Current Gastroenterology Reports

, Volume 10, Issue 3, pp 302–307 | Cite as

Alternative strategies for the use of infliximab in pediatric inflammatory bowel disease



Infliximab is approved for the induction and 1-year maintenance of remission in pediatric Crohn’s disease unresponsive to conventional therapy. Despite significant experience with the use of this agent in children and adolescents who have inflammatory bowel disease, many questions about its optimal use remain. Recent safety concerns raised debate over the common practice of using infliximab in combination with conventional immunomodulatory agents. Additionally, although regularly scheduled administration maintains remission more effectively than episodic therapy, it is not known whether all patients who start infliximab must continue it for maintenance. Some patients may be able to use infliximab for induction and another agent for maintenance. Finally, the optimal placement of infliximab in the algorithm for the medical treatment of pediatric inflammatory bowel disease remains an open question.


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References and Recommended Reading

  1. 1.
    Turunen P, Kolho KL, Auvinin A, et al.: Incidence of inflammatory bowel disease in Finnish children, 1987–2003. Inflamm Bowel Dis 2006, 12:677–683.PubMedCrossRefGoogle Scholar
  2. 2.
    Baldassano R, Ferry G, Griffiths A, et al.: Transition of the patient with inflammatory bowel disease from pediatric to adult care: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2002, 34:245–248.PubMedCrossRefGoogle Scholar
  3. 3.
    Faubion WA Jr, Loftus EV Jr, Harmsen WS, et al.: The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 2001, 121:255–260.PubMedCrossRefGoogle Scholar
  4. 4.
    Markowitz J, Hyams J, Mack D, et al.: Corticosteroid therapy in the age of infliximab: acute and 1-year outcomes in newly diagnosed children with Crohn’s disease. Clin Gastroenterol Hepatol 2006, 4:1124–1129.PubMedCrossRefGoogle Scholar
  5. 5.
    Hyams J, Markowitz J, Lerer T, et al.: The natural history of corticosteroid therapy for ulcerative colitis in children. Clin Gastroenterol Hepatol 2006, 3:1118–1123.CrossRefGoogle Scholar
  6. 6.
    Day AS, Whitten KE, Sidler M, Lemberg DA: Systematic review: nutritional therapy in paediatric Crohn’s disease. Aliment Pharmacol Ther 2007, 27:293–307.PubMedCrossRefGoogle Scholar
  7. 7.
    Kornbluth A, Sachar DB: Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 1997, 92:204–211.PubMedGoogle Scholar
  8. 8.
    Cottone M, Camma C: Mesalamine and relapse prevention in Crohn’s disease. Gastroenterology 2000, 119:597.PubMedGoogle Scholar
  9. 9.
    Markowitz J, Grancher K, Kohn N, et al.: A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology 2000, 119:895–902.PubMedCrossRefGoogle Scholar
  10. 10.
    Kirschner B: Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease. Gastroenterology 1998, 115:813–821.PubMedCrossRefGoogle Scholar
  11. 11.
    Fegan BG, Fedorak RN, Irvine EJ, et al.: A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s disease. North American Crohn’s Study Group Investigators. N Engl J Med 2000, 342:1627–1632.CrossRefGoogle Scholar
  12. 12.
    Fegan BG, Rochon J, Fedorak RN, et al.: Methotrexate for the treatment of Crohn’s disease. The North American Crohn’s Study Group Investigators. N Engl J Med 1995, 332:330–331.CrossRefGoogle Scholar
  13. 13.
    Uhlen S, Belbouab R, Narebski K, et al.: Efficacy of methotrexate in pediatric Crohn’s disease: a French multicenter study. Inflamm Bowel Dis 2006, 12:1053–1057.PubMedCrossRefGoogle Scholar
  14. 14.
    Turner D, Grossman AB, Rosh JR, et al.: Methotrexate following unsuccessful thiopurine therapy in pediatric Crohn’s disease. Am J Gastroenterol 2007, 102:2804–2812.PubMedCrossRefGoogle Scholar
  15. 15.
    Ten Hove T, van Montfrans C, Peppelenbosch MP, et al.: Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn’s disease. Gut 2003, 50:206–211.CrossRefGoogle Scholar
  16. 16.
    Baumgart DC, Sandborn WJ: Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007, 369:1641–1657.PubMedCrossRefGoogle Scholar
  17. 17.
    Derkx B, Taminiau J, Radema S, et al.: Tumor-necrosis-factor antibody treatment in Crohn’s disease. Lancet 1993, 342:173–174.PubMedCrossRefGoogle Scholar
  18. 18.
    De Ridder L, Benninga MA, Taminiau J, et al.: Infliximab use in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2007, 45:3–14.PubMedCrossRefGoogle Scholar
  19. 19.
    Sands BE, Anderson FH, Bernstein CN, et al.: Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004, 350:934–936.CrossRefGoogle Scholar
  20. 20.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al.: Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet 2002, 359:1541–1549.PubMedCrossRefGoogle Scholar
  21. 21.
    Rutgeerts P, Van Assche G, Vermeire S: Review article: infliximab therapy for inflammatory bowel disease—seven years on. Aliment Pharmacol Ther 2006, 23:451–463.PubMedCrossRefGoogle Scholar
  22. 22.
    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, 132:863–873.PubMedCrossRefGoogle Scholar
  23. 23.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al.: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005, 353:2462–2476.PubMedCrossRefGoogle Scholar
  24. 24.
    Remicade (infliximab) for IV injection (package insert). Malvern, PA: Centocor; 2007.Google Scholar
  25. 25.
    Rutgeerts P, Feagan BG, Lichtenstein GR: Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology 2004, 126:402–413.PubMedCrossRefGoogle Scholar
  26. 26.
    Kevans D, Keegan D, Mulcahy HE, O’Donoghue DP: Infliximab therapy in Crohn’s disease: a pragmatic approach? Aliment Pharmacol Ther 2006, 24:351–359.PubMedCrossRefGoogle Scholar
  27. 27.
    Lemann M, Mary JY, Duclos B, et al.: Infliximab plus azathioprine for steroid dependant Crohn’s disease patients: a randomized placebo-controlled trial. Gastroenterology 2006, 130:1054–1061.PubMedCrossRefGoogle Scholar
  28. 28.
    Feldman T, Youssef NN, Irizarry R, Rosh JR: Infliximab as an induction agent versus ongoing maintenance therapy in mild-moderate pediatric Crohn’s disease [abstract]. Gastroenterology 2007, 2069:A444.Google Scholar
  29. 29.
    Chaudhary R, Butler M, Playford R, et al.: Combination immunomodulatory therapy with infliximab increases mononuclear cell apoptosis in-vitro compared to infliximab alone. Gastroenterology 2005:A149.Google Scholar
  30. 30.
    Roblin X, Serre-Debeauvais F, Phelip JM, et al.: Drug interaction between infliximab and azathioprine in patients with Crohn’s disease. Aliment Pharmacol Ther 2003, 18:917–925.PubMedCrossRefGoogle Scholar
  31. 31.
    Klotz U, Teml A, Schwab M: Clinical pharmacokinetics and use of infliximab. Clin Pharmacokinet 2007, 46:645–660.PubMedCrossRefGoogle Scholar
  32. 32.
    Hanauer SB, Wager CL, Bala M, et al.: Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2004, 2:542–543.PubMedCrossRefGoogle Scholar
  33. 33.
    Rutgeerts P, Feagan BG, Lichtenstein GR: Comparison of scheduled and episodic treatment strategies of infliximab in Crohn’s disease. Gastroenterology 2004, 126:402–413.PubMedCrossRefGoogle Scholar
  34. 34.
    Faffell RJ, Alsahli M, Jeen T, et al.: Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 2003, 124:917–924.CrossRefGoogle Scholar
  35. 35.
    Vermeire S, Noman M, Van Assche GV, et al.: Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut 2007, 56:1226–1231.PubMedCrossRefGoogle Scholar
  36. 36.
    Van Assche G, Paintaud G, Magdelaine C, et al.: Concomitant immunosuppression does not impact on the outcome of maintenance infliximab therapy in Crohn’s disease [abstract]. Gastroenterology 2007, 132:A103.CrossRefGoogle Scholar
  37. 37.
    Kugathasan S, Ehlert R, Stephens MC, et al.: Immunomodulators are not required to maintain efficacy with infliximab in pediatric inflammatory bowel disease [abstract]. Gastroenterology 2007, 132:A443.Google Scholar
  38. 38.
    Colombel JF, Sandborn WJ, Rutgeerts P, et al.: Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: The CHARM trial. Gastroenterology 2007, 132:52–65.PubMedCrossRefGoogle Scholar
  39. 39.
    Sandborn WJ, Rutgeerts P, Enns SB, et al.: Adalimumab induction therapy for Crohn disease previously treated with infliximab. A randomized trial. Ann Intern Med 2007, 146:829–838.PubMedGoogle Scholar
  40. 40.
    Kandiel A, Fraser AG, Korelitz BI, et al.: Increased risk of lymphoma in among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005, 54:1121–1125.PubMedCrossRefGoogle Scholar
  41. 41.
    Khanna D, McMahon M, Furst DE: Safety of tumor necrosis factor-alpha antagonists. Drug Saf 2004, 27:307–324.PubMedCrossRefGoogle Scholar
  42. 42.
    Mackey AC, Green L, Liang LC, et al.: Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2007, 44:265–267.PubMedCrossRefGoogle Scholar
  43. 43.
    Rosh JR, Gross T, Mamula P, et al.: Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn disease: a cautionary tale? Inflamm Bowel Dis 2007, 13:1024–1030.PubMedCrossRefGoogle Scholar
  44. 44.
    Cosnes J, Nion-Larmurier I, Beaugerie L, et al.: Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery. Gut 2005, 54:237–241.PubMedCrossRefGoogle Scholar
  45. 45.
    Kugathasan S, Werlin SL, Martinez A, et al.: Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol 2000, 95:3189–3194.PubMedCrossRefGoogle Scholar
  46. 46.
    D’Haens G, Baert F, van Assche G, et al.: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 2008, 371:660–667.PubMedCrossRefGoogle Scholar
  47. 47.
    Romeo E, Viola F, De Angelis G, et al.: Infliximab as a first choice therapy in children with newly diagnosed Crohn’s disease (CD) promotes long-term sustained remission and alters the course of the disease. Gastroenterology 2006, 130:A142.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Pediatric GastroenterologyGoryeb Children’s Hospital at Atlantic HealthMorristownUSA

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