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 ± 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 ± 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.

• Klíčová slova
• Crohn’s disease, adalimumab, infliximab, ulcerative colitis,
• MeSH
• dítě MeSH
• idiopatické střevní záněty * farmakoterapie   komplikace   MeSH
• infliximab terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• nadváha * komplikace   MeSH
• následné studie MeSH
• obezita * komplikace   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• infliximab MeSH
• TNF-alfa * MeSH

BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. METHODS: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical, and laboratory data, as well as adverse events (AEs), were recorded at Week 8 post-induction. RESULTS: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. Adverse events were recorded in 37 children, including 1 serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n = 13), acne (n = 12), and infections (n = 10, 5 of whom with herpes viruses). CONCLUSIONS: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

• Klíčová slova
• Inflammatory bowel disease, JAK inhibitors, children,
• MeSH
• C-reaktivní protein analýza   MeSH
• dítě MeSH
• heterocyklické sloučeniny tricyklické * terapeutické užití   škodlivé účinky   MeSH
• indukce remise metody   MeSH
• indukční chemoterapie metody   MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé MeSH
• mladiství MeSH
• retrospektivní studie MeSH
• ulcerózní kolitida * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• C-reaktivní protein MeSH
• heterocyklické sloučeniny tricyklické * MeSH
• leukocytární L1-antigenní komplex MeSH
• upadacitinib MeSH Prohlížeč

BACKGROUND: There are scarce data available on upadacitinib in children with Crohn's disease (CD). AIM: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD. METHODS: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle. RESULTS: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy. CONCLUSION: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.

• Klíčová slova
• JAK inhibitors, children, inflammatory bowel disease,
• MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• heterocyklické sloučeniny tricyklické * terapeutické užití   škodlivé účinky   MeSH
• indukce remise MeSH
• lidé MeSH
• mladiství MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• heterocyklické sloučeniny tricyklické * MeSH
• upadacitinib MeSH Prohlížeč

The aim was to explore factors associated with intestinal tissue levels of anti-TNF alpha (anti-TNF), anti-TNF antibodies, and cytokines in pediatric patients with Crohn Disease (CD). In a prospective exploratory study of CD patients undergoing ileocecal resection or colonoscopy between 6/2020 and 1/2023, we analysed tissue levels of anti-TNF, anti-TNF antibodies, and cytokines (TNF-α, IL-17, IL-1β, IFN-γ) from intestinal biopsies. Mixed-effects regression models, adjusted for potential confounders, were used. Data from 27 CD patients (18 females, 66.7%) were analysed. Fourteen (52%) received adalimumab (ADA) and thirteen received infliximab (IFX), with a median therapy duration of 17 (IQR 4.5-41.5) months. Higher levels of free anti-TNF were found in macroscopically inflamed tissue compared to non-inflamed tissue (β = 3.42, 95% CI 1.05-6.10). No significant association was found between serum and tissue anti-TNF levels (β= -0.06, 95% CI - 0.70-0.58). Patients treated longer with anti-TNF had increased IL-17 levels (β = 0.19, 95% CI 0.05-0.33), independent of disease duration and age. IFN-γ levels were linked with both follow-up duration and anti-TNF length. Our study shows significantly higher free drug levels in inflamed tissue. Long-term anti-TNF treatment has been linked to increased IL-17 levels, suggesting a possible impact on the cytokine response pathway. We did not observe a relationship between serum and tissue anti-TNF levels.

• Klíčová slova
• Biologics, Crohn disease, Inflammatory bowel disease, Paediatrics,
• MeSH
• adalimumab * terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   metabolismus   krev   patologie   MeSH
• cytokiny * metabolismus   krev   MeSH
• dítě MeSH
• infliximab * terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• prospektivní studie MeSH
• střeva patologie   účinky léků   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• TNF-alfa * antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adalimumab * MeSH
• cytokiny * MeSH
• infliximab * MeSH
• TNF-alfa * MeSH

BACKGROUND: We aimed to evaluate the predictors of sustainability of biologic drugs for paediatric patients with Crohn's disease (CD). METHODS: The Czech National Prospective Registry of Biologic and Targeted Therapy of Inflammatory Bowel Disease (CREdIT) was used to identify the biologic treatment courses in paediatric patients with CD. Mixed-effects Cox models and propensity score analyses were employed to evaluate predictors of treatment sustainability. RESULTS: Among the 558 observations of 473 patients, 264 were treated with adalimumab (47%), 240 with infliximab (43%), 41 with ustekinumab (7%), and 13 with vedolizumab (2%). Multivariable analysis revealed higher discontinuation risk with infliximab compared to adalimumab (HR = 0.600, 95%CI 0.389-0.926), both overall and in first-line treatment (HR = 0.302, 95%CI 0.103-0.890). Infliximab versus adalimumab was associated with shorter time to escalation (HR = 0.094, 95%CI 0.043-0.203). Propensity-score analysis demonstrated lower sustainability of infliximab (HR = 0.563, 95%CI 1.159-2.725). The time since diagnosis to treatment initiation (HR = 0.852, 95%CI 0.781-0.926) was the most important predictor. Baseline immunosuppressive therapy prolonged sustainability with infliximab (HR = 2.899, 95%CI 1.311-6.410). CONCLUSIONS: Given the results suggesting shorter sustainability, the need for earlier intensification and thus higher drug exposure, and the greater need for immunosuppression with infliximab than with adalimumab, the choice of these drugs cannot be considered completely equitable. IMPACT: Our study identified predictors of sustainability of biologic treatment in paediatric patients with Crohn's disease, including adalimumab (versus infliximab), early initiation of biologic treatment, and normalised baseline haemoglobin levels. Infliximab treatment was associated with earlier intensification, higher drug exposure, and a greater need for immunosuppression. Parents and patients should be fully informed of the disadvantages of intravenous infliximab versus adalimumab during the decision-making process. This study emphasises the importance of not delaying the initiation of biologic therapy in paediatric patients with Crohn's disease.

• MeSH
• adalimumab * terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• infliximab * terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• registrace * MeSH
• tendenční skóre MeSH
• ustekinumab terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adalimumab * MeSH
• biologické přípravky MeSH
• humanizované monoklonální protilátky MeSH
• infliximab * MeSH
• ustekinumab MeSH
• vedolizumab MeSH Prohlížeč

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

• Klíčová slova
• Children, Crohn’s disease, Exclusive enteral nutrition, Ustekinumab, wPCDAI,
• MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dítě MeSH
• indukce remise MeSH
• lidé MeSH
• mladiství MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• ustekinumab * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• ustekinumab * MeSH

PURPOSE: Children diagnosed with Crohn's disease (CD) often undergo ileocecal resection (ICR) during childhood. Anastomotic recurrence is a frequent finding following this procedure. Data addressing the effect of the anastomosis type on disease recurrence are scarce in the pediatric population. The Kono-S anastomosis has shown promise in reducing endoscopic, clinical, and surgical recurrence rates in adults. We aimed to report our experience with Kono-S anastomosis in children, focusing on its feasibility and postoperative complications. METHODS: We retrospectively analyzed pediatric CD patients who underwent ICR with Kono-S anastomosis between August 2022 and May 2023. Data on demographics, clinical characteristics, surgery, hospitalization, and follow-up including colonoscopy were collected. Complications were classified using the Clavien-Dindo classification. RESULTS: Twelve patients (7 females, 58.3%) were included. Six (50%) of the patients had the B3 luminal form of the disease (according to Paris classification). Median surgery duration was 174 (interquartile range [IQR] 161-216) minutes. Anastomosis creation took a median of 62 (IQR, 54.5-71) minutes. Median hospitalization length was 6 (IQR 4-7) days. No short- or mid-term complications were observed. Median follow-up duration was 9.5 (IQR 6.8-12) months. CONCLUSION: According to our results, Kono-S anastomosis is safe and feasible in pediatric CD patients, with no observed postoperative complications. These findings support the potential benefit of using Kono-S anastomosis as a treatment approach in children with CD.

• Klíčová slova
• Crohn’s disease, Endoscopy, Kono-S, Pediatric surgery, Postoperative complication,
• MeSH
• anastomóza chirurgická MeSH
• Crohnova nemoc * chirurgie   MeSH
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• pooperační komplikace epidemiologie   MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. METHODS: Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. RESULTS: We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. CONCLUSIONS: Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

• Klíčová slova
• Crohn’s disease, IBD, anti-TNF, children, metabolomics, microbiome,
• MeSH
• Bacteria MeSH
• Crohnova nemoc * patologie   MeSH
• dítě MeSH
• infliximab farmakologie   terapeutické užití   MeSH
• inhibitory TNF farmakologie   terapeutické užití   MeSH
• lidé MeSH
• metabolom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• infliximab MeSH
• inhibitory TNF MeSH

BACKGROUND: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy. METHODS: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse. RESULTS: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031). CONCLUSIONS: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision. IMPACT: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

• MeSH
• azathioprin terapeutické užití   škodlivé účinky   MeSH
• Crohnova nemoc * komplikace   diagnóza   farmakoterapie   MeSH
• dítě MeSH
• imunosupresiva terapeutické užití   škodlivé účinky   MeSH
• indukce remise MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azathioprin MeSH
• imunosupresiva MeSH

PURPOSE: To investigate potential early risk factors for anastomotic stricture formation and assess the predictive role of post-operative esophagrams. METHODS: A retrospective study of patients with esophageal atresia with distal fistula (EA/TEF) operated between 2011 and 2020. Fourteen predictive factors were tested for stricture development. Esophagrams were used to calculate early (SI1) and late (SI2) stricture index (SI = anastomosis diameter/upper pouch diameter). RESULTS: Of 185 patients operated for EA/TEF in the 10-year period, 169 patients met the inclusion criteria. Primary anastomosis was performed in 130 patients and delayed anastomosis in 39 patients. Stricture formed in 55 patients (33%) within 1 year from anastomosis. Four risk factors showed strong association with stricture formation in unadjusted models: long gap (p = 0.007), delayed anastomosis (p = 0.042), SI1 (p = 0.013) and SI2 (p < 0.001). A multivariate analysis showed SI1 as significantly predictive of stricture formation (p = 0.035). Cut-off values using a receiver operating characteristic (ROC) curve were 0.275 for SI1 and 0.390 for SI2. The area under the ROC curve demonstrated increasing predictiveness from SI1 (AUC 0.641) to SI2 (AUC 0.877). CONCLUSIONS: This study identified an association between long gap and delayed anastomosis with stricture formation. Early and late stricture indices were predictive of stricture formation.

• Klíčová slova
• Esophageal atresia, Esophagram, Risk factors, Stricture, Stricture index,
• MeSH
• anastomóza chirurgická škodlivé účinky   MeSH
• atrézie jícnu * chirurgie   MeSH
• lidé MeSH
• pooperační komplikace etiologie   MeSH
• retrospektivní studie MeSH
• stenóza jícnu * etiologie   MeSH
• stenóza komplikace   MeSH
• tracheoezofageální píštěl * chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH