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Medical Therapy for Pediatric Inflammatory Bowel Disease

  • Inflammatory Bowel Disease (SB Hanauer, Section Editor)
  • Published:
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Abstract

Pediatric inflammatory bowel disease encompasses a spectrum of disease phenotype, severity, and responsiveness to treatment. Intestinal healing rather than merely symptom control is an especially important therapeutic goal in young patients, given the potential for growth impairment as a direct effect of persistent chronic inflammation and the long life ahead, during which other disease complications may occur. Corticosteroids achieve rapid symptom control, but alternate steroid-sparing strategies with greater potential to heal the intestine must be rapidly adopted. Exclusive enteral nutrition is an alternate short-term treatment in pediatric Crohn’s disease. The results of multi-center pediatric clinical trials of both infliximab and adalimumab in Crohn’s disease and of infliximab in ulcerative colitis (all in children with unsatisfactory responses to other therapies) have now been reported and guide treatment regimens in clinical practice. Optimal patient selection and timing of anti-TNF therapy requires clinical judgment. Attention must be paid to sustaining responsiveness safely.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Benchimol E, Fortinsky K, van der Heuvel M, van Limbergen J, Griffiths AM. Epidemiology of pediatric IBD: a systematic review of international trends. Inflamm Bowel Dis. 2011;17:423–39.

    Article  PubMed  Google Scholar 

  2. Braegger C, Balabbeni P, Rogler D, et al. Epidemiology of inflammatory bowel disease: is there a shift towards onset at an earlier age? J Pediatr Gastro Nutr. 2011;53:141–4.

    Article  Google Scholar 

  3. Imielinski M, Baldassano R, Griffiths AM, et al. Common variants at 16p11 implicate IL-27 in childhood-onset inflammatory bowel disease. Nat Genet. 2009;41:1335–40.

    Article  PubMed  CAS  Google Scholar 

  4. •• Glocker EO, Kotlarz D, Boztug K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009;361:2033–45. A landmark paper which breaks new ground in infantile-onset multi-system inflammatory disorders that include intestinal inflammation and even perianal disease, but also stimulates research into the role of the IL-10 pathway in complex IBD.

    Article  PubMed  CAS  Google Scholar 

  5. • Levine A, Griffiths AM, Markowitz J, et al. Pediatric Modification of the Montreal Classification for Inflammatory Bowel Disease - the Paris Classification. Infl Bowel Dis Inflamm Bowel Dis. 2011;17:1314–21. A critical attempt to define important phenotypic characteristics of pediatric onset IBD.

    Article  Google Scholar 

  6. •• Van Limbergen J, Russell RK, Drummond HE, et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008;135(4):1114–22. A careful prospective analysis of the clinical evolution of pediatric IBD in comparison to adult onset IBD diagnosed in Scotland.

    Article  PubMed  Google Scholar 

  7. •• Vernier-Massouille G, Balde M, Salleron J, et al. Natural history of pediatric Crohn’s disease: a population-based cohort study. Gastroenterology. 2008;135(4):1106–13. Appearing at the same time, an examination of the phenotypic evolution of pediatric IBD in a population-based French cohort.

    Article  PubMed  Google Scholar 

  8. • Walters TD, Griffiths AM. Mechanisms of Disease: growth impairment in paediatric Crohn’s disease. Nature Rev Gastroenterol Hepatol. 2009;6:513–23. A comprehensive review of pathogenetic mechanisms of growth impairment in pediatric CD.

    Article  CAS  Google Scholar 

  9. • Wilson D, Thomas A, Croft N, et al. Systematic Review of the Evidence Base for the Medical Treatment of Paediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2010 Jan 13. A comprehensive magnum opus, which recognizes the paucity of randomized controlled trials in children.

  10. Griffiths AM. Specificities of inflammatory bowel disease in childhood. Best Pract Res Clin Gastroenterol. 2004;18(3):509–23.

    Article  PubMed  Google Scholar 

  11. Seow CH, Benchimol EI, Griffiths AM, Otley AR, Steinhart AH. Budesonide for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2008 Jul 16;(3)(3):CD000296.

  12. Levine A. Comparison of two dosing methods for induction of response and remission with oral budesonide in active pediatric Crohn’s disease: A randomized placebo-controlled trial. Inflamm Bowel Dis. 2009;15:1055–61.

    Article  PubMed  Google Scholar 

  13. Buchanan E, Gaunt WW, Cardigan T, et al. The use of exclusive enteral nutrition for induction of remission in children with Crohn’s disease demonstrates that disease phenotype does not influence clinical remission. Aliment Pharmacol Ther. 2009;30(5):501–7.

    Article  PubMed  CAS  Google Scholar 

  14. Borrelli O, Cordischi L, Cirulli M, et al. Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn’s disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol. 2006;4(6):744–53.

    Article  PubMed  Google Scholar 

  15. Day AS, Whitten KE, Sidler M, Lemberg DA. Systematic review: nutritional therapy in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2008;27(4):293–307.

    Article  PubMed  CAS  Google Scholar 

  16. • Leach ST, Mitchell HM, Eng WR, Zhang L, Day AS. Sustained modulation of intestinal bacteria by exclusive enteral nutrition used to treat children with Crohn’s disease. Aliment Pharmacol Ther. 2008;28(6):724–33. An interesting attempt to investigate the mechanism of action of enteral nutrition as primary therapy.

    Article  PubMed  CAS  Google Scholar 

  17. Hyams J, Crandall W, Kugathasan S, et al. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn’s disease in children. Gastroenterology. 2007;132(3):863–73.

    Article  PubMed  CAS  Google Scholar 

  18. • Hyams J, Griffiths AM, Markowitz J et al Induction and Maintenance Adalimumab for Moderate to Severe Crohn’s Disease in Children: A Randomized Double-Blind Trial. Gastroenterology 2011;140:S90. A large multi-center trial by pediatric standards, with nice stratification of patients according to prior anti-TNF exposure.

  19. Hanauer SB, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet. 2002;359:1451–9.

    Article  Google Scholar 

  20. Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med. 2007;357(3):228–38.

    Article  PubMed  CAS  Google Scholar 

  21. Borelli O, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn’s disease. Dig Liver Dis. 2004;36:342–7.

    Article  Google Scholar 

  22. Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829–38.

    PubMed  Google Scholar 

  23. D’Haens G, et al. Early combined immunesuppression or conventional management in recently diagnosed patients with Crohn’s disease: an open randomized trial. Lancet. 2008;371:660–7.

    Article  PubMed  Google Scholar 

  24. Sipponen T, Karkkainen P, Savilahti E, et al. Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn’s disease and histological findings. Aliment Pharmacol Ther. 2008;28:1221–9.

    Article  PubMed  CAS  Google Scholar 

  25. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology. 2000;119(4):895–902.

    Article  PubMed  CAS  Google Scholar 

  26. Turner D, Grossman AB, Rosh J, et al. Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol. 2007;102(12):2804–12.

    Article  PubMed  CAS  Google Scholar 

  27. Uhlen S, Belbouab R, Narebski K, et al. Efficacy of methotrexate in pediatric Crohn’s disease: a French multicenter study. Inflamm Bowel Dis. 2006;12(11):1053–7.

    Article  PubMed  CAS  Google Scholar 

  28. Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4(10):1248–54.

    Article  PubMed  CAS  Google Scholar 

  29. •• Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–95. Conducted in adult patients, but addressing what has been a major question about optimal treatment regimens with infliximab therapy (mono- versus combination). Also provides prospective data on mucosal healing rates with azathioprine and with infliximab and with combination therapy.

    Article  PubMed  CAS  Google Scholar 

  30. • Schnitzler F, et al. Longterm outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut. 2009;58:492–8. Excellent single-center account of real-world experience in adults. Similar is needed in pediatrics!.

    Article  PubMed  CAS  Google Scholar 

  31. deRidder L, et al. Infliximab Dependency in Pediatric Crohn’s Disease: Longterm follow-up of an Unselected Cohort. Inflamm Bowel Dis. 2008;14:353–8.

    Article  Google Scholar 

  32. • Shale M, et al. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut. 2008;57:1639–41. Excellent summary and analysis.

    Article  PubMed  Google Scholar 

  33. Rosh JR, Gross T, Mamula P, Griffiths A, Hyams J. Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn’s disease: a cautionary tale. Inflamm Bowel Dis. 2007;13(8):1024–30.

    Article  PubMed  Google Scholar 

  34. • Kotlyar DS, Osterman MT, Diamond RH, et al. A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2011;9(1):36–41.e1. Another up to date summary and analysis.

    Article  PubMed  CAS  Google Scholar 

  35. Melmud G, et al. The appropriateness of concomitant immunemodulators with anti-TNF agents for Crohn’s disease: one size does not fit all. Clin Gastro Hepatol. 2010;8:655.

    Article  Google Scholar 

  36. Maini RN, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998;41:1552–63.

    Article  PubMed  CAS  Google Scholar 

  37. Walters TD, Gilman AR, Griffiths AM. Linear growth improves during infliximab therapy in children with chronically active severe Crohn disease. Inflamm Bowel Dis. 2007;13:1–7.

    Article  Google Scholar 

  38. Russell RK, Wilson ML, Loganathan S, et al. A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33(8):946–53.

    Article  PubMed  CAS  Google Scholar 

  39. Turner D, Otley AR, Mack D, et al. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology. 2007;133(2):423–32.

    Article  PubMed  Google Scholar 

  40. Zeisler B, Lerer T, Markowitz J et al. Outcome following aminosalicylate therapy in children newly diagnosed with ulcerative colitis: a prospective multi-center registry experience.

  41. Hyams J, Markowitz J, Lerer T, et al. The natural history of corticosteroid therapy for ulcerative colitis in children. Clin Gastro Hepatol. 2006;4(9):1118–23.

    Article  CAS  Google Scholar 

  42. Hyams J, Damaraju L, Blank M et al. A randomized multi-center open label phase 3 study to evaluate the safety and efficacy of infliximab in pediatric patients with moderate to severe ulcerative colitis. Clin Gastro Hepatol 2011. doi:10.1016/j.cgh.2011.11.026.

  43. Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104(2):437–43.

    Article  PubMed  CAS  Google Scholar 

  44. Hyams JS, Lerer T, Mack D, et al. Outcome following thiopurine use in children with ulcerative colitis: a prospective multicenter registry study. Am J Gastroenterol. 2011;5:981–7.

    Article  Google Scholar 

  45. Turner D, Walsh CM, Benchimol EI, et al. Severe paediatric ulcerative colitis: incidence, outcomes, and optimal timing for second line therapy. Gut. 2008;57:1–10.

    Article  Google Scholar 

  46. Turner D, Griffiths A. Acute severe paediatric ulcerative colitis: a systematic review. Inflamm Bowel Dis. 2011;17:440–9.

    Article  PubMed  Google Scholar 

  47. • Turner D, Mack D, Leleiko N, et al. Severe pediatric ulcerative colitis: a prospective multicenter study of outcomes and predictors of response. Gastroenterology. 2010;138(7):2282–91. The first sizeable prospective assessment of intravenous corticosteroid therapy for acute severe pediatric ulcerative colitis.

    Article  PubMed  CAS  Google Scholar 

  48. • Turner D, Travis SP, Griffiths AM, et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastro. 2011;106:574–88. A useful guide to management of this severe cohort of patients.

    Article  CAS  Google Scholar 

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Disclosure

Dr. M. Sherlock has been an advisory board member and honoraria recipient for Merck; Dr. A. Griffiths has been a consultant for Abbott, Centocor, Janssen, Merck, Nestle, and Shire; has received speaker's honoraria from Abbott, Janssen, and Merck; has participated in clinical trials initiated by Abbott, Centocor, and UCB Pharma; has received research support for investigator-initiated research from Schering Canada.

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Authors and Affiliations

  1. Division of Gastroenterology, McMaster Children’s Hospital, Hamilton, Canada

    Mary E. Sherlock

  2. Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, M5G 1X8, Canada

    Anne M. Griffiths

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  1. Mary E. Sherlock
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  2. Anne M. Griffiths
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Correspondence to Anne M. Griffiths.

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Sherlock, M.E., Griffiths, A.M. Medical Therapy for Pediatric Inflammatory Bowel Disease. Curr Gastroenterol Rep 14, 166–173 (2012). https://doi.org/10.1007/s11894-012-0249-5

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