W1182 Bone Mineral Density Deficits in Crohn's Disease Are Associated with Reduced Muscle Function

AGA Abstracts

each visit decreased over time.Analyses were based on observed data.Results:60 pts entered OLE:33,12,and 15 received IFX 5mg/kg q8wks,5mg/kg q12wks,and 10mg/kg q8wks,respectively.Numbers of pts at 1,2,and 3yrs were 50,35,and 5,respectively.For those pts who discontinued,3 did so for unsatisfactory therapeutic effect and 1 for AE.Global assessments are summarized(Table).Height status(age and gender-specific z-scores)was assessed in a subset of 20pts (with 1yr delay in bone age at baseline)who entered OLE.At baseline of the main study,the mean z-score was -1.45,and at baseline of OLE,the mean change from baseline of the main study was 0.47.This improvement continued during OLE, with mean change from baseline of the main study of 0.83 at 1yr(n=15),1.11 at 2yrs(n=10)and 1.58 at 3yrs(n= 4).90% of pts had ≥1AE during OLE;proportions of pts with AE were similar across groups.Upper respiratory infections occurred most frequently(41.7%).Serious AEs were reported in 33.3% of pts the most common of which were gastrointestinal disorders.9 serious infections were reported in 6pts including abscess,bacterial infection,pneumonia,upper respiratory tract infection,pseudomembranous colitis,and appendicitis.There were no TB reports,death or malignancy. Conclusions:Through OLE,IFX showed continued clinical efficacy including trend towards growth improvements.IFX was an effective long-term treatment for pediatric CD with safety consistent with previous observations. Table. Global Assessment During OLE*

Activity Index (PCDAI) was determined for all patients and demographic and auxologic data were collected for all subjects. Plasma citrulline levels were determined using the Hitachi L-8800 Amino Acid Analyzer, using blood specimens obtained after an overnight fast. CD and control patients were compared on categorical and continuous factors using Chi-square, Fisher's exact, or Wilcoxon rank sum tests as appropriate. The association between plasma citrulline levels and continuous characteristics was assessed using Spearman correlation coefficients for all subjects and separately for each cohort. Results: Patients with small bowel CD had a median age of 15.1 years (range: 9.2- 18.2 years); the median age of controls was 13.9 years (range: 9.2-18.6 yrs). Plasma citrulline levels did not differ significantly between males and females. However, CD patients had significantly lower plasma citrulline levels (median: 21 vs 33 micromolar; p<0.001) and lower BMI (median percentile: 36 vs 73; p=0.037) compared to age-matched controls. There also was an inverse relationship between PCDAI scores and plasma citrulline levels. In addition, there was correlation between the PCDAI score and BMI in CD patients, implying that a lower BMI indicates more severe disease status. Conclusion: Pediatric patients with small bowel CD have significantly lower plasma citrulline levels than age-matched controls. The PCDAI scores in CD patients inversely correlate with their plasma citrulline concentrations. These data suggest that determination of plasma citrulline may be a non-invasive marker of small bowel inflammation in pediatric patients with small bowel CD. W1184 Methotrexate for Induction and Maintenance of Remission of Paediatric IBD: A Regional Cohort Study in the Era of Biologics Aniela T. Tybulewicz, Pamela Rogers, David Hoole, Jack Satsangi, Peter M. Gillett, David C. Wilson Background and Aim: There is limited data on the use of Methotrexate (MTX) for induction and maintenance of remission of paediatric Crohn's Disease (CD), and many proceed to biological therapy if Azathioprine (AZA) fails. We reviewed our patients treated with MTX, in terms of both induction and maintenance of remission. Methods: A cohort study of all 244 patients diagnosed with early-onset (<18 years of age) IBD and managed in a UK regional centre over a 10 year period (1/8/97-31/12/07). Within this cohort were 165 patients with CD; we studied those resistant to or intolerant of AZA/6-MP who were treated with MTX (16 week induction course of s/c MTX (15mg/m squared) followed by the equivalent oral dose if response occurred). Paediatric Crohn's Disease Activity Index (PCDAI) was used to objectively measure disease activity during treatment; PCDAI ≤10 indicated full remission, ≤15 indicated partial remission and a score >30 indicated severe disease. Minimum follow up was 6 months for those who entered remission on MTX. Results: 122 patients with CD were treated with AZA/6-MP; 53 children (52 with previous AZA, 1 who refused AZA) received a MTX induction course. These 53 patients had CD diagnosed at a median (range) age of 10.9yrs (4.0-16.5) and received MTX at 14.0yrs (6.8-17.9) years. The median PCDAI at start of treatment was 35 (IQR 20-37.5). 41 (78%) patients entered remission; median (range) time to partial/complete remission was 11 (3-16) weeks. 2 of 41 had recalcitrant OFG and were excluded from maintenance evaluation; the remaining 39 had luminal CD and a median (range) duration of follow-up of 85 (26-310) weeks. 20 (51%) maintained long-term remission with no relapse; 7 (18%) had only a single relapse of which 6 (15%) re-entered remission, and 12 (31%) had >1 relapses. The median (range) time to first relapse was 39 (20-181) weeks. Of the 19 relapsing, 14 proceeded to repeat s/c courses of MTX, 9 to infliximab, 6 to surgery and 4 to adalimumab. On MTX treatment, 24 (46%) had nausea/ vomiting, 18 (34%) had raised ALT (1 subsequently undergoing liver biopsy, treatment then continued), 1 had shingles and none had bone marrow toxicity. Conclusions: MTX appears to be effective in inducing (78%) and maintaining (51%) remission of CD in paediatric patients who are resistant to or intolerant of AZA/6-MP, even if biological therapy is available. MTX also appears to be well tolerated and safe. Those who have had multiple relapses have all had complicated clinical courses and severe intractable disease. However, a stronger evidence base is needed from well- designed RCTs for both induction and maintenance of remission of early-onset CD by MTX.

*OLE: open-label extension W1182 Bone Mineral Density Deficits in Crohn's Disease Are Associated with Reduced Muscle Function David R. Mack, Leanne Ward BACKGROUND: Skeletal health is a result of dynamic processes that in some patients with Crohn's disease (CD) are altered leading to deficits in bone mineral content. In newly diagnosed children with CD, we have previously determined that there are disturbances of skeletal metabolism with low bone turnover and histomorphometric alterations on transilial bone biopsies with thinning of the cortices but a normal trabecular bone volume. As mechanical stress exerted by skeletal muscle increases cortical bone mass and strength, muscle hypofunction may have an adverse effect on cortical skeletal development. AIM: To evaluate muscle function in children with newly diagnosed Crohn's disease and assess if there is a relation to bone mineral content. METHODS: Children with newly diagnosed CD were recruited with severity of their disease determined by the Pediatric Crohn's Disease Activity index (PCDAI). Peak jump force was measured by jumping mechanography (Leonardo jumping platform™) as a measure of muscle force. Peripheral quantitative computerized tomography (pQCT) of the distal tibial cortical area was measured as a surrogate of bone strength and bone mineral content was measured by dual energy x-ray absorptiometry (DXA). Results are expressed as mean±SD unless otherwise specified. Age- and gendermatched z-scores arising from anthropometry, densitometry, pQCT and peak jump force were tested for significant deviation from 0 using one sample t-test. RESULTS: Eleven children (6 males) have been studied with a median age of 13.6 years (25% IQR: 8.9 years, 75% IQR: 15.1 years). Nine of the participants had moderate/severe CD (PCDAI>30). Peak jump force z-score was -1.1±0.66, p<0.001. Tibial cortical cross sectional area z-score was -0.31± 0.78, p<0.2 and tibial muscle cross-sectional area z-score was -0.68±0.69, p<0.0009. The total body bone mineral content (BMC) z-score by DXA was -1.15±0.99, p<003 and height corrected total body lean body mass (LBM) z-score median was -0.44 ((25% IQR: -1.21, 75% IQR: 0.18), p=0.04. Total body BMC/LBM z-score was -0.56 (95% CI -1.34 2.40), p=0.65. CONCLUSIONS: Children with clinically significant CD manifest significant deficits in muscle function and mass at the time of diagnosis. There can be reduced bone mass in newly diagnosed CD however, bone mineral content appears to be adapted for coexisting low lean body mass. These results suggest that both therapy for the underlying disease process and interventions to foster muscle development may be beneficial to bone health in children with active CD.

W1185 Assessment of IBD Serology 7 and Histology in Pediatric Patients Undergoing Evaluation for Possible Inflammatory Bowel Disease Leonardo R. Hormaza, Lina M. Felipez, Ranjana Gokhale, Matthew Tierney, Barbara S. Kirschner Background: Inflammatory bowel disease (IBD) immune markers are reported to be associated with complicated disease phenotypes in both children and adults. IBD Serology 7 (Prometheus Labs., San Diego, CA) utilizes “smart diagnostic algorithm technology” to improve predictive accuracy with the new marker, CBir1. Aim: To assess the accuracy of IBD Serology 7 in predicting IBD in a group of children undergoing colonoscopy for suspected IBD. Methods: From July 2006 to March 2008, all pediatric patients (pts) referred to the University of Chicago Pediatric Gastroenterology outpatient clinic or inpatient service for initial assessment of possible IBD were eligible for this study. Pts consented for colonoscopy, as part of a prospective protocol relating to infectious agents, were included in this study. The charts of these pts were reviewed to identify those who had IBD Serology 7, obtained during their initial assessment. The diagnosis of IBD was established according to clinical, radiological and endoscopic data. Serum markers were assessed for their accuracy to diagnose ulcerative colitis (UC) or Crohn's disease (CD). Results: A total of 67 charts were reviewed, of which 54 included serologic markers and were considered for further analysis. Four charts were excluded secondary to inadequate information. 25 pts were found to have IBD, with a prevalence of 50%. IBD pts included: CD (n=16), UC (n=8) and indeterminate colitis (n= 1). 15 out of 50 (30%) pts had positive IBD serology 7 without histologic evidence of IBD. Of the 25 pts with histologic evidence of IBD, 17 (68%) were correctly predicted with IBD. Of these 17 pts, 14 (82 %) were correctly sub-categorized as UC or CD. Overall, serologic testing for IBD had 68% sensitivity, 40% specificity, 53% PPV and 55 % NPV. Non-IBD pts had an average CBir1 of 31.8 EU/ml (normal <21.0 EU/ml) and IBD pts 35.4 EU/ml (p=0.8). CD pts had an average CBir1 of 42.9 EU/ml versus 19.9 EU/ml in UC pts (p=0.2). Conclusions: Our preliminary data shows that IBD Serology 7 demonstrates 68% sensitivity

W1183 Plasma Citrulline Levels in Pediatric Patients with Small Bowel Crohn's Disease-a Novel Biomarker of Inflammation Orhan K. Atay, Kadakkal R. Radhakrishnan, Susan Parlow, Lori Mahajan, Marvin Natowicz Objectives: The amino acid citrulline is primarily synthesized in small intestine enterocytes. Plasma citrulline is decreased in diseases with diminished mass of functional small bowel enterocytes, such as short bowel syndrome. The purpose of this study was to determine whether plasma citrulline concentrations are decreased in pediatric patients with active small bowel Crohn's disease (CD). There are no prior data regarding plasma citrulline levels in pediatric CD. Methods: 28 patients with small bowel CD and 25 healthy control subjects were recruited from the Cleveland Clinic Children's Hospital. The Pediatric Crohn's Disease

AGA Abstracts

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