M. Sladek

ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents

Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy. Conclusions: These revised Porto criteria for the diagnosis of PIBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.

Results of the 2nd scientific workshop of the ECCO (IV): Therapeutic strategies to enhance intestinal healing in inflammatory bowel disease

Evidence supporting the importance of assessment of mucosal healing in inflammatory bowel disease has increased in the last years. Mucosal healing has been integrated in the assessment of treatment efficacy in ulcerative colitis, but in Crohns disease this thought has arised after biological agents have been evaluated in clinical trials. Although a validated definition of mucosal healing still does not exist, its use is also assuming an increasingly important role in the follow-up of individual patients in clinical practice. Corticosteroids induce mucosal healing in a small proportion of patients with Crohns disease and are of no benefit to maintain it. By contrast, mucosal healing in Crohns disease can be achieved and maintained, with varying degrees of evidence and success, with thiopurines and biological agents. In ulcerative colitis, the ability of corticosteroids to induce mucosal healing is well recognized. 5-aminosalicylates, thiopurines and biological agents are also able to induce mucosal healing and, additionally, to maintain it. Mucosal healing assessment should be considered in clinical practice when symptoms persist despite therapy or when treatment discontinuation is being considered. Conversely, in patients whose clinical remission is not associated with mucosal healing, intensification of treatment is not currently recommended because of lack of evidence.

Comparison of outcomes parameters for induction of remission in new onset pediatric Crohn's disease: Evaluation of the porto IBD group "growth relapse and outcomes with therapy" (GROWTH CD) study

Background:Robust evaluation of induction therapies using both clinical and inflammatory outcomes in pediatric Crohns disease (CD) are sparse. We attempted to evaluate clinical, inflammatory, and composite outcomes of induction of remission therapies (normal C reactive protein [CRP] remission) in a large pediatric prospective multicenter study. Methods:Patients enrolled at diagnosis into the growth relapse and outcomes with therapy in Crohns disease study were evaluated for disease activity, CRP, and fecal calprotectin at 8, 12 and 52 weeks after starting treatment. The primary endpoint was week-12 steroid-free remission defined by pediatric Crohns disease activity index and CRP <0.5 mg/dL. The protocol required tapering off corticosteroids by week 11. Results:We analyzed 222 patients (mean age, 12.9 ± 3.2 yr) main evaluated treatment options included: 5-ASA (n = 29), exclusive enteral nutrition (n = 43), and corticosteroids (n = 114). Clinical remission at week 12 was achieved in 155 (73%) patients; both exclusive enteral nutrition and steroids were associated with normal CRP remission at week 12, although in a post hoc subgroup analysis exclusive enteral nutrition was superior in mild-to-moderate disease for this outcome. Among those in steroid-free remission in week 12, normal CRP predicted 1-year sustained remission (86% for normal CRP versus 61% for elevated CRP; P = 0.02). Baseline severity and early immunomodulation were similar in both groups. Conclusions:Normal CRP steroid-free remission at week 12 was impacted by type of induction therapy, but not by early immunomodulation. It was associated with more corticosteroids-free remission at week 52 and a trend for less relapses.

Rapid test for fecal calprotectin levels in children with Crohn disease.

ABSTRACT Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue, versus the conventional enzyme-linked immunosorbent assay in 134 stool samples from 56 pediatric patients with Crohn disease. The intraclass correlation coefficient analysis reflected good agreement (intraclass correlation coefficient 0.97 [95% confidence interval 0.95–0.98]) but agreement was better in lower values, where dilutions were not required. Using a cutoff of 100 &mgr;g/g for normal values, the percentage agreement between the 2 tests was 87%. The optimal cutoff values to guide clinical decisions in the therapy of inflammatory bowel disease have yet to be determined.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

Background:The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. Methods:A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006–2011. Results:We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0–14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein–Barr virus–associated lymphomas. Conclusions:Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Monotherapy with infliximab versus combination therapy in the maintenance of clinical remission in children with moderate to severe Crohn disease.

Objectives: The aim of the present study was to compare the efficacy and safety of 2 protocols of maintenance therapy with infliximab (IFX) and an immunomodulatory agent in pediatric patients with Crohn disease (CD): withdrawal of immunomodulators versus continuation of immunosuppressants. Methods: The present multicenter randomized open-label trial included 99 patients with CD (ages 14.5 ± 2.6 years) who were administered IFX (5 mg/kg body weight) along with an immunomodulatory agent (azathioprine 1.5–3 mg/kg body weight per day, methotrexate 10–25 mg/week). After 10 weeks of the induction therapy, 84 responders were centrally randomized into 1 of the following groups: group I (n = 45) in which IFX and an immunomodulatory agent were continued up to week 54 and group II (n = 39) in which the immunomodulatory agent was discontinued after 26 weeks. Results: The induction therapy was reflected by a significant decrease in Pediatric Crohns Disease Activity Index (PCDAI) and Simplified Endoscopic Activity Score for Crohns Disease (SES-CD) values. After the maintenance phase, the analyzed groups did not differ significantly in terms of the clinical response loss rates and final PCDAI and SES-CD scores. Furthermore, no significant intragroup differences were documented between mean PCDAI scores determined at the end of induction and maintenance phases. Intensification/modification of the treatment was required in 13 of 45 (29%) and 11 of 39 (28%) patients of groups I and II, respectively. A total of 9 serious adverse events were documented; none of the patients died during the trial. Conclusions: Twenty-six weeks likely represent the safe duration of combined IFX/immunomodulatory therapy in our sample of pediatric patients with CD.

Horizontal distribution of the fecal microbiota in adolescents with inflammatory bowel disease.

Background and Aims: The commensal microbiota of the gastrointestinal tract plays an important role in the pathogenesis of inflammatory bowel disease. We examined the horizontal structure of the fecal microbiota in the colon in adolescents with Crohn disease or ulcerative colitis and a control group. Patients and Methods: Fecal samples were collected in 3 fractions from patients with Crohn disease (n = 22), ulcerative colitis (n = 12), and controls (n = 24) during preparation for colonoscopy. Additionally, biopsies from colon tissue were taken. Samples were examined using a culture technique and a fluorescent in situ hybridization method. The mucin degradation assay was carried out. Results: Quantitative composition of the microbiota was different in the consecutive 3 fecal fractions and in the colon tissue of the study groups, but in patients from the control group, the composition of microbiota in the consecutive fractions was similar. Statistical analyses showed that the total distribution of the studied bacterial taxons in the contents in all 3 fecal fractions and in the colon tissue in the given disease group, and in the control group was characteristic for the studied patient group. Differences in species distribution among the cohorts studied were highly significant (P < 0.0001). Moreover, it was shown that in the fecal fraction I and in the colon tissue samples, there is no significant difference for any of the analyzed bacterial groups, using the culture methods or fluorescent in situ hybridization, but significant results were demonstrated in the II and III fractions for specific bacterial groups. The bacterial flora attached to the mucus layer in the UC group had significantly more degraded mucus in comparison with the control group (P = 0.045). Conclusions: Distribution of the microbiota in the colon is layered, which can be called horizontal distribution of the fecal flora. Only in the ulcerative colitis group, the bacterial flora attached to the mucous layer exerts action on the mucin.

Serum concentrations of VEGF and TGF-β1 during exclusive enteral nutrition in IBD.

Background and Aim: Exclusive enteral nutrition (EEN) is an effective method of treatment in achieving remission in inflammatory bowel disease (IBD); however, its mechanism of action is still poorly understood. The objective of our study was to assess the influence of EEN on serum vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-&bgr;1) in children and adolescents with IBD. Patients and Methods: Thirty-nine children and adolescents with IBD (24 with Crohn disease [CD] and 15 with ulcerative colitis [UC]) and 25 healthy controls were enrolled in the study. VEGF and TGF-&bgr;1 were assessed at the baseline and after 2 and 4 weeks of EEN in CD and UC groups and once in controls using enzyme-linked immunosorbent assay immunoassays. Results: At the baseline, we found increased serum VEGF in the CD versus UC group and controls (P < 0.05) and serum TGF-&bgr;1 in the UC versus CD group and controls (P < 0.05). During EEN, VEGF decreased in the UC and CD groups, whereas TGF-&bgr;1 increased in the CD group and decreased in the UC group. The CD group achieved disease remission faster than the UC group, and the weight gain of patients with CD during EEN was higher compared with patients with UC. Additionally, TGF-&bgr;1 concentration correlated with protein and energies daily intake in the CD group (R = 0.95; P < 0.05). Conclusions: Different effectiveness of EEN in achieving remission in CD and UC may result from a modification of growth factor production. EEN stimulated TGF-&bgr;1 production in CD but not in UC, which possibly resulted in higher effectiveness of EEN in this group of patients.

Evaluation of the infliximab therapy of severe form of pediatric Crohn’s disease in Poland: Retrospective, multicenter studies

BACKGROUND Registration of infliximab in Poland has increased chances to induce clinical remission and mucosal healing in the severe form of pediatric Crohns disease. OBJECTIVES The aim of this retrospective study was to assess the results and safety of infliximab therapy in the severe form of pediatric Crohns disease. MATERIAL AND METHODS The study included 153 children with severe form of non-fistulizing Crohns disease treated with infliximab. The clinical activity of Crohns disease was assessed according to PCDAI scale, endoscopic scoring was graded according to SES-CD, body mass was measured with body mass index (BMI). Infliximab was administered at the dose 5 mg/kg body mass in the 0.2 and 6th week, and then, after clinical response, every 8 for the period of 12 months. RESULTS One hundred thirty-six children (88.89%) achieved clinical response after induction therapy and 75.21% of children after the maintenance therapy. 39.68% of children achieved remission as graded with endoscopic scoring SES-CD. There was a statistically significant increase in body weight following the treatment. Side effects such as anaphylaxis, rash, and the activation of EBV infection appeared in 9 children at the time of infliximab injection. In other children the drug was well tolerated. CONCLUSIONS Induction and maintenance therapy with infliximab resulted in clinical remission of Crohns disease in 75.21% of children, and in the intestinal mucosa healing in 39.68% of children.

P255 Exclusive enteral nutrition is superior to corticosteroids and mesalamine for achieving remission with normalization of CRP in new onset pediatric Crohn's disease

to correct for decay. HC and QALYs in ET and MT were estimated for 10 years and compared with ST. Costs were discounted 3% per annum. Results: IFX was given in 441 cycles in ET, 5404 cycles in MT. Drug-refractory cycles totaled 1690 in ST, 77 in ET, 3 in MT. Surgery cycles were 65 in ST, 9 in ET, 0 in MT. HC/patient/10 years in Euros were: ST 23,224, ET 22,312 and MT 56,516. From year 2 HC was steady in all treatments but 2.43X higher in MT. QALYs were significantly different, with 10 year totals/patient of 91.88 in ST, 96.47 in ET and 99.54 in MT. Conclusions: MT was the most expensive but gave the highest QALYs, whereas ET achieved more QALYs than ST for the same cost. These data will be useful in planning budgets for CD patients requiring IFX where resources are limited.