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P037 LONG-TERM EFFICACY AND SAFETY OF MAINTENANCE INFLIXIMAB THERAPY FOR THE TREATMENT OF MODERATE-TO-SEVERE PEDIATRIC CROHN'S DISEASE: RESULTS FROM THE REACH STUDY
10 of CRMO preceded the diagnosis of IBD (2 weeks-3.9 years), although in 2 patients bowel symptoms developed 2 months / 3 years before diagnosis of CRMO. Bones that were affected by CRMO included humerus, femur, tibia, sternum, os ileum, and vertebral bodies. 2 patients showed only one bone lesion, the other two had multiple lesions. Clinical NBO score varied from 32 to 47 (no NBO 0 28, possible NBO 29 38, definite NBO 39 63). NSAID were discontinued after IBD had been diagnosed. In 3 patients therapy for IBD (sulfasalazine/mesalazine, steroids, azathioprine) resulted in an improvement of bone lesions in addition to intestinal remission. One patient with severe CRMO and pancolitis ulcerosa who required multiple blood transfusions and was unresponsive to steroids, came into sustained remission with infliximab. Conclusion: Arthritis is a common extraintestinal manifestation of IBD. Clinicians should be aware that patients suffering from IBD might develop NBO vice versa. Non-invasive screening methods for IBD such as fecal calprotectin can be used in patients with NBO and unspecific intestinal symptoms. P035 LONGITUDINAL ASSESSMENT OF BONE MINERAL DENSITY IN A POPULATION OF CHILDREN AND ADOLESCENTS WITH INFLAMMATORY BOWEL DISEASE S. Schmidt1 *, D. Mellstr¨ om2 , E. Norjavaara3 , V. Sundh4 , R. Saalman5 . 1 Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska oteborg Pediatric Growth Research Academy, 2 Center for Bone Research, 3 G¨ Center, Sahlgrenska University Hospital, 4 Department of Public Health and Community Medicine, Sahlgrenska Academy, 5 Department of Pediatric Gastroenterology, Hepatology and Nutrition, Sahlgrenska University Hospital, G¨ oteborg, Sweden Background: Low BMD has been recognized as a potential problem in children with IBD. Objectives: To describe the longitudinal development of BMD in Swedish children with IBD. Methods: In this population-based study, 144 pediatric IBD patients underwent a DXA of the whole body and the lumbar spine. At follow-up after 2 years 125 of the initially 144 patients were examined with DXA. BMD values were expressed as Z-scores using pediatric reference data from Lunar© . Results: BMD mean Z-score LS was significantly decreased both in boys (-1.0 SD, ±1.6 SD, p < 0.001) and in girls (-0.4 SD, ±1.5 SD, p < 0.05). This finding remained unchanged at follow-up. At baseline, in boys the lowest BMD values were seen in the age group 17 19 years (Z-score LS -1.47 SD, ±1.9 SD). In contrast, at follow-up these boys had almost normalized their BMD (-0.34 SD, ±1.48 SD). However, at baseline in the group of the girls, the lowest BMD values were found in the same age group (mean Z-score LS -1.26 SD, ±1.6 SD). At follow-up BMD of these girls remained low (-1.47 SD, ±0.15). Conclusion: In this longitudinal population-based study, low bone mass is prevalent in Swedish pediatric patients with IBD both at baseline and at follow-up after 2 years. There might be some evidence that boys with low BMD have the potential for “catch-up” into early adulthood. P036 PHOSPHATE, CALCIUM AND ALKALINE PHOSPHATASE LEVELS IN PEDIATRIC AND ADULT PATIENTS WITH INFLAMMATORY BOWEL DISEASE S. Shehada1 , I. Chermesh2 , A. Lanir3 , R. Shaoul4 *. 1 Pediatrics, Bnai Zion Medical Center; 2 Gastroenterology, Rambam Medical Center; 3 Clinical Biochemistry, Bnai Zion Medical Center; 4 Pediatric Gastroenterology, Rambam Medical Center, Haifa, Israel Background: There is only one study that studied phosphate levels in adult IBD patients and found normal values. Objective: The aim of the study was to assess the levels of phosphate, as well as calcium and alkaline phosphatase (AP) levels in pediatric and adult IBD. Methods: We retrieved data on phosphate, calcium and AP serum levels during clinical remission and active disease. Seventy-one healthy adults and 95 children served as control groups. Results: 323 patients were included. The IBD groups consisted of 61 adults (47 with CD and 14 with UC) and 96 children (73 with CD and 23 with UC). AP levels were significantly lower in the childhood IBD group (mainly CD) and were even lower in active disease. Although more phosphate samples were reported as high in children with IBD compared to controls (41.7% vs. 15.8%, p = 0.0001), phosphate levels were significantly lower in children with active disease. Adults with IBD had significantly lower phosphate and calcium levels compared to controls especially in active disease. Conclusion: Although phosphate levels are reported as high in many children with IBD, values are lower in active disease. AP levels are lower in IBD children and may reflect disease activity. Adults with IBD had significantly lower phosphate and calcium levels compared to controls especially in active disease. These findings may reflect disease effects on growth (children), bone disease, low zinc levels and nutritional status.
Abstracts of PIBD 2009, 9 12 September 2009, Paris, France P037 LONG-TERM EFFICACY AND SAFETY OF MAINTENANCE INFLIXIMAB THERAPY FOR THE TREATMENT OF MODERATE-TO-SEVERE PEDIATRIC CROHN’S DISEASE: RESULTS FROM THE REACH STUDY G. Veereman-Wauters1 *, R. Baldassano2 , M. Blank2 , W. Crandall2 , A. Griffiths2 , R. Heuschkel2 , T.D. Walters2 , J. Hyams2 . 1 Queen Paola Children’s Hospital, Antwerp, Belgium, 2 REACH STUDY GRP, United States Objective: To evaluate long-term IFX in moderate/severe pediatric CD. Methods: 112 pts with a PCDAI score >30 received IFX5 mg/kg at wks 0, 2, 6. Responding pts at wk10 were randomized to IFX5 mg/kg q8 or q12wks to wk46 and could increase dose/decrease dosing frequency once. Pts who completed treatment through wk46 could enter the open-label extension (OLE) at wk54. Global assessment scores, height, and safety were collected for a maximum of 3yrs or until marketing authorization. Pts had different lengths of f/u; the number of pts who completed visits decreased over time. Analyses based on observed data. Results: 60 pts entered the OLE (33, 5 mg/kg q8wks; 12, 5 mg/kg q12wks; 15, 10 mg/kg q8wks). The numbers of pts at 1, 2, and 3yrs were 50, 35, and 5, respectively. Inactive disease at the start of OLE and at 1, 2, and 3yrs were 57%, 73%, 74%, and 80%, respectively. Height status was assessed in a subset of 20 pts (>1 yr delay in bone age at baseline); at baseline of the main study, mean z-score 1.45, and at baseline of the OLE, the mean change from baseline of the main study was 0.47. This improvement continued during the OLE, with a mean change from baseline of the main study of 0.83 at 1 yr (n = 15), 1.11 at 2yrs (n = 10) and 1.58 at the end of 3yrs (n = 4). 90% of pts had >1 AE during the OLE; upper respiratory infections were most frequent (42%). SAEs were reported in 33% of pts. 9 serious infections were reported in 6 pts, none opportunistic. No reports of TB, death or malignancy. Conclusion: These data support IFX as an effective long-term treatment for pediatric CD with safety consistent with previous observations. P038 RESPONSE TO MEDICAL TREATMENT IN PATIENTS WITH CROHN’S DISEASE B. Weiss1 *, O. Leibovitz2 , H. Fidder3 , A. Levine4 , R. Shaoul5 , S. Reif6 , Y. Bujanover7 , A. Karban8 . 1 Division of Pediatric Gastroenterology and Nutrition, Safra Children’s Hospital, and Sackler Faculty of Medicine, Tel Aviv University; 2 Division of Pediatric Gastroenterology, Sackler Faculty of Medicine, Tel Aviv Univesity, Tel-Aviv; 3 Department of Gastroenterology, Sheba Medical Center, Ramat Gan; 4 Division of Pediatric Gastroenterology, Wolfson Medical Center, Holon; 5 Division of Pediatric Gastroenterology, Bnei Zion Medical Center, Haifa; 6 Division of Pediatric Gastroenterology, Dana Children’s Hospital, Tel-Aviv; 7 Division of Pediatric Gastroenterology and Nutrition, Safra Children’s Hospital, Tel-Hashomer; 8 Department of Gastroenterology, Rambam Medical Center, and Rappaport School of Medicine, Technion, Haifa, Israel Background: It is unclear which factors affect the outcome of medical treatment in Crohn’s disease patients. Our aim was to examine the effects of disease characteristics and NOD2/CARD15 gene mutations on the outcome of the medical treatment with steroids, immunomodulators and infliximab. Methods: A retrospective analysis of 199 medical records of Crohn’s disease patients. Patients were treated with steroids, immunomodulators (6-mercaptopurine or azathioprine) or infliximab. Each of the participants has a previous evaluation for the presence of one of three mutations in the NOD2/CARD15 gene (G908R, R702W, fs1007). Demographic, genotype and phenotype details were reviewed. Remission or response to medical therapy was assessed using the Harvey-Bradshaw score. Results: 38.7% of patients carried a mutation in the NOD2/CARD15 gene. No relation was found between the presence of mutations and the outcome of medical treatment, in any of the treatment medications. Disease location was related to response to medical treatment: Patients with colonic disease were prone to steroid dependency in comparison to patients without colonic involvement (P = 0.009), while patients with small intestinal and upper gastrointestinal disease had less steroids dependency (P = 0.07), and a better response to immunomodulators (P = 0.035). Age of diagnosis, extra intestinal manifestations and other forms of disease behavior were not related to response to medical therapy, nor to the presence of NOD2/CARD15 mutations. Conclusion: Disease location in Crohn’s disease patients is associated with response to immunomodulatory drugs and steroid dependency. NOD2/CARD15 mutations are not related to outcome of medical treatment in these patients.
Abstracts of PIBD 2009, 9 12 September 2009, Paris, France P037 LONG-TERM EFFICACY AND SAFETY OF MAINTENANCE INFLIXIMAB THERAPY FOR THE TREATMENT OF MODERATE-TO-SEVERE PEDIATRIC CROHN’S DISEASE: RESULTS FROM THE REACH STUDY G. Veereman-Wauters1 *, R. Baldassano2 , M. Blank2 , W. Crandall2 , A. Griffiths2 , R. Heuschkel2 , T.D. Walters2 , J. Hyams2 . 1 Queen Paola Children’s Hospital, Antwerp, Belgium, 2 REACH STUDY GRP, United States Objective: To evaluate long-term IFX in moderate/severe pediatric CD. Methods: 112 pts with a PCDAI score >30 received IFX5 mg/kg at wks 0, 2, 6. Responding pts at wk10 were randomized to IFX5 mg/kg q8 or q12wks to wk46 and could increase dose/decrease dosing frequency once. Pts who completed treatment through wk46 could enter the open-label extension (OLE) at wk54. Global assessment scores, height, and safety were collected for a maximum of 3yrs or until marketing authorization. Pts had different lengths of f/u; the number of pts who completed visits decreased over time. Analyses based on observed data. Results: 60 pts entered the OLE (33, 5 mg/kg q8wks; 12, 5 mg/kg q12wks; 15, 10 mg/kg q8wks). The numbers of pts at 1, 2, and 3yrs were 50, 35, and 5, respectively. Inactive disease at the start of OLE and at 1, 2, and 3yrs were 57%, 73%, 74%, and 80%, respectively. Height status was assessed in a subset of 20 pts (>1 yr delay in bone age at baseline); at baseline of the main study, mean z-score 1.45, and at baseline of the OLE, the mean change from baseline of the main study was 0.47. This improvement continued during the OLE, with a mean change from baseline of the main study of 0.83 at 1 yr (n = 15), 1.11 at 2yrs (n = 10) and 1.58 at the end of 3yrs (n = 4). 90% of pts had >1 AE during the OLE; upper respiratory infections were most frequent (42%). SAEs were reported in 33% of pts. 9 serious infections were reported in 6 pts, none opportunistic. No reports of TB, death or malignancy. Conclusion: These data support IFX as an effective long-term treatment for pediatric CD with safety consistent with previous observations. P038 RESPONSE TO MEDICAL TREATMENT IN PATIENTS WITH CROHN’S DISEASE B. Weiss1 *, O. Leibovitz2 , H. Fidder3 , A. Levine4 , R. Shaoul5 , S. Reif6 , Y. Bujanover7 , A. Karban8 . 1 Division of Pediatric Gastroenterology and Nutrition, Safra Children’s Hospital, and Sackler Faculty of Medicine, Tel Aviv University; 2 Division of Pediatric Gastroenterology, Sackler Faculty of Medicine, Tel Aviv Univesity, Tel-Aviv; 3 Department of Gastroenterology, Sheba Medical Center, Ramat Gan; 4 Division of Pediatric Gastroenterology, Wolfson Medical Center, Holon; 5 Division of Pediatric Gastroenterology, Bnei Zion Medical Center, Haifa; 6 Division of Pediatric Gastroenterology, Dana Children’s Hospital, Tel-Aviv; 7 Division of Pediatric Gastroenterology and Nutrition, Safra Children’s Hospital, Tel-Hashomer; 8 Department of Gastroenterology, Rambam Medical Center, and Rappaport School of Medicine, Technion, Haifa, Israel Background: It is unclear which factors affect the outcome of medical treatment in Crohn’s disease patients. Our aim was to examine the effects of disease characteristics and NOD2/CARD15 gene mutations on the outcome of the medical treatment with steroids, immunomodulators and infliximab. Methods: A retrospective analysis of 199 medical records of Crohn’s disease patients. Patients were treated with steroids, immunomodulators (6-mercaptopurine or azathioprine) or infliximab. Each of the participants has a previous evaluation for the presence of one of three mutations in the NOD2/CARD15 gene (G908R, R702W, fs1007). Demographic, genotype and phenotype details were reviewed. Remission or response to medical therapy was assessed using the Harvey-Bradshaw score. Results: 38.7% of patients carried a mutation in the NOD2/CARD15 gene. No relation was found between the presence of mutations and the outcome of medical treatment, in any of the treatment medications. Disease location was related to response to medical treatment: Patients with colonic disease were prone to steroid dependency in comparison to patients without colonic involvement (P = 0.009), while patients with small intestinal and upper gastrointestinal disease had less steroids dependency (P = 0.07), and a better response to immunomodulators (P = 0.035). Age of diagnosis, extra intestinal manifestations and other forms of disease behavior were not related to response to medical therapy, nor to the presence of NOD2/CARD15 mutations. Conclusion: Disease location in Crohn’s disease patients is associated with response to immunomodulatory drugs and steroid dependency. NOD2/CARD15 mutations are not related to outcome of medical treatment in these patients.