Pediatric Drugs

, Volume 8, Issue 5, pp 279–302

Current Therapy of Inflammatory Bowel Disease in Children

Therapy In Practice


Ulcerative colitis (UC) and Crohn disease (CD) are chronic intestinal inflammatory diseases that can present as bloody diarrhea, abdominal pain, and malnutrition. Collectively, these disorders are referred to as inflammatory bowel disease (IBD). All patients with IBD share a common pathophysiology. However, there are a number of developmental, psychosocial, and physiologic issues that are unique to the ≈20% of patients that present during childhood or adolescence. These include the possibility of disease-induced delays in linear growth or physical development, differences in drug dosing, and the changes in social and cognitive development that occur as children move from school-age years into adolescence and early adulthood. Gastroenterologists caring for these children must therefore develop an optimal regimen of pharmacologic therapies, nutritional management, psychologic support, and properly timed surgery (when necessary) that will maintain disease remission, minimize disease and drug-induced adverse effects, and optimize growth and development. This article reviews current approaches to the management of patients with UC and CD and highlights issues specific to the treatment of children with IBD.

The principal medical therapies used to induce disease remission in patients with UC are aminosalicylates (for mild disease), corticosteroids (for moderate disease), and cyclosporine (ciclosporin) [for severe disease]. If a patient responds to the induction regimen, maintenance therapies that are used to prevent disease relapse include aminosalicylates, mercaptopurine, and azathioprine. Colectomy with creation of an ileal pouch anal anastomosis (J pouch) has become the standard of care for patients with severe or refractory colitis and results in an improved quality of life in most patients. Therefore, the risks associated with using increasingly potent immunosuppressant agents must be balanced in each case against a patient’s desire to retain their colon and avoid a temporary or potentially permanent ileostomy.

Decisions about drug therapy in the management of patients with CD are more complex and depend on both the location (e.g. gastroduodenal vs small intestinal vs colonic), as well as the behavior of the disease (inflammatory/mucosal vs stricturing vs perforating) in a given patient. Induction therapies for CD typically include aminosalicylates and antibiotics (for mild mucosal disease), nutritional therapy (including elemental or polymeric formulas), corticosteroids (for moderate disease), and infliximab (for corticosteroid-resistant or fistulizing disease). Aminosalicylates, mercaptopurine, azathioprine, methotrexate, and infliximab can be used as maintenance therapies. Because surgical treatment of CD is not curative, it is typically reserved for those patients either with persistent symptoms and disease limited to a small section of the intestine (e.g. the terminal ileum and cecum) or for the management of complications of the disease including stricture or abdominal abscess. When surgery is necessary, maintenance medications administered postoperatively will postpone recurrence.

Patients with UC and CD are at risk for the development of micronutrient deficiencies (including folate, iron, and vitamin D deficiencies) and require close nutritional monitoring. In addition, patients with UC and CD involving the colon are at increased risk of developing colon cancer, and should be enrolled into a colonoscopy surveillance program after 8–10 years of disease duration.


  1. 1.
    Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998; 115(1): 182–205PubMedCrossRefGoogle Scholar
  2. 2.
    Mathew CG, Lewis CM. Genetics of inflammatory bowel disease: progress and prospects. Hum Mol Genet 2004; 13Suppl. 1: R161–8PubMedCrossRefGoogle Scholar
  3. 3.
    Girardin SE, Travassos LH, Herve M, et al. Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J Biol Chem 2003; 278(43): 41702–8PubMedCrossRefGoogle Scholar
  4. 4.
    Logan RF. Inflammatory bowel disease incidence: up, down or unchanged? Gut 1998; 42(3): 309–11PubMedCrossRefGoogle Scholar
  5. 5.
    Calkins BM. A meta-analysis of the role of smoking in inflammatory bowel disease. Dig Dis Sci 1989; 34(12): 1841–54PubMedCrossRefGoogle Scholar
  6. 6.
    Kugathasan S, Judd RH, Hoffman RG, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr 2003; 143: 525–31PubMedCrossRefGoogle Scholar
  7. 7.
    Bousvaros A, Murray K, Leichtner A. Clinical manifestations and diagnosis of Crohn’s disease in children and adolescents [online]. Available from URL: [Accessed 2006 Sep 27]
  8. 8.
    Kane SV, Sandborn WJ, Rufo PA, et al. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol 2003; 98(6): 1309–14PubMedCrossRefGoogle Scholar
  9. 9.
    Poullis A, Foster R, Shetty A, et al. Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2004; 13(2): 279–84PubMedCrossRefGoogle Scholar
  10. 10.
    Tibble J, Teahon K, Thjodleifsson B, et al. A simple method for assessing intestinal inflammation in Crohn’s disease. Gut 2000; 47(4): 506–13PubMedCrossRefGoogle Scholar
  11. 11.
    Vaishnavi C, Bhasin DK, Singh K. Fecal lactoferrin assay as a cost-effective tool for intestinal inflammation. Am J Gastroenterol 2000; 95(10): 3002–3PubMedCrossRefGoogle Scholar
  12. 12.
    Kayazawa M, Saitoh O, Kojima K, et al. Lactoferrin in whole gut lavage fluid as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol 2002; 97(2): 360–9PubMedCrossRefGoogle Scholar
  13. 13.
    van der Sluys Veer A, Biemond I, Verspaget HW, et al. Faecal parameters in the assessment of activity in inflammatory bowel disease. Scand J Gastroenterol Suppl 1999; 230: 106–10PubMedGoogle Scholar
  14. 14.
    Sugi K, Saitoh O, Hirata I, et al. Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol 1996; 91(5): 927–34PubMedGoogle Scholar
  15. 15.
    Bousvaros A, Leichtner A. Overview of the management of Crohn’s disease in children and adolescents [online]. Available from URL: [Accessed 2006 Sep 27]
  16. 16.
    Kornbluth AA, Salomon P, Sacks HS, et al. Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis. J Clin Gastroenterol 1993; 16: 215–8PubMedCrossRefGoogle Scholar
  17. 17.
    Crohn’s and Colitis Foundation of America. Medications for inflammatory bowel disease, 2003 [online]. Available from URL: [Accessed 2006 Sep 27]
  18. 18.
    Ferry GD, Kirschner BS, Grand RJ, et al. Olsalzine versus sulfasalazine in mild to moderate childhood ulcerative colitis: results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial. J Pediatr Gastroenterol Nutr 1993; 17: 32–8PubMedCrossRefGoogle Scholar
  19. 19.
    Pruitt R, Hanson J, Safdi M, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis. Am J Gastroenterol 2002; 97(12): 3078–86PubMedCrossRefGoogle Scholar
  20. 20.
    Green JR, Lobo AJ, Holdsworth CD, et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis: the Abacus Investigator Group. Gastroenterology 1998; 114(1): 15–22PubMedCrossRefGoogle Scholar
  21. 21.
    Gilat T, Suissa A, Leichtman G, et al. A comparative study of metronidazole and sulfasalazine in active, not severe, ulcerative colitis: an Israeli multicenter trial. J Clin Gastroenterol 1987; 9(4): 415–7PubMedCrossRefGoogle Scholar
  22. 22.
    Davies PS, Rhodes J, Heatley RV, et al. Metronidazole in the treatment of chronic proctitis: a controlled trial. Gut 1977; 18(8): 680–1PubMedCrossRefGoogle Scholar
  23. 23.
    Gilat T, Leichtman G, Delpre G, et al. A comparison of metronidazole and sulfasalazine in the maintenance of remission in patients with ulcerative colitis. J Clin Gastroenterol 1989; 11(4): 392–5PubMedCrossRefGoogle Scholar
  24. 24.
    Turunen U, Farkkila MA, Valtonen V. Long-term treatment of ulcerative colitis with ciprofloxacin. Gastroenterology 1999; 117(1): 282–3PubMedGoogle Scholar
  25. 25.
    Rowe FA, Walker JH, Karp LC, et al. Factors predictive of response to cyclosporine treatment for severe, steroid resistant ulcerative colitis. Am J Gastroenterol 2000; 95(8): 2000–8PubMedCrossRefGoogle Scholar
  26. 26.
    Werlin SL, Grand R. Severe colitis in children and adolescents: diagnosis, course, treatment. Gastroenterology 1977; 73: 828–32PubMedGoogle Scholar
  27. 27.
    Lichtiger S, Present DH. Preliminary report: cyclosporin in treatment of severe active ulcerative colitis. Lancet 1990; 336: 16–9PubMedCrossRefGoogle Scholar
  28. 28.
    Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994; 330: 1841–5PubMedCrossRefGoogle Scholar
  29. 29.
    Van Assche G, D’Haens G, Noman M, et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology 2003; 125(4): 1025–31PubMedCrossRefGoogle Scholar
  30. 30.
    Actis GC, Aimo G, Priolo G, et al. Efficacy and efficiency of oral microemulsion cyclosporin versus intravenous and soft gelatin capsule cyclosporin in the treatment of severe steroid-refractory ulcerative colitis: an open-label retrospective trial. Inflamm Bowel Dis 1998; 4(4): 276–9PubMedGoogle Scholar
  31. 31.
    Naftali T, Novis B, Pomeranz I, et al. Cyclosporine treatment for severe ulcerative colitis. Isr Med Assoc J 2000; 2: 588–91PubMedGoogle Scholar
  32. 32.
    Treem WR, Davis PM, Hyams JS. Cyclosporine treatment of severe ulcerative colitis in children. J Pediatr 1991; 119(6): 994–7PubMedCrossRefGoogle Scholar
  33. 33.
    Barabino A, Torrente F, Castellano E, et al. The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience. Aliment Pharmacol Ther 2002; 16(8): 1503–7PubMedCrossRefGoogle Scholar
  34. 34.
    Cohn RD, Stein R, Hanauer SB. Intravenous cyclosporine in ulcerative colitis: a five-year experience. Am J Gastroenterol 1999; 94(6): 1587–92CrossRefGoogle Scholar
  35. 35.
    Carbonnel F, Boruchowicz A, Duclos B, et al. Intravenous cyclosporine in attacks of ulcerative colitis: short-term and long-term responses. Dig Dis Sci 1996; 41(12): 2471–6PubMedCrossRefGoogle Scholar
  36. 36.
    Bousvaros A, Wang A, Leichtner AM. Tacrolimus (FK-506) treatment of fulminant colitis in a child. J Pediatr Gastroenterol Nutr 1996; 23(3): 329–33PubMedCrossRefGoogle Scholar
  37. 37.
    Bousvaros A, Kirschner BS, Werlin SL, et al. Oral tacrolimus treatment of severe colitis in children. J Pediatr 2000; 137(6): 794–9PubMedCrossRefGoogle Scholar
  38. 38.
    Fellermann K, Tanko Z, Herrlinger KR, et al. Response of refractory colitis to intravenous or oral tacrolimus (FK506). Inflamm Bowel Dis 2002; 8(5): 317–24PubMedCrossRefGoogle Scholar
  39. 39.
    Hogenauer C, Wenzl HH, Hinterleitner TA, et al. Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis. Aliment Pharmacol Ther 2003; 18(4): 415–23PubMedCrossRefGoogle Scholar
  40. 40.
    Baumgart DC, Wiedenmann B, Dignass AU. Rescue therapy with tacrolimus is effective in patients with severe and refractory inflammatory bowel disease. Aliment Pharmacol Ther 2003; 17(10): 1273–81PubMedCrossRefGoogle Scholar
  41. 41.
    Ogata II, Matsui T, Nakamura M, et al. A randomized dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006 Sep; 55(9): 1255–62PubMedCrossRefGoogle Scholar
  42. 42.
    Cohen RD, Stein R, Hanauer SB. Intravenous cyclosporin in ulcerative colitis: a five-year experience. Am J Gastroenterol 1999; 94(6): 1587–92PubMedCrossRefGoogle Scholar
  43. 43.
    Rutgeerts P, Sandborn WJ, Feagan B, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005 Dec 8; 353(23): 2462–76PubMedCrossRefGoogle Scholar
  44. 44.
    Mamula P, Markowitz JE, Brown KA, et al. Infliximab as a novel therapy for pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2002; 34(3): 307–11PubMedCrossRefGoogle Scholar
  45. 45.
    Russell GH, Katz AJ. Infliximab is effective in acute but not chronic childhood ulcerative colitis. J Pediatr Gastroenterol Nutr 2004 Aug; 39(2): 166–70PubMedCrossRefGoogle Scholar
  46. 46.
    Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol 1997; 92: 204–11PubMedGoogle Scholar
  47. 47.
    Marshall JK, Irvine EJ. Rectal aminosalicylate therapy for distal ulcerative colitis: a meta-analysis. Aliment Pharmacol Ther 1995; 9(3): 293–300PubMedCrossRefGoogle Scholar
  48. 48.
    D’Arienzo A, Panarese A, D’Armiento FP, et al. 5-aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. Am J Gastroenterol 1990; 85(9): 1079–82PubMedGoogle Scholar
  49. 49.
    Vecchi M, Meucci G, Gionchetti P, et al. Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind, double-dummy, randomized multicentre study. Aliment Pharmacol Ther 2001; 15(2): 251–6PubMedCrossRefGoogle Scholar
  50. 50.
    Hanauer SB, Robinson M, Pruitt R, et al. Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. US Budesonide Enema Study Group. Gastroenterology 1998; 115(3): 525–32PubMedCrossRefGoogle Scholar
  51. 51.
    Danielsson A, Hellers G, Lyrenas E, et al. A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Scand J Gastroenterol 1987; 22(8): 987–92PubMedCrossRefGoogle Scholar
  52. 52.
    Marshall JK, Irvine EJ. Rectal corticosteroids versus alternative treatments in ulcerative colitis: a meta-analysis. Gut 1997; 40(6): 775–81PubMedCrossRefGoogle Scholar
  53. 53.
    Lee FL, Jewell DP, Mani V, et al. A randomized trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis. Gut 1996; 38: 229–33PubMedCrossRefGoogle Scholar
  54. 54.
    Sandborn WJ, Tremaine WJ, Schroeder KW, et al. A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis. Gastroenterology 1994; 106: 1429–35PubMedGoogle Scholar
  55. 55.
    Sutherland L, Roth D, Beck P, et al. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2002; (4): CD000544Google Scholar
  56. 56.
    Sutherland LR, Roth DE, Beck PL. Alternatives to sulfasalazine: a meta-analysis of 5-ASA in the treatment of ulcerative colitis. Inflamm Bowel Dis 1997; 3: 65–78PubMedGoogle Scholar
  57. 57.
    Ferry GD. Aminosalicylates in the treatment of children with inflammatory bowel disease: summary of the workshop on aminosalicylate pharmacology. Inflamm Bowel Dis 1998; 4(2): 113–4PubMedCrossRefGoogle Scholar
  58. 58.
    Biddle WL, Greenberger NJ, Swan JT, et al. 5-aminosalicylic acid enemas: effective agent in maintaining remission in left-sided ulcerative colitis. Gastroenterology 1988; 94: 1075–9PubMedGoogle Scholar
  59. 59.
    d’Albasio G, Trallori G, Ghetti A, et al. Intermittent therapy with high dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis. Dis Colon Rectum 1990; 33: 394–7PubMedCrossRefGoogle Scholar
  60. 60.
    d’Albasio G, Pacini F, Camarri E, et al. Combined therapy with 5-aminosalicylic acid tablets and enemas for maintaining remission in ulcerative colitis: a randomized double-blind study. Am J Gastroenterol 1997; 92: 1143–7PubMedGoogle Scholar
  61. 61.
    George J, Present DH, Pou R. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine. Am J Gastroenterol 1996; 91(9): 1711–4PubMedGoogle Scholar
  62. 62.
    Kader HA, Mascarenhas MR, Piccoli DA, et al. Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis. J Pediatr Gastroenterol Nutr 1999; 28(1): 54–8PubMedCrossRefGoogle Scholar
  63. 63.
    Verhave M, Winter HS, Grand RJ. Azathioprine in the treatment of children with inflammatory bowel disease. J Pediatr 1990; 117(5): 809–14PubMedCrossRefGoogle Scholar
  64. 64.
    Seidman EG. Clinical use and practical application of TPMT enzyme and 6-mercaptopurine metabolite monitoring in IBD. Rev Gastroenterol Disord 2003; 3Suppl. 1: S30–8PubMedGoogle Scholar
  65. 65.
    Dubinsky MC, Lamothe S, Yang HY, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118(4): 705–13PubMedCrossRefGoogle Scholar
  66. 66.
    Farrell RJ, Peppercorn MA. Medical management of Crohn’s disease in adults [online]. Available from URL: [Accessed 2006 Sep 27]
  67. 67.
    Escher JC, Taminiau JA, Nieuwenhuis EE, et al. Treatment of inflammatory bowel disease in childhood: best available evidence. Inflamm Bowel Dis 2003; 9(1): 34–58PubMedCrossRefGoogle Scholar
  68. 68.
    Griffiths AM, Ohlsson A, Sherman PM, et al. Meta-analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology 1995; 108(4): 1056–67PubMedCrossRefGoogle Scholar
  69. 69.
    Heuschkel RB, Menache CC, Megerian JT, et al. Enteral nutrition and corticosteroids in the treatment of acute Crohn’s disease in children. J Pediatr Gastroenterol Nutr 2000; 31(1): 8–15PubMedCrossRefGoogle Scholar
  70. 70.
    Griffiths AM. Enteral nutrition: the neglected primary therapy of active Crohn’s disease. J Pediatr Gastroenterol Nutr 2000; 31(1): 3–5PubMedCrossRefGoogle Scholar
  71. 71.
    Yang YX, Lichtenstein GR. Corticosteroids in Crohn’s disease. Am J Gastroenterol 2002; 97(4): 803–23PubMedCrossRefGoogle Scholar
  72. 72.
    Afzal NA, Van Der Zaag-Loonen HJ, Arnaud-Battandier F, et al. Improvement in quality of life of children with acute Crohn’s disease does not parallel mucosal healing after treatment with exclusive enteral nutrition. Aliment Pharmacol Ther 2004; 20(2): 167–72PubMedCrossRefGoogle Scholar
  73. 73.
    Singleton JW, Hanauer SB, Gitnick GL, et al. Mesalamine capsules for the treatment of active Crohn’s disease: results of a 16-week trial. Pentasa Crohn’s Disease Study Group. Gastroenterology 1993; 104(5): 1293–301PubMedGoogle Scholar
  74. 74.
    Messori A, Brignola C, Trallori G, et al. Effectiveness of 5-aminosalicylic acid for maintaining remission in patients with Crohn’s disease: a meta-analysis. Am J Gastroenterol 1994; 89(5): 692–8PubMedGoogle Scholar
  75. 75.
    Hildebrand H, Berg NO, Hoevels J, et al. Treatment of Crohn’s disease with metronidazole in childhood and adolescence: evaluation of a six months trial. Gastroenterol Clin Biol 1980; 4(1): 19–25PubMedGoogle Scholar
  76. 76.
    Ursing B, Alm T, Barany F, et al. A comparative study of metronidazole and sulfasalazine for active Crohn’s disease: the cooperative Crohn’s disease study in Sweden. II. Result. Gastroenterology 1982; 83(3): 550–62PubMedGoogle Scholar
  77. 77.
    Colombel JF, Lemann M, Cassagnou M, et al. A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn’s disease: Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID). Am J Gastroenterol 1999; 94(3): 674–8PubMedCrossRefGoogle Scholar
  78. 78.
    McKeage K, Goa KL. Budesonide (Entocort EC capsules): a review of its therapeutic use in the management of active Crohn’s disease in adults. Drugs 2002; 62(15): 2263–82PubMedCrossRefGoogle Scholar
  79. 79.
    Mack DR, Young R, Kaufmann SS, et al. Methotrexate in patients with Crohn’s disease after 6-mercaptopurine. J Pediatr 1998; 132(5): 830–5PubMedCrossRefGoogle Scholar
  80. 80.
    Sandborn WJ, Hanauer SB. Infliximab in the treatment of Crohn’s disease: a user’s guide for clinicians. Am J Gastroenterol 2002; 97(12): 2962–72PubMedCrossRefGoogle Scholar
  81. 81.
    Candy S, Wright J, Gerber M, et al. A controlled double blind study of azathioprine in the management of Crohn’s disease. Gut 1995; 37(5): 674–8PubMedCrossRefGoogle Scholar
  82. 82.
    Bouhnik Y, Lemann M, Mary J, et al. Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet 1996; 347(8996): 215–9PubMedCrossRefGoogle Scholar
  83. 83.
    Layer PH, Goebell H, Keller J, et al. Delivery and fate of oral mesalamine microgranules within the human small intestine. Gastroenterology 1995; 108(5): 1427–33PubMedCrossRefGoogle Scholar
  84. 84.
    Kugathasan S, Werlin SI, Martinez A, et al. Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol 2000 Nov; 95(11): 3189–94PubMedCrossRefGoogle Scholar
  85. 85.
    Nugent FW, Roy MA. Duodenal Crohn’s disease: an analysis of 89 cases. Am J Gastroenterol 1989; 84(3): 249–54PubMedGoogle Scholar
  86. 86.
    Dejaco C, Harper M, Waldhoer T, et al. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn’s disease. Aliment Pharmacol Ther 2003; 18(11–12): 1113–20PubMedCrossRefGoogle Scholar
  87. 87.
    Brandt LJ, Bernstein LH, Boley SJ, et al. Metronidazole therapy for perineal Crohn’s disease: a follow-up study. Gastroenterology 1982; 83(2): 383–7PubMedGoogle Scholar
  88. 88.
    Korelitz BI, Present DH. Favorable effect of 6-mercaptopurine on fistulae of Crohn’s disease. Dig Dis Sci 1985; 30(1): 58–64PubMedCrossRefGoogle Scholar
  89. 89.
    Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999; 340(18): 1398–405PubMedCrossRefGoogle Scholar
  90. 90.
    Present DH, Lichtiger S. Efficacy of cyclosporine in treatment of fistula of Crohn’s disease. Dig Dis Sci 1994; 39(2): 374–80PubMedCrossRefGoogle Scholar
  91. 91.
    Rutgeerts P, Hiele M, Geboes K, et al. Controlled trial of metronidazole treatment for prevention of Crohn’s recurrence after ileal resection. Gastroenterology 1995; 108(6): 1617–21PubMedCrossRefGoogle Scholar
  92. 92.
    Rutgeerts P, Geboes K, Vantrappen G, et al. Predictability of the postoperative course of Crohn’s disease. Gastroenterology 1990; 99(4): 956–63PubMedGoogle Scholar
  93. 93.
    Bergman L, Krause U. Postoperative treatment with corticosteroids and salazosulphapyridine (salazopyrin) after radical resection for Crohn’s disease. Scand J Gastroenterol 1976; 11(7): 651–6PubMedGoogle Scholar
  94. 94.
    Achkar JP, Hanauer SB. Medical therapy to reduce postoperative Crohn’s disease recurrence. Am J Gastroenterol 2000; 95(5): 1139–46PubMedCrossRefGoogle Scholar
  95. 95.
    Camma C, Giunta M, Rosselli M, et al. Mesalamine in the maintenance treatment of Crohn’s disease: a meta-analysis adjusted for confounding variables. Gastroenterology 1997; 113(5): 1465–73PubMedCrossRefGoogle Scholar
  96. 96.
    Caprilli R, Andreoli A, Capurso L, et al. Oral mesalazine (5-aminosalicylic acid; Asacol) for the prevention of post-operative recurrence of Crohn’s disease: Gruppo Italiano per lo Studio del Colon e del Retto (GISC). Aliment Pharmacol Ther 1994; 8(1): 35–43PubMedCrossRefGoogle Scholar
  97. 97.
    Markowitz J, Grancher K, Kohn N, et al. Immunomodulatory therapy for pediatric inflammatory bowel disease: changing patterns of use 1990–2000. Am J Gastroenterol 2002; 97(4): 928–32PubMedGoogle Scholar
  98. 98.
    Hanauer SB, Korelitz BI, Rutgeerts P, et al. Postoperative maintenance of Crohn’s disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Gastroenterology 2004; 127(3): 723–9PubMedCrossRefGoogle Scholar
  99. 99.
    Ardizzone S, Maconi G, Sampieto GM, et al. Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn’s disease. Gastroenterology 2004; 127(3): 730–40PubMedCrossRefGoogle Scholar
  100. 100.
    Peppercorn MA. Sulfasalazine. Ann Intern Med 1984; 101(3): 377–86PubMedGoogle Scholar
  101. 101.
    Kalogeris T, Grisham MB. Mode of action of anti-inflammatory agents. In: Bayless TM, Hanauer SB, editors. Advanced therapy of inflammatory bowel disease. London: BC Decker Inc., 2001: 63–7Google Scholar
  102. 102.
    Nikolaus S, Folscn U, Schreiber S. Immunopharmacology of 5-aminosalicylic acid and of glucocorticoids in the therapy of inflammatory bowel disease. Hepato-gastroenterology 2000; 47(31): 71–82PubMedGoogle Scholar
  103. 103.
    Wahl C, Liptay S, Adler G, et al. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest 1998; 101(5): 1163–74PubMedCrossRefGoogle Scholar
  104. 104.
    Pearson DC, Jourd’heuil D, Meddings JB. The anti-oxidant properties of 5-aminosalicylic acid. Free Radic Biol Med 1996; 21(3): 367–73PubMedCrossRefGoogle Scholar
  105. 105.
    Miyachi Y, Yoshioka A, Imamura S, et al. Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. Gut 1987; 28(2): 190–5PubMedCrossRefGoogle Scholar
  106. 106.
    Barden L, Lipson A, Pert P, et al. Mesalazine in childhood inflammatory bowel disease. Aliment Pharmacol Ther 1989; 3(6): 597–603PubMedCrossRefGoogle Scholar
  107. 107.
    Radke M, Bartolomaeus G, Muller M, et al. Acute pancreatitis in Crohn’s disease due to 5-ASA therapy. J Pediatr Gastroenterol Nutr 1993; 16(3): 337–9PubMedCrossRefGoogle Scholar
  108. 108.
    D’Agata ID, Vanounou T, Siedman E. Mesalamine in pediatric inflammatory bowel disease: a 10-year experience. Inflamm Bowel Dis 1996; 2: 229–35PubMedCrossRefGoogle Scholar
  109. 109.
    Boyer DL, Li BU, Fyda JN, et al. Sulfasalazine-induced hepatotoxicity in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1989; 8(4): 528–32PubMedCrossRefGoogle Scholar
  110. 110.
    Ransford RA, Langman MJ. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut 2002; 51(4): 536–9PubMedCrossRefGoogle Scholar
  111. 111.
    Goldstein F, DiMarino Jr AJ. Diarrhea as a side effect of mesalamine treatment for inflammatory bowel disease. J Clin Gastroenterol 2000; 31(1): 60–2PubMedCrossRefGoogle Scholar
  112. 112.
    Solem CA, Tremaine WJ. Sequential and combination therapy for ulcerative colitis. In: Bayless TM, Hanauer SB, editors. Seminars in inflammatory bowel disease. New York: Crohn’s and Colitis Foundation of America, 2003Google Scholar
  113. 113.
    Schreiber S, Nikolaus S, Hampe J. Activation of nuclear factor kappa B inflammatory bowel disease. Gut 1998; 42(4): 477–84PubMedCrossRefGoogle Scholar
  114. 114.
    Honda M, Orii F, Ayabe T, et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis. Gastroenterology 2000; 118(5): 859–66PubMedCrossRefGoogle Scholar
  115. 115.
    Lichtenstein GR. Approach to corticosteroid-dependent and corticosteroid-refractory Crohn’s disease. Inflamm Bowel Dis 2001; 7Suppl. 1: S23–9PubMedCrossRefGoogle Scholar
  116. 116.
    Bousvaros A. Mucosal healing in children with Crohn’s disease: appropriate therapeutic goal or medical overkill? Inflamm Bowel Dis 2004; 10(4): 481–3PubMedCrossRefGoogle Scholar
  117. 117.
    Modigliani R, Mary JY, Simon JF, et al. Clinical, biological, endoscopic picture of attacks of Crohn’s disease: evolution on prednisolone. Groupe d’Etude Therapeutique des Affections Inflammatoires Digestives. Gastroenterology 1990; 98(4): 811–8PubMedCrossRefGoogle Scholar
  118. 118.
    Lundin PD, Edsbacker S, Bergstrand M, et al. Pharmacokinetics of budesonide controlled ileal release capsules in children and adults with active Crohn’s disease. Aliment Pharmacol Ther 2003; 17(1): 85–92PubMedCrossRefGoogle Scholar
  119. 119.
    Keller R, Stoll R, Foerster EC, et al. Oral budesonide therapy for steroid-dependent ulcerative colitis: a pilot trial. Aliment Pharmacol Ther 1997; 11(6): 1047–52PubMedCrossRefGoogle Scholar
  120. 120.
    Kundhal P, Zachos M, Holmes JL, et al. Controlled ileal release budesonide in pediatric Crohn disease: efficacy and effect on growth. J Pediatr Gastroenterol Nutr 2001; 33(1): 75–80PubMedCrossRefGoogle Scholar
  121. 121.
    Levine A, Weizman Z, Broide E, et al. A comparison of budesonide and prednisone for the treatment of active pediatric Crohn’s disease. J Pediatr Gastroenterol Nutr 2002; 36: 248–52CrossRefGoogle Scholar
  122. 122.
    Levine A, Broide E, Stein M, et al. Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn’s disease in children. J Pediatr 2002; 140(1): 75–80PubMedCrossRefGoogle Scholar
  123. 123.
    Levine A, Watermberg N, Hager H, et al. Benign intracranial hypertension associated with budesonide treatment in children with Crohn’s disease. J Child Neurol 2001; 16(6): 458–61PubMedGoogle Scholar
  124. 124.
    Escher JC. Budesonide versus prednisolone for the treatment of active Crohn’s disease in children: a randomized, double-blind, controlled, multicentre trial. Eur J Gastroenterol Hepatol 2004; 16(1): 47–54PubMedCrossRefGoogle Scholar
  125. 125.
    Krook A, Jamerot G, Danielsson D. Clinical effect of metronidazole and sulfasalazine on Crohn’s disease in relation to changes in the fecal flora. Scand J Gastroenterol 1981; 16: 569–75PubMedCrossRefGoogle Scholar
  126. 126.
    Gnarpe H, Belsheim J, Persson S. Influence of nitroimidazole derivatives on leukocyte migration. Scand J Infect Dis Suppl 1981; 26: 68–71PubMedGoogle Scholar
  127. 127.
    Grove DI, Mahmound AA, Warren KS. Suppression of cell-mediated immunity by metronidazole. Int Arch Allergy Appl Immunol 1977; 54(5): 422–7PubMedCrossRefGoogle Scholar
  128. 128.
    Muller M. Mode of action of metronidazole on anaerobic bacteria and protozoa. Surgery 1983; 93 (1 Pt 2): 165–71PubMedGoogle Scholar
  129. 129.
    Smilack JD, Wilson WR, Cockerill III FR. Tetracyclines, chloramphenicol, erythromycin, clindamycin, metronidazole. Mayo Clin Proc 1991; 66(12): 1270–80PubMedCrossRefGoogle Scholar
  130. 130.
    Corey WA, Doebbeling BN, DeJong KJ, et al. Metronidazole-induced acute pancreatitis. Rev Infect Dis 1991; 13(6): 1213–5PubMedCrossRefGoogle Scholar
  131. 131.
    Finegold SM. Metronidazole. Ann Intern Med 1980; 93(4): 585–7PubMedGoogle Scholar
  132. 132.
    West RL, van der Woude CJ, Hansen BE, et al. Clinical and endosonograpic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn’s disease with infliximab: a double-blind placebo-controlled study. Aliment Pharmacol Ther 2004 Dec; 20(11–12): 1329–36PubMedCrossRefGoogle Scholar
  133. 133.
    Arnold GL, Beaves MR, Pryjdun VO, et al. Preliminary study of ciprofloxacin in active Crohn’s disease. Inflamm Bowel Dis 2002 Jan; 8(1): 10–5PubMedCrossRefGoogle Scholar
  134. 134.
    Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis 2003; 36(11): 1404–10PubMedCrossRefGoogle Scholar
  135. 135.
    Segev S, Yaniv I, Haverstock D, et al. Safety of long-term therapy with ciprofloxacin: data analysis of controlled clinical trials and review. Clin Infect Dis 1999; 28(2): 299–308PubMedCrossRefGoogle Scholar
  136. 136.
    Lomaestro BM. Fluoroquinolone-induced renal failure. Drug Saf 2000; 22(6): 479–85PubMedCrossRefGoogle Scholar
  137. 137.
    Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, prebiotics. Gastroenterology 2004; 126(6): 1620–33PubMedCrossRefGoogle Scholar
  138. 138.
    Rajapakse R, Korelitz BI. Azathiprine and 6-mercaptopurine use in Crohn’s disease. In: Bayless TM, Hanauer SB, editors. Advanced therapy of inflammatory bowel disease. London: BC Decker Inc., 2001: 373–7Google Scholar
  139. 139.
    Cuffari C. Azathioprine metabolism in inflammatory bowel disease: correlation with efficacy and toxicity. In: Bayless TM, Hanauer SB, editors. Advanced therapy of inflammatory bowel disease. London: BC Decker Inc., 2001: 377–81Google Scholar
  140. 140.
    Szumlanski CL, Weinshilboum RM. Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. Br J Clin Pharmacol 1995; 39(4): 456–9PubMedCrossRefGoogle Scholar
  141. 141.
    Markowitz J, Rosa J, Grancher K, et al. Long-term 6-mercaptopurine treatment in adolescents with Crohn’s disease. Gastroenterology 1990; 99(5): 1347–51PubMedGoogle Scholar
  142. 142.
    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(4): 895–902PubMedCrossRefGoogle Scholar
  143. 143.
    Jeshion WC, Larsen KL, Jawad AF, et al. Azathioprine and 6-mercaptopurine for the treatment of perianal Crohn’s disease in children. J Clin Gastroenterol 2000; 30(3): 294–8PubMedCrossRefGoogle Scholar
  144. 144.
    D’Haens G, Geboes K, Ponette E, et al. Healing of severe recurrent ileitis with azathioprine therapy in patients with Crohn’s disease. Gastroenterology 1997; 112(5): 1475–81PubMedCrossRefGoogle Scholar
  145. 145.
    Kirschner BS. Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease. Gastroenterology 1998; 115(4): 813–21PubMedCrossRefGoogle Scholar
  146. 146.
    Connell WR, Kamm MA, Dickson M, et al. Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet 1994; 343(8908): 1249–52PubMedCrossRefGoogle Scholar
  147. 147.
    Dayharsh GA, Loftus Jr EV, Sandborn WJ, et al. Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology 2002; 122(1): 72–7PubMedCrossRefGoogle Scholar
  148. 148.
    Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn’s disease: benefits outweigh the risk of lymphoma. Gastroenterology 2000; 118(6): 1018–24PubMedCrossRefGoogle Scholar
  149. 149.
    Present DH, Meltzer SJ, Krumholz MP, et al. 6-mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med 1989; 111(8): 641–9PubMedGoogle Scholar
  150. 150.
    Laurentaci G, Catalano G, Chiumarulo C, et al. Immunosuppressive action and effects of amethopterin on the lymphoid tissue of the rabbit appendix. Minerva Med 1980; 71(2): 103–10PubMedGoogle Scholar
  151. 151.
    Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate: increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92(6): 2675–82PubMedCrossRefGoogle Scholar
  152. 152.
    Feagan 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(22): 1627–32PubMedCrossRefGoogle Scholar
  153. 153.
    Feagan 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(5): 292–7PubMedCrossRefGoogle Scholar
  154. 154.
    Arora S, Katkov W, Cooley J, et al. Methotrexate in Crohn’s disease: results of a randomized, double-blind, placebo-controlled trial. Hepatogastroenterology 1999; 46(27): 1724–9PubMedGoogle Scholar
  155. 155.
    Oren R, Moshkowitz M, Odes S, et al. Methotrexate in chronic active Crohn’s disease: a double-blind, randomized, Israeli multicenter trial. Am J Gastroenterol 1997; 92(12): 2203–9PubMedGoogle Scholar
  156. 156.
    Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. Gastroenterology 1996; 110(5): 1416–21PubMedCrossRefGoogle Scholar
  157. 157.
    Weinblatt ME. Methotrexate for chronic diseases in adults. N Engl J Med 1995; 332(5): 330–1PubMedCrossRefGoogle Scholar
  158. 158.
    Lemann M, Zenjan T, Bouhnik Y, et al. Methotrexate in Crohn’s disease: long-term efficacy and toxicity. Am J Gastroenterol 2000; 95(7): 1730–4PubMedGoogle Scholar
  159. 159.
    Feagan BG, Kumaranayake P. Methotrexate in inflammatory bowel disease. In: Bayless TM, Hanauer SB, editors. Advanced therapy of inflammatory bowel disease. London: BC Decker Inc, 2001: 383–6Google Scholar
  160. 160.
    Kremer JM, Alarcon GS, Lightfoot Jr RW, et al. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. American College of Rheumatology. Arthritis Rheum 1994; 37(3): 316–28PubMedCrossRefGoogle Scholar
  161. 161.
    Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today 1992; 13(4): 136–42PubMedCrossRefGoogle Scholar
  162. 162.
    Ina K, Kusugami K, Shimada M, et al. Suppressive effects of cyclosporine A on neutrophils and T cells may be related to therapeutic benefits in patients with steroid-resistant ulcerative colitis. Inflamm Bowel Dis 2002; 8(1): 1–9PubMedCrossRefGoogle Scholar
  163. 163.
    D’Haens G, Lemmens L, Geboes K, et al. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology 2001; 120(6): 1323–9PubMedCrossRefGoogle Scholar
  164. 164.
    Procupek DA, Kashyap PK, Targan SR, et al. Cyclosporin in the treatment of refractory UC: clinical determinants of a successful outcome after 6 months [abstract]. Gastroenterology 1994; 106Suppl. A: A756Google Scholar
  165. 165.
    Treem WR, Cohen J, Davis PM, et al. Cyclosporine for the treatment of fulminant ulcerative colitis in children: immediate response, long-term results, impact on surgery. Dis Colon Rectum 1995; 38(5): 474–9PubMedCrossRefGoogle Scholar
  166. 166.
    Treem WR, Cohen J, Davis PM, et al. Cyclosporine treatment for the treatment of fulminant ulcerative colitis in children. Dis Colon Rectum 1994; 38(5): 474–8CrossRefGoogle Scholar
  167. 167.
    McCormack G, McCormick PA, Hyland JM, et al. Cyclosporin therapy in severe ulcerative colitis: is it worth the effort? Dis Colon Rectum 2002; 45(9): 1200–5PubMedCrossRefGoogle Scholar
  168. 168.
    Cohen RD. Intravenous cyclosporine in severe ulcerative colitis: ready to stand alone? Gastroenterology 2001; 120(6): 1541–3PubMedCrossRefGoogle Scholar
  169. 169.
    Vincent F, Bensousan TA. Cyclosporine in severe ulcerative colitis [letter]. N Engl J Med 1995; 332(2): 127PubMedGoogle Scholar
  170. 170.
    Taylor AC, Connell WR, Elliott RR, et al. Oral cyclosporine in refractory inflammatory bowel disease. Aust J Med 1998; 28: 179–83CrossRefGoogle Scholar
  171. 171.
    Lugering A, Schmidt M, Lugering N, et al. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway. Gastroenterology 2001; 121(5): 1145–57PubMedCrossRefGoogle Scholar
  172. 172.
    Paleolog E. The therapeutic potential of TNF-alpha blockade in rheumatoid arthritis. Expert Opin Investig Drugs 2003; 12(7): 1087–95PubMedCrossRefGoogle Scholar
  173. 173.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002; 359(9317): 1541–9PubMedCrossRefGoogle Scholar
  174. 174.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350(9): 876–85PubMedCrossRefGoogle Scholar
  175. 175.
    Present DH. The efficacy of infliximab in Crohn’s disease: healing of fistulae. Aliment Pharmacol Ther 1999; 13Suppl. 4: 23–8PubMedCrossRefGoogle Scholar
  176. 176.
    Baldassano R, Braegger CP, Escher JC, et al. Infliximab (Remicade) therapy in the treatment of pediatric Crohn’s disease. Am J Gastroenterol 2003; 98(4): 833–8PubMedCrossRefGoogle Scholar
  177. 177.
    Papadakis KA, Treyzon L, Abreu MT, et al. Infliximab in the treatment of medically refractory indeterminate colitis. Aliment Pharmacol Ther 2003; 18(7): 741–7PubMedCrossRefGoogle Scholar
  178. 178.
    Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol 2006 May; 4(5): 621–30PubMedCrossRefGoogle Scholar
  179. 179.
    Sandborn WJ, Hanauer SB. Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results, safety. Inflamm Bowel Dis 1999; 5(2): 119–33PubMedCrossRefGoogle Scholar
  180. 180.
    Crandall WV, Mackner LM. Infusion reactions to infliximab in children and adolescents: frequency, outcome and a predictive model. Aliment Pharmacol Ther 2003; 17(1): 75–84PubMedCrossRefGoogle Scholar
  181. 181.
    Baumgart DC, Dignass AU. Tacrolimus (FK506) in refractory ulcerative colitis: an alternative to proctocolectomy? Z Gastroenterol 2003; 41(5): 478–9PubMedCrossRefGoogle Scholar
  182. 182.
    Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet 2004; 363(9423): 1802–11PubMedCrossRefGoogle Scholar
  183. 183.
    Ehrenpreis ED, Kane SV, Cohen LB, et al. Thalidomide therapy for patients with refractory Crohn’s disease: an open-label trial. Gastroenterology 1999; 117(6): 1271–7PubMedCrossRefGoogle Scholar
  184. 184.
    Vasiliauskas EA, Kam LY, Abreu-Martin MT, et al. An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn’s disease. Gastroenterology 1999; 117(6): 1278–87PubMedCrossRefGoogle Scholar
  185. 185.
    Bariol C, Meagher AP, Vickers CK, et al. Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease. J Gastroenterol Hepatol 2002; 17(2): 135–9PubMedCrossRefGoogle Scholar
  186. 186.
    Kho YH, Pool MO, Jansman FG, et al. Pharmacotherapeutic options in inflammatory bowel disease: an update. Pharm World Sci 2001; 23(1): 17–21PubMedCrossRefGoogle Scholar
  187. 187.
    Neurath MF, Wanitschke R, Peters M, et al. Mycophenolate mofetil for treatment of active inflammatory bowel disease: clinical and immunological studies. Ann N Y Acad Sci 1998; 859: 315–8PubMedCrossRefGoogle Scholar
  188. 188.
    Fellermann K, Steffen M, Stein J, et al. Mycophenolate mofetil: lack of efficacy in chronic active inflammatory bowel disease. Aliment Pharmacol Ther 2000; 14(2): 171–6PubMedCrossRefGoogle Scholar
  189. 189.
    Orth T, Peters M, Schlaak JF, et al. Mycophenolate mofetil versus azathioprine in patients with chronic active ulcerative colitis: a 12-month pilot study. Am J Gastroenterol 2000; 95(5): 1201–7PubMedCrossRefGoogle Scholar
  190. 190.
    Ford AC, Towler RJ, Moayyedi P, et al. Mycophenolate mofetil in refractory inflammatory bowel disease. Aliment Pharmacol Ther 2003; 17(11): 1365–9PubMedCrossRefGoogle Scholar
  191. 191.
    Youdim A, Vasiliauskasea EA, Targan SR, et al. A pilot study of adalimumab in infliximab-allergic patients. Inflamm Bowel Dis 2004; 10(4): 333–8PubMedCrossRefGoogle Scholar
  192. 192.
    Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology 2006 Feb; 130(2): 323–33PubMedCrossRefGoogle Scholar
  193. 193.
    Sandborn WJ, Yednock TA. Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin. Am J Gastroenterol 2003; 98(11): 2372–82PubMedCrossRefGoogle Scholar
  194. 194.
    Tubridy N, Behan PO, Capildeo R, et al. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS: the UK Antegren Study Group. Neurology 1999; 53(3): 466–72PubMedCrossRefGoogle Scholar
  195. 195.
    Gordon FH, Hamilton MI, Donoghue S, et al. A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha-4 integrin. Aliment Pharmacol Ther 2002; 16(4): 699–705PubMedCrossRefGoogle Scholar
  196. 196.
    Gordon FH, Lai CW, Hamilton MI, et al. A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn’s disease. Gastroenterology 2001; 121(2): 268–74PubMedCrossRefGoogle Scholar
  197. 197.
    Ghosh S, Goldin E, Gordon FH, et al. Natalizumab for active Crohn’s disease. N Engl J Med 2003; 348(1): 24–32PubMedCrossRefGoogle Scholar
  198. 198.
    Creed TJ, Norman MR, Probert CS, et al. Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis. Aliment Pharmacol Ther 2003; 18(1): 65–75PubMedCrossRefGoogle Scholar
  199. 199.
    Van Assche G, Dalle I, Noman M, et al. A pilot study on the use of the humanized anti-interleukin-2 receptor antibody daclizumab in active ulcerative colitis. Am J Gastroenterol 2003; 98(2): 369–76PubMedCrossRefGoogle Scholar
  200. 200.
    Venturi A, Gionchetti P, Pizzello F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999; 13(8): 1103–8PubMedCrossRefGoogle Scholar
  201. 201.
    Kruis W, Schultz E, Fric P, et al. Double-blind comparison of an oral Escherichiacoli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 1997; 11(5): 853–8PubMedCrossRefGoogle Scholar
  202. 202.
    Rembacken BJ, Snelling AM, Hawkey PM, et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomized trial. Lancet 1999; 354: 635–9PubMedCrossRefGoogle Scholar
  203. 203.
    Malchow HA. Crohn’s disease and Escherichia coli: a new approach in therapy to maintain remission of colonic Crohn’s disease? J Clin Gastroenterol 1997; 25(4): 653–8PubMedCrossRefGoogle Scholar
  204. 204.
    Guandalini S. Use of Lactobacillus-GG in paediatric Crohn’s disease. Dig Liver Dis 2002; 34Suppl. 2: S63–5PubMedCrossRefGoogle Scholar
  205. 205.
    Gupta P, Andrew H, Kirschner BS, et al. Is Lactobacillus GG helpful in children with Crohn’s disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 2000; 31(4): 453–7PubMedCrossRefGoogle Scholar
  206. 206.
    Bousvaros A, Guandalini S, Baldassano RN, et al. A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis 2005 Sep; 11(9): 833–9PubMedCrossRefGoogle Scholar
  207. 207.
    Gionchetti P, Rizello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003; 124(5): 1202–9PubMedCrossRefGoogle Scholar
  208. 208.
    Gionchetti P, Rizello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000; 119(2): 305–9PubMedCrossRefGoogle Scholar
  209. 209.
    Strobel CT, Byrne WJ, Ament ME. Home parenteral nutrition in children with Crohn’s disease: an effective management alternative. Gastroenterology 1979; 77(2): 272–9PubMedGoogle Scholar
  210. 210.
    Morin CL, Roulet M, Roy CC, et al. Continuous elemental enteral alimentation in the treatment of children and adolescents with Crohn’s disease. J Parenter Enteral Nutr 1982; 6(3): 194–9CrossRefGoogle Scholar
  211. 211.
    Navarro J, Vargas J, Cezard JP, et al. Prolonged constant rate elemental enteral nutrition in Crohn’s disease. J Pediatr Gastroenterol Nutr 1982; 1(4): 541–6PubMedCrossRefGoogle Scholar
  212. 212.
    Wilschanski M, Sherman P, Pencharz P, et al. Supplementary enteral nutrition maintains remission in paediatric Crohn’s disease. Gut 1996; 38(4): 543–8PubMedCrossRefGoogle Scholar
  213. 213.
    Chinea B, Rosa A, Oharriz JJ, et al. Osteopenia in Puerto Ricans with Crohn’s disease. P R Health Sci J 2000; 19(4): 329–33PubMedGoogle Scholar
  214. 214.
    Murray JJ. Ulcerative colitis: indications for elective colectomy. In: Allan RN, Keighley MRB, Rhodes J, et al. editors. Inflammatory bowel diseases. New York: Churchill Livingstone, 1997: 733–40Google Scholar
  215. 215.
    Mignon M, Settler C, Phillips SF. Pouchitis: a poorly understood entity. Dis Colon Rectum 1995; 38: 100–3PubMedCrossRefGoogle Scholar
  216. 216.
    Sandborn WJ, Tremaine WJ, Batts KP, et al. Pouchitis after ileal pouch-anal anastamosis: a pouch disease activity index. Mayo Clin Proc 1994; 69: 409–15PubMedCrossRefGoogle Scholar
  217. 217.
    Shen B, Achkar JP, Lashner BA, et al. A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Inflamm Bowel Dis 2001; 7(4): 301–5PubMedCrossRefGoogle Scholar
  218. 218.
    Fonkalsrud EW. Surgery for pediatric ulcerative colitis. Curr Opin Pediatr 1995; 7(3): 323–7PubMedCrossRefGoogle Scholar
  219. 219.
    Mekhjian HS, Switz DM, Watts HD, et al. National Cooperative Crohn’s Disease Study: factors determining recurrence of Crohn’s disease after surgery. Gastroenterology 1979; 77 (4 Pt 2): 907–13PubMedGoogle Scholar
  220. 220.
    Chardavoyne R, Flint GW, Pollack S, et al. Factors affecting recurrence following resection for Crohn’s disease. Dis Colon Rectum 1986; 29(8): 495–502PubMedCrossRefGoogle Scholar
  221. 221.
    Rutgeerts P. Strategies in the prevention of post-operative recurrence in Crohn’s disease. Best Pract Res Clin Gastroenterol 2003; 17(1): 63–73PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Center for Inflammatory Bowel Diseases, Combined Program in Gastroenterology and NutritionChildren’s HospitalBostonUSA

Personalised recommendations