Predictors of proctocolectomy in children with ulcerative colitis.

OBJECTIVES: Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database. METHODS: Children diagnosed with UC at age <18 years were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999 to November 2003 were extracted alongside incidence and surgical staging. RESULTS: Review of the PediIBDC database identified 406 children with UC. Approximately half were girls (51%) with an average age at diagnosis of 10.6 ±â€Š4.4 years in both boys and girls. Average follow-up was 6.8 (±4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (interquartile range 4.9) years after initial diagnosis. Children presenting with weight loss (hazard ratio [HR] 2.55, 99% confidence interval [CI] 1.21-5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15-17.04) at time of diagnosis and children with a first-degree relative with UC (HR 1.81, 99% CI 1.25-2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90-9.57) or tacrolimus (HR 3.66, 99% CI 1.60-8.39) also required earlier surgical management. Other symptoms, laboratory tests, and medical therapies were not predictive for need of surgery. CONCLUSION: Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC, and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis.

Rising incidence of inflammatory bowel disease among children: a 12-year study.

OBJECTIVE: Data suggest an increase in the incidence of pediatric inflammatory bowel disease (IBD). We examined the trend of the incidence of IBD in children. PATIENTS AND METHODS: A retrospective investigation was conducted on a cohort of children diagnosed with IBD between 1991 and 2002 who were registered in the IBD center at Texas Children's Hospital. The diagnosis of IBD was based on clinical, radiological, endoscopic, and histological examinations. RESULTS: There were 272 children eligible for the analysis; 56% diagnosed with Crohn disease (CD), 22% with ulcerative colitis (UC), and 22% with indeterminate colitis. The male-to-female ratio was 1.2:1 in CD, 0.6:1 in UC, and 0.8:1 in indeterminate colitis. From 1991 to 2002, the incidence rate has doubled from 1.1/100,000/year (95% confidence interval [CI] 0.85-1.36) to 2.4/1001,000/year (95% CI 2.10-2.77). This trend was valid for CD but not for UC. Whites had higher incidence rate of IBD than African Americans or Hispanics: 4.15/100,000/year (95% CI 3.48-4.82) versus 1.83/100,000/year (95% CI 1.14-2.51), and 0.61/100,000/year (95% CI 0.33-0.89), respectively. African Americans were predominantly diagnosed with CD. CONCLUSIONS: The results demonstrate the rising incidence of IBD among children with evidence of more CD than UC. Recognition of these results will have important implications for diagnosis and management of IBD in children.

Repeat endoscopy affects patient management in pediatric inflammatory bowel disease.

OBJECTIVES: Endoscopy is commonly performed in the diagnosis of children with inflammatory bowel disease (IBD). The utility of repeat endoscopy for the management of pediatric IBD has not been subject to investigation. The frequency and determinants of changes in medical management resulting from endoscopy are unknown. METHODS: We conducted a cross-sectional cohort study to assess the frequency and determinants of management change in all children (0-21 years) who underwent endoscopy for the surveillance or evaluation of established IBD between July 2002 and July 2006 at 2 referral centers in the United States. Patients were sampled from the Pediatric Endoscopy Database System Clinical Outcomes Research Initiative and a chart review was performed to identify demographic features (age, gender), blood work (hemoglobin, albumin, erythrocyte sedimentation rate, C-reactive protein), and endoscopy results (endoscopic and histologic). An endoscopic score was used to assess mucosal injury. Subjects were divided into two groups for comparative analysis: (i) patients with management changes based on endoscopic or histologic findings, and (ii) patients without changes. RESULTS: We analyzed 285 endoscopic procedures (137 colonoscopies, 109 esophagogastroduodenoscopy (EGD) with colonoscopy, 25 sigmoidoscopies, 8 EGDs, 6 EGDs with sigmoidoscopy) performed in 230 children (mean age 14.5) with established IBD, including 147 with Crohn's disease, 80 with ulcerative colitis, and 3 with indeterminant colitis. Management changes were documented in 119 (42%) procedures, including 58 (20%) immediately after endoscopy, 52 (18%) after histology review, and 9 (3%) after both. Management changes included new medications in 86 cases, discontinuation of a medication in 3 cases, hospital admission in 11, and surgical consult in 14. No significant differences between groups occurred with regard to age, gender, endoscopy type, or infliximab use. The presence of anemia, hypoalbuminemia, or elevated markers of inflammation (ESR, CRP) did not correlate with management outcome. Management changes after endoscopy were more frequent in patients with Crohn's disease as compared to patients with ulcerative colitis. Patients with mucosal injury were more likely to have a management change than those with mucosal healing (80% vs. 20%; P<0.001). CONCLUSIONS: The overall rate of management change after endoscopic evaluation in children with IBD is approximately 42%. Addition of a new medication is the most common intervention. Blood work and patient symptoms before the procedure did not predict management outcome; however, mucosal healing may be an important end point. Our findings suggest that endoscopy is valuable for the evaluation of children with IBD.

Use of complementary medicine in pediatric patients with inflammatory bowel disease: results from a multicenter survey.

OBJECTIVES: We examined the use of complementary and alternative medicine (CAM) at 3 US pediatric medical centers, comparing a group of children with inflammatory bowel disease (IBD) with children presenting with chronic constipation. MATERIALS AND METHODS: Surveys were administered by postal mail and at pediatric IBD centers in San Francisco, Houston, and Atlanta from 2001 to 2003. A comparison group consisting of pediatric patients with chronic constipation also was surveyed. Data were analyzed by t tests and by exact tests of contingency tables. RESULTS: In all, 236 surveys were collected from the IBD group; 126 surveys were collected from the chronic constipation comparison group. CAM therapies were used by 50% in the IBD group and 23% in the chronic constipation group. The overall regional breakdown of CAM use in IBD revealed no differences, although the types of CAM therapy used varied by site. The most commonly used CAM therapies in the IBD group were spiritual interventions (25%) and nutritional supplements (25%). Positive predictors for CAM use in IBD include the patient's self-reported overall health, an increase in the number of side effects associated with allopathic medications, white ethnicity, and parental education beyond high school. CONCLUSIONS: This is the first US study to characterize CAM use in pediatric patients with IBD with another chronic gastrointestinal disorder. CAM use was twice as common with the IBD group compared with the chronic constipation group. Regional variations exist with the types of CAM therapy used. Practitioners should know that half of their pediatric patients with IBD may be using CAM in conjunction with or as an alternative to other treatments and that certain predictors can help identify those using CAM therapies.

Infliximab therapy in children with concurrent perianal Crohn disease: observations from REACH.

OBJECTIVE: Post hoc analyses evaluated the effect of infliximab upon concurrent perianal Crohn disease (CD) in a subpopulation of 31 patients from REACH, a randomized trial of 112 children with moderately to severely active luminal CD. MATERIALS AND METHODS: The Pediatric Crohn Disease Activity Index perirectal subscore was used to assess perianal symptom activity and therapeutic response. Patients with no symptoms or asymptomatic tags received a score of 0; those with "1-2 indolent fistula, scant drainage, no tenderness" received a score of 5; and those with "active fistula, drainage, tenderness or abscess" received a score of 10. Initial perirectal subscores of 10 or 5 decreasing to 0 were considered complete response. Subscores of 10 decreasing to 5 were considered partial response. All patients were followed for efficacy and safety through week 54. RESULTS: Twenty-two patients with baseline perianal disease were randomized at week 10 following a 3-dose infliximab induction regimen. At week 2, 40.9% (9/22) of patients with signs and symptoms of perianal disease at baseline attained response (4 partial and 5 complete). At week 54, 72.7% (16/22) of patients with signs and symptoms of perianal disease attained response (1 partial and 15 complete). Nine patients developed perianal signs and symptoms during treatment; 7 had complete response and 2 had no response at week 54. The incidence of adverse events for patients with perianal symptoms at baseline and for those in the overall REACH population was similar (95.7% vs 94.6%). CONCLUSIONS: Infliximab rapidly reduced concurrent perianal disease signs and symptoms in this REACH cohort.

Inflammatory bowel disease in African American children compared with other racial/ethnic groups in a multicenter registry.

BACKGROUND & AIMS: Few epidemiologic investigations characterize inflammatory bowel disease (IBD) in non-Caucasian children. Our study compared IBD characteristics between African Americans and non-African Americans enrolled in a multicenter pediatric IBD registry with endoscopic- and pathology-based diagnosis. METHODS: The study retrieved data entered from January 2000 to October 2003 on children 1 to 17 years old, inclusive, followed by a consortium of academic and community US pediatric gastroenterology practices. Analyses examined racial/ethnic differences by comparing the proportions of African Americans and non-African Americans in the following categories: each diagnostic disease classification (any IBD, Crohn's disease, ulcerative colitis, indeterminate colitis); age group (<6 y, 6-12 y, or >12 y) at diagnosis or symptom onset; presence of extraintestinal manifestations, Z-scores for height and weight, immunomodulatory therapy, anatomic disease location, and abnormal hemoglobin, albumin, or sedimentation rate at diagnosis. RESULTS: A total of 1406 patients had complete data, 138 (10%) of whom were African American. African Americans more often were older than 12 years of age at diagnosis (52% vs 37%; odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.28-2.59) and symptom onset (46% vs 30%; OR, 1.99; 95% CI, 1.40-2.84); had Crohn's disease (78% vs 59%; OR, 2.36; 95% CI, 1.56-3.58); and had a low hemoglobin level at diagnosis (39% vs 17%; OR, 3.15; 95% CI, 1.92-5.17). CONCLUSIONS: IBD in African American children and adolescents presents more commonly with Crohn's disease and at older ages compared with non-African Americans. Racial/ethnic differences in the epidemiology of IBD, particularly Crohn's disease, among American youths require further investigation.

Presentation and disease course in early- compared to later-onset pediatric Crohn's disease.

BACKGROUND: The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis. METHODS: We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient. RESULTS: In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P < 0.001). The 6-17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients. CONCLUSIONS: The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.

Growth hormone treatment for growth failure in pediatric patients with Crohn's disease.

OBJECTIVE: To investigate the effect of human growth hormone (GH) injections on growth velocity in growth-impaired children with Crohn's disease (CD). STUDY DESIGN: Ten children and adolescents (mean age, 12.6 +/- 4.5 years; 6 males) with CD and poor height growth were treated with open-label recombinant GH, 0.043 mg/kg/day administered via subcutaneous injection, for 1 year. Patients were retrospectively matched with untreated patients (3 comparisons per case) by race, age, sex, and baseline height. Primary endpoint was height velocity; secondary endpoints were disease activity, body composition, and bone density determined by dual-energy x-ray absorptiometry scan. RESULTS: Mean height velocity increased by 5.33 +/- 3.40 (mean +/- standard deviation) cm/year in the GH-treated patients during the year of GH treatment, compared with 0.96 +/- 3.52 cm/year in the comparison group (P = .03). Height z-score increased by 0.76 +/- 0.38 in the treated group, compared with 0.16 +/- 0.40 in the comparison group (P < .01), and weight z-score increased by 0.81 +/- 0.89 in the treated group, compared with 0.00 +/- 0.57 in the comparison group (P < .01). Bone density revealed an increase of 0.31 +/- 0.33 in the lumbar spine z-score (P = .03 vs baseline). CONCLUSIONS: GH treatment increases height velocity and may enhance bone mineralization in children with CD. A randomized controlled trial in a large cohort of children is needed to evaluate the ultimate impact of GH treatment.

Measuring quality of life in pediatric patients with inflammatory bowel disease: psychometric and clinical characteristics.

OBJECTIVE: To extend development of a pediatric inflammatory bowel disease (IBD) health-related quality of life (HRQoL) measure by determining its factor structure and associations of factors with generic HRQoL measures and clinical variables. PATIENTS AND METHODS: Cross-sectional survey of children and adolescents ages 8 years to 18 years and their parents attending any of 6 US IBD centers, recruited from either existing registry of age-eligible subjects or visits to participating centers. The survey included generic (Pediatric Quality of Life Inventory) and IBD-specific (Impact Questionnaire) quality of life measures, disease activity, and other clinical indicators. We carried out factor analysis of Impact responses, comparing resulting factors with results on the generic HRQoL and the clinical measures. RESULTS: We included 220 subjects (161 with Crohn disease and 59 with ulcerative colitis). Initial confirmatory factor analysis did not support the 6 proposed Impact domains. Exploratory factor analysis indicated 4 factors with good to excellent reliability for IBD responses: general well-being and symptoms, emotional functioning, social interactions, and body image. Two items did not load well on any factor. The 4 factors correlated well with the Pediatric Quality of Life Inventory and subscales. Children with higher disease activity scores and other indicators of clinical activity reported lower HRQoL. CONCLUSIONS: This study provides further characteristics of a HRQoL measure specific to pediatric IBD and indicates ways to score the measure based on the resulting factor structure. The measure correlates appropriately with generic HRQoL measures and clinical severity indicators.

Knowledge, attitudes and practice styles of North American pediatricians regarding gastroesophageal reflux disease.

BACKGROUND: The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition launched a provider and public education campaign in 2002 to raise awareness of gastroesophageal reflux disease (GERD). To determine the effectiveness of campaign messages, we conducted a knowledge, attitudes, and practice styles (KAPS) survey of pediatric providers. Understanding the spectrum of management styles of GERD in children is critical to achieve better health outcomes and reduce health care costs. MATERIALS AND METHODS: The KAPS questionnaire was administered to 6000 randomly selected members of the American Academy of Pediatrics. RESULTS: A total of 1245 members responded; 82% worked in a primary care setting and 18% in subspecialty practices. Overall, 66% of the members order diagnostic testing in routine practice, 54% start testing for GERD in neonates, and 38% start testing after 1 month of age. The most common tests ordered were barium esophagram (45%) and esophageal pH monitoring (37%). GERD treatment with acid suppression before ordering diagnostic testing was a choice of 82% of the respondents. However, 19% believed acid suppression was best achieved by H2 blockers. If acid suppression was indicated, then only 36% followed guideline recommendations for therapy duration and 52% followed guideline recommendations for dosing. Antireflux surgery was recommended only as a last resort by 92%. Overall, 69% of providers believed the amount of GERD-related information available was not enough. Respondents who were not aware of available GERD practice guidelines ranged from 74% to 92%. CONCLUSIONS: Pediatric providers appear to frequently order diagnostic testing and treatment for GERD, yet knowledge about evidence-based GERD management among this random sample appeared limited. Moreover, a significant number of providers were not aware of different guideline publications.

Challenges in pediatric inflammatory bowel disease.

It is estimated that of the >1 million individuals in the United States with inflammatory bowel disease (IBD), approximately 100,000 are children. IBD that begins in childhood affects the individual at a critical period of growth and development. Children with Crohn's disease and ulcerative colitis may experience complications such as growth failure, school absence, and depression. In addition, because children with IBD have fewer environmental confounders such as smoking, children may be an excellent population to study microbial and immune interactions. Despite these opportunities, the discipline of pediatric IBD investigation is still in its infancy. In September of 2005, a group of investigators with expertise in pediatric IBD met in Boston (Massachusetts) to review the current status of childhood IBD research and to develop research priorities that warranted funding from the Crohn's and Colitis Foundation of America. The group included pediatricians, internists, basic scientists, clinical investigators, and members of the administrative staff and board of the Crohn's and Colitis Foundation of America. The research needs in respective areas were outlined by the heads of 10 focus groups, each with expertise in their respective fields (genetics, psychosocial issues, epidemiology, microbiology, immunology, quality improvement, pharmacogenomics, nutrition, growth and skeletal health, and clinical trials). Before the conference, heads of the research focus groups developed their proposals with experts in the field. At the end of the conference, members of the focus groups and members of the steering committee rated the proposed areas of study in terms of feasibility and importance. It was recommended that the Crohn's and Colitis Foundation of America focus its initial efforts in pediatric IBD in 5 areas: the effects of inflammation on growth and skeletal development, the genetics of early-onset IBD, the development of quality improvement interventions to standardize and improve clinical care of children with IBD, the immunology of childhood IBD, and the diagnosis and treatment of psychosocial sequelae of childhood IBD. At the conclusion of the meeting, investigators discussed the formation of a multicenter collaborative network to advance clinical and basic research in the field.

Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota.

The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis.

A review of activity indices and end points for clinical trials in children with Crohn's disease.

The necessity to include children and adolescents in clinical trials is increasingly recognized. Two recent workshops provided the impetus for pediatric gastroenterologists to develop evidence-based recommendations concerning end points and outcome assessment in cases of pediatric Crohn's disease. The overall goal was to facilitate clinical trial design by standardizing the methodology. This article critically reviews the available assessment tools and provides consensus recommendations for the evaluation of linear growth, disease activity, and health-related quality of life in clinical trials in pediatric Crohn's disease.

Premedication and infusion reactions with infliximab: results from a pediatric inflammatory bowel disease consortium.

BACKGROUND: Infusion reactions (IRs) are the most common adverse events associated with the use of infliximab for inflammatory bowel disease (IBD). Antipyretics, antihistamines, and corticosteroids have been used to prevent the development of IRs, but their efficacy is not known. We studied the proportion of pediatric patients receiving infliximab for IBD that developed IRs and the potential effects of premedication on IR. METHODS: Uniformly collected data from a cohort of pediatric patients with IBD enrolled between January 2000 and May 2003 at 6 pediatric centers were analyzed. Data were retrospectively reviewed and analyzed. RESULTS: A total of 1652 infusions given to 243 patients in 6 centers was analyzed. Overall, 60 IRs were recorded in 40 patients (3.6% of infusions, 16.5% of patients). Thirty-three of 243 patients received premedication before the first IR (group 1). Two hundred ten patients did not receive premedication until the development of IRs, if at all (group 2). IRs were more common among patients in group 1 than in group 2 (12/33 versus 28/210, P < 0.01). Of the 28 patients in group 2 with IRs, 10 began receiving premedication with each subsequent infusion, 12 continued without premedications, and 6 had no further infusions recorded. Two of 10 who began receiving premedication had a subsequent IR versus 6 of 12 who did not receive premedication (P = 0.15). CONCLUSIONS: IRs occur in a small proportion of infusions among pediatric patients receiving infliximab for IBD. Premedication does not seem to prevent the development of IRs; however, once an IR has occurred, premedication may be indicated to prevent subsequent IRs.

Design issues and outcomes in IBD clinical trials.

Successful clinical trials in inflammatory bowel disease are based on precise definitions of study populations, standardized and well-defined interventions, reliable indices of disease activity, and clearly stipulated outcome measures. Interpretation of research results is often complicated by the differentiation of goals of therapy (remission induction and maintenance, quality of life) and the multitude of patient subsets. Choosing the correct patient subtype to enroll in a clinical trial is critical to the results of a study, its conclusions, and its applicability to the clinical setting. Validated, easy-to-use disease activity indices allow interpretation of results across trials. The use of biomarkers as surrogate clinical endpoints provides reproducibility, ease of statistical handling as a continuous variable, and consistent measurement of response to treatment. Despite these potential advantages, biomarkers of disease activity lack specificity and will need to be validated against clinically meaningful outcomes. Careful subject selection, standardization of disease activity indices, and precise outcome measurement are the keys to continued improvement of the inflammatory bowel disease research process.

A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn's disease.

Probiotics are widely used by patients with Crohn's disease (CD) in an attempt to improve their health, but few controlled studies have been done to evaluate the efficacy of these therapies. We conducted a randomized, placebo-controlled trial of the probiotic Lactobacillus rhamnosus strain GG (LGG) to see if the addition of LGG to standard therapy prolonged remission in children with CD. Concomitant medications allowed in the study included aminosalicylates, 6-mercaptopurine, azathioprine, and low-dose alternate day corticosteroids. Seventy-five children (age range, 5-21 yr) with CD in remission were randomized to either LGG (n=39) or placebo (n=36) and followed for up to 2 years. The median time to relapse was 9.8 months in the LGG group and 11.0 months in the placebo group (P=0.24); 31% (12/39) of patients in the LGG group developed a relapse compared with 6/36 (17%) of the placebo group (P=0.18). The LGG was well tolerated, with a side effect profile comparable with placebo. This study suggests that LGG does not prolong time to relapse in children with CD when given as an adjunct to standard therapy.

CDP571, a humanized anti-tumor necrosis factor-alpha monoclonal antibody in pediatric Crohn's disease.

OBJECTIVES: The objectives of this study were to evaluate the safety, pharmacokinetics, and immunogenicity of CDP571 in pediatric patients with Crohn's disease. METHODS: A single dose of CDP571, 10 mg/kg, was administered by infusion to pediatric patients (aged 6-17 years) with Crohn's disease in a 12-week open-label study. Adverse events were monitored during infusion and throughout the study. Plasma concentrations of CDP571 and standard clinical and laboratory values were assessed. Changes in disease activity were monitored using the Pediatric Crohn's Disease Activity Index (PCDAI). RESULTS: Twenty patients were enrolled and stratified by age: 6 to 13 (n = 9) and 14 to 17 years (n = 11). Fourteen patients experienced adverse events, which were mainly mild or moderate in intensity. The plasma concentration profile was consistent with a half-life of approximately 2 weeks. At Week 4, 4 patients in the 6- to 13-year-old group and 2 patients in the 14- to 17-year-old group had detectable anti-CDP571 antibodies. By Week 2, 7 patients in the 6- to 13-year-old group and 6 patients in the 14- to 17-year-old group had responded to treatment (reduction in PCDAI score >10 points). CONCLUSION: In conclusion, CDP571 was well tolerated among pediatric patients with Crohn's disease.

DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis.

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn's disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P<0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.