Paradoxical Psoriasiform Skin Eruption in Pediatric Patients with Inflammatory Bowel Disease Treated with TNFα Inhibitors.

BACKGROUND: Tumor necrosis factor α inhibitors (TNFαI)-induced psoriasiform eruptions are a well-known phenomenon among adults. However, data are limited regarding this reaction in children. OBJECTIVES: To describe in pediatric patients with inflammatory bowel diseases (IBD), the clinical characteristics of TNFαI-induced psoriasiform eruptions and the outcomes of various therapeutic options. METHODS: We reviewed the medical charts of pediatric patients (aged <18 years old) with IBD who developed TNFαI-induced psoriasiform eruptions during 2006-2022. RESULTS: Among 454 patients with IBD treated with TNFαI, 58 (12.8%) were diagnosed with TNFαI-induced psoriasiform eruptions, of whom 51 were included in the study. The female to male ratio was 1:1.3. The median age at skin eruption was 14.1 [interquartile range, 12.11-16.05] years. The median elapsed time to eruption appearance was 15 [interquartile range, 7-24] months after initiation of the treatment. All the patients were treated with topical steroids and 17 (33%) needed systemic treatment (phototherapy, methotrexate or acitretin). Sixteen patients (31%) needed to stop TNFαI treatment due to an intractable eruption. Female patients, patients with inflammatory alopecia and patients who were treated with methotrexate or phototherapy were more prone to stop TNFαI. CONCLUSIONS: TNFαI-induced psoriasiform eruptions are common in pediatric patients with IBD. The eruption may appear months or even years after treatment initiation. Almost one-third of the described patients had to replace their treatment due to a recalcitrant cutaneous eruption. This indicates that a multidisciplinary approach is required for effective management.

Effect of Overweight and Obesity on the Response to Anti-TNF Therapy and Disease Course in Children With IBD.

BACKGROUND: This study aimed to evaluate the effect of overweight and obesity at the start of anti-TNF therapy on treatment response and relapse rate in children with inflammatory bowel disease (IBD). METHODS: This multicenter, retrospective cohort study included 22 IBD centers in 14 countries. Children diagnosed with IBD in whom antitumor necrosis factor (anti-TNF) was introduced were included; those who were overweight/obese were compared with children who were well/undernourished. RESULTS: Six hundred thirty-seven children (370 [58%] males; mean age 11.5 ±â€…3.5 years) were included; 140 (22%) were in the overweight/obese group (OG) and 497 (78%) had BMI ≤1 SD (CG). The mean follow-up time was 141 ±â€…78 weeks (median 117 weeks). There was no difference in the loss of response (LOR) to anti-TNF between groups throughout the follow-up. However, children in OG had more dose escalations than controls. Male sex and lack of concomitant immunomodulators at the start of anti-TNF were risk factors associated with the LOR. There was no difference in the relapse rate in the first year after anti-TNF introduction; however, at the end of the follow-up, the relapse rate was significantly higher in the OG compared with CG (89 [64%] vs 218 [44%], respectively, P < .001). Univariate and multivariate analysis revealed that being overweight/obese, having UC, or being of male sex were factors associated with a higher risk for relapse. CONCLUSIONS: Overweight/obese children with IBD were not at a higher risk of LOR to anti-TNF. Relapse in the first year after anti-TNF was introduced, but risk for relapse was increased at the end of follow-up.

Overweight and obese children with inflammatory bowel disease required more frequent dose escalations, but overall loss of response to anti-TNF therapy was not increased. Furthermore, in the long term, they tend to have a higher risk for relapse.

Different infliximab induction dosing regimens do not affect remission rates up to 1 year in children with Crohn's disease.

OBJECTIVES: Multiple studies in patients with Crohn's disease (CD) treated with anti-tumor necrosis factor alpha agents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated (IFX) administration during induction resulted in improved outcomes. METHODS: This retrospective study included CD patients aged 5-17.9 years that were treated with IFX. We compared outcomes of patients treated during induction with 5-8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of IFX. Primary outcome was steroid-free clinical remission by Week 52. RESULTS: Sixty-eight patients were included, of whom seven discontinued IFX before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at IFX initiation. Despite receiving significantly more IFX, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn's disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5-20] vs. 5 [0-15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough IFX levels by Week 52. CONCLUSION: Accelerated IFX dosing during induction did not result in improved outcomes up to 12 months follow-up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied.

Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis.

OBJECTIVES: Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG. METHODS: This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data. RESULTS: Thirty-three patients, (23 females [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eight patients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor. Helicobacter pylori was identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients. CONCLUSIONS: AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.

Sexual health in adolescents with inflammatory bowel disease - The paediatric gastroenterologists' point of view.

AIM: Although sexual health (SH) impairment and sexually transmitted infections (STI) are occasionally encountered in patients with inflammatory bowel disease (IBD), paediatric gastroenterologists (PedGI) do not often discuss these issues. Literature about SH in the paediatric IBD population is limited. We aimed to assess PedGI knowledge and common practice related to sexual advice and STI workups in patients with IBD. METHODS: A questionnaire comprising 25 questions addressing sexual activity in youth, SH, recommendations, and workup for STI in adolescents with IBD was sent to all registered PedGI in Israel. RESULTS: Fifty-two physicians completed the questionnaire (27 males,52%). Only 50% correctly predicted the mean age that Israeli youth start practicing sex. Seventy-five per cent responded that providers should discuss sexual activity with their patients, but only 19% do so, most often in response to a patient's query. Ninety six percent answered that they do not have enough knowledge about SH in IBD. Finally, only 2% obtain rectal swabs for STI in patients with refractory proctitis. CONCLUSION: Sexual issues and recommendations are not routinely discussed by the majority of PedGI in paediatric IBD clinics. Providers should obtain more knowledge in the field and initiate discussion of these issues with adolescent patients with IBD.

A significant increase in anthropometric indices during long-term follow-up of pediatric patients with celiac disease, with no endocrine disorders.

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

Dual Biologic or Small Molecule Therapy in Refractory Pediatric Inflammatory Bowel Disease (DOUBLE-PIBD): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND: Current data on dual biologic therapy in children are limited. This multicenter study aimed to evaluate the effectiveness and safety of dual therapy in pediatric patients with inflammatory bowel disease (IBD). METHODS: A retrospective study from 14 centers affiliated with the Pediatric IBD Interest and Porto Groups of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Included were children with IBD who underwent combinations of biologic agents or biologic and small molecule therapy for at least 3 months. Demographic, clinical, laboratory, endoscopic, and imaging data were collected. Adverse events were recorded. RESULTS: Sixty-two children (35 Crohn's disease, 27 ulcerative colitis; median age 15.5 [interquartile range, 13.1-16.8] years) were included. They had all failed previous biologic therapies, and 47 (76%) failed at least 2 biologic agents. The dual therapy included an anti-tumor necrosis factor agent and vedolizumab in 30 children (48%), anti-tumor necrosis factor and ustekinumab in 21 (34%) children, vedolizumab and ustekinumab in 8 (13%) children, and tofacitinib with a biologic in 3 (5%) children. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Normalization of C-reactive protein and decrease in fecal calprotectin to <250 µg/g were achieved in 75% and 64%, respectively, at 12 months of follow-up. Twenty-nine (47%) children sustained adverse events, 8 of which were regarded as serious and led to discontinuation of therapy in 6. CONCLUSIONS: Dual biologic therapy may be effective in children with refractory IBD. The potential efficacy should be weighed against the risk of serious adverse events.

This multicenter study describes 62 children with refractory inflammatory bowel disease who received dual biologic therapy. Clinical remission was observed in 21 (35%), 30 (50%), and 38 (63%) children at 3, 6, and 12 months, respectively. Several serious adverse events were reported.

Adherence to the Mediterranean Diet Is Associated with Decreased Fecal Calprotectin Levels in Children with Crohn's Disease in Clinical Remission under Biological Therapy.

INTRODUCTION: Adherence to the Mediterranean diet (MD) was shown to be associated with decreased disease activity in adult patients with Crohn's disease (CD). Nevertheless, data on its association with fecal calprotectin (FC), particularly in children, remain limited. This study aimed to assess the association between adherence to the MD and FC as an indicator of mucosal healing in patients who are predominantly in remission while undergoing biological therapy. METHODS: This was a cross-sectional study among children with CD. Adherence to MD was evaluated using both the KIDMED questionnaire and a food frequency questionnaire (FFQ). Israeli Mediterranean Diet Adherence Screener (I-MEDAS) score was calculated, and FC samples were obtained. RESULTS: Of 103 eligible patients, 99 were included (mean age 14.3 ± 2.6 years; 38.4% females); 88% were in clinical remission, and 30% presented with elevated FC. The mean KIDMED score was higher among patients who had FC <200 µg/g compared to patients with FC >200 µg/g (5.48 ± 2.58 vs. 4.37 ± 2.47, respectively; p = 0.04). A moderate correlation between the KIDMED score and the I-MEDAS score was observed (r = 0.46; p = 0.001). In a multivariate regression analysis, adherence to MD was associated with decreased calprotectin levels, OR 0.75 [95% CI: 0.6-0.95], p = 0.019. Vegetable consumption was found to be inversely associated with elevated FC (0.9 portion/day [0.3-2.9] in FC >200 µg/g vs. 2.2 portions/day [0.87-3.82] in FC <200 µg/g; p = 0.049). CONCLUSIONS: In children with CD who are mostly in clinical remission under biological therapy, high adherence to MD is associated with decreased FC levels. Encouraging vegetable consumption, especially during remission, may benefit these patients.

De Novo Crohn's Disease in Children With Ulcerative Colitis Undergoing Ileal Pouch-Anal Anastomosis: A Multicenter, Retrospective Study From the Pediatric IBD Porto Group of the ESPGHAN.

BACKGROUND AND AIMS: We sought to define the prevalence and to characterize possible predictive factors of Crohn's disease (CD) occurring in children with ulcerative colitis (UC) after ileal pouch-anal anastomosis (IPAA). METHODS: This was a multicenter, retrospective study including 15 centers of the Porto IBD group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Children with a confirmed diagnosis of UC undergoing colectomy with IPAA and a minimal follow up of 6 months were identified. The following data were collected: demographic data; endoscopic and histologic data; disease activity; laboratory exams; therapeutic history; indication for surgery, type, and timing; and IPAA functional outcomes and complications. In de novo CD cases, time of diagnosis, phenotype, location, and therapies were gathered. RESULTS: We identified 111 UC children undergoing IPAA from January 2008 to June 2018 (median age at colectomy: 13 years; age range: 1-18 years; female/male: 59/52). The median time from diagnosis to colectomy was 16 (range, 0-202) months. At the last follow-up, 40 (36%) of 111 children developed pouchitis. The criteria for de novo CD were met in 19(17.1%) of 111 children with a 25-month median (range, 3-61 months). At last follow-up, 12 (63.1%) of 19 were treated with biologics and in 5 (26.3%) of 19 children, the pouch was replaced with definitive ileostomy. In a multivariable logistic regression model, decreased preoperative body mass index z scores (odds ratio, 2.2; 95% confidence interval, 1.1-4.4; P = .01) resulted as the only variable associated with CD development. CONCLUSIONS: Children with UC undergoing IPAA carry a high risk of developing subsequent CD. De novo CD cases showed decreased preoperative body mass index z scores, identifying a poor nutritional status as a possible predictive factor.

This is the largest European study describing the prevalence of Crohn's disease (CD) development in children with ulcerative colitis undergoing subtotal colectomy with ileal pouch­anal anastomosis. Children affected by ulcerative colitis carry a higher risk when compared with adults to develop de novo CD after surgery. On the other hand, the multivariate analysis identified decreased values of preoperative body mass index z scores as a possible predictor of new-onset CD.

Outcome of Very Early Onset Inflammatory Bowel Disease Associated With Primary Sclerosing Cholangitis: A Multicenter Study From the Pediatric IBD Porto Group of ESPGHAN.

BACKGROUND: Whether primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed before 6 years (ie, VEO-IBD) has a distinct phenotype and disease course is uninvestigated. We aimed to analyze the characteristics and natural history of VEO-PSC-IBD, compared with early and adolescent-onset PSC-IBD. METHODS: This is a multicenter, retrospective, case-control study from 15 centers affiliated with the Porto and Interest IBD group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every 6 months. Inflammatory bowel disease-related (clinical remission, need for systemic steroids and biologics, and surgery) and PSC-related (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, or death) outcomes were compared between the 2 groups. RESULTS: Sixty-nine children were included, with a median follow-up of 3.63 years (interquartile range, 1-11): 28 with VEO-PSC-IBD (23 UC [82%], 2 IBD-U [7%] and 3 [11%] CD), and 41 with PSC-IBD (37 UC [90%], 3 IBDU [7.5%] and 1 [2.5%] CD). Most patients with UC presented with pancolitis (92% in VEO-PSC-UC vs 85% in PSC-UC, P = .2). A higher number of patients with VEO-PSC-IBD were diagnosed with PSC/autoimmune hepatitis overlap syndrome than older children (24 [92%] vs 27 [67.5%] PSC-IBD, P = .03), whereas no other differences were found for PSC-related variables. Time to biliary strictures and infective cholangitis was lower in the VEO-PSC-IBD group (P = .01 and P = .04, respectively), while no difference was found for other outcomes. No cases of cholangiocarcinoma were reported. CONCLUSIONS: Primary sclerosing cholangitis related to inflammatory bowel disease has similar baseline characteristics whether diagnosed as VEO-IBD or thereafter. A milder disease course in terms of biliary complications characterizes VEO-PSC-IBD.

Very early onset primary sclerosing cholangitis associated with IBD (VEO-PSC-IBD) often presents with autoimmune features and shows a milder PSC disease course than later-onset disease. These findings highlight the significance of studying the distinctive genetic and pathophysiological factors specific to VEO disease.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: In a retrospective study of patients with ileocolonic CD, adalimumab and infliximab had comparable outcomes by 52 weeks.

Gluten Immunogenic Peptides Are Not Correlated With Reported Adherence to Gluten-Free Diet in Children With Celiac Disease.

OBJECTIVE: There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence. METHODS: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis. RESULTS: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8-11.7) years, and median (IQR) duration on GFD of 2.5 (2-5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms. CONCLUSIONS: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.

Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model.

OBJECTIVES: In patients with inflammatory bowel diseases (IBD), data on trough concentration (TC) response to adjustments of anti-tumor necrosis factor (TNFα) are scarce. METHODS: We included pediatric patients with IBD who were treated with anti-TNFα agents and had sequential monitoring of TC pre- and post-adjustment. Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded. RESULTS: For the entire cohort (86 patients), median age at diagnosis was 13.2 (interquartile range, 10.7-14.9) years [females, 48%; Crohn disease (CD), 72%]. For infliximab, 58 patients had 201 interval changes and 26 had dose increase. Increase in TC following dose increase could not be predicted due to significant variability (P = 0.9). For every 10% decrease in interval, TC was increased by 1.6 µg/mL or by 57.2% (P = 0.014). Perianal disease was associated with attenuated response. For every 10% increase in interval, TC was decreased by 0.66 µg/mL or by 4.2%. The diagnosis of CD was associated with reduced response to interval increase. For adalimumab, 28 patients had 31 and 12 events of interval decrease or increase, respectively. Interval decrease resulted in increased median TC from 4.5 (3.5-5.3) µg/mL to 8.1 (6.5-10.5) µg/mL (X1.8) while interval increase resulted in TC change from 15.5 (12.8-18.6) µg/mL to 9.7 (6.5-14.6) µg/mL (:1.6) (P < 0.001 for both). Increase in delta TC was associated with younger age, and with absence of perianal disease (P = 0.001). CONCLUSION: Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab while response to infliximab adjustment are more variable.

Correlation Between the Nancy Histopathology Index and Markers of Disease Activity in Pediatric Ulcerative Colitis.

The Nancy Histological Index (NHI) was developed to assess histological disease activity in adult ulcerative colitis (UC) patients. However, data in pediatrics is limited. Our aim was to determine whether the NHI correlates with different indices of disease activity in pediatric UC patients. We retrospectively reviewed the NHI in rectal biopsies from 61 pediatric UC patients (median age 14.3 years), of whom 34 (55.7%) were newly diagnosed. The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score among participants was 30 (interquartile range 5-55). Most patients exhibited an NHI of 3 (41/61, 67.2%) or 4 (8/61, 13.1%), reflecting moderate-severe histologic inflammation. A moderate positive correlation was identified between the NHI and PUCAI, fecal calprotectin, and Mayo endoscopic scores ( r = 0.60, 0.54, and 0.56 respectively, P ≤ 0.001), but not with CRP or albumin. These results indicate that the NHI has a modest correlation with clinical, laboratory and endoscopic indices of disease activity in pediatric UC patients.

Recurrence rates following ileo-colic resection in pediatric patients with Crohn's disease.

BACKGROUND: Ileo-colic resection (ICR) is an important therapeutic option for Crohn's disease (CD) patients. There are limited updated data of clinical and endoscopic post-operative recurrence (POR) in pediatric patients with CD for the long run. We aimed to determine recurrence rates following ICR over an extended period of time and asses its risk factors. METHODS: This is a single-center retrospective review of 35 patients with CD between the ages of 6 and 17.9 years who required ICR between 2003 and 2021 at Schneider Children Medical Center of Israel. Medical charts were reviewed at different time-points post-ICR. RESULTS: Clinical recurrence following ICR was demonstrated in only 11.4% and 28.6% (n = 4, n = 10) in the first two and five years-much lower rates than what was reported so far. We found no specific risk factor that correlated with clinical recurrence, although patients that were treated with early prophylaxis of anti-TNF medications following ICR tend to have less recurrence. CONCLUSIONS: We found lower POR following ICR, especially in the first years after surgery-which can be attributed to close surveillance and early medical treatment. Such surveillance seems to improve recurrence rates in the first years following ICR.

Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study.

BACKGROUND: Scarce data are available on the use of vedolizumab in children with inflammatory bowel disease (IBD). We aimed to evaluate the safety, effectiveness, and dosing of vedolizumab to induce remission of IBD. METHODS: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort. Children (aged 0-18 years) with IBD who had commenced vedolizumab were followed up at baseline and at 2, 6, and 14 weeks. Children were managed according to local prescribing practices without standardisation of dosing or criteria for escalation, but the study protocol suggested dosing of 177 mg/m2 body surface area (up to 300 mg maximum). The primary outcome was steroid-free and exclusive enteral nutrition-free remission at 14 weeks, analysed according to the intention-to-treat principle. Serum samples were taken for analysis of drug concentration and faecal calprotectin at baseline, and at 2, 6, and 14 weeks. Adverse events were recorded in real time and classified as severe or non-severe and related or unrelated to vedolizumab. This study is registered with ClinicalTrials.gov, NCT02862132. FINDINGS: Between May 19, 2016, and April 1, 2022, 142 children (76 [54%] girls and 66 [46%] boys; mean age 13·6 years [SD 3·6]) were enrolled. 65 (46%) children had Crohn's disease, 68 (48%) had ulcerative colitis, and nine (6%) had unclassified IBD (those with unclassified IBD were analysed with the ulcerative colitis group). 32 (42% [95% CI 30-54]) of 77 children with ulcerative colitis and 21 (32% [23-45]) of 65 children with Crohn's disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks. Median drug concentrations at week 14 were higher in children with ulcerative colitis than in those with Crohn's disease (11·5 µg/mL [IQR 5·5-18·1] vs 5·9 µg/mL [3·0-12·7]; p=0·006). In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 µg/mL at week 14 (area under the curve 0·69 [95% CI 0·41-0·98]), corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg. 32 (23%) of 142 children reported at least one adverse event, the most common were headache (five [4%]), myalgia (four [3%]), and fever (three [2%]). None of the adverse events were classified as severe, and only two (1%) patients discontinued treatment due to adverse events. INTERPRETATION: Vedolizumab showed good safety and effectiveness at inducing remission in children with IBD at 14 weeks, especially those with ulcerative colitis. Vedolizumab should be considered in children when other approved drug interventions for IBD are unsuccessful. In children who weigh less than 30 kg, vedolizumab should be dosed by the child's body surface area (200 mg/m2) or weight (10 mg/kg). FUNDING: The European Crohn's and Colitis Organization, the European Society for Paediatric Gastroenterology Hepatology and Nutrition, and Takeda.

Pediatric inflammatory bowel disease: Fecal calprotectin response to Anti-tumor necrosis factor alpha.

BACKGROUND: Fecal calprotectin (FC) is a marker of mucosal inflammation in inflammatory bowel disease (IBD). We aimed to assess the effect of anti-tumor necrosis factor alpha (TNFα) therapy on FC levels in children with IBD. METHODS: The medical records of pediatric patients treated with anti-TNFα agents (2015-2020) were reviewed retrospectively. 63 patients had FC levels measured prior to anti TNFα induction with sequential measurements during follow-up. The main outcome measures were time to FC response according to cutoffs of 250, 150, 100 and 50 µgr/gr. RESULTS: Mean age was 13.6 ± 3 years [females 28 (44.4%), Crohn's 55 (87%)]. Outcomes of < 250, < 150, < 100 and < 50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%), respectively. The median time for achieving these cutoffs was 4.8 (1.8-15.6), 7.9 (2.6-16.4), 10.0 (3.5-20.5) and 18.5 (7.0-64.7) months, respectively. Shorter time from diagnosis to treatment was associated with achievement of FC < 50 µgr/gr (p = 0.03). There was no association between age, disease type, anti-TNFα type, inflammatory markers, disease activity indices at baseline and induction anti-TNFα trough concentration and FC response. CONCLUSIONS: FC response was achieved by the majority of patients treated with anti-TNFα within a short period of time. FC normalization in responders required almost one year. IMPACT: Fecal calprotectin response was achieved by the majority of pediatric patients within a relatively short period of time after anti-TNFα induction and maintenance therapy. Fecal calprotectin normalization required an average period of approximately one year in responders. The faster response of fecal calprotectin is associated with shorter time from diagnosis to anti-TNFα treatment. Inflammatory bowel disease treating physicians should be aware of the relatively prolonged time to fecal calprotectin normalization and to allow enough time for anti-TNFα therapy to express its full potential prior to significant interventions.

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.

Risk of consecutive immunogenic failure in switchers of anti-tumor necrosis factor alpha among patients with inflammatory bowel diseases.

BACKGROUND: Evidence regarding the risk of immunogenicity in patients with inflammatory bowel disease (IBD) who switched anti-tumor necrosis factor alpha (anti-TNFα) therapies to a subsequent anti-TNFα (either infliximab or adalimumab) is conflicting. We aimed to assess the risk of consecutive immunogenicity to anti-TNFα in a large cohort of patients. METHODS: This was a multicenter retrospective study. Medical records of adult and pediatric IBD switchers who had pharmacokinetic data for both agents between 2014 and 2020 were retrieved. Data including age, sex, disease type, duration of therapies, and concomitant use of immunomodulators (IMMs) were recorded. RESULTS: Overall, 164 patients were included [52% female; 88% Crohn's disease; mean age = 24.4 ± 14.6 years; 108 (66%) switched from infliximab to adalimumab and 56 (34%) vice versa]; 120 (73.1%) patients switched due to an immunogenic failure. Among patients switching therapy from infliximab to adalimumab due to an immunogenic failure immunogenicity to infliximab was significantly associated with consecutive immunogenicity to adalimumab (p = 0.026). Forthy four out of 120 patients (36.6%) with an immunogenic failure to the first anti-TNFα started an IMM with the second anti-TNFα. This combination with IMM was not associated with reduction of consecutive immunogenicity (p = 0.31), but it was associated with longer drug retention (p = 0.007). Multivariate analysis demonstrated that older age at second anti-TNFα, adjusted to the chronology of therapy and sex, was associated with increased immunogenicity to the second anti-TNFα. CONCLUSION: Patients with IBD who switch from infliximab to adalimumab following an immunogenic failure are at increased risk for consecutive immunogenicity to adalimumab. IMM use after a switch prolongs drug retention.