-
1.
A Systematic Review and Meta-analysis of Paediatric Inflammatory Bowel Disease Incidence and Prevalence Across Europe.
Roberts, SE, Thorne, K, Thapar, N, Broekaert, I, Benninga, MA, Dolinsek, J, Mas, E, Miele, E, Orel, R, Pienar, C, et al
Journal of Crohn's & colitis. 2020;(8):1119-1148
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease [IBD] is often one of the most devastating and debilitating chronic gastrointestinal disorders in children and adolescents. The main objectives here were to systematically review the incidence and prevalence of paediatric IBD across all 51 European states. METHODS We undertook a systematic review and meta-analysis based on PubMed, CINAHL, the Cochrane Library, searches of reference lists, grey literature and websites, covering the period from 1970 to 2018. RESULTS Incidence rates for both paediatric Crohn's disease [CD] and ulcerative colitis [UC] were higher in northern Europe than in other European regions. There have been large increases in the incidence of both paediatric CD and UC over the last 50 years, which appear widespread across Europe. The largest increases for CD have been reported from Sweden, Wales, England, the Czech Republic, Denmark and Hungary, and for UC from the Czech Republic, Ireland, Sweden and Hungary. Incidence rates for paediatric CD have increased up to 9 or 10 per 100 000 population in parts of Europe, including Scandinavia, while rates for paediatric UC are often slightly lower than for CD. Prevalence reported for CD ranged from 8.2 per 100 000 to approximately 60 and, for UC, from 8.3 to approximately 30. CONCLUSIONS The incidence of paediatric IBD continues to increase throughout Europe. There is stronger evidence of a north-south than an east-west gradient in incidence across Europe. Further prospective studies are needed, preferably multinational and based on IBD registries, using standardized definitions, methodology and timescales.
-
2.
Protocol for a multinational risk-stratified randomised controlled trial in paediatric Crohn's disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course.
Harris, RE, Aloi, M, de Ridder, L, Croft, NM, Koletzko, S, Levine, A, Turner, D, Veereman, G, Neyt, M, Bigot, L, et al
BMJ open. 2020;(7):e034892
Abstract
INTRODUCTION Immunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (ADA) are well established for maintenance of remission within paediatric Crohn's disease (CD). It remains unclear, however, which maintenance medication should be used first line in specific patient groups. AIMS To compare the efficacy of maintenance therapies in newly diagnosed CD based on stratification into high and low-risk groups for severe CD evolution; MTX versus AZA/6MP in low-risk and MTX versus ADA in high-risk patients. Primary end point: sustained remission at 12 months (weighted paediatric CD activity index ≤12.5 and C reactive protein ≤1.5 fold upper limit) without relapse or ongoing requirement for exclusive enteral nutrition (EEN)/steroids 12 weeks after treatment initiation. METHODS AND ANALYSIS REDUCE-RISK in CD is an international multicentre open-label prospective randomised controlled trial funded by EU within the Horizon2020 framework (grant number 668023). Eligible patients (aged 6-17 years, new-onset disease receiving steroids or EEN for induction of remission for luminal ± perianal CD are stratified into low and high-risk groups based on phenotype and response to induction therapy. Participants are randomised to one of two treatment arms within their risk group: low-risk patients to weekly subcutaneous MTX or daily oral AZA/6MP, and high-risk patients to weekly subcutaneous MTX or fortnightly ADA. Patients are followed up for 12 months at prespecified intervals. Electronic case report forms are completed prospectively. The study aims to recruit 312 participants (176 low risk; 136 high risk). ETHICS AND DISSEMINATION ClinicalTrials.gov Identifier: (NCT02852694), authorisation and approval from local ethics committees have been obtained prior to recruitment. Individual informed consent will be obtained prior to participation in the study. Results will be published in a peer-reviewed journal with open access. TRIAL REGISTRATION NUMBER NCT02852694; Pre-results.
-
3.
Combination of Biological Agents in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series and Review of the Literature.
Olbjørn, C, Rove, JB, Jahnsen, J
Paediatric drugs. 2020;(4):409-416
-
-
Free full text
-
Abstract
BACKGROUND Treatment with biological agents such as anti-tumor necrosis factors (TNFs) has become standard of care in moderate to severe pediatric inflammatory bowel disease (IBD). However, a significant proportion of patients experience loss of response to anti-TNFs, need treatment escalation, or develop side effects. There is no data in the literature regarding combination of biological agents in pediatric IBD. METHODS At our hospital, which is a tertiary referral center, we have combined the anti-TNF infliximab with either vedolizumab or ustekinumab in patients with severe pediatric IBD. The indications for dual biological therapy were insufficient efficacy of infliximab or vedolizumab monotherapy, or side effects such as psoriasis due to anti-TNFs. RESULTS Eight patients (four boys) aged 14-17.5 years received a combination of infliximab and vedolizumab due to only a partial response to infliximab, four with Crohn's disease (CD) and four with ulcerative colitis (UC). Clinical remission was achieved in four patients (3 UC) and four had a colectomy (3 CD, 1 UC). Five CD patients (3 girls) aged 11-17 years, on maintenance therapy with infliximab, developed psoriasis resistant to topical treatment. A combination of infliximab and ustekinumab resulted in clinical remission of CD without skin symptoms. No serious adverse events occurred in any of the patients on combination therapy. Thirteen publications report on combining biologicals, all in adult IBD. CONCLUSION In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The safety should be addressed in long-term follow-up studies.
-
4.
Inducing remission in paediatric Crohn's disease using nutritional therapies - A systematic review.
McVeigh, L, Payne, A
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2020;(2):170-186
Abstract
BACKGROUND Exclusive enteral nutrition (EEN) is known to be a safe and effective treatment option for managing active Crohn's disease (CD) in children, although no uniform protocol exists. The aim of this systematic review was to evaluate and compare the clinical effectiveness of aspects of EEN protocols to ascertain whether an optimum regimen can be identified. METHODS A systematic search of the Cochrane Library, PubMed, MEDLINE, EMBASE, CINAHL and AMED was conducted for studies published between 1998 and 2018 that examined paediatric patients being treated with an enteral nutrition protocol to induce remission. Studies that included patients receiving concurrent medication for active disease were excluded. Quality assessment was performed using separate tools for randomised controlled trials, cohort studies and for studies without a control group. RESULTS Sixteen studies met the inclusion criteria. Of these, six found insufficient evidence to support use of a specific formula. One study examined the route of EEN, finding no difference between oral or nasogastric tube administration with respect to inducing remission. Three examined the use of partial enteral nutrition to induce remission, although conflicting results were seen. No studies explored the effect of length of treatment or energy prescription on remission rates CONCLUSIONS An optimum enteral nutrition protocol for inducing remission cannot be identified. Further focused research is required by well designed, adequately powered prospective clinical trials to examine aspects of enteral feeding protocols that remain uncertain, including the use of partial enteral nutrition as a potential alternative to EEN.
-
5.
ORAL AND ENTERAL NUTRITION THERAPY IN INFLAMMATORY BOWEL DISEASES AMONG THE PEDIATRIC POPULATION: A LITERATURE REVIEW.
Souza, GN, Draghi, PF, Yonamine, GH
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2020;:e2019032
Abstract
OBJECTIVES To review the literature on oral and enteral nutrition therapy and investigate the evidence of its efficacy as a treatment, as well as in preventing relapses and reducing symptoms of inflammatory bowel diseases in the pediatric population. DATA SOURCE We performed a bibliographic search in the PubMed, Web of Science, and Latin American and Caribbean Health Sciences Literature (Literatura Latino-Americana e do Caribe em Ciências da Saúde - Lilacs) databases, using the keywords "inflammatory bowel disease," "diet," and "diet therapy" in English and Portuguese, with filters for pediatric studies published in the previous five years. DATA SUMMARY We selected 16 articles for this study, nine on exclusive and/or partial enteral nutrition and seven on modified oral diets, such as the specific carbohydrate diet (SCD) and the Crohn's Disease exclusion diet (CDED). The studies found evaluated the anthropometric profile of patients and the inflammatory profile of diseases in children before and after the introduction of each specific nutrition therapy. All interventions presented positive changes in these parameters; however, the results were inconclusive regarding the efficacy of SCD and CDED in the treatment and prevention of relapses. CONCLUSIONS Exclusive enteral nutrition has proven to be effective in inducing remission of Crohn's Disease, and the use of partial enteral nutrition for maintenance treatment has shown promising results. Other modified oral diets are inconclusive concerning their effectiveness, requiring further randomized controlled clinical trials.
-
6.
Effects of an Omega-3 and Vitamin D Supplement on Fatty Acids and Vitamin D Serum Levels in Double-Blinded, Randomized, Controlled Trials in Healthy and Crohn's Disease Populations.
Brennan Laing, B, Cavadino, A, Ellett, S, Ferguson, LR
Nutrients. 2020;(4)
Abstract
Two trials separately measured the bioavailability and impact on inflammation of a supplement taken daily containing 510 mg Docosahexaenoic acid (DHA), 344 mg Eicosapentaenoic acid (EPA), and 1000 IU of vitamin D (25-hydroxyvitamin D; 25(OH)D), for healthy and Crohn's disease (CD) populations. Both trials were double blinded, randomized, placebo-controlled with cross-over. Participants were randomly allocated to groups A (placebo then supplement) or B (supplement then placebo). Both included a washout. Fatty acid (N-3 PUFAs) and vitamin D serum levels, plasma C-reactive protein (CRP), and stool calprotectin were measured before and after each treatment period. Outcome measures were analyzed using generalized linear mixed models, including terms for treatment, period, and a treatment-by-period interaction. The supplement significantly increased serum levels in healthy and CD groups for EPA (p < 0.001 and p < 0.001, respectively), Docosapentaenoic acid (p < 0.001 and 0.005), DHA (p < 0.001 and 0.006), the omega-3 index (p < 0.001 and 0.001), and (vitamin D (p < 0.001 and 0.027). CRP and calprotectin measures showed no evidence of a treatment effect on inflammation; however, model estimation was imprecise for both outcomes, hence further research is required to elucidate potential inflammation effects. The nutrient supplement increased serum levels of key N-3 PUFAs and vitamin D in both populations, showing the preparation was readily bioavailable.
-
7.
Partial enteral nutrition induces clinical and endoscopic remission in active pediatric Crohn's disease: results of a prospective cohort study.
Urlep, D, Benedik, E, Brecelj, J, Orel, R
European journal of pediatrics. 2020;(3):431-438
Abstract
The aim of this study was to evaluate rates of clinical remission, endoscopic remission, and mucosal healing after a 6-week treatment period with partial enteral nutrition (PEN) and to compare them to those obtained by standard exclusive enteral nutrition (EEN) treatment in children with active Crohn's disease (CD). Twenty-five patients with active CD (median age 13.6 years, range 3.6-18.0) were recruited to either PEN (n = 12) or EEN (n = 13) treatment groups. The PEN group received 75% of their dietary needs from a polymeric formula plus one meal per day from an anti-inflammatory diet (AID). Patients were assessed at weeks 0, 1, 3, and 6 using clinical and laboratory parameters. Endoscopic assessment was performed at induction and week 6. On intention to treat analysis, clinical remission (Pediatric CD Activity Index < 10) was achieved in 69.2% and 75.0% of EEN and PEN patients, respectively (p = 0.999). The endoscopic remission (Simple Endoscopic Score for CD (SES-CD) ≤ 2) rates were 45.5% in both groups, while mucosal healing rates (SES-CD = 0) were 45.5% with EEN and 27.3% with PEN (p = 0.659).Conclusion: The results of our prospective pilot study suggest that PEN, allowing one meal from AID, could be as effective as EEN in inducing clinical and endoscopic remission in children with active CD. However, larger randomized controlled studies are warranted to confirm our findings.Trial registration: This clinical trial was registered under the number ClinicalTrials.govidentifier: NCT03176875.What is Known:• Exclusive enteral nutrition is a first-line treatment in active pediatric Crohn's disease; however, patients often find it difficult to adhere to.• Exclusive enteral nutrition is more effective than corticosteroids in achieving mucosal healing.What is New:• This is the first prospective study on partial enteral nutrition in active pediatric Crohn's disease, evaluating not only clinical, but also endoscopic remission.• A novel approach of partial enteral nutrition that allows one meal per day from an anti-inflammatory diet was as effective as exclusive enteral nutrition in inducing clinical and endoscopic remission in active Crohn's disease.
-
8.
A modern multidisciplinary approach to the treatment of enterocutaneous fistulas in Crohn's disease patients.
Papa, A, Lopetuso, LR, Minordi, LM, Di Veronica, A, Neri, M, Rapaccini, G, Gasbarrini, A, Papa, V
Expert review of gastroenterology & hepatology. 2020;(9):857-865
Abstract
INTRODUCTION Enterocutaneous fistulas (ECFs) is a manifestation of penetrating Crohn's disease (CD) that is challenging to treat and has considerable morbidity and mortality rates. AREAS COVERED This review aims to explore the practical and updated principles for the optimal treatment of ECFs in CD patients. EXPERT OPINION Optimal ECF management requires a multidisciplinary approach. Treatment first includes fluid resuscitation and electrolyte rebalancing with control of sepsis by means of antibiotics and, when indicated, drainage of infected collections. Subsequent therapeutic steps include nutritional support, control of the fistula output and treatment of peristomal skin. Anti-TNF-α therapy seems to have limited utility only after sepsis is resolved and intestinal stenosis excluded. However, ECFs heal in only approximately one-third of cases without surgical intervention. Thus, correct surgical timing combined with adequate nutritional support, sepsis resolution and skin care is considered the appropriate preoperative setting.
-
9.
The association between de novo inflammatory bowel disease and celiac disease.
Manceñido Marcos, N, Pajares Villarroya, R, Salinas Moreno, S, Arribas López, MR, Comas Redondo, C
Revista espanola de enfermedades digestivas. 2020;(1):7-11
Abstract
INTRODUCTION controversial data have been reported on the potential association between celiac disease (CeD) and inflammatory bowel disease (IBD). OBJECTIVE to study the prevalence of CeD in patients newly diagnosed cases with IBD. METHODS an observational, retrospective study was performed in patients with newly diagnosed IBD who were screened for CeD by anti-tissue transglutaminase antibodies (anti-tTG) measurements and an endoscopic duodenal biopsy. No patients had received corticosteroids, immunosuppressants or biologic drugs within the three months prior to gastroscopy. In the presence of Marsh 1, other causes were ruled out. CeD was diagnosed in patients positive for anti-tTG, compatible duodenal biopsy findings and a good response to a gluten-free diet. RESULTS a total of 163 patients were screened for CeD. Of these, six (3.7%) were positive for anti-tTG and four were diagnosed with CeD (three had ulcerative colitis, one had Crohn's disease). All patients with both CeD and IBD had normal IgA levels, positive anti-tTG and CeD genetic markers. CONCLUSIONS the prevalence of CeD in our patients with IBD was higher than that reported in the literature for other series of patients with IBD. A combination of anti-tTG testing and CeD genetics may screen patients for CeD in this population of patients with IBD.
-
10.
The fate of myofibroblasts during the development of fibrosis in Crohn's disease.
Li, C, Kuemmerle, JF
Journal of digestive diseases. 2020;(6):326-331
Abstract
Intestinal fibrosis is a devastating complication in patients with inflammatory bowel disease. Its characteristics include the loss of regular peristalsis and nutrition absorption, excessive deposition of extracellular matrix (ECM) components, thickness of intestinal lumen due to the formation of strictures and of scar tissue. As a major cell type involved in fibrogenesis, the myofibroblasts have already been shown to have a plastic and heterogeneous function in producing abundant collagen, fibronectin and connective tissue growth factor. The primary sources of ECM-producing and vimentin-positive myofibroblasts come from different precursor cells, including bone marrow-derived mesenchymal cells, fibrocytes, pericytes, epithelial to mesenchymal transition and endothelial to mesenchymal transition. Recent immunological research findings suggest that numerous cytokines and chemokines made from macrophages, in addition to T cells and other myeloid cell types, are also important drivers of myofibroblast differentiation and hence of the activation of myofibroblast-mediated transforming growth factor and collagen production. In this review we discuss the origins, roles and cell signaling of myofibroblasts during the development of fibrosis in different organs, particularly in Crohn's disease. Finally, we suggest that the epigenetic and immunological regulation of myofibroblast differentiation may provide a novel antifibrotic strategy in the near future.