Pediatric Crohn's Disease Patients Research Articles

NOD2 Sequencing in Iranian Children with Crohn’s Disease

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Although the exact etiology of disease is still unknown, mutations in the CARD15/NOD2 gene have been reported in association with CD in several studies. This study was performed to determine whether the CARD15/NOD2 gene confers susceptibility to Iranian pediatric patients with CD. All 12 coding exons of the CARD15/NOD2 gene were sequenced in 16 enrolled pediatric onset CD patients. Sequencing of the CARD15/NOD2 gene showed no mutation. However, two patients harbored polymorphisms within this gene. A heterozygous single nucleotide polymorphism rs3135500 C > Y in the exon 12.3 was detected in a 10-year-old girl with mild severity of CD and history of rectovaginal and perianal fistula, and multiple skin tags. The other 5-year-old boy with moderate to severe CD and a history of perianal fissures and oral candidiasis harbored heterozygous single nucleotide polymorphisms in exons 4.1 and 12.1. The results of the present study show that the CARD15/NOD2 mutations in Iranian patients with pediatric onset CD are not responsible for the pathogenesis of disease.

Usage prolongé de l’infliximab dans la maladie de Crohn chez l’enfant

The efficacy of infliximab (IFX) in inducing and maintaining remission in pediatric Crohn disease is currently well documented. However, the optimal treatment strategy beyond 1year has not been established. In particular, systematic continuation of maintenance therapy and its association with immunomodulators have not yet been analyzed. The aim of this study was to describe the long-term outcome of pediatric Crohn disease patients on IFX therapy and to evaluate the clinical response to the therapy and the effect on growth. A single-center and retrospective chart review was conducted. The clinical maintenance response to treatment, effect on the linear growth, and long-term outcome were examined. These parameters were analyzed according to the age of the patients, duration and localization of the disease, as well as associated therapies. We identified 52children with Crohn disease younger than 16years of age at the time of diagnosis. Of these patients, 20 (38%) received a biologic therapy at a mean age of 13.9±2years. Fifteen patients received IFX therapy and 13 (86%) were in clinical remission 10weeks after the first infusion. Among the responders, 82% were still in remission after 1year of therapy and 66% after 2years. Among patients treated for more than 1year, we observed IFX dependency in 89%. Thirty-eight percent of patients with initial IFX response showed a loss of response after a median of 30months (range, 3-42months). At 2years, the median Z score for height among patients with presumed growth potential had improved slightly, from -0.7to -0.55DS. No serious adverse events were observed. Our results confirm the continuous efficacy of IFX in pediatric Crohn disease patients after 1year of treatment. However, a high level of dependency was observed (89%). A slight beneficial effect on growth was observed after 2years of treatment.

Plasma citrulline as surrogate marker of intestinal inflammation in pediatric and adolescent with Crohn’s disease: preliminary report

Several researchers have found that plasma citrulline could be a marker of reduced enterocyte mass. The aim of this study was to assess the relationship between plasma citrulline and bowel inflammation and/or disease location in pediatric and adolescent Crohn's disease (CD) patients. Between January 2008 and January 2010, 31 CD patients and 44 controls were included in our study, and 15 out of the 31 CD patients continued a prospective survey. We evaluated the differences between groups, at baseline, in plasma citrulline and glutamine and between their baseline and final values during the prospective survey, and correlation between baseline values of citrulline and duration of disease, C-reactive protein, and fecal calprotectin. Mean citrulline value was 33.0 ± 7.5μmol/L in controls and 23.5 ± 8.4μmol/L in CD patients (P < 0.0001). Plasma citrulline was significantly lower in patients with small bowel (SB) location than in patient with only ileo-colon disease (14.2 ± 5.5 and 24.7 ± 8.0, respectively; P = 0.0037). Citrulline ≤22μmol/L reached sensitivity of 100% (95% confidence interval (CI) 54-100) and specificity of 98% (CI 89-99) in differentiating control subjects from CD with SB location. CD patients have reduced concentration of plasma citrulline than controls. Intestinal damage rather than inflammation seems to be responsible for the reduced biosynthesis of citrulline, which decreases particularly in CD patients with SB location. This finding suggests the potential role of citrulline as marker of disease location, but future works will be needed to confirm this suggestion.

Polyomavirus JC reactivation and noncoding control region sequence analysis in pediatric Crohn's disease patients treated with infliximab

The recent introduction of monoclonal antibodies in Crohn's disease (CD) management has been associated with the development of serious complications, such as the progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus (JCV) reactivation. Therefore, the aims of our study have been the investigation of the possible JCV reactivation in pediatric CD patients treated or not with infliximab, performing quantitative PCR in urine, plasma, and intestinal biopsies at the time of recruitment (t0) and every 4months in 1year of follow-up (t1, t2, and t3), and the analysis of the JCV noncoding control region (NCCR) to detect cellular transcription factors binding site mutations. Results obtained showed that, in urine and ileal specimens, JCV load significantly increased in infliximab-treated patients after 1year of treatment (t3), while viremia was significantly higher at t1. JCV NCCR sequence analysis showed a structure similar to CY archetype in 65/80 analyzed sequences, but the remaining 15/80, obtained exclusively from plasma and biopsies, evidenced a CY NCCR organization with two recurrent nucleotide changes, the 37-T to G transversion in box A Spi-B binding site and the 217-G to A transition in box F, and a box D deletion. These rearrangements were always found at t3 within seven infliximab-treated CD patients, who presented a very severe disease at t0. We can conclude that our rearranged NCCR sequences could be considered a marker of JCV virulence during mAb treatment, although none of our examined patients developed PML, and further studies on a larger cohort of patients should be performed.

Predictors of Abdominal Pain in Depressed Pediatric Crohn's Disease Patients

Predictors of Abdominal Pain in Depressed Pediatric Crohn's Disease Patients

Risk Factors for Ionizing Radiation Exposure in Newly Diagnosed Pediatric and Adult Crohn's Disease Patients

Risk Factors for Ionizing Radiation Exposure in Newly Diagnosed Pediatric and Adult Crohn's Disease Patients

Profile of Belgian Pediatric Crohn's Disease (CD) Patients: Associations Between Variables at Diagnosis

GCAP. CONCLUSIONS: The present method could reveal a trend of different intestinal microflora between UC patients' family and UC patients. We believe that a further study including more factors for analyses is warranted to better understand the significance of intestinal microflora in the immunopathogenesis of IBD. REFERENCES 1. Osborn, AM, et al. An evaluation of terminal-restriction fragment length polymorphism (T-RFLP) analysis for the study of microbial community structure and dynamics. Environ Microbiol 2000;2:3950. 2. Nagashima K, et al. Application of new primer-enzyme combinations to terminal restriction fragment length polymorphism profiling of bacterial populations in human feces. Appl Environ Microbiol 2003; 69:1251-62. 3. Suzuki Y, et al. Selective granulocytes and monocyte adsorptive apheresis as a first-line treatment for steroid naive patients with active ulcerative colitis. Dig Dis Sci 2004;49:565-71.

Outcome in the 2 years following a course of exclusive enteral nutrition in a cohort of >100 paediatric crohn's disease patients

IntroductionEEN is an effective 1st line treatment for active paediatric Crohn's disease (CD). We explored the short & long term effects of EEN including anthropometric parameters and evaluated factors that...

Immediate and long-term outcomes of corticosteroid therapy in pediatric crohnʼs disease patients

Although a mainstay of treatment of moderate to severe Crohn's disease (CD), corticosteroids use presents significant challenges because of large interindividual variability in response. Corticosteroid-dependence is of particular concern in children, where high rates have been reported. We examined the burden of corticosteroid-resistance and dependence in a well-characterized cohort of pediatric CD patients and investigated potential predictors of response. Children diagnosed with CD (<18 years), were recruited from two Canadian pediatric gastroenterology clinics. Immediate and long-term responses to corticosteroid therapy were retrospectively ascertained. Response rates (resistance and dependence) were estimated and potential predictors assessed using logistic regression analysis. Of the 645 CD patients, 364 (56.2%) received corticosteroids. The frequency of corticosteroid-resistance was (8.0%) (95% confidence interval [CI]: 5.0%-11%) and 40.9% (95% CI: 39.0%-46.0%) became dependent. In univariate analysis female gender (odds ratio [OR] = 2.49, 95% CI: 1.1-5.5, P = 0.025), disease severity (OR = 2.43, 95% CI: 1.10-5.38, P = 0.029), and complicated disease (OR = 2.75, 95% CI: 1.18-6.41, P = 0.019) were associated with resistance. In multivariate analysis lower age at diagnosis (OR = 1.34,95% CI: 1.03-3.01, P = 0.040), coexisting upper digestive tract involvement (OR = 1.35, 95% CI: 1.06-3.07, P = 0.031), and concomitant immunomodulator use (OR = 0.35, 95% CI: 0.16-0.75, P = 0.007) were significantly associated with steroid dependency. Our results demonstrate that steroid dependency is a frequent complication in children with CD. Children with an earlier age at diagnosis and coexisting upper digestive tract involvement could be potentially targeted for steroid-sparing therapy.

Granulocyte-macrophage colony stimulating factor blockade promotes ccr9+ lymphocyte expansion in Nod2 deficient mice

Ileal involvement in Crohn's disease (CD) is associated with NOD2 mutations and granulocyte-macrophage colony stimulating factor autoantibodies (GM-CSF Ab), and GM-CSF blockade promotes ileitis in Nod2/Card15-deficient (C15KO) mice. RALDH2-expressing dendritic cells (DC) and IL-4 promote CCR9 imprinting and small bowel homing of T lymphocytes, in conjunction with CCL25 expression by ileal epithelial cells (IEC). We hypothesized that GM-CSF neutralization promotes ileal disease by modulating expression of CCL25 by IEC and CCR9 by T lymphocytes via Nod2-dependent and independent pathways. CCL25 and CCR9 expression were determined in pediatric CD patients stratified by GM-CSF Ab. Ileitis was induced in C15KO mice via GM-CSF Ab administration followed by nonsteroidal antiinflammatory drug (NSAID) exposure, and expression of CCL25, CCR9, FOXP3, intracellular cytokines, and RALDH2 was determined in IEC and immune cell populations. The frequency of CCL25(+) IEC and CCR9(+) T lymphocytes was increased in CD patients with elevated GM-CSF Ab. In the murine model, GM-CSF blockade alone induced IEC CCL25 expression, and reduced the frequency of mesenteric lymph node (MLN) CD4(+) FOXP3(+) cells, while Card15 deficiency alone enhanced MLN DC RALDH2 expression. Both GM-CSF neutralization and Card15 deficiency were required for downregulation of MLN DC IL-10 expression; under these conditions NSAID exposure led to an expansion of IL-4(+) and IL-17(+) CCR9(+) lymphocytes in the ileum. GM-CSF prevents ileal expansion of CCR9(+) lymphocytes via Nod2-dependent and independent pathways. CCR9 blockade may be beneficial in CD patients with elevated GM-CSF Ab.

Innate Dysfunction Promotes Linear Growth Failure in Pediatric Crohnʼs Disease and Growth Hormone Resistance in Murine Ileitis§

Growth failure remains a common complication of pediatric Crohn's disease (CD) and has been associated with small bowel involvement and need for surgery. We have reported that patients with elevated (≥ 1.6 μg/mL) granulocyte macrophage colony stimulating factor autoantibodies (GM-CSF Ab) are more likely to experience complicated ileal disease requiring surgery. We hypothesized that concurrent GM-CSF Ab and CARD15 risk allele carriage (C15(+) GMAb(+) ) would be associated with growth failure in CD and growth hormone (GH) resistance in murine ileitis. We enrolled 229 pediatric CD patients at two sites and determined CARD15 genotype, serum GM-CSF Ab, and GH binding protein (GHBP), and height (HTz) and weight (WTz) z-scores at diagnosis. Ileitis was induced in card15-deficient mice by GM-CSF neutralization and nonsteroidal antiinflammatory drug (NSAID) exposure. Hepatic GH receptor (GHR) abundance and GH-dependent Stat5 activation were determined by western blot and Igf-I mRNA expression by real-time polymerase chain reaction (PCR). Mean (95% confidence interval [CI]) HTz at diagnosis was reduced to -0.48 (-4.2, 2.3) in C15(+) GMAb(+) patients, compared to -0.07 (-4.9, 3.4) in disease controls (P ≤ 0.05). Circulating GHBP, as a marker for tissue GHR abundance, was reduced in C15(+) GMAb(+) patients. Hepatic GHR abundance, GH induction of Stat5 tyrosine phosphorylation, and Igf-I mRNA expression were reduced in male card15-deficient mice with ileitis due to GM-CSF neutralization and NSAID exposure. Innate dysfunction due to concurrent genetic variation in CARD15 and neutralizing GM-CSF Ab is associated with linear growth failure in pediatric CD, and hepatic GH resistance in murine ileitis.

Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients

Background. Inflammatory bowel disease (IBD) of pediatric and adult onset differs in several aspects although little knowledge exists about pathogenic disparity. Regulatory T cells (Tregs) characterized as CD4+CD25+Foxp3+ are modulators of gut homeostasis, but their role in human IBD remains unclear. Objective. To evaluate the mucosal distribution of Foxp3+ and CD25+ cells in untreated pediatric IBD patients at the time of diagnosis. Material and methods. Untreated pediatric (n = 14) and adult (n = 12) Crohn's disease (CD) patients were prospectively included together with age-matched symptomatic controls. Colonic and ileal mucosal biopsies collected at diagnosis were studied by immunohistochemistry for enumeration of T cells and for mucosal expression of Foxp3 and CD25. Multicolor immunofluorescence staining was performed in situ to phenotype Foxp3+ cells as Tregs and characterize the CD25+ cells. Results. The density of mucosal T cells displayed only small variations, while that of Foxp3+ cells and CD25+ cells was increased in CD patients. Multicolor immunofluorescence showed that most CD25+ cells were macrophages. Interestingly, in the ileum of pediatric CD patients the density of Foxp3+ cells was significantly higher than in adult CD patients. Co-expression of Foxp3 and CD25, as well as Foxp3 and CTLA-4, indicated that the Foxp3+ cells were Tregs. Conclusion. Mucosal numbers of Foxp3+ Tregs and activated (CD25+) macrophages are elevated in both pediatric and adult ileal CD. The greater increase of ileal Foxp3+ Tregs in pediatric CD than in adult CD might contribute to the relatively less frequent phenotype of isolated ileal enteritis in CD children.

Tolerance and efficacy of azathioprine in pediatric Crohnʼs disease

Thiopurines are considered first-line immunomodulators for the prevention of relapse in moderate to severe pediatric Crohn's disease (CD). Early introduction of thiopurines was shown in a pediatric trial to maintain steroid-free remission in 90% of patients for 18 months. In the present study we analyzed the tolerance and efficacy of azathioprine (AZA) to maintain remission in a homogenous single-center observational cohort of children with CD. In all, 105 pediatric CD patients (male/female 68/37) were retrospectively evaluated for the efficacy of AZA (doses 1.4-4 mg/kg) to maintain remission at 6, 12, 18, and 24 months of follow-up. Overall, 93 children were included with active disease (pediatric Crohn's disease activity index [PCDAI] >30), steroid/enteral-nutrition dependency, or postileocecal resection. Remission was defined as PCDAI ≤10 without steroids. Patients requiring antitumor necrosis factor (TNF) medication, other immunomodulators, or surgery were considered to experience a relapse. Based on PCDAI, steroid-free remission was achieved in 56/93 (60.2%), 37/93 (39.8%), 31/93 (33.3%), and 29/93 (31.2%) at visits month (M)6, M12, M18, and M24, respectively. Within the first 4 weeks, AZA was stopped in 10/93 patients due to adverse reactions (pancreatitis, nausea, vomiting, skin reactions, general weakness), or not introduced due to low thiopurine methyl transferase (TPMT) activity (n = 3). No neutropenia occurred in patients with normal TPMT activity. Three infectious episodes were documented requiring temporary AZA suspension. AZA is efficacious in maintaining remission in pediatric CD patients, but to a lesser extent than previously suggested. The majority of patients who are in steroid-free remission at 12 months remained in prolonged remission. Overall tolerance of AZA was excellent.

Associations between variants in the ABCB1 (MDR1) gene and corticosteroid dependence in children with Crohnʼs disease

Corticosteroids (CS) effectively induce remission in patients with moderate to severe Crohn's disease (CD). However, CS dependence in children is a significant clinical problem associated with numerous side effects. Identification of molecular markers of CS dependence is of paramount importance. The ABCB1 gene codes for P-glycoprotein, a transporter involved in the metabolism of CS. We examined whether DNA variation in the ABCB1 gene was associated with CS dependency in children with CD. A retrospective study was carried out in two Canadian tertiary pediatric gastroenterology centers. Clinical information was abstracted from medical charts of CD patients (N = 260) diagnosed with CD prior to age 18 and administered a first course of CS during the 1 year since diagnosis. Patients were classified as CS-dependent if they relapsed during drug tapering or after the end of therapy. DNA was extracted from blood or saliva. Thirteen tagging single nucleotide polymorphisms (tag-SNPs) and a synonymous variation (C3435T) in the ABCB1 gene were genotyped. Allelic, genotype, and haplotype associations were examined using logistic regression and Haploview. Tag-SNP rs2032583 was statistically significantly associated with CS dependency. The rare C allele of this SNP (odds ratio [OR] = 0.56, 95% confidence interval [CI]: 0.34-0.95, P = 0.029) and heterozygous genotype TC (OR = 0.52, 95% CI: 0.28-0.95, P = 0.035) conferred protection from CS dependency. A three-marker haplotype was significantly associated with CS dependence (multiple comparison corrected P-value = 0.004). Our results suggest that the ABCB1 gene may be associated with CS dependence in pediatric CD patients.

The duration of effect of infliximab maintenance treatment in paediatric Crohn’s disease is limited

Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). To evaluate the long-term efficacy of infliximab treatment in paediatric CD. In this observational, multicentre study, all paediatric CD patients in The Netherlands treated with infliximab from October 1992 to November 2009 and with minimal follow-up of 3 months since start of infliximab, were studied. One hundred and fifty-two CD patients [81M; median age at start of infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5 infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was 25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative probability of losing response to infliximab in patients who initially required repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively. Seventy-four patients (49%) needed dose adjustments, with a median time to any adjustment of 6 months. Duration of effect of infliximab is limited as 50% of patients on infliximab maintenance treatment lose their therapeutic response after 5 years. Dose adjustments after start of infliximab are frequently needed to regain therapeutic benefit. These findings emphasise the need for effective, long-term treatment strategies for paediatric CD.

Interaction of Crohn's Disease Susceptibility Genes in an Australian Paediatric Cohort

Genetic susceptibility is an important contributor to the pathogenesis of Crohn's disease (CD). We investigated multiple CD susceptibility genes in an Australian paediatric onset CD cohort. Newly diagnosed paediatric onset CD patients (n = 72) and controls (n = 98) were genotyped for 34 single nucleotide polymorphisms (SNPs) in 18 genetic loci. Gene-gene interaction analysis, gene-disease phenotype analysis and genetic risk profiling were performed for all SNPs and all genes. Of the 34 SNPs analysed, four polymorphisms on three genes (NOD2, IL23R, and region 3p21) were significantly associated with CD status (p<0.05). All three CD specific paediatric polymorphisms on PSMG1 and TNFRSF6B showed a trend of association with p<0.1. An additive gene-gene interaction involving TLR4, PSMG1, TNFRSF6B and IRGM was identified with CD. Genes involved in microbial processing (TLR4, PSMG1, NOD2) were significantly associated either at the individual level or in gene-gene interactive roles. Colonic disease was significantly associated with disease SNP rs7517847 (IL23R) (p<0.05) and colonic and ileal/colonic disease was significantly associated with disease SNP rs125221868 (IBD5) and SLC22A4 & SLC22A4/5 variants (p<0.05). We were able to demonstrate genetic association of several genes to CD in a paediatric onset cohort. Several of the observed associations have not been reported previously in association with paediatric CD patients. Our findings demonstrate that CD genetic susceptibility in paediatric patients presents as a complex interaction between numerous genes.

768 Exclusive Enteral Nutrition in Paediatric Crohn's Disease

Background: The British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) guidance (October 2008) advocates the use of Exclusive Enteral Nutrition (EEN) as an alternative first line treatment to oral corticosteroids for induction of remission in paediatric Crohn's disease. Compared to steroids, EEN is not known to produce any harmful consequences. Aims: To assess whether EEN was being offered at two neighbouring district general hospitals (DGHs) in accordance with BSPGHAN standards and whether EEN courses were producing a remission rate similar to that in the literature. Methods: All patients on the Crohn's Disease Register were included. Data was collected from medical and dietician records and analysed using Microsoft Excel. Results: 95% children were offered and tolerated a full course of EEN. 83% EEN courses lasted 6-8 weeks. Remission was acheived in 78% overall (consistent with the literature). The length of period for food reintroduction was much more variable. Average number of dietician consultations for induction of remission and food reintroduction were also variable. 71% of those patients who achieved complete remission with EEN had a relapse ( 3 years). Conclusions: EEN was widely used in both the DGH settings. It was tolerated well and proved to be an effective treatment acheiving complete remission in 78% of patients. Our findings support the use of EEN as a first line treatment for paediatric crohn's disease. There is a need for more collabortive research and regular audits into the care of paediatric Crohn's disease patients.

Real-time tool to display the predicted disease course and treatment response for children with Crohnʼs disease

Immunomodulators and biologics are effective treatments for children with Crohn's disease (CD). The challenge of communicating the anticipated disease course with and without therapy to patients and parents is a barrier to the timely use of these agents. The aim of this project was to develop a tool to graphically display the predicted risks of CD and expected benefits of therapy. Using prospectively collected data from 796 pediatric CD patients we developed a model using system dynamics analysis (SDA). The primary model outcome is the probability of developing a CD-related complication. Input variables include patient and disease characteristics, magnitude of serologic immune responses expressed as the quartile sum score (QSS), and exposure to medical treatments. Multivariate Cox proportional analyses show variables contributing a significant increase in the hazard ratio (HR) for a disease complication include female gender, older age at diagnosis, small bowel or perianal disease, and a higher QSS. As QSS increases, the HR for early use of corticosteroids increases, in contrast to a decreasing HR with early use of immunomodulators, early or late biologics, and early combination therapy. The concordance index for the model is 0.81. Using SDA, results of the Cox analyses are transformed into a simple graph displaying a real-time individualized probability of disease complication and treatment response. We have developed a tool to predict and communicate individualized risks of CD complications and how this is modified by treatment. Once validated, it can be used at the bedside to facilitate patient decision making.

Long-term efficacy of adalimumab in Paediatric Crohn's disease patients naïve to other anti-TNF therapies

IntroductionAdalimumab is a fully-humanized anti-TNF a antibody that has showed its efficacy in Crohn’s disease (CD) adult patients. Its less immunogenic composition seems to be an advantage compared to previous anti-TNF α, mainly infliximab. Good response to adalimumab has been reported in patients naïve to infliximab, in those in whom infliximab has shown no efficacy and in those intolerant or who have lost previous response to it. Adalimumab has shown also its efficacy as a second-line anti-TNF α in small series of paediatric CD but data regarding its use in children naïve to infliximab are scarce. AimTo report our experience with adalimumab as first line anti-TNF α treatment in paediatric CD. Patients and methodsFour CD paediatric patients (2 boys) previously naïve to infliximab have received adalimumab. Mean age at diagnosis: 13years, 4months. Adalimumab was initiated in our patients soon after diagnosis (mean time from diagnosis: 8.5months, range: 1month 15days–14months) at decreasing loading doses (160mg and 80mg two weeks after) and then 40mg subsequently every two weeks. ResultsThe four patients entered in remission after the first dose of adalimumab (mean previous PCDAI: 35, mean PCDAI after first dose: 3.6). No adverse effects were registered. Azathioprine was stopped after 4months of combination therapy, without loss of efficacy or adverse reactions attributable to immunogenicity. All the 4 patients have remained in remission on adalimumab monotherapy for a mean follow-up of 17months (range 9–20months). ConclusionAdalimumab has shown its efficacy in our paediatric CD patients naïve to other anti-TNF α drugs. Early introduction of anti-TNF α antibodies in these patients could help to a better control of the disease. Its less immunogenicity and the possibility of a home-based administration are advantages when compared to other parenteral anti-TNF treatments. Change to monotherapy after prior successful combination therapy with azathioprine and adalimumab is a safe strategy that can help to minimize possible risks of intensive immunomodulation.

S2016 Serum Anti-Glycan Antibodies Can Contribute to Differential Diagnosis and Disease Stratification of Pediatric Crohn's Disease Patients

S2016 Serum Anti-Glycan Antibodies Can Contribute to Differential Diagnosis and Disease Stratification of Pediatric Crohn's Disease Patients