for disordered eating is not performed in pediatric patients with IBD. The goal of this longitudinal study was to use the Eating Attitudes Test (EAT-26) to screen pediatric patients with IBD for disordered eating, estimate our population's prevalence, identify potential risk factors, and correlate positive EAT-26 screen results with evaluation in adolescent medicine clinic. Eighty patients with IBD between 10 and 21 years completed the EAT-26 questionnaire during gastroenterology clinic visit. Disease activity was measured using Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI). Patients also rated their own disease activity on a numerical scale. Five patients had a positive EAT-26 screen and were evaluated in the adolescent medicine clinic. One hundred percent of those who screened positive were diagnosed with a concomitant eating disorder once evaluated. Only 20% of those who screened positive had active IBD. Higher weight, body mass index, and patient perception of disease activity were associated with increased EAT-26 score. Pediatric patients with IBD are at risk for disordered eating, with a prevalence of 6% in our population, which is twice the prevalence of disordered eating in the general population. The EAT-26 questionnaire is a feasible tool to screen pediatric IBD patients for disordered eating.

CLINICAL, BIOCHEMICAL, AND INTESTINAL ULTRASONOGRAPHY RESPONSE TO CURCUMIN-QINGDAI (CURQD) COMBINATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND There are few FDA-approved therapies for pediatric patients with inflammatory bowel disease (IBD). Clinical remission rates plateau at 60%, even with the currently available biologic therapies. Nutraceuticals are novel alternative treatments that can be used as adjunct treatments. AIM In this case series of 8 patients, we aim to present the clinical and radiological response to a novel nutraceutical agent, CurQD, composed of QingDai (Indigo Naturalis) and Curcumin. METHODS Patients included required a baseline pre-treatment clinical assessment and at least a single follow-up examination. Clinical status was evaluated based on the Physician General Assessment (PGA, determined independently from the clinical scoring systems) and the pediatric Crohn’s disease activity index (PCDAI) or the pediatric ulcerative colitis activity index (PUCAI), as appropriate. Baseline biomarkers (Hgb, ESR, CRP, albumin, and calprotectin(FC)) were collected pre and post-treatment when available. When available, intestinal ultrasound (IUS) features were also noted. On the IUS, bowel wall thickness (BWT, in mm) and color Doppler signaling (measured by the modified Limberg score graded 0,1,2, or 3 based on severity) were collected. The longitudinal changes were demonstrated on the most inflamed segment. Considering the small sample size, only descriptive statistics were applied. RESULTS Primary therapies received included anti-TNFα for 3 patients, ustekinumab in 3 patients, 1 on vedolizumab, and mesalamine in 1. Baseline assessment was done at a median time of 1.8 weeks (IQR 0.9-3.6 weeks) before starting the supplement, and the follow-up was 3.9 weeks (IQR 2.8-5.4 weeks) after starting the supplement. Two patients were in clinical remission at baseline but had active disease based on Doppler activity on IUS, 3 patients had mild active disease, and 3 patients had either moderate or severe disease activity. At follow-up, all patients but one were in clinical remission. (Table 1) Median baseline FC decreased from 1047.4 ug/g (IQR 532.4-1107) to 27.1 (IQR 27.5-341.3). Five patients had complete IUS information. When isolating the most inflamed segment on IUS, all patients demonstrated a response to treatment, noted by a decrease in BWT and/or a decrease in Doppler signaling. (Figure 1) No patient had a baseline therapy change after their follow-up. One patient reported abdominal bloating after starting CurQD and discontinued the product after five weeks. CONCLUSION CurQD is a promising nutraceutical that may assist in breaking the therapeutic ceiling of biological therapies in IBD. Based on this small experience, a larger randomized controlled trial in children would be needed to assess the safety and efficacy of this product in this vulnerable patient group. Furthermore, IUS is a practical tool for evaluating response to therapy in a pragmatic clinical setting. Table 1 Change in clinical disease scores in patients receiving CurQD Figure 1 Description of changes in a) bowel wall thickness (BWT) and b) color Doppler signaling (measured by the modified Limberg score) in patients treated with CurQD.

IMPROVEMENT IN GROWTH AND NUTRITION STATUS AFTER ANTI-TNF THERAPY INITIATION AMONG PATIENTS WITH PEDIATRIC CROHN’S DISEASE: RESULTS FROM THE COMBINE TRIAL

Abstract BACKGROUND Growth failure impacts 15-40% of children with Crohn’s disease (CD). Potential causes of growth failure include chronic inflammation, malabsorption, and poor nutritional intake. Control of inflammation is key to improving growth outcomes. Anti-TNF therapy has been associated with improved growth and nutritional status in affected children. Large studies of serial outcomes of growth after anti-TNF therapy initiation are limited. OBJECTIVE We sought to 1) describe baseline weight, height, and BMI status at anti-TNF initiation in children with CD in a large, multicenter clinical trial, 2) compare the demographic and clinical characteristics of children with and without weight, height, and BMI disturbance, and 3) describe follow-up anthropometric parameters at approximately 12 and 24 months after anti-TNF initiation. METHODS We analyzed data from the COMBINE trial, a multicenter study comparing infliximab or adalimumab in combination with oral methotrexate to anti-TNF monotherapy for children with CD. We obtained demographic, clinical, and anthropometric data at time of enrollment and after 12 and 24 months. Weight, height, and BMI Z-scores were dichotomized as normal (≥ -1) versus disturbance (&amp;lt; -1) at each time point. We used standard descriptive statistics to summarize the distribution of Z-scores and bivariate statistics to compare demographic, clinical, and treatment characteristics among participants with versus without growth disturbance at baseline. RESULTS Our study population included 199 children (25% female, 83% white, mean age 12 years). Of these, 53 (26.6%) had a weight disturbance at baseline (Table 1). Of 188 children with height data available at baseline, 52 (27.7%) had a height disturbance and 37 (19.7%) had a BMI disturbance. The mean short pediatric CD activity index (sPCDAI) was higher in those defined with weight, height, and BMI disturbance at baseline compared to those with normal parameters (Table 2). Gender, race, ethnicity, and age at time of anti-TNF initiation were not different between groups with and without weight, height, or BMI disturbances. Approximately 12 months after enrollment, the proportion of patients with height disturbance was 6.1% with a continued decrease to 0.9% at 24 months. BMI disturbance was observed in 7.5% of participants at 12 months and 2.8% at 24 months. Weight disturbance was observed among 5.7% and 0.8% of participants at 12 and 24 months respectively. DISCUSSION A substantial proportion of children with CD had weight, height, and BMI disturbance at time of anti-TNF initiation. These proportions decreased at approximately 12 months and 24 months, demonstrating significant improvement in growth disturbances after anti-TNF therapy. Table 1 % of children with weight, height, and BMI disturbance (Z-score &amp;lt;-1) at time of enrollment in addition to 12 and 24 months after anti-TNF therapy initiation. Table 2 Mean short pediatric Crohn’s disease activity index (sPCDAI) for BMI, weight, and height at time of anti-TNF initiation.

P648 Dietary therapy using a short course of Exclusive Enteral Nutrition followed by the Crohn’s Disease Exclusion Diet in children with mild to severe Crohn’s Disease; maintenance update on the DIETOMICS trial

Abstract Background Exclusive enteral nutrition (EEN) is the first-line treatment for active Crohn’s disease (CD) in children. CD Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) has demonstrated better tolerance with a comparable effect in inducing remission among children with mild to moderate CD. This study evaluated the effectiveness of 2 weeks of EEN followed by CDED+PEN for maintaining remission for up to 24 weeks in children with mild-severe disease. Methods We conducted an international, multicenter, randomized controlled trial comparing 2 weeks of EEN using Modulen®, followed by 3 phases of the CDED+PEN (hereafter CDED), to 8 weeks of EEN followed by PEN with a free diet (hereafter EEN), all extended up to week 24 with a follow up till week 52. Children aged 8-18 with luminal CD duration less than 3 years, mild-severe disease [pediatric CD activity index (PCDAI),15-47.5], and active inflammation [elevated C-reactive protein (CRP),or fecal calprotectin (FC)] were included. Remission was defined as PCDAI≤10. Stable immunomodulator (IM) treatment was allowed, and naïve patients could initiate IM from week 4. Results We randomized 56 patients into two groups: Group CDED (n=30) and Group EEN (n=26); mean age 12.7±2.4, 37% female. Intention-to-treat analysis revealed remission in 18/30(60%) patients with CDED compared to 11/26(42%) with EEN at week 24,p=0.18 and 27% in CDED and 23% in EEN at week 52,p=0.75. Per protocol analysis showed 18/20(90%) remission in CDED compared to 11/14(78%) in EEN at week 8, p=0.35. Among patients who achieved remission at week 8, 18/23(78%) with CDED and 9/14(64%) with EEN maintained remission up to week 24, p=0.15. In CDED,15/20(75%) and 100% of EEN used IM, p=0.04. All CDED patients without IM remained in remission. Reduction of &amp;gt;50% in FC from baseline was obtained in 55% in the CDED and 28% in EEN, p=0.12. PCDAI improved from 31.2[20-35.6] to 5[0-12.5] in CDED and from 22.5[20-29.3] to 5[0-15.6] at week 24 in EEN, p&amp;lt;0.001 to all. CRP and FC significantly improved in both groups. Z score BMI improved from -1.3 [-2.1-(-0.1)] to -0.2 [-0.9-0.4], p=0.003 in CDED and from 0.08[-1.1-0.4] to 0.2[-1.7-0.7] at week 24 in EEN,p=0.098. Remission at week 2 (p=0.006) and overall high compliance (p=0.009) were identified as predictors of response at week 24. Conclusion While 2 weeks of EEN followed by CDED+PEN was not superior to EEN at 14 weeks (as previously reported), extending CDED+PEN for 24 weeks successfully maintained remission for up to 52 weeks in children with mild-to-severe CD. Moreover, a subset of patients maintained sustained clinical remission following CDED monotherapy. The long-term implementation of dietary therapy using CDED+PEN resulted in a significant improvement in nutritional status.

P910 Salivary calprotectin as a prognostic biomarker in Early Onset Inflammatory Bowel Disease: a cohort study

Abstract Background Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD) affects children in 25% of cases. In Early Onset IBD (EOIBD) oral involvement is common and oral manifestations (OM) are frequently the first presenting sign of disease. This study compared salivary calprotectin (SCp) between EOIBD and healthy controls (HC), differentiating patients based on their history of OM. Furthermore, this report correlated salivary and faecal calprotectin (FCp) in EOIBD and assessed the prognostic accuracy of SCp in predicting disease relapses. Methods A cohort study was conducted; 9 HC and 27 EOIBD (18 UC and 9 CD) were recruited at the University of Naples Federico II. EOIBD were divided in two subgroups based on the history of OM. A sample of stimulated whole saliva was collected by each participant by spitting. The samples were then processed by ELISA for determining SCp. For each patient clinical disease activity was measured through Paediatric Ulcerative Colitis Activity Index (PUCAI) and Paediatric Crohn’s Disease Activity Index (PCDAI), at baseline and during follow-up (4/8/12 weeks). At baseline, patients provided a stool specimen for FCp determination. SCp levels were compared between groups. In EOIBD SCp was correlated to clinical data and to FCp. Results At baseline all the patients were in treatment with immunosuppressive drugs; 19 were in clinical remission (PUCAI/PCDAI &amp;lt;10) and 8 had mild disease (PUCAI/PCDAI&amp;lt;35). 13 EOIBD had an history of OM: 12 suffered from aphthous-like manifestations while 3 reported granulomatous lesions; 10 experienced oral involvement before IBD diagnosis. OM were more prevalent in CD than in UC and were associated to ileocolic, perianal and upper gastrointestinal tract involvement. EOIBD with OM reported significantly higher SCp than EOIBD without OM and HC: 155,79±60,08 pg/mL in EOBD with OM vs 82,95±51,58 pg/mL in EOIBD without OM (P&amp;lt;0,01**) and 98,21±39,67 pg/mL in HC (P=0,21). Despite the systemic therapy and the clinical remission, in 7 EOIBD with OM oral lesions persisted. These patients had higher SCp compared to those who experienced OM remission (P&amp;lt;0,05*). In EOIBD with OM higher SCp was associated to higher FCp (P&amp;lt;0,05*) while in EOIBD without OM this correlation was not described. No correlation was found between SCp values and PUCAI/PCDAI at baseline. EOIBD with OM who reported higher SCp were found to have increased risk of relapse (P&amp;lt;0,05*) while no association was reported in EOIBD without OM. Conclusion In EOIBD with OM SCp is significantly higher, mirrors intestinal inflammation and predicts relapses. Our results suggest the use of SCp as a prognostic biomarker in EOIBD with OM although more studies are needed.

P273 Defining the prognosis of children with Crohn Disease with the support of magnetic resonance enterography: a multi-center multi-reader study

Abstract Background Ileocolonoscopic assessment is the most accurate method for detecting intestinal inflammation in Crohn disease (CD), but it allows the assessment only of a limited tract of the small intestine and does not provide data on inflammation beyond the mucosa. The auxiliary use of magnetic resonance enterography (MRE) can overcome these limitations and allow to predict the course of CD. Paediatric Inflammatory Crohn's MRE Index (PICMI) is a multi-point index of intestinal inflammation (mucosal and transmural) in children with CD created on the basis of MRI. The aim of the present study is to assess whether this completely non-invasive index at diagnosis could predict the course of CD in children and to test the inter-reader agreement as surrogate of index reproducibility. Methods All children diagnosed with CD in two tertiary referral centres with a 1-year minimum follow-up were enrolled in the study. MRE at diagnosis was blindly evaluated by 3 expert radiologists and PICMI was calculated for all patients. Children’s disease was stratified according to PICMI at diagnosis into remission (&amp;lt;10), mild (11-55), moderate (56-120) and severe (&amp;gt;120). Inter-observer agreement among radiologist was calculated. Data at follow-up were collected at 6-8 weeks, 1 year, 3 years and 5 years after CD diagnosis. Association between PICMI at diagnosis and CD prognosis was evaluated. Results A total of 71 children (52 males) with proven CD were enrolled in the study and PICMI was calculated for 68. PICMI at diagnosis was stratified into remission 6 (8.8%), mild 29 (42.6%), moderate 24 (35.3%), severe 9 (13.2%). Inter-observer agreement was calculated with an intraclass correlation coefficient of 0.65 which indicates moderate reliability between the 3 raters. PICMI score at diagnosis significantly correlated with PCDAI (Paediatric Crohn's Disease Activity Index) at diagnosis (p: 0.036). Steroid-free remission at 1, 3 and 5 years was comparable between PICMI groups: remission + mild vs moderate + severe (p: 0.606). CRP and calprotectin negative steroid free remission at 1,3,5 was also comparable (p: 0.578). PICMI at diagnosis was associated with the probability of biologic introduction at 1 year: incidence rate ratio IRR: 2.17 (1.09-4.42); p=0.019, 3-year IRR: 2.12 (1.15-3.96); p=0.011, and 5 years: 2.21 (1.20-4.08); p=0.007 (figure 1). Conclusion PICMI score is a reliable and reproducible index to determine activity in children with Crohn’s disease. Children with more active disease at diagnosis according to PICMI have shown an increased need to progression to biologic treatment in order to gain a comparable rate of steroid free remission and inflammatory marker negativity if compared with children with lower PICMI scores.

P354 Tryptophan metabolites as predictive biomarkers for dietary therapy outcomes in paediatric Crohn's disease

Abstract Background Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6 was associated with changes in tryptophan (Trp) metabolism.1 Our aim was to investigate whether baseline Trp metabolites could predict dietary therapy outcomes in paediatric CD. Methods In total, 26 mild-to-moderate treatment-naive paediatric CD patients from a prior randomized controlled trial 2, were classified as having remission 6 (R, n =19 (CDED+PEN=10 and EEN=9)) and No-Remission (NR, n=7 (CDED+PEN=3 and EEN=4)) following 6 weeks of CDED+PEN or EEN therapy, based on the Paediatric Crohn’s Disease Activity Index (PDCAI) score (≤10 remission, &amp;gt;10 no remission). We performed targeted quantitative analysis of 21 tryptophan metabolites in baseline faecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiving Operator Characteristic Curve (ROC) and Random Forest Analysis were used to assess the predictive power of Trp metabolites for dietary outcomes. Results Baseline clinical characteristics were comparable between R and NR. Baseline fecal kynurenine was significantly higher in NR compared to R for CDED+PEN (p=0.02) (Fig 1A) and EEN (p=0.04) (Fig 2A). ROC analysis highlighted the robust predictive power of kynurenine for CDED+PEN (area under the curve (AUC)=0.97) (Fig 1B) and EEN (AUC=0.88) (Fig 2B) induced remission. Random Forest analysis corroborated these observations. Ratios of Trp metabolites were compared to investigate different downstream Trp pathways. The ratio serotonin/kynurenine was the strongest predictor of CDED+PEN-induced remission (AUC=1) (Fig 1C). The ratio 5-OH-Tryptophan/kynurenine (AUC=0.88) (Fig 2C) predicted EEN-induced remission. When data from CDED+PEN and EEN were combined, kynurenine (AUC=0.91) and the ratios of quinolinic acid/kynurenine (AUC=0.93) and kynurenine/indole-3-acetic acid (AUC=0.88) demonstrated strong predictive performance for dietary therapy in general (Fig 3A,B and C). Conclusion Baseline faecal kynurenine has potential as a prognostic biomarker for dietary therapies. Trp metabolite ratios, notably serotonin/kynurenine for CDED+PEN and 5-OH-tryptophan/kynurenine for EEN, showed promising predictive capabilities. If confirmed in validation studies, baseline faecal Trp markers may be able to provide much needed guidance to personalize dietary intervention within the management of paediatric CD.

P1063 Comparison of all paediatric patients and young adults with Crohn’s Disease treated with ustekinumab in the REALITI Real-World Evidence Effectiveness Study

Abstract Background Treatment of paediatric patients (pts) with Crohn’s disease (CD) can offer some challenges to providers. There is an urgent need to inform prescribers about paediatric efficacy, safety, and dosing. REALITI evaluated the effectiveness and safety of ustekinumab (UST) routine clinical care in paediatric pts (age 2 to &amp;lt;18) regardless of disease severity or baseline corticosteroid use. Reference data are shown for young adults (age 18 to 25) with CD, for whom UST is approved. Data were obtained from the ImproveCareNow (ICN) Registry. Methods Data from pts from ICN with CD initiating treatment with UST between 10 January 2010 and 29 February 2020 were evaluated. A supplemental, retrospective chart review collected data not in ICN. The primary endpoint was clinical remission (Short Paediatric CD Activity Index [sPCDAI] score ≤10) at Week (Wk) 52. Data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence intervals (CI) were calculated along with rates of inflammatory bowel disease (IBD)-related hospitalization and surgeries and serious/opportunistic infections. Results Overall, 479 pts in ICN with CD were treated with UST. We report an analysis of paediatric pts (n=348) compared to young adults (n=131). Most paediatric pts (98.9%) and young adults (95.4%) had received prior biologic therapy, with approximately half (47.1% and 50.4%, respectively) receiving corticosteroids at baseline. Slightly higher proportions of pts had moderate to severe disease (sPCDAI ≥30) among paediatric pts (49.7%) vs young adults (44.8%). Clinical remission at Wk52 was achieved in 30.2% of paediatric pts (105/348; 95% CI: [25.6%, 35.2%]) vs 28.2% of young adults (37/131; 95% CI: [21.2%, 36.5%]) (Figure 1A). Clinical remission rates decreased slightly over time from Wk 20-52 (Figure 1B); discontinuation rates through WK 52 remained low and were similar between groups (21.0%, 22.9%, respectively). Overall, 31.9% of paediatric pts and 19.8% of young adults had IBD-related hospitalizations; IBD-related surgery was reported in 16.1% and 9.2% of pts, respectively. Serious infections occurred in 7.5% of paediatric pts and 3.8% of young adults. Rates of opportunistic infections were low (1.4%, 0%, respectively). No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred. One death, deemed by investigators as unrelated to IBD or UST treatment, was reported among paediatric pts; no deaths were reported among young adults. Conclusion Using real-world data from the ICN Registry, the remission rates for using UST to treat CD were found to be generally comparable between paediatric pts and young adults. No new safety signals were identified.

Efficacy of infliximab after loss of response of/intolerance to adalimumab in pediatric Crohn's disease: A retrospective multicenter cohort study of the "GETAID pédiatrique".

Infliximab (IFX) and adalimumab (ADA) are recommended for induction and maintenance of remission in pediatric Crohn's disease (CD). ADA is now often used in first line due to its efficacy and tolerability, but a loss of response (LOR) can occur over time. The aim was to assess the efficacy of IFX as second line therapy after LOR or intolerance to ADA in pediatric CD patients at 1 year. We conducted a retrospective and multicenter study in France among the "GETAID pédiatrique" centers between April 2019 and April 2022. CD patients under 18 years old and treated with IFX after ADA failure or intolerance were included. We collected anthropometric, clinical, and biological data at baseline (start of IFX), at 6 and 12 months. Clinical remission was defined by a Weighted Pediatric CD Activity Index (wPCDAI) score less than 12.5 points. Of the 32 patients included in our study, 27 (84.4%) were still on IFX at 12 months of the switch. Among them, 13 had discontinued ADA because of a LOR, 12 for insufficient response and 2 due to primary nonresponse. At M12, 22 patients were in corticosteroid free clinical remission (68.7%). Under IFX, the wPCDAI decreased over time (47.5 ± 24.1, 16.6 ± 21.2 and 9.7 ± 19.0 at M0, M6 and M12 respectively). The only factor associated with clinical remission at 12 months was absence of perianal disease at the end of the IFX induction. IFX is effective in maintaining remission at 1 year in pediatric CD patients experiencing a LOR or intolerance with ADA, and IFX could be an interesting therapeutic choice instead of other biologics in this situation.

Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.

Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD. This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up. Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegaloviruscolitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively. While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.

Intestinal ultrasound score predicts therapeutic outcomes of infliximab in pediatric patients with Crohn’s disease

Background and aims Objective evaluation of treatment response is critical in the management of Crohn’s disease (CD). Compared with endoscopy, intestinal ultrasound (IUS) is non-invasive and well-tolerated. This study is aimed to assess the predictive value of IUS score for treatment response in pediatric CD patients. Methods We conducted a retrospective study in pediatric CD patients who underwent endoscopy and IUS at start of infliximab treatment [T0] and after 22–38 weeks [T1] between February 2021 and January 2023. Pediatric Crohn’s Disease Activity Index (PCDAI), biochemical parameters, the Simple Endoscopic Score for Crohn’s disease (SES-CD) and IUS parameters were collected at two timepoints. IUS scores were assessed by International Bowel Ultrasound Segment Activity Score (IBUS-SAS). Results Thirty patients were included, with 53.3% reaching endoscopic response and 43.3% endoscopic remission. After infliximab treatment, IBUS-SAS (58.5 ± 24.2 vs 34.4 ± 21.6, p = .0001) was significantly decreased. At T1, change in IBUS-SAS (−38.2 ± 22.0 vs −7.9 ± 24.1, p = .0015) were pronounced in patients with endoscopic response compared with endoscopic non-response. Significant correlation were observed between IBUS-SAS and SES-CD, PCDAI, C-reaction protein, erythrocyte sedimentation rate, hemoglobin, albumin. The most accurate cutoff values for predicting endoscopic response were 57.4% decrease of IBUS-SAS (AUROC: 0.862, p < .001). The optimal cut-off of IBUS-SAS to correlate endoscopic remission was 26.0 (AUROC: 0.686, p = .017). Conclusions The validated ultrasound-base score, IBUS-SAS is an effective index for monitoring endoscopic response to infliximab therapy in CD. IUS evaluation could guide treatment decision for pediatric CD.

Relationship between disease activity index and sleep disorders in children with inflammatory bowel diseases.

The aim of the study was to assess the prevalence of sleep disturbance in pediatric IBD patients and evaluate the relationship between clinical features of IBD, disease activity, inflammatory markers and quality of sleep. A total of 99 patients who were followed-up with the diagnosis of IBD (44 Crohn's disease (CD), 55 Ulcerative colitis (UC)) between 2015-2020 and 80 healthy controls were enrolled in the study. The clinical and demographic characteristics, laboratory parameters and disease activities were obtained from medical reports retrospectively. Pittsburgh sleep quality index (PSQI) was administered to all participants. PSQI score was significantly higher in patient group than the control group (P < 0.001). The sleep time of patient group, especially patients with UC was later than the control group (P = 0.008). Sleep duration was longer in control group than the patient group (P < 0.001). A positive strong correlation was obtained in disease activity index (r = 0.886; P < 0.001) and abdominal pain (r = 0.781; P < 0.001) with PSQI scores of CD patients. Disease activity index, rectal bleeding, diarrhea and number of stool had statistically significant positive strong correlation with PSQI scores of UC patients (P < 0.001). Pediatric Crohn's disease activity index and Pediatric ulcerative colitis activity index were the only independent risk factors affecting sleep disturbances (80% sensitivity and 91.67% specificity, 93.1% sensitivity and %96.15 specificity, respectively). Conclusion: Increased disease activity has adverse effects on sleep quality. PSQI and PCDAI were strong tests for predicting sleep disorders in pediatric patients with IBD. What is Known: •Sleep disturbances are common complaint in inflammatory bowel disease (IBD), even in clinical remission. •Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality of patients. What is New: •PSQI and Pediatric Crohn Disease Activity index (PCDAI) were strong tests for predicting sleep disorders in pediatric patients with IBD. •PSQI and PCDAI scores correlated significantly with the severity of the sleep disturbances.

Can We Rely on Resting Metabolic Rate Equations? Large Variance in Crohn Disease Pediatric Patients.

Inadequate caloric intake is common in Crohn disease (CD) and nutrition support plays an important role in remission induction and in meeting nutritional needs. For nutritional planning, determining resting metabolic rate (RMR) is essential in pediatric patients with CD. To measure RMR in CD pediatric patients using indirect calorimetry, and compare it with estimated RMR (eRMR) calculated by Schofield equation. Children with CD treated in a tertiary pediatric inflammatory bowel disease center in Israel participated in the cross-sectional study. At study visits, weight, height, clinical and laboratory assessments, bioelectrical impedance, and RMR measured by indirect calorimetry were done. Additionally, disease severity was determined by the Pediatric Crohn Disease Activity Index and eRMR was calculated using the Schofield equation. The ratio of the measured RMR to eRMR was performed in addition to the Spearman correlation test. The study group included 73 children (49 boys) with mean age of 13.9 ± 2.3 years. Children with moderate or severe disease had lower weight for age z score, lower BMI- z , and lower RMR compared to children with mild disease. However, when RMR was adjusted for fat free mass (n = 50), the association between RMR and disease severity disappeared. Variance in RMR was high between subjects. Our data suggest that the Schofield equation is inadequate for determining RMR in pediatric CD and that RMR should be measured to guarantee the most appropriate nutritional intervention.

Comparison of Clinical Outcomes in Pediatric Patients with Ileocolonic Crohn Disease Treated with Infliximab Versus Adalimumab.

Infliximab is considered superior to adalimumab in patients with ulcerative colitis, especially in severe cases. Whether this is true for Crohn disease (CD) patients with colonic involvement is unclear. Our aim was to compare the clinical effectiveness of infliximab versus adalimumab in pediatric ileocolonic (L3) CD. This retrospective study included patients <18 years with ileocolonic CD treated with infliximab or adalimumab between 2014 and 2021. Primary outcome was steroid-free clinical remission by week 52. Secondary outcomes were treatment modifications, drug discontinuation, inflammatory bowel disease (IBD)-associated hospitalizations, and surgery during the first year of treatment. We identified 74 patients treated with adalimumab and 41 with infliximab, with comparable demographic features. Concomitant immunomodulator therapy at biologic initiation was significantly lower in the adalimumab group (28% vs 85%, P < 0.001). Rates of drug intensification were higher in the infliximab group at end of induction (EOI) and at 52 weeks (55% vs 32% and 88% vs 46%, P < 0.001). Given significant differences between initial median Pediatric Crohn Disease Activity Index scores (20.0 [interquartile range, IQR 15.0-27.5] vs 11.0 [IQR 7.5-20.0] for infliximab and adalimumab groups, respectively, P < 0.001), propensity score matching was performed. Following matching, the rate of patients in steroid-free clinical remission by EOI was significantly higher in the adalimumab group (93.8% vs 46.9%, P < 0.001), but comparable by 1 year. Moreover, inflammatory markers and fecal calprotectin values were also similar at these time points. Rates of drug discontinuation, IBD-associated admissions, and surgery were similar between groups. In a retrospective study of patients with ileocolonic CD, adalimumab and infliximab had comparable outcomes by 52 weeks.

The effectiveness of two-stage surgical treatment of children with complicated Crohn’s disease

Introduction. Crohn’s disease (CD) is an inflammatory disease of the digestive tract of unknown etiology with segmental transmural inflammation of various parts of the gastrointestinal tract. The annual increase in the number of children with newly diagnosed CD, late diagnosis and untimely surgical treatment is one of the urgent problems due to the lack of a single algorithm of surgical treatment.&#x0D; The aim: to determine the effectiveness of surgical treatment of CD in children.&#x0D; Materials and methods. The study included thirty six patients with complicated CD Over the period from 2018 to 2022, a re­trospective and prospective analysis of children who received medical care for CD with two-stage surgical treatment (resection of the affected area with enterostomy and subsequent restoration of gastrointestinal continuity) was carried out. &#x0D; Results. Clinical activity according to Pediatric Crohn’s Disease Activity Index (PCDAI) in 23 (63.8%) children before treatment was recorded as high (30.0–75.2 points), in 15 (36.2%) children had average activity (11–29 points). After the staged surgical treatment, there was a change in the indicators — the onset of remission in 2 (5.5%) children and in 34 (94.5%) mild course &#x0D; (p &lt; 0.05). Statistical analysis of anthropometric indicators revealed positive changes (HAZ p &lt; 0.05 and BAZ p &lt; 0.001) with increase in weight and height criteria. Assessment of laboratory dynamics revealed positive changes (p &lt; 0.001) — the absence of anemia, hypoalbuminemia and relief of bacterial inflammation. CD debuted before the age of 10 years in 7 children (19.4%), aged 10 to 16 years — in 29 (80.5%). In 24 (66.7%) children, genetic engineering biological therapy (GEBT) at the time of the development of surgical complications was not performed, from them 15 (62.5%) received hormonal and immunomodulatory therapy while it was not effective, while for 9 (37.5%) patients the timely verification was diagnosed at the stage of development of CD complications. However, the development of surgical complications was noted in 12 (33.3%) children, despite the timely verification and appointment of treatment for genetic engineering biologic therapy (GEBT). Biological therapy was continued for 7 (58.3%) children who received GEBT before surgery, and in 5 (41.7%) patients, treatment was continued with a change of GEBT. The period of stay with a stoma was found to be from 7 to 31 months (Me = 8).&#x0D; Conclusions. In complicated forms of CD in children, despite drug therapy, including GEBT, the development of complications requiring surgical treatment was noted, which indicates an aggressive and progressive course of CD. However, the use of stage-by-stage surgical treatment showed efficiency due to the positive dynamics of anthropometric indicators, laboratory markers, the potency of surgical treatment, and made it possible to achieve stable remission against the background of specific therapy and improve the quality of life in CD children.