Durability of the First Biologic in Children and Adults With Ulcerative Colitis: A Nationwide Study from the epi-IIRN.

BACKGROUND: In this nationwide study, our objective was to compare the durability of first-line biologics in ulcerative colitis (UC), categorized into monotherapy and combotherapy with immunomodulators. METHODS: We utilized data from the nationwide epi-IIRN cohort from 2005 to 2020. Durability was defined as consistent treatment without surgery. Comparisons were based on stringent propensity score-matching. RESULTS: We included 15 111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years (interquartile range, 3.8-11.0). The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively; P = .8). Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively; n = 182 matched pairs, P = .3) or combotherapy (78%/56% vs 91%/58%, respectively; n = 46 matched pairs, P = .4). Durability of infliximab was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; n = 174 matched pairs, P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%; n = 53 matched pairs, P = .4). The durability rate was similar for vedolizumab monotherapy (77%/56%) compared with adalimumab monotherapy (69%/52%; n = 125 matched patients, P = .1), and infliximab monotherapy (73%/55% vs 62%/44%; n = 78 matched patients, P = .1). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%, respectively; n = 131 matched pairs, P = .02). CONCLUSION: After 5 years of treatment, 43% of the patients with UC sustained their first biologic, with similar durability in pediatric and adult-onset onset disease. Anti-TNFs had similar durability to vedolizumab and superior durability when prescribed as combotherapy.

Durability of Adalimumab and Infliximab in Children With Crohn's Disease: A Nationwide Comparison From the epi-IIRN Cohort.

BACKGROUND: In a nationwide cohort, we aimed to compare the durability of infliximab and adalimumab as first biologic treatment in children with Crohn's disease (CD), stratified as combotherapy or monotherapy. METHODS: We used data from the epi-IIRN cohort that includes all patients with inflammatory bowel diseases in Israel. Durability was defined as consistent treatment without surgery or treatment escalation. All comparisons followed stringent propensity-score matching in Cox proportional hazard models. RESULTS: Of the 3487 children diagnosed with CD since 2005, 2157 (62%) received biologics (1127 [52%] infliximab, 964 [45%] adalimumab and 52 [2%] vedolizumab as first biologic), representing a higher proportion than that among adults diagnosed during the same time period (5295 of 15 776 [34%]; P < .001). Time from diagnosis to initiation of biologic was shorter in pediatric-onset compared with adult-onset disease (median time during the last 3 years was 2.7 months [interquartile range 1.2-5.4] vs 5.2 months [2.6-8.9]; P < .001). The durability of adalimumab monotherapy after 1 and 5 years from initiation of treatment was better than infliximab monotherapy (79%/54% vs 67%/37%, respectively; n = 452 matched children; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.3; P < .001), while in those treated with combotherapy, durability was similar (94%/66% with infliximab vs 90%/54% with adalimumab; n = 100; HR, 1.7; 95% CI, 0.9-3.3; P = .1). Durability was higher in children treated with infliximab combotherapy vs infliximab monotherapy (87%/45% vs 75%/39%; n = 440; HR, 1.4; 95% CI, 1.1-1.8; P = .01). The durability of adalimumab monotherapy was similar to infliximab combotherapy (83%/53% vs 89%/56%, respectively; n = 238; HR, 0.9; 95% CI, 0.7-1.2; P = .4). CONCLUSION: Our results support using adalimumab monotherapy as a first-line biologic in children with CD. When infliximab is used, combotherapy may be advantageous over monotherapy.

Prevalence and Outcomes of No Treatment Versus 5-ASA in Ulcerative Colitis: A Nationwide Analysis From the epi-IIRN.

BACKGROUND: Data regarding patients with ulcerative colitis (UC) not receiving maintenance treatment are scarce. In this nationwide study, we aimed to explore the frequency and long-term outcomes of untreated patients with UC vs treated patients. METHODS: We retrieved data from Israel's Health Maintenance Organizations, covering 98% of the population. No maintenance treatment (NMT) was defined as lack of treatment during the period from 3 to 6 months from diagnosis, allowing at most 3 months for induction treatment. RESULTS: A total of 15 111 patients have been diagnosed with UC since 2005, of whom 4410 (29%) have had NMT, with 36 794 person-years of follow-up. NMT was more likely in adults (31%) and in elderly-onset UC (29%) than in pediatric-onset UC (20%; P < .001) and decreased from 38% in 2005 to 18% in 2019 (P < .001). The probability of remaining without treatment was 78%, 49%, and 37% after 1, 3, and 5 years from diagnosis, respectively. In propensity score-matched analysis of 1080 pairs of treated (93% with 5-aminosalicylic acid) and untreated patients, outcomes were comparable for time to biologics (P = .6), surgery (P = .8), steroid dependency (P = .09), and hospitalizations (P = .2). Multivariable modeling indicated that failing NMT was less likely in adults or elderly-onset patients who received at most rectal therapy or antibiotics as induction therapy. CONCLUSIONS: Nowadays, 18% of patients with UC do not receive maintenance therapy, of whom half remain without treatment after 3 years. Matched pairs of patients on NMT and 5-aminosalicylic acid, representing the mildest patients of the latter, had similar outcomes. Prospective studies are needed to further explore the role of NMT in UC.

The rate of no maintenance treatment (NMT) decreased in the last years, but in a propensity score­matched analysis, 5-aminosalicylic acid monotherapy did not demonstrate any therapeutic advantage over NMT. NMT seems to be a viable option in a subset of patients with mild ulcerative colitis.

Durability of the First Biologic in Patients with Crohn's Disease: A Nationwide Study from the epi-IIRN.

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 7452 [39%] received biologics with a median follow-up of 6.8 years (interquartile range [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 1 and 3 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 1/3 years; p <0.001] and it was similar in adalimumab monotherapy vs infliximab combotherapy [87%/63% vs 80%/58%, respectively; p = 0.1]. Durability was higher in combotherapy compared with monotherapy for both infliximab [85%/64% vs 67%/43%, respectively; n = 496 matched pairs, p <0.001], and adalimumab [93%/76% vs 82%/62%, respectively; n = 540 matched pairs, p <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-tumour necrosis factors [TNFs] as first-line biologics in CD, particularly adalimumab if monotherapy is advised.

Thiopurines Maintenance Therapy in Children With Ulcerative Colitis: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Thiopurines are an established treatment for pediatric ulcerative colitis (UC). However, data regarding safety and efficacy are lacking. We aimed to determine short and long-term outcome following thiopurines use in children with UC. METHODS: We conducted a retrospective review of children (2-18 years) with UC treated with thiopurines between January 2008 and January 2019 at 7 medical centers in Israel. The primary outcome was corticosteroid (CS)-free clinical remission at week 52 following thiopurines initiation without the need for rescue therapy (infliximab, calcineurin inhibitors, or colectomy). RESULTS: A total of 133 children were included [median age at diagnosis of 12.4 (interquartile range 11.0-15.8) years, 30 (23%) left-sided colitis, 113 (85%) with moderate or severe disease at diagnosis]. At diagnosis 58 patients (44%) were treated with 5-aminosalicylates and 72 (54%) with CS. Sixty patients (45%) received thiopurines as 1st line maintenance therapy. Seventy-four patients (56%) had CS-free clinical remission at week 52 without rescue therapy. Predictors of clinical remission were not identified. In a sub-analysis among patients with steroid-responsive moderate to severe UC, 59 (55%) patients achieved this outcome. The likelihood of remaining free of rescue therapy among thiopurines-treated patients was 83%, 62%, 45%, and 37% at 1, 2, 3, and 4 years, respectively. CONCLUSION: More than half of children with UC starting thiopurines without previous or concomitant biologic therapy have CS-free clinical remission at 52 weeks later without the need for rescue therapy. Thiopurines are effective in pediatric UC and could be considered prior to biologics.

Nutritional aspects of inflammatory bowel disease.

INTRODUCTION: The number of people diagnosed with inflammatory bowel disease (IBD) continues to increase in most parts of the world. Although the exact etiology of this chronic intestinal disease is not fully understood, nutritional factors appear to play key roles. Furthermore, individuals with IBD are at increased risk of adverse nutritional impacts, including micronutrient deficiencies. AREAS COVERED: This review aims to summarize recent reports focusing on nutritional factors relevant to the development of IBD and to also review data on nutritional deficiencies seen in individuals with IBD. EXPERT OPINION: The typical western diet, characterized by high-fat/high-sugar foods, along with food additives, appears to contribute to the etiopathogenesis of IBD. In contrast, some reports indicate that some foods are likely protective. However, there are inconsistencies in the currently available data, reflecting study design and other confounding factors. Furthermore, some of the conclusions are inferred from animal or in vitro studies. The presence of IBD can compromise the nutrition of individuals with one of these disorders: ongoing monitoring is critical. Nutrition and diet in the setting of IBD remain key areas for further and ongoing study.

The significance of isolated aspartate aminotransferase elevation in healthy paediatric patients.

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.

Bariatric Surgery-Associated Myelopathy.

Bariatric surgery is gaining acceptance as an efficient treatment modality for adults and adolescents with morbid obesity. The early postbariatric period has the potential to induce an immunomodulatory imbalance due to the development or worsening of nutritional deficiencies, changes in hormonal balance (specifically after sleeve gastrectomy), and a shift in the proinflammatory cytokine profile along with a major change in the gut microbiome and permeability. These changes may induce encephalomyelitic T cell activity, change neural barrier permeability, and induce gut dysbioisis, favoring a proinflammatory metabolic profile. Such changes, in genetically prone individuals or those with additional risk factors, may lead to the development of myelopathy, particularly MS. Key Message: Postbariatric myelopathy is rare but should be considered in bariatric patients with relevant complaints in the postoperative period.

The management and course of eosinophilic oesophagitis in Israeli children.

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.

Prolonged abnormal isolated aminotransferase levels in healthy children is a benign condition.

AIM: Hypertransaminasaemia is a common incidental finding in children. It has been demonstrated that even prolonged elevation usually resolves spontaneously without clear aetiology. The aim of this study was to evaluate whether a longer follow-up period, on a larger group, supports the previous findings. METHODS: We retrospectively reviewed medical charts of children diagnosed with prolonged idiopathic hypertransaminasaemia, which spontaneously resolved over the follow-up period. RESULTS: Of the 468 patients screened for elevated transaminases levels, 87 patients younger than 5 years of age were included in the study. An aetiology was found in half of the patients, and the most common aetiologies were fatty liver and cytomegalovirus (CMV) infection. Aminotransferase abnormality persisted for a median of 10 months, and alanine aminotransferase (ALT) levels ranged from 1.5 to 15.9-fold of the upper limit of normal (ULN). After normalisation of transaminase levels, the values remained normal for a documented mean period of 6.4 ± 3.0 years. CONCLUSION: Although idiopathic asymptomatic aminotransferase elevation in healthy children resolves spontaneously in most children, the abnormality may be prolonged. Comprehensive workup finds aetiology only in half of the patients, and the most common aetiologies are fatty liver and CMV hepatitis, which can be diagnosed by non-invasive methods.