Infliximab Therapy for Pediatric Crohn Disease and Ulcerative Colitis

  • Ilse HoffmanEmail author
  • Tania Claeys
  • Séverine Vermeire
  • Gert Van Assche
  • Peter Witters
  • Paul Rutgeerts


The natural history of Crohn disease (CD) and ulcerative colitis (UC) is characterized by recurrent exacerbations interspersed with periods of inactive disease. The goal of therapy should be to induce and maintain clinical remission and strive for endoscopic healing of the intestinal mucosa in order to improve the quality of life. Common complications include failure to thrive and impaired psychosocial development. The advent of infliximab has been very beneficial for pediatric patients suffering from CD and UC. In children and young adolescents, the short-term response and remission rates are high. Infliximab in children with IBD has shown to be steroid sparing and restores growth, two most important goals of therapy in this patient group. Systematic maintenance dosing with infliximab infusions (5 mg/kg) every 8 weeks is superior to episodic therapy or infusions every 12 weeks in maintaining response and remission. The safety profile of infliximab is overall favorable although continued vigilance remains necessary for the occurrence of infrequent but serious events, including opportunistic infection and malignancies, especially in patients with concomitant immunosuppressive treatment.


Inflammatory Bowel Disease Ulcerative Colitis Inflammatory Bowel Disease Patient Ulcerative Colitis Patient Infusion Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Burnham JM, Shults J, Semeao E, et al. Body-composition alterations consistent with cachexia in children and young adults with Crohn disease. Am J Clin Nutr. 2005;82:413–20.PubMedGoogle Scholar
  2. 2.
    Munkholm P, Langholz E, Davidsen M, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn disease. Gut. 1994;35:360–2.PubMedCrossRefGoogle Scholar
  3. 3.
    Faubion Jr WA, Loftus Jr EV, Harmsen WS, et al. The natural ­history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121:255–60.PubMedCrossRefGoogle Scholar
  4. 4.
    Candy S, Wright J, Gerber M, et al. A controlled double blind study of azathioprine in the management of Crohn disease. Gut. 1995;37:674–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Markowitz J, Grancher K, Kohn N, et al. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn disease. Gastroenterology. 2000;119:895–902.PubMedCrossRefGoogle Scholar
  6. 6.
    Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn disease. The North American Crohn Study Group Investigators. N Engl J Med. 1995;332:292–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn ­disease. North American Crohn Study Group Investigators. N Engl J Med. 2000;342:1627–32.PubMedCrossRefGoogle Scholar
  8. 8.
    Moskovitz DN, Van Assche G, Maenhout B, et al. Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis. Clin Gastroenterol Hepatol. 2006;4:760–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Ording Olsen K, Juul S, Berndtsson I, et al. Ulcerative colitis: female fecundity before diagnosis, during disease, and after surgery compared with a population sample. Gastroenterology. 2002;122:15–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Griffiths AM, Ohlsson A, Sherman PM, et al. Meta-analysis of enteral nutrition as a primary treatment of active Crohn disease. Gastroenterology. 1995;108:1056–67.PubMedCrossRefGoogle Scholar
  11. 11.
    Lochs H, Dejong C, Hammarqvist F, et al. ESPEN Guidelines on Enteral Nutrition: Gastroenterology. Clin Nutr. 2006;25:260–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Reinecker HC, Steffen M, Witthoeft T, et al. Enhanced secretion of tumour necrosis factor-alpha IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn disease. Clin Exp Immunol. 1993;94:174–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Nicholls S, Stephens S, Braegger CP, et al. Cytokines in stools of children with inflammatory bowel disease or infective diarrhea. J Clin Pathol. 1993;46:757–60.PubMedCrossRefGoogle Scholar
  14. 14.
    Breese E, Michie C, Nicholls S, et al. Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology. 1994;106:1455–66.PubMedGoogle Scholar
  15. 15.
    Cornillie F, Shealy D, D’Haens G, et al. Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn disease. Aliment Pharmacol Ther. 2001;15:463–73.PubMedCrossRefGoogle Scholar
  16. 16.
    Lugering A, Schmidt M, Lugering N, et al. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn disease by using a caspase-dependent pathway. Gastroenterology. 2001;121:1145–57.PubMedCrossRefGoogle Scholar
  17. 17.
    ten Hove T, van Montfrans C, Peppelenbosch MP, van Deventer SJ. Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn disease. Gut. 2002;50:206–11.PubMedCrossRefGoogle Scholar
  18. 18.
    Van den Brande JM, Braat H, van den Brink GR, et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn disease. Gastroenterology. 2003;124:1774–85.PubMedCrossRefGoogle Scholar
  19. 19.
    Shen C, Maerten P, Geboes K, et al. Infliximab induces apoptosis of monocytes and T lymphocytes in a human-mouse chimeric model. Clin Immunol. 2005;115:250–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Scallon BJ, Moore MA, Trinh H, et al. Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine. 1995;7:251–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn disease. Crohn Disease Study Group. N Engl J Med. 1997;337:1029–35.PubMedCrossRefGoogle Scholar
  22. 22.
    Rutgeerts P, D’Haens G, Targan S, et al. Safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn disease. Gastroenterology. 1999;117:761–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. ACCENT I Study Group. Maintenance infliximab for Crohn disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Rutgeerts P, Diamond RH, Bala M, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn disease. Gastrointest Endosc. 2006;63:433–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn disease. N Engl J Med. 1999;340:1398–405.PubMedCrossRefGoogle Scholar
  26. 26.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn disease. N Engl J Med. 2004;350:934–6.CrossRefGoogle Scholar
  27. 27.
    Van Assche G, Vanbeckevoort D, Bielen D, et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn disease. Am J Gastroenterol. 2003;98:332–9.PubMedCrossRefGoogle Scholar
  28. 28.
    van Bodegraven AA, Sloots CE, Felt-Bersma RJ, Meuwissen SG. Endosonographic evidence of persistence of Crohn disease-associated fistulas after infliximab treatment, irrespective of clinical response. Dis Colon Rectum. 2002;45:39–45. discussion 45–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Bell SJ, Halligan S, Windsor AC, et al. Response of fistulating Crohn disease to infliximab treatment assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2003;17:387–93.PubMedCrossRefGoogle Scholar
  30. 30.
    Kugathasan S. Prolonged duration of response to infliximab in early pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2001;33:S40–43.PubMedCrossRefGoogle Scholar
  31. 31.
    Baldassano R, Braegger CP, Escher JC, et al. Infliximab (REMICADE) therapy in the treatment of pediatric Crohn disease. Am J Gastroenterol. 2003;98:833–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Lamireau T, Cezard JP, Dabadie A, French-Speaking Group for Pediatric Gastroenterology Nutrition, et al. Efficacy and tolerance of infliximab in children and adolescents with Crohn disease. Inflamm Bowel Dis. 2004;10:745–50.PubMedCrossRefGoogle Scholar
  33. 33.
    de Ridder L, Escher JC, Bouquet J, et al. Infliximab therapy in 30 patients with refractory pediatric Crohn disease with and without fistulas in the Netherlands. J Pediatr Gastroenterol Nutr. 2004;39:46–52.PubMedCrossRefGoogle Scholar
  34. 34.
    Borrelli O, Bascietto C, Viola F, et al. Infliximab heals intestinal inflammatory lesions and restores growth in children with Crohn disease. Dig Liver Dis. 2004;36:342–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Cezard JP, Nouaili N, Talbotec C, et al. A prospective study of the efficacy and tolerance of a chimeric antibody to tumor necrosis factors (remicade) in severe pediatric crohn disease. J Pediatr Gastroenterol Nutr. 2003;36:632–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Wewer V, Riis L, Vind I, et al. Infliximab dependency in a national cohort of children with Crohn disease. J Pediatr Gastroenterol Nutr. 2006;42:40–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Hyams J, Crandall W, Kugathasan S, et al. Maintenance therapy with infliximab every 8 weeks is superior to every 12 weeks in maintaining response and remission in pediatric patients with moderately to severely active Crohn disease. Gastroenterology. 2007;132(3):863–73.Google Scholar
  38. 38.
    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;132:863–73.PubMedCrossRefGoogle Scholar
  39. 39.
    Hyams J, Lerer T, et al. Long-term outcome of maintenace infliximab therapy in children with Crohn’s desease. Inflamm Bowel Dis. 2009;15:816–22.PubMedCrossRefGoogle Scholar
  40. 40.
    Hyams J, Walters TD, et al. Safety and efficacy of maintenance infliximab therapy for moderate to severe Crohn’s disease in children: REACH open-label extension. Curr Med Res Opin. 2011;27(3):651–62.PubMedCrossRefGoogle Scholar
  41. 41.
    Griffiths A, Hyams J, Crandall W, et al. Height and growth delayed children with active Crohn disease improves during treatment with infliximab. Gastroenterol 2009;48(2):168–74.Google Scholar
  42. 42.
    Thayu M, Leonard M, et al. Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn’s disease: results of the REACH. Clin Gastroenterol Hepatol. 2008;6:1378–84.PubMedCrossRefGoogle Scholar
  43. 43.
    Pfefferkorn M, Nurke G, et al. Growth abnormalities persist in newly diagnosed children with crohn disease despite current treatment paradigms. J Pediatr Gastroenterol Nutr. 2009;48:168–74.PubMedCrossRefGoogle Scholar
  44. 44.
    Stephens MC, Shepanski MA, Mamula P, et al. Safety and steroid-sparing experience using infliximab for Crohn disease at a pediatric inflammatory bowel disease center. Am J Gastroenterol. 2003;98:104–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Markowitz J, Hyams J, Mack D, Pediatric IBD Collaborative Research Group, et al. Corticosteroid therapy in the age of infliximab: acute and 1-year outcomes in newly diagnosed children with Crohn Disease. Clin Gastroenterol Hepatol. 2006;4(9):1124–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Punati J, Markowitz J, et al. Effect of early immunomodulator use in moderate to severe pediatric Crohn disease. Inflamm Bowel Dis. 2008;14:949–54.PubMedCrossRefGoogle Scholar
  47. 47.
    Lionetti P, Bronzini F, Salvestrini C, et al. Response to infliximab is related to disease duration in pediatric Crohn disease. Aliment Pharmacol Ther. 2003;18:425–31.PubMedCrossRefGoogle Scholar
  48. 48.
    Butcher S, Chahel H, Lord JM. Aging and the neutrophil: no appetite for killing? Immunology. 2000;100:411–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Vermeire S, Louis E, Carbonez A, Belgian Group of Infliximab Expanded Access Program in Crohn Disease, et al. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn disease. Am J Gastroenterol. 2002;97:2357–63.PubMedCrossRefGoogle Scholar
  50. 50.
    Parsi MA, Achkar JP, Richardson S, et al. Predictors of response to infliximab in patients with Crohn disease. Gastroenterology. 2002;123:707–13.PubMedCrossRefGoogle Scholar
  51. 51.
    Arnott ID, McNeill G, Satsangi J. An analysis of factors influencing short-term and sustained response to infliximab treatment for Crohn disease. Aliment Pharmacol Ther. 2003;17:1451–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Mortimore M, Gibson PR, Selby WS, et al. Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The Infliximab User Group. Intern Med J. 2001;31:146–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Hommes D, Baert F, Van Assche G, et al. A randomized controlled trial evaluating the ideal medical management for Crohn disease (CD): top-down versus step-up strategies. Gastroenterology. 2005;128:A-577.Google Scholar
  54. 54.
    Romeo E, Viola F, et al. Infliximab as a first choice therapy in children with newly diagnosed Crohn’s disease promotes long-term sustained remission and alters course of the disease. Gastroenterology. 2006;130(4 Suppl 2). abstr 11.Google Scholar
  55. 55.
    Kim M, Lee J, et al. Infliximab therapy in children with Crohn’s disease: a one-year evaluation of efficacy comparing ‘top-down’ and ‘step-up’ strategies. Acta pediatrica. 2011;100:451–5.CrossRefGoogle Scholar
  56. 56.
    Gupta N, Cohen SA, Bostrom AG, et al. Risk factors for initial surgery in pediatric patients with Crohn disease. Gastroenterology. 2006;130:1069–77.PubMedCrossRefGoogle Scholar
  57. 57.
    Schaeffer M, Machan J, et al. Factors that determine risk for surgery in pediatric patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2010;8:789–94.CrossRefGoogle Scholar
  58. 58.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.PubMedCrossRefGoogle Scholar
  59. 59.
    Hyams JS, Lerer T, Griffiths A, et al. Outcome following infliximab therapy in children with ulcerative colitis. Am J Gastroenterol. 2010;105(6):1430–6.PubMedCrossRefGoogle Scholar
  60. 60.
    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.PubMedCrossRefGoogle Scholar
  61. 61.
    Hyams J, Damaraju L, Blank M, et al. Induction and Maintenance Therapy With Infliximab for Children With Moderate to Severe Ulcerative Colitis. Clin Gastroenterol Hepatol. 2012;10(4):391–9.e1.PubMedCrossRefGoogle Scholar
  62. 62.
    Jarnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005;128:1805–11.PubMedCrossRefGoogle Scholar
  63. 63.
    Baert F, Noman M, Vermeire S, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn disease. N Engl J Med. 2003;348:601–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn disease. Gastroenterology. 2004;126:402–13.PubMedCrossRefGoogle Scholar
  65. 65.
    Friesen CA, Calabro C, Christenson K, et al. Safety of infliximab treatment in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2004;39:265–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Fidder H, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut. 2009;58(4):501–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Deslandres C, Faure C, Dirks M, et al. Open label experience with adalimumab in pediatric Crohn disease patients who lost response or were intolerant to infliximab. Gastroenterol. 2006;Suppl. 2006:AW1199.Google Scholar
  68. 68.
    Vermeire S, Noman M, Van Assche G, et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn disease: a prospective cohort study. Gastroenterology. 2003;125:32–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345:1098–104.PubMedCrossRefGoogle Scholar
  70. 70.
    Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–30.PubMedCrossRefGoogle Scholar
  71. 71.
    Toruner M, Loftus Jr EV, Harmsen WS, et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008;134(4):929–36.PubMedCrossRefGoogle Scholar
  72. 72.
    Lawrance IC, Radford-Smith GL, Bampton PA, et al. Serious infections in patients with inflammatory bowel disease receiving anti-tumor-necrosis-factor-alpha therapy: an Australian and New Zealand experience. J Gastroenterol Hepatol. 2010;25(11):1732–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Van Assche G, Paintaud G, D’Haens G, Baert F, Vermeire S, Noman M, et al. Continuation of immunomodulators is not required to maintain adequate infliximab efficacy in patients with Crohn disease but may improve pharmacokinetics. Gastroenterol Suppl. 2006;130:A-142.Google Scholar
  74. 74.
    Mahadevan U, Cucchiara S, Hyams JS, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn’s and Colitis Organisation: pregnancy and pediatrics. Am J Gastroenterol. 2011;106(2):214–23.PubMedCrossRefGoogle Scholar
  75. 75.
    Diak P, Siegel J, La Grenade L, et al. Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum. 2010;62(8):2517–24.PubMedCrossRefGoogle Scholar
  76. 76.
    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.PubMedCrossRefGoogle Scholar
  77. 77.
    Caspersen S, Elkjaer M, Riis L, et al. Infliximab for inflammatory bowel disease in Denmark 1999–2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin Gastroenterol Hepatol. 2008;6(11):1212–7.PubMedCrossRefGoogle Scholar
  78. 78.
    O’Donnell S, Murphy S, Anwar MM, et al. Safety of infliximab in 10 years of clinical practice. Eur J Gastroenterol Hepatol. 2011;23(7):603–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Wong AK, Kerkoutian S, Said J, et al. Risk of lymphoma in patients receiving antitumor necrosis factor therapy: a meta-­analysis of published randomized controlled studies. Clin Rheumatol. 2012;31(4):631–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Girolomoni G, Altomare G, Ayala F, et al. Safety of anti-TNF agents in the treatment of psoriasis and psoriatic arthritis. Immunopharmacol Immunotoxicol. 2012;34:548–60.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ilse Hoffman
    • 1
    Email author
  • Tania Claeys
    • 1
  • Séverine Vermeire
    • 2
  • Gert Van Assche
    • 2
  • Peter Witters
    • 1
  • Paul Rutgeerts
    • 2
  1. 1.Department of Pediatric GastroenterologyUniversity Hospital LeuvenLeuvenBelgium
  2. 2.Department of Medicine, Department of GastroenterologyUniversity Hospital LeuvenLeuvenBelgium

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