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.

Background: 5-aminosalicylates (5-ASA) are widely used in Crohn's disease (CD) despite guidelines advising otherwise. We aimed to assess in nationwide study the outcomes of first-line 5-ASA maintenance therapy (5-ASA-MT) compared with no maintenance treatment (no-MT) in patients with newly diagnosed CD. Methods:We utilised data from the epi-IIRN cohort, including all patients with CD diagnosed in Israel between 2005 and 2020. Propensity score (PS) matching was utilised to compare outcomes in the 5-ASA-MT versus no-MT groups.Results: Of the 19,264 patients diagnosed with CD, 8610 (45%) fulfilled the eligibility criteria (3027 [16%] received 5-ASA-MT and 5583 [29%] received no-MT). Both strategies declined over the years; 5-ASA-MT from 21% of CD patients diagnosed in 2005 to 11% in 2019 (p < 0.001) and no-MT from 36% to 23% (p < 0.001). The probability of maintaining therapy at 1, 3 and 5 years from diagnosis: 5-ASA-MT-78%, 57% and 47% and no-MT-76%, 49% and 38% respectively (p < 0.001). PS analysis successfully matched 1993 pairs of treated and untreated patients and demonstrated comparable outcomes of time to: biologic (p = 0.2), steroid dependency (p = 0.9), hospitalisation (p = 0.5) and CD-related surgery (p = 0.1). Rates of acute kidney injury (5.2% vs. 3.3%; p < 0.001) and pancreatitis (2.4% vs. 1.8%; p = 0.03) were higher in the 5-ASA-MT group compared with the no-MT group but after PS matching the rates of adverse events were similar. Conclusion:First-line 5-ASA monotherapy was not superior to no-MT but associated with a slightly higher rates of adverse events, while both strategies have declined over the years. These findings suggest that a subset of patients with mild CD may be offered a watchful waiting approach.

Aim Eosinophilic oesophagitis (EoE) is a chronic inflammatory oesophageal disease, which has become more recognised in the past decade. We wanted to characterise our patients and review their course of disease and response to treatment. Methods We retrospectively reviewed the medical records of EoE patients from January 2010 to May 2018 in our Gastroenterology Institute. A hundred and two children were included in this study. We investigated the characteristics of patients and the response to three treatment options: proton pump inhibitors, elimination diet and topical steroids. The response to treatment was analysed according to 3 aspects: clinical, endoscopic appearance and histological features. Results Clinical improvement was noted in 55%, 75% and 87.5% on PPIs, diet and budesonide, respectively. Endoscopic improvement was noted in 38.4%, 51.4% and 65.4% on PPIs, diet and budesonide, respectively. Histological improvement was noted in 43.7%, 62.2% and 88.5% on PPIs, diet and budesonide, respectively. Conclusion Our findings suggest that Israeli paediatric EoE patients have characteristics that resemble previous reports. Although there is a correlation between symptoms, endoscopic and histological appearance, we cannot rely on patients reports alone, and therefore, repeated endoscopy and biopsies are mandated. Topical steroids seem to be the most effective treatment option.

Aim Aspartate aminotransferase (AST) is an enzyme expressed in several organs; therefore, AST elevation may reflect outside of liver pathology. AST elevation may also be associated with macro‐AST (m‐AST). The aim of this study was to evaluate the long‐term course of children with prolonged isolated AST elevation and the prevalence of m‐AST in our cohort. Methods We retrospectively reviewed the medical charts of children diagnosed with prolonged isolated AST elevation and were evaluated for m‐AST. Results Thirty‐two patients were included. AST elevation persisted for a median of 66.6 months and ranged from 1.23 to 12‐fold upper limit of normal (ULN). Twenty‐two percent were m‐AST positive and 44% had borderline levels of m‐AST. A statistically significant difference was found for age at presentation between the borderline and the positive m‐AST groups (31 vs. 69 months, respectively. p = 0.045). None of the patients with elevated AST developed significant liver disease. Conclusion We confirm the benign course of prolonged isolated AST elevation in general and m‐AST in particular. A fifth of the patients with isolated AST elevation were m‐AST positive. No differences have been found in AST levels between negative, borderline or positive m‐AST.

Background In this nationwide study we aimed to compare the durability of the first initiated biologic in Crohn's disease (CD), stratified by monotherapy and combotherapy. Methods We used data from the epi-IIRN cohort, which includes 98% of the Israeli inflammatory bowel disease population (2005-2020). Durability was defined as consistent treatment without surgery or added medications (except for combination therapy with thiopurines or methotrexate). All comparisons were based on stringent propensity-score matching and paired time-to-event analyses. Results A total of 19,264 patients with CD were included, of whom 7,452 (39%) received biologics with a median follow-up of 6.8 years (IQR 3.6-10.7). Time to biologics decreased gradually from 6.7 years (IQR 2.7-10.4) in 2005 to 0.2 years (0.07-0.23) in 2020. The durability of the first biologic after one and three years was higher with adalimumab-monotherapy (88%/61%) than vedolizumab-monotherapy (81%/59%; n=394 matched patients, p=0.04) and similar between infliximab-monotherapy and vedolizumab-monotherapy (65%/43%; n=182 matched patients, p=0.1). Durability was higher in adalimumab-monotherapy vs infliximab-monotherapy (83%/62% vs. 71%/48% at one/three years; p&lt;0.001), while it was similar in adalimumab-monotherapy vs infliximab-combotherapy (87%/63% vs. 80%/58%, respectively; p=0.1). Durability was higher in combotherapy compared to monotherapy for both infliximab (85%/64% vs. 67%/43%, respectively; n=496 matched pairs, p&lt;0.001), and adalimumab (93%/76% vs. 82%/62%, respectively; n=540 matched pairs, p&lt;0.001). Conclusion Durability of the first biologic in CD was highest for adalimumab-monotherapy. Combotherapy further increased the durability of adalimumab and infliximab. Unless otherwise indicated, our data may support using anti-TNFs as first-line biologics in CD, particularly adalimumab if monotherapy is advised.