Parental perspectives on pediatric inflammatory bowel disease: Unraveling concerns, and study participation willingness.

OBJECTIVES: The impact of disease burden extends beyond pediatric inflammatory bowel disease (IBD) patients to include their parents. Previous studies, predating the biologic era, have highlighted parental concerns about potential side effects associated with IBD medications. However, there is a notable gap in the literature regarding parents' perceptions of clinical studies involving pediatric IBD patients. This study aims to explore the specific concerns troubling parents of children with IBD, identifying factors influencing these concerns, and assesses parental willingness to allow their child's participation in clinical studies. METHODS: Utilizing social media, we disseminated an anonymous questionnaire to parents of pediatric IBD patients. The questionnaire encompassed queries about parental willingness for their child to partake in clinical studies, aspects of the disease deemed bothersome, and the sense of coherence scale (SOC). RESULTS: Responses were obtained from 101 parents, with a mean age of 46.4, of whom 82.2% were female. Concerns about potential future side effects of their child's medications surpassed worries about disease symptoms (80.04% vs. 73.47%). Linear regression analysis revealed that parents with lower SOC scores, limited medical care accessibility, and a higher age of the child at diagnosis, exhibited heightened concerns about the future impact of the disease on their child (p = 0.016, 0.003, and 0.045, respectively). While a majority rejected participation in studies involving new medications (54.5%), there was greater agreement for studies on nutritional therapies (84.2%) and complementary medicine (91.1%). Classification tree analysis indicated that women were more inclined to permit their child's participation in studies focusing on complementary medicine (adjusted p = 0.002). CONCLUSION: Parents of IBD patients express greater apprehension about potential side effects from IBD medications and display reluctance toward their child participating in clinical studies related to medications.

Proton pump inhibitors in eosinophilic esophagitis (EoE) related to oral immunotherapy: is it as effective as in other EoE?

Oral immunotherapy (OIT) may induce eosinophilic esophagitis (EoE). Proton pump inhibitors (PPIs) are an effective treatment for EoE. However, the effect of PPI treatment is not well established in patients with EoE induced by OIT. Our primary aim was to compare the clinical, endoscopic, and histological response rates to PPIs in children with EoE induced by OIT (EoE+OIT) versus EoE patients without OIT (EoE-OIT). The secondary aims are to describe the clinical and histological features of EoE+OIT. Demographic, clinical, endoscopic, and histological findings of patients with EoE in the gastroenterology clinic at Shamir Medical Center between March 2015 and December 2022 were collected. Comparisons were performed between EoE+OIT and EoE-OIT patients. The study included 42 children (74% male, mean age 11.2), of whom 31 had EoE-OIT and 11 had EoE+OIT. There were no significant differences between groups regarding sex, comorbidities, symptoms, or endoscopic and histological characteristics at diagnosis. All 42 children were treated with PPIs after diagnosis with or without diet changes. The rates of any clinical response were 83.9% and 90.1% in the EoE-OIT group and EoE+OIT group, respectively (p = 1.0). The rate of any endoscopic response was 74.2% for EoE-OIT and 81.8% for EoE+OIT (p = 0.54). Histologically, PPIs were even more effective in the EoE+OIT group, where only 18.2% had no histological response at all compared to 51.6% in the EoE-OIT group (p = 0.1). CONCLUSION: PPI treatment is as effective in EoE with OIT as it is in EoE due to other etiologies. WHAT IS KNOWN: • Proton pump inhibitor (PPI) treatment is effective for achieving clinical response and histologic remission in some patients with eosinophilic esophagitis (EoE). • EoE has also been reported to be triggered by oral immunotherapy (OIT). WHAT IS NEW: • PPI treatment in EoE with OIT is as effective as treatment for EoE due to other etiologies.

Factors Associated With Adherence to a Gluten-Free Diet in Celiac Patients Diagnosed in Childhood as Compared to Adulthood.

Past studies have reported differences between pediatric and adult celiac disease patients. We aimed to compare factors associated with adherence to a gluten-free diet between these groups. An anonymous online questionnaire was sent via the Israeli Celiac Association and social networks to celiac patients. The Biagi questionnaire was used to assess dietary adherence. A total of 445 subjects participated. Mean age was 25.7 ± 17.5 years and 71.9% were female. Subjects were divided into six groups according to age at diagnosis: younger than 6 years (134 patients, 30.7%), 6-12 (79 patients, 18.1%), 12-18 (41 patients, 9.4%), 18-30 (81 patients, 18.5%), 30-45 (79 patients, 18.1%), and 45 years and above (23 patients, 5.3%). There were several significant differences between childhood- and adulthood-diagnosed patients. Pediatric patients were less likely to be noncompliant with a gluten-free diet (3.7% vs. 9.4%, p < .001). They were also more frequently followed by a gastroenterologist ( p < .001), a dietitian ( p < .001), and participated in a celiac support group ( p = .002). In logistic regression analyses, longer duration of disease was associated with poor compliance. In conclusion, pediatric-diagnosed celiac patients are more adherent to a gluten-free diet than those diagnosed in adulthood, with better social support and nutritional follow-up possibly contributing.

The Perception among Israeli Gastroenterologists Regarding Treatment of Patients with Biosimilar Medications.

Background and Objectives: The ever-expanding entry of biosimilar drugs into the Israeli market requires doctors to decide whether to prescribe these medications. We aimed to assess the prevalence of biosimilar use and Israeli gastroenterologists' knowledge, experience, and perception of biosimilar treatment. Materials and Methods: A cross-sectional survey was conducted among Israeli Gastroenterology Association (IGA) members between March and May 2022 using a structured 20-item questionnaire. Results: The questionnaire was completed by 108 gastroenterologists. Sixty-two percent prescribed biosimilars to their patients in the past year. Most of the patients (81%) were biologically naïve and only 19% were switched to a biosimilar. Most gastroenterologists (75%) answered that the effectiveness is the same. The rates of resistance to switching were 19%, 36%, and 70% for patients in remission for over two years, pregnant women, and difficulty reaching remission, respectively. In cases seeing a lack of response after switching, most physicians chose to change the mechanism of action, with only a small percentage returning to the brand-name drug. Conclusions: Most Israeli gastroenterologists are not concerned about biosimilars' safety and efficacy. Despite this, most physicians will prefer the brand-name drug, especially regarding adalimumab. The populations in which physicians most oppose switching are those who have had difficulty achieving remission and pregnant women.

Caustic Ingestion in Children: The Otolaryngologist Perspective.

OBJECTIVES: Caustic ingestion in children is a significant cause of morbidity despite preventive measures. Upon arrival to the emergency department, these children are often initially seen by the otolaryngologist and later on by the gastroenterologist. This study aimed to determine which otolaryngological and gastrointestinal signs and symptoms can better predict abnormal findings on imaging, esophagogastroduodenoscopy (EGD), and complications development. METHODS: We performed a retrospective chart review of children 18 years or younger admitted because of caustic ingestion between January 2007 and November 2019. RESULTS: Forty-one children with a median age of 4.2 years (interquartile range, 1.7-16.7 years) were included; of them, 22 (53.6%) were males. Nineteen children (46.3%) underwent EGD, which revealed no pathology in 13 cases (68.4%). Most ingested substances were in the form of liquid (82.9%), accidentally ingested (82.9%), and with an alkaline pH (57.5%). Stridor, dyspnea, drooling, abnormal oral cavity findings, dysphagia, and vomiting were significantly associated with pathological findings on imaging and/or EGD and/or complications development ( P = 0.028, P = 0.028, P = 0.022, P = 0.02, P < 0.001, and P = 0.01 respectively). Laryngopharyngeal group of findings (dyspnea, stridor, hoarseness, sore throat, and/or drooling) predicted a higher risk for complications development than the gastrointestinal group (dysphagia, abdominal pain, vomiting, or abdominal swelling and/or tenderness) ( P = 0.011, P = 0.31 respectively). CONCLUSIONS: In children, after caustics ingestion, laryngopharyngeal signs and symptoms may predict a higher risk for complications development in comparison with gastrointestinal signs and symptoms. We therefore stress the importance of otolaryngological examination upon arrival to the emergency department.

Video Capsule Endoscopy Has a Minor Long-term Therapeutic Impact on Patients with Iron Deficiency Anemia.

BACKGROUND: One of the main causes of iron deficiency anemia (IDA) is chronic gastrointestinal blood loss. The use of video capsule endoscopy (VCE) after negative bidirectional endoscopy in patients with IDA is controversial. OBJECTIVES: To evaluate the effect of VCE in the management and long-term outcomes of IDA patients. METHODS: A retrospective case-control study was performed on all patients with IDA undergoing VCE over a 5-year period. We compared those with positive findings on VCE to those with normal findings. All participants previously underwent a negative bidirectional endoscopy. RESULTS: We performed 199 VCE examinations; median follow-up time was 4 years (IQR 2-5). Positive findings were identified in 66 patients (diagnostic yield 33.2%). Double balloon enteroscopy or push enteroscopy was performed in eight patients (18.6%); only one was therapeutic. The main therapy in both groups was iron supplementation. There were no significant differences in iron treatment before and after VCE in each group and between groups. Anemia improved in both groups. There was no difference in the level of hemoglobin change between the groups during each year of follow-up compared to the baseline level prior to VCE. Anemia resolved in 15 patients (35%) in the positive VCE group and in 19 (45%) in the negative VCE group (P = 0.33). CONCLUSIONS: Positive findings on VCE led to subsequent endoscopic interventions only in a small percentage of patients with IDA. Anemia improved and resolved equally whether or not there were VCE findings. The main intervention that appears to help IDA is iron supplementation.

Monitoring Enables Progress: A Nationwide Quality Improvement Program in Children With Crohn Disease.

OBJECTIVES: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country. METHODS: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values. RESULTS: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ±â€Š3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 µg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001). CONCLUSIONS: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators.

Proactive Monitoring of Adalimumab Trough Concentration Associated With Increased Clinical Remission in Children With Crohn's Disease Compared With Reactive Monitoring.

BACKGROUND & AIMS: Proactive monitoring of drug trough concentrations and antibodies against drugs might help determine whether patients are likely to respond to treatment and increase efficacy. We investigated whether proactive drug monitoring is associated with higher rates of clinical remission in pediatric patients with Crohn's disease (CD). METHODS: We performed a nonblinded, randomized controlled trial of 78 children with CD (6-18 years old; 29% female; mean age, 14.3 ± 2.6 years) who had not received prior treatment with a biologic agent but had responded to adalimumab induction therapy, under scheduled monitoring of clinical and biologic measures (based on clinical factors and levels of C-reactive protein and fecal calprotectin), at pediatric gastroenterology units in Israel from July 2015 through December 2018. The patients were randomly assigned to groups that received proactive monitoring (trough concentrations measured at weeks 4 and 8 and then every 8 weeks until week 72, n = 38) or reactive monitoring (physicians were informed of trough concentrations after loss of response, n = 40). In both groups, doses and intervals of adalimumab were adjusted to achieve trough concentrations of 5 µg/mL. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (week 8 through week 72). RESULTS: The primary endpoint was achieved by 31 children (82%) in the proactive group and 19 children (48%) in the reactive group (P = .002). Sixteen patients in the proactive monitoring group (42%) achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein ≤0.5 mg/dL, and level of fecal calprotectin ≤150 µg/g compared with 5 patients in the reactive monitoring group (12%) (P = .003). By week 72 of treatment, 33 patients in the proactive monitoring group had received adalimumab intensification (87%) compared with 24 patients in the reactive monitoring group (60%) (P = .001). CONCLUSIONS: In a randomized controlled trial of pediatric patients with CD, we found that proactive monitoring of adalimumab trough concentrations and adjustment of doses and intervals resulted in significantly higher rates corticosteroid-free clinical remission than reactive monitoring (measuring trough concentration after loss of response). Clinicaltrials.gov no.: NCT02256462.

The Safety and Feasibility of a New Through-the-scope Balloon-assisted Enteroscopy in Children.

OBJECTIVES: Small bowel involvement in Crohn disease (CD) is clinically important for diagnosis and treatment. Single and double-balloon enteroscopy have already become important diagnostic tools in such cases. The on-demand NaviAid AB device enables deep advancement into the small bowel, using an anterograde or retrograde approach. In adults, this procedure is feasible, safe, and rapid. This work aimed to assess the safety and feasibility of NaviAid AB enteroscopy in pediatric patients. METHODS: Single-center, prospective study using the through-the-scope balloon-assisted-enteroscopy (TTS-BAE) NaviAid AB device for the evaluation of the small bowel in children with suspected or known inflammatory bowel disease (IBD). The system consists of a single-use balloon catheter inserted through the instrument channel of a standard colonoscope. It consists of an inflation/deflation system (NaviAid SPARK), which is inflated to anchoring pressure. The repetitive push-pull technique enables the advancement of the colonoscope along the small intestine. RESULTS: Fifty analyzed endoscopic procedures (30 retrograde, 20 anterograde) were performed in 34 children (52.9% boys, mean age 13.7 years). Average maximal depth of insertion (MDI), advancement depth using the NaviAid AB and average total procedure time were 138 cm (range 100-190 cm), 81 cm (range 40-120 cm), and 12.8 minutes (range 7.3-19.0 minutes), respectively, for the anterograde approach and 143 cm (range 100-170 cm), 64 cm (range 20-95 cm), and 21.9 minutes (range 13.9-32.0 minutes), respectively, for the retrograde approach. No serious or device-related adverse events were reported. CONCLUSIONS: NaviAid AB enteroscopy in children is safe, feasible, and enables assessment of the small intestine in a short period of time.

The Effect of Adalimumab Treatment on Linear Growth in Children With Crohn Disease: A Post-hoc Analysis of the PAILOT Randomized Control Trial.

OBJECTIVES: Growth impairment is common in children with Crohn disease (CD). We aimed to assess the effect of adalimumab (ADL) treatment on linear growth in children with CD in a post-hoc analysis of the Pediatric Crohn's Disease AdalImumab Level-based Optimization Treatment randomized controlled trial. METHODS: Children 6 to 17 years who responded to ADL induction were assessed consecutively for anthropometric parameters. Associations of these parameters with disease characteristics and disease activity were analyzed. RESULTS: Overall, 66 patients completed 72 weeks of follow-up (25% girls, mean age of 15.6 ±â€Š2.5 years). Median (interquartile range [IQR]) height z score improved from -0.6 (-1.6-0.15) at baseline to -0.33 (-1.3-0.5) at week 72 (P = 0.005) with lesser improvement in patients with perianal disease. Similar effect was noted in children with growth potential (boys younger than 16 years, girls younger than 14 years). Median (IQR) height velocity standard deviation was -0.32 (-1.5-0.8) at week 26, and +0.11 (-1.1-1.3) at week 72. Median weight z score increased from -0.54 (-1.2-0.15) to -0.1 (-0.9-0.6), P < 0.001 and body mass index from -0.4 (-1.0-0.5) to 0.0 (-0.8-0.9), P = 0.005. Pediatric CD activity index and erythrocyte sedimentation rate at week 4 correlated negatively with height z score changes (P = 0.043 and P = 0.048, respectively), whereas sustained clinical and biologic remission (week 4-72) were positively associated with changes in height z scores. Significant improvement in linear growth was predicted by lower pediatric CD activity index and erythrocyte sedimentation rate at the end of induction and sustained clinical remission (P = 0.05) and sustained normal C-reactive protein (P = 0.001) at all visits. CONCLUSION: In children with moderate-to-severe CD, ADL treatment had a significant effect on linear growth, with normalization of weight and body mass index (clinicaltrials.gov no: NCT02256462).

Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The POETIC Study.

OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period AAAs were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), AAA formation rate over time was significantly lower (p = 0.01) and AAA were much more specific-85% of AAA events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and AAA seemed comparable between four time-points during a single cycle both in patients with or without AAA (n = 8, n = 21, respectively). CONCLUSIONS: When followed prospectively and serially, AAAs are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and AAA levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug monitoring of adalimumab.

Genetic and electrophysiological characteristics of recurrent acute pancreatitis.

OBJECTIVES: The aim was to present the workup of patients with acute recurrent pancreatitis (ARP) for genetic analysis and electrophysiological testing. METHODS: Patients with ARP with unknown etiology were referred for genetic testing and evaluation of cystic fibrosis transmembrane conductor regulator (CFTR) function by nasal potential difference (NPD) testing. RESULTS: A total of 67 patients were evaluated. The mean age was 23 ±â€Š17 years (median 17.0 years, range 1.5-72 years); 90% were Jewish and 10% Arab. Ten (15%) patients carried PRSS1 gene mutation (K23R(7), R122H(2), and D21A(1)). One patient had K172E/- (chymotrypsin C [CTRC]) mutation, 1 had I42M (serine protease inhibitor Kazal type 1 [SPINK1])/V235I (CTRC) together with ΔF508/5T, 1 patient had R67H (SPINK1)/V235I (CTRC), and 1 patient had V235I (CTRC)/-. Ten of 67 (15%) patients submitted for CFTR gene testing carried mutations (ΔF508/L997F, ΔF508/5T(11TG), W1282/5T(12TG), W1282X/Y1014C, ΔF508/R31C, R117H/-, R117H/Y1014C, D1152H/-, 5T(11TG)/-, and L997F/-). Fifty-four (80%) patients underwent sweat testing. Of these, 5 had sweat chloride ≥60 mEq/L, and 22 patients had sweat chloride from 40 to 60 mEq/L. Of the 56 (83%) patients had nasal potential difference testing, 4 (6%) with abnormal results. CONCLUSIONS: One-third (34%) of patients with ARP carry mutations for hereditary pancreatitis including rare mutations (K23R), and 12.5% have evidence of cftr mutations and 10% had CFTR dysfunction underscoring the importance of genetic and functional workup of these patients.

Switching from Intravenous to Subcutaneous Biological Therapy for Inflammatory Bowel Disease Patients Remains a Challenge.

Biological inflammatory bowel disease (IBD) medications, once limited to intravenous (IV) administration, can now be administered both via IV and subcutaneously (SC). This study investigates patient preferences, willingness to switch from IV to SC, and associated factors. A questionnaire covering demographics, disease-related inquiries, quality of life, and IBD medication preferences was distributed via email, the Israeli Crohn's Disease and Ulcerative Colitis Foundation, infusion centers, and clinics. From 454 IBD patients (median age: 42 years; 55.7% female), responses revealed a preference for SC every 8 weeks, which is comparable to daily oral dosing. Both options were significantly favored over IV every 8 weeks and SC every 2 weeks, with no statistically significant differences between the latter two. However, among patients who were experienced with both SC and IV administration, a clear preference for SC administration every 2 weeks over IV every 8 weeks surfaced. Among IV-treated patients, 54.5% resisted switching to SC. Key reasons for this included medical staff presence (57.7%), a fear of needles (46.4%), belief in infusion efficacy (37.1%), and longer intervals between infusions (36.1%). Findings suggest that transitioning from IV to SC treatment is challenging due to patient resistance, which is influenced by specific factors. Identifying and addressing these obstacles is crucial for optimizing IBD management.

Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study.

BACKGROUND AND AIMS: Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. METHODS: A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. RESULTS: Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83]. CONCLUSIONS: Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.

Cannabis Improves Clinical Outcomes and Quality of Life in Patients With Chronic Pouchitis.

Many patients with ulcerative colitis after ileoanal pouch anastomosis report improvement of pouchitis with the use of cannabis. Nine patients with chronic pouchitis used 1 g/d of cannabis: 7 patients were male with average age 51 ± 16 years. Average partial pouchitis disease activity index were 11 (range 8-17), 6 (range 5-8), and 5 (range 4-8); endoscopic subscores were 7 .3 ± 2.3, 6 ± 1.1, and 4.4 ± 0.9; average bowel movements per day were 14 (range 8-20), 8 (range 2-13), and 10 (range 13-8); and quality of life increased from 72 ± 1 to 90 ± 16 and 97 ± 10 (P = 0.001) before cannabis treatment and after 8-12 and 52 weeks, respectively. No adverse events were reported.

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.

Infantile-onset inflammatory bowel disease has variable long-term outcomes.

Objective and aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed at age 2 years or younger, tends to be more severe and refractory to conventional treatment than IBD diagnosed at a later age. However, data about IO-IBD and its long-term follow up are limited. We thus aimed to evaluate the presentation and long-term outcomes of patients with IO-IBD in a retrospective multicenter study. Methods: Medical records of patients diagnosed with IO-IBD in eight medical centers during 2000-2017 with at least 1-year follow up were reviewed. Demographics and disease characteristics at diagnosis including age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions were recorded. Results: Twenty-three patients with IO-IBD (16 males, 70%) were identified and followed for a median (range) of 51.2 (26.0-110.3) months. The mean ages at presentation and at the last follow up were 14 ± 9.8 and 101 ± 77 months, respectively. Six (26%) patients needed ileostomy already at the time of diagnosis and 20 (87%) were treated with corticosteroids. During long-term follow up, remission was achieved in 16 (73%) patients; of whom, 3 (14%) were without medications and 7 (32%) were in remission with the use of 5-aminosalicylic acid only. One patient needed hemicolectomy and one developed a severe EBV related infection. Conclusion: The majority of patients with IO-IBD achieved long-term remission, despite a severe disease presentation at diagnosis. Surgery rate however is high, mainly during the first months from diagnosis.

Effect of inflammatory bowel disease and related medications on COVID-19 incidence, disease severity, and outcome: the Israeli experience.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic raised concerns among inflammatory bowel disease (IBD) patients fearing an increased risk of infection and poor outcomes. We aimed to evaluate the incidence of COVID-19 among IBD patients; its influence on disease severity and outcome; its relationship to medication use and how the pandemic affected IBD management. METHODS: An anonymous questionnaire was posted online to members of the Israel Crohn's Disease and Ulcerative Colitis Foundation (November 2020-January 2021). The questionnaire addressed the course of IBD disease and COVID-19 infection over the past year. RESULTS: Total 2152 IBD patients completed the questionnaire. Of which 104 (4.8%) had been infected with COVID-19, significantly lower than the 'expected' infected cases among the Israeli population (P = 0.033). The median age of participants was 39 years; 60.5% were female. Most patients (75.6%) had no comorbidities other than IBD. No correlation was found between IBD type or disease severity and COVID-19 infection. Most IBD patients reported mild COVID-19 disease, regardless of the type of IBD medications. Multivariable logistic regression analysis revealed that younger age, elevated BMI and diabetes were independent risk factors for COVID-19 infection. IBD treatment methods including 5-aminosalicylic acid, smoking and hypertension were protective factors. In total 25.2% of COVID-19 patients discontinued their IBD treatment, compared to 8.5% of non-COVID-19-infected patients. IBD flares were significantly higher in those who discontinued treatment (P < 0.001). CONCLUSIONS: IBD patients do not have an increased risk for COVID-19, regardless of IBD activity or treatment. Patients should be encouraged to continue effective IBD therapy, including biologics and steroids, to minimize active IBD.

Do inflammatory bowel disease patient preferences from treatment outcomes differ by ethnicity and gender? A cross-sectional observational study.

BACKGROUND: Inflammatory bowel disease (IBD) patients' expectations of treatment outcomes may differ by ethnicity. AIM: To investigate treatment preferences of Jewish and Arabs patients. METHODS: This prospective survey ranked outcomes treatment preferences among Arab IBD patients, based on the 10 IBD-disk items compared to historical data of Jews. An anonymous questionnaire in either Arabic or Hebrew was distributed among IBD patients. Patients were required to rank 10 statements describing different aspects of IBD according to their importance to the patients as treatment goals. Answers were compared to the answers of a historical group of Jewish patients. RESULTS: IBD-disk items of 121 Arabs were compared to 240 Jewish patients. The Jewish patients included more females, [151 (62.9%) vs 52 (43.3%); P < 0.001], higher education level (P = 0.02), more urban residence [188 (78.3%) vs 54 (45.4%); P < 0.001], less unemployment [52 (21.7%) vs 41 (33.9%); P = 0.012], higher income level (P < 0.001), and more in a partnership [162 (67.8%) vs 55 (45.4%); P < 0.001]. Expectations regarding disease symptoms: abdominal pain, energy, and regular defecation ranked highest for both groups. Arabs gave significantly lower rankings (range 4.29-6.69) than Jewish patients (range 6.25-9.03) regarding all items, except for body image. Compared to Arab women, Jewish women attached higher priority to abdominal pain, energy, education/work, sleep, and joint pain. Multivariable regression analysis revealed that higher patient preferences were associated with Jewish ethnicity (OR 4.77; 95%CI 2.36-9.61, P < 0.001) and disease activity. The more active the disease, the greater the odds ratio for higher ranking of the questionnaire items (1-2 attacks per year: OR 2.13; 95%CI 1.02-4.45, P = 0.043; and primarily active disease: OR 5.29; 95%CI 2.30-12.18, P < 0.001). Factors inversely associated with higher patient preference were male gender (OR 0.5; 95%CI 0.271-0.935, P = 0.030), UC (OR 0.444; 95%CI 0.241-0.819, P = 0.009), and above average income level (OR 0.267; 95%CI: 0.124-0.577, P = 0.001). CONCLUSION: The highest priority for treatment outcomes was symptom relief., Patients preferences were impacted by ethnicity, gender, and socio-economic disparity. Understanding patients' priorities may improve communication and enable a personalized approach.

The effect of direct-acting antiviral regimens and telemedicine on the treatment of inmates with hepatitis C virus infection in Israeli prisons.

BACKGROUND: Direct-acting antiviral (DAA) regimens and telemedicine services are both options for treating hepatitis C virus (HCV) within the prison setting. We aimed to compare factors associated with HCV treatment success over the past decade in Israeli prisons, specifically the influence of DAAs and telemedicine. METHODS: We retrospectively reviewed the medical records of inmates with HCV infection in Israeli prisons from 2010 through 2020. Demographic, clinical, and laboratory data were recorded, including treatment regimens and success rates. RESULTS: A total of 273 inmates were treated; mean age 45 ± 9.36 years; 98.2% males; 63.9% with a history of drug abuse. Advanced fibrosis was documented in 42.9%. The most common genotypes were 1 (46%) followed by 3 (40.7%). Interferon-based regimens were given to 68 inmates between 2010 and 2017. DAA agents were introduced in 2016, with pan-genotype regimens being exclusively used since 2019. Telemedicine services were used in 140 patients (51.3%), starting in February 2019. The sustained viral response (SVR) rate with interferon-based therapy was 78.8% and 98.8% with DAA treatment, giving an overall SVR of 93.2%. This difference between regimens proved to be the only statistically significant predictor of treatment success. The number of prisoners being treated with DAAs increased exponentially after telemedicine was introduced. Comparable SVR rates were achieved with either in-person or telemedicine consultation. CONCLUSION: Screening of this high-risk population and using telemedicine for treatment may be an effective strategy for the elimination of HCV from the prison population.