Drugs

, Volume 67, Issue 12, pp 1703–1723 | Cite as

Infliximab Therapy in Children and Adolescents with Inflammatory Bowel Disease

  • Gabor Veres
  • Robert N. Baldassano
  • Petar Mamula
Review Article

Abstract

This review summarises the present knowledge of infliximab therapy in children with inflammatory bowel disease (IBD) based on the available published literature.

Infliximab, the chimeric monoclonal IgG1 antibody to tumour necrosis factor-α, is indicated for medically refractory luminal and fistulising paediatric Crohn’s disease. Recently, ulcerative colitis case series in children and adolescents suggested that infliximab might also be effective for treatment of ulcerative colitis resistant to standard medical therapy.

Induction therapy with infliximab 5 mg/kg at weeks 0, 2 and 6 is routinely used. Since the majority of patients will relapse if not re-treated, a long-term approach with systematic re-treatment with 5 mg/kg every 8–12 weeks is recommended. Maintenance therapy every 8 weeks was superior to 12 weeks’ administration in maintaining response and remission in the largest-to-date paediatric randomised trial. Concomitant immunosuppressive therapy reduces the risk of infliximab antibody formation and infusion reactions, and prolongs the duration of treatment success. Severe reactions may not be an absolute contraindication to future infliximab therapy. Premedication does not prevent the development of infusion reactions; however, it is indicated for prevention of subsequent infusion reactions. Adverse events and safety findings in children are comparable to those observed in adults. Latent tuberculosis needs to be screened for. Malignancy rates in paediatric patients treated with infliximab do not seem to be increased. However, newly reported cases of hepatosplenic T-cell lymphoma in young patients with IBD treated with infliximab and mercaptopurine therapy raise concern, and long-term follow-up studies are necessary to determine the true malignancy risk.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Laroux FS, Pavlick KP, Wolf RE, et al. Dysregulation of intestinal mucosal immunity: implications in inflammatory bowel disease. News Physiol Sci 2001; 16: 272–7PubMedGoogle Scholar
  2. 2.
    Kugathasan S, Judd RH, Hoffmann 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
  3. 3.
    Hildebrand H, Finkel Y, Grahnquist L, et al. Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990–2001. Gut 2003; 52: 1432–4PubMedCrossRefGoogle Scholar
  4. 4.
    Lindberg E, Lindquist B, Holmquist L, et al. Inflammatory bowel disease in children and adolescents in Sweden, 1984–1995. J Pediatr Gastroenterol Nutr 2000; 30: 259–64PubMedCrossRefGoogle Scholar
  5. 5.
    Griffiths AM, Nguyen P, Smith C, et al. Growth and clinical course of children with Crohn’s disease. Gut 1993; 34: 939–43PubMedCrossRefGoogle Scholar
  6. 6.
    Sawczenko A, Sandhu BK. Presenting features of inflammatory bowel disease in Great Britain and Ireland. Arch Dis Child 2003; 88: 995–1000PubMedCrossRefGoogle Scholar
  7. 7.
    Cuffari C. Inflammatory bowel disease in children: a pediatrician’s perspective. Minerva Pediatr 2006; 58: 139–57PubMedGoogle Scholar
  8. 8.
    IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis-the Porto criteria. J Pediatr Gastroenterol Nutr 2005; 41: 1–7CrossRefGoogle 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 disease. Gastroenterology 2000; 119: 895–902PubMedCrossRefGoogle Scholar
  10. 10.
    Baldassano RN. Surpassing conventional therapies: the role of biologic therapy. J Pediatr Gastroenterol Nutr 2001; 33 Suppl. 1: S19–26PubMedCrossRefGoogle Scholar
  11. 11.
    Caprilli R, Angelucci E, Cocco A. Early or late guided missile in the treatment of Crohn disease? Dig Liver Dis 2005; 37: 973–9PubMedCrossRefGoogle Scholar
  12. 12.
    Han PD, Cohen RD. Managing immunogenic responses to infliximab: treatment implications for patients with Crohn disease. Drugs 2004; 64: 1767–77PubMedCrossRefGoogle Scholar
  13. 13.
    Rutgeerts P, Van Assche G, Vermeire S. Infliximab therapy for inflammatory bowel disease: seven years on. Aliment Pharmacol Ther 2006; 23: 451–63PubMedCrossRefGoogle Scholar
  14. 14.
    Homan M, Baldassano RN, Mamula P. Managing complicated Crohn disease in children and adolescents. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 572–9PubMedCrossRefGoogle Scholar
  15. 15.
    Hyams J, Crandall W, Kugathasan S, et al. A randomized, multicenter, open-label study to evaluate the safety and efficacy of infliximab in pediatric patients with moderate-to-severe Crohn’s disease [abstract]. J Pediatr Gastroenterol Nutr 2005; 41: 539CrossRefGoogle Scholar
  16. 16.
    Brynskov J, Foegh P, Pedersen G, et al. Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonie mucosa of patients with inflammatory bowel disease. Gut 2002; 51: 37–43PubMedCrossRefGoogle Scholar
  17. 17.
    Mullberg J, Althoff K, Jostock T, et al. The importance of shedding of membrane proteins for cytokine biology. Eur Cytokine Netw 2000; 11: 27–38PubMedGoogle Scholar
  18. 18.
    Louis E, Ribbens C, Godon A, et al. Increased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease. Clin Exp Immunol 2000; 120: 241–6PubMedCrossRefGoogle Scholar
  19. 19.
    Breese EJ, Michie CA, Nicholls SW, et al. Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology 1994; 106: 1455–66PubMedGoogle Scholar
  20. 20.
    Nicholls S, Stephens S, Braegger CP, et al. Cytokines in stools of children with inflammatory bowel disease or infective diarrhoea. J Clin Pathol 1993; 46: 757–60PubMedCrossRefGoogle Scholar
  21. 21.
    Tsukada Y, Nakamura T, Iimura M, et al. Cytokine profile in colonic mucosa of ulcerative colitis correlates with disease activity and response to granulocytopheresis. Am J Gastroenterol 2002; 97: 2820–8PubMedCrossRefGoogle Scholar
  22. 22.
    Ardizzone S, Porro G. Inflammatory bowel disease: new insights into pathogenesis and therapy. J Intern Med 2002; 252: 475–96PubMedCrossRefGoogle Scholar
  23. 23.
    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: 463–73PubMedCrossRefGoogle Scholar
  24. 24.
    Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology 2004; 126: 1593–610PubMedCrossRefGoogle Scholar
  25. 25.
    Ardizzone S, Bianchi Porro G. Biologic therapy for inflammatory bowel disease. Drugs 2005; 65: 2253–86PubMedCrossRefGoogle Scholar
  26. 26.
    Zeissig S, Bojarski C, Buergel N, et al. Downregulation of epithelial apoptosis and barrier repair in active Crohn disease by tumour necrosis factor-alpha antibody treatment Gut 2004; 53: 1295–1302PubMedCrossRefGoogle Scholar
  27. 27.
    Begue B, Wajant H, Bambou JC, et al. Implication of TNF-related apoptosis-inducing ligand in inflammatory intestinal epithelial lesions. Gastroenterology 2006; 130: 1962–74PubMedCrossRefGoogle Scholar
  28. 28.
    Van den Brande JM, Braat H, van den Brink GP, et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn disease. Gastroenterology 2003; 124: 1774–85PubMedCrossRefGoogle Scholar
  29. 29.
    Di Sabatino A, Ciccocioppo R, Cinque B, et al. Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn disease. Gut 2004; 53: 70–7PubMedCrossRefGoogle Scholar
  30. 30.
    Sandborn WJ, Feagen BG, Hanauer SB, et al. An engineered human antibody to TNF (CDP571) for active Crohn disease: a randomized double-bind, placebo-controlled trial. Gastroenterology 2001; 120: 1330–8PubMedCrossRefGoogle Scholar
  31. 31.
    Mamula P, Cohen SA, Ferry GD, et al. CDP571, a humanized anti-tumor necrosis factor-alpha monoclonal antibody in pediatric Crohn’s disease. Inflamm Bowel Dis 2004; 10: 723–30PubMedCrossRefGoogle Scholar
  32. 32.
    Papadakis CA, Targan SA. Tumor necrosis factor: biology and therapeutic inhibitors. Gastroenterology 2000; 119: 1148–57PubMedCrossRefGoogle Scholar
  33. 33.
    Shen C, Maerten P, Geboes K, et al. Infliximab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther 2005; 21: 251–8PubMedCrossRefGoogle Scholar
  34. 34.
    Shen C, Van Assche G, Colpaert S, et al. Adalimumab induces apoptosis of human monocytes and T lymphocytes in a human-mouse chimeric model. Clin Immunol 2005; 115: 250–9PubMedCrossRefGoogle Scholar
  35. 35.
    Danese S, Sans M, Scaldaferri F, et al. TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn disease. J Immunol 2006; 176: 2617–24PubMedGoogle Scholar
  36. 36.
    Suenaert P, Bulteel V, Lemmens L, et al. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn disease. Am J Gastroenterol 2002; 97: 2007–11CrossRefGoogle Scholar
  37. 37.
    Derkx B, Taminiau J, Radema S, et al. Tumour-necrosis-factor antibody treatment in Crohn disease. Lancet 1993; 342: 173–4PubMedCrossRefGoogle Scholar
  38. 38.
    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 cA2 Study Group. N Engl J Med 1997; 337: 1029–35Google Scholar
  39. 39.
    Hanauer SB, Feagen BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn disease: the ACCENT I randomized trial. Lancet 2002; 359: 1541–9PubMedCrossRefGoogle Scholar
  40. 40.
    Rutgeerts P, Feagan BG, Lichtenstein GR, et al. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn disease. Gastroenterology 2004; 126: 402–13PubMedCrossRefGoogle Scholar
  41. 41.
    Baldassano RN, Braegger CP, Escher JC, et al. Infliximab (REMICADE) therapy in the treatment of pediatrie Crohn disease. Am J Gastroenterol 2003; 98: 833–8PubMedCrossRefGoogle Scholar
  42. 42.
    Kugathasan S, Werlin SL, Martinez A, et al. Prolonged duration of response to infliximab in early but not late pediatric Crohn disease. Am J Gastroenterol 2000; 95: 3189–94PubMedCrossRefGoogle Scholar
  43. 43.
    Kugathasan S. Prolonged duration of response to infliximab in early pediatric Crohn disease. J Pediatr Gastroenterol Nutr 2001; 33 Suppl. 1: S40–3PubMedCrossRefGoogle Scholar
  44. 44.
    Hyams JS, Markowitz J, Wyllie R. Use of infliximab in the treatment of Crohn disease in children and adolescents. J Pediatr 2000; 137: 192–6PubMedCrossRefGoogle Scholar
  45. 45.
    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: 632–6PubMedCrossRefGoogle Scholar
  46. 46.
    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: 342–7PubMedCrossRefGoogle Scholar
  47. 47.
    Kooros K, Katz AJ. Infliximab therapy in pediatric Crohn’s pouchitis. Inflamm Bowel Dis 2004; 10: 417–20PubMedCrossRefGoogle Scholar
  48. 48.
    Rutgeerts P, D’Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn disease. Gastroenterology 1999; 117: 761–9PubMedCrossRefGoogle Scholar
  49. 49.
    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: 46–52PubMedCrossRefGoogle Scholar
  50. 50.
    Ruemmele FM. Infliximab: how to use it in pediatric Crohn disease. J Pediatr Gastroenterol Nutr 2004; 39: 12–4PubMedCrossRefGoogle Scholar
  51. 51.
    Lionetti P, Bronzini F, Salvestrini C. Response to infliximab is related to disease duration in paediatric Crohn disease. Aliment Pharmacol Ther 2003; 18: 425–31PubMedCrossRefGoogle Scholar
  52. 52.
    Lamireau T, Cezard JP, Dabadie A, et al. Efficacy and tolerance of infliximab in children and adolescents with Crohn disease. Inflamm Bowel Dis 2004; 10: 745–50PubMedCrossRefGoogle Scholar
  53. 53.
    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: 40–5PubMedCrossRefGoogle Scholar
  54. 54.
    Candon S, Mosca A, Ruemmele F, et al. Clinical and biological consequences of immunization to infliximab in pediatric Crohn disease. Clin Immunol 2006; 118: 11–9PubMedCrossRefGoogle Scholar
  55. 55.
    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: 1398–405PubMedCrossRefGoogle Scholar
  56. 56.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn disease. N Engl J Med 2004; 350: 876–85PubMedCrossRefGoogle Scholar
  57. 57.
    Lichtenstein GR, Yan S, Bala M, et al. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn disease. Gastroenterology 2005; 128: 862–9PubMedCrossRefGoogle Scholar
  58. 58.
    Sands BE, Blank MA, Diamond RH, et al. Maintenance infliximab does not result in increased abscess development in fistulizing Crohn disease: results from the ACCENT II study. Aliment Pharmacol Ther 2006; 23: 1127–36PubMedCrossRefGoogle Scholar
  59. 59.
    Sands BE, Blank MA, Patel K, et al. Long-term treatment of rectovaginal fistulas in Crohn disease: response to infliximab in the ACCENT II Study. Clin Gastroenterol Hepatol 2004; 2: 912–20PubMedCrossRefGoogle Scholar
  60. 60.
    Miehsler W, Reinisch W, Kazemi-Shirazi L, et al. Infliximab: lack of efficacy on perforating complications in Crohn disease. Inflamm Bowel Dis 2004; 10: 36–40PubMedCrossRefGoogle Scholar
  61. 61.
    Asteria CR, Ficari F, Bagnoli S, et al. Treatment of perianal fistulas in Crohn’s disease by local injection of antibody to TNF-alpha accounts for a favourable clinical response in selected cases: a pilot study. Scand J Gastroenterol 2006; 41: 1064–72PubMedCrossRefGoogle Scholar
  62. 62.
    Barabino A, Castellano E, Gandullia P, et al. A girl with severe fistulizing Crohn disease. Dig Liver Dis 2000; 32: 792–4PubMedCrossRefGoogle Scholar
  63. 63.
    Park SH, Jeen YT, Chun HR, et al. A case of refractory pediatric Crohn disease with a successful treatment by infliximab therapy. Korean J Gastroenterol 2005; 46: 297–301PubMedGoogle Scholar
  64. 64.
    Teitelbaum JE, Saeed S, Triantafyllopoulou M, et al. Infliximab in pediatric Crohn disease patients with enterovesicular fistulas. J Ped Gastroent Nutr 2007; 44: 279–82CrossRefGoogle Scholar
  65. 65.
    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: 332–9PubMedCrossRefGoogle Scholar
  66. 66.
    Bell SJ, Halligan S, Windsor AC, et al. Response of fistulizing Crohn disease to infliximab treatment assessed by magnetic resonance imaging. Aliment Pharmacol Ther 2003; 17: 387–93PubMedCrossRefGoogle Scholar
  67. 67.
    Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis 2003; 9: 98–103PubMedCrossRefGoogle Scholar
  68. 68.
    Sands BE, Tremaine WJ, Sandborn WJ, et al. Infliximab in the treatment of severe, corticosteroid-refractory ulcerative colitis: a pilot study. Inflamm Bowel Dis 2001; 7: 83–8PubMedCrossRefGoogle Scholar
  69. 69.
    Probert CS, Hearing SD, Schreiber S, et al. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Gut 2003; 52: 998–1002PubMedCrossRefGoogle Scholar
  70. 70.
    Ochsenkuhn T, Sackmann M, Goke B. Infliximab for acute, not corticosteroid-refractory ulcerative colitis: a randomized pilot study. Eur J Gastroenterol Hepatol 2004; 16: 1167–71PubMedCrossRefGoogle Scholar
  71. 71.
    Isaacs KL, Lewis JD, Sandborn WJ, et al. State of the art: IBD therapy and clinical trials in IBD. Inflamm Bowel Dis 2005; 11 Suppl. 1: S3–12PubMedCrossRefGoogle Scholar
  72. 72.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005; 353: 2462–76PubMedCrossRefGoogle Scholar
  73. 73.
    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: 1805–11PubMedCrossRefGoogle Scholar
  74. 74.
    Lawson M, Thomas A, Akobeng A. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2006; (3): CD005112Google Scholar
  75. 75.
    Mamula P, Markowitz JE, Brown KA, et al. Infliximab as a novel therapy for pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2002; 34: 307–11PubMedCrossRefGoogle Scholar
  76. 76.
    Mamula P, Markowitz JE, Cohen LJ, et al. Infliximab in pediatric ulcerative colitis: two-year follow-up. J Pediatr Gastroenterol Nutr 2004; 38: 298–301PubMedCrossRefGoogle Scholar
  77. 77.
    Eidelwein AP, Cuffari C, Abadom V, et al. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis 2005; 11: 213–8PubMedCrossRefGoogle Scholar
  78. 78.
    Serrano MS, Schmidt-Sommerfeld E, Kilbaugh TJ, et al. Use of infliximab in pediatric patients with inflammatory bowel disease. Ann Pharmacother 2001; 35: 823–8PubMedCrossRefGoogle Scholar
  79. 79.
    Oliva-Hemker M, Roper S, Cuffari C, et al. Infliximab therapy for pediatric ulcerative colitis [abstract]. Gastroenterology 2002; 122: A616Google Scholar
  80. 80.
    Fanjiang G, Russell GH. Katz AJ. Short- and long-term response to and weaning from infliximab therapy in pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2007; 44: 312–7Google Scholar
  81. 81.
    Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. New Engl J Med 1994; 330: 1841–5PubMedCrossRefGoogle Scholar
  82. 82.
    Thukral C, Cheifetz A, Peppercorn MA. Anti-tumour necrosis factor therapy for ulcerative colitis: evidence to date. Drugs 2006; 66: 2059–65PubMedCrossRefGoogle Scholar
  83. 83.
    Papadakis KA, Treyzon L, Abreu MT, et al. Infliximab in the treatment of medically refractory indeterminate colitis. Aliment Pharmacol Ther 2003; 18: 741–7PubMedCrossRefGoogle Scholar
  84. 84.
    Gornet JM, Couve S, Hassani Z, et al. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Aliment Pharmacol Ther 2003; 18: 175–81PubMedCrossRefGoogle Scholar
  85. 85.
    Regueiro M, Valentine J, Plevy S, et al. Infliximab for treatment of Pyoderma gangrenosum associated with inflammatory bowel disease. Am J Gastroenterol 2003; 98: 1821–6PubMedCrossRefGoogle Scholar
  86. 86.
    Brooklyn TN, Dunnill MG, Shetty A, et al. Infliximab for the treatment of Pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 2006; 55: 505–9PubMedCrossRefGoogle Scholar
  87. 87.
    Kugathasan S, Miranda A, Nocton J, et al. Dermatologie manifestations of Crohn disease in children: response to infliximab. J Pediatr Gastroenterol Nutr 2003; 37: 150–4PubMedCrossRefGoogle Scholar
  88. 88.
    Batres LA, Mamula P, Baldassano RN. Resolution of severe peristomal Pyoderma gangrenosum with infliximab in a child with Crohn disease. J Pediatr Gastroenterol Nutr 2002; 34: 558–60PubMedCrossRefGoogle Scholar
  89. 89.
    Read RW. Uveitis: advances in understanding of pathogenesis and treatment. Curr Rheumatol Rep 2006; 8: 260–6PubMedCrossRefGoogle Scholar
  90. 90.
    Rajaraman RT, Kimura Y, Li S, et al. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology 2006; 113: 308–14PubMedCrossRefGoogle Scholar
  91. 91.
    Quarta L, Corrado A, Melillo N, et al. Juvenile idiopathic arthritis: an update on clinical and therapeutic approaches. Ann Ital Med Int 2005; 20: 211–7PubMedGoogle Scholar
  92. 92.
    Richards JC, Tay-Kearney ML, Murray K, et al. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Experiment Ophthalmol 2005; 33: 461–8PubMedCrossRefGoogle Scholar
  93. 93.
    Silbermintz A, Krishnan S, Banquet A, et al. Granulomatous pneumonitis, sclerosing cholangitis, and pancreatitis in a child with Crohn disease: response to infliximab. J Pediatr Gastroenterol Nutr 2006; 42: 324–6PubMedCrossRefGoogle Scholar
  94. 94.
    Braun J, Brandt J, Listing J, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002; 359: 1187–93PubMedCrossRefGoogle Scholar
  95. 95.
    Van den Bosch F, Kruithof E, De Vos M, et al. Crohn’s disease associated with spondyloarthropathy: effect of TNF-alpha blockade with infliximab on articular symptoms. Lancet 2000; 356: 1821–2PubMedCrossRefGoogle Scholar
  96. 96.
    Escher JC, Stoof TJ, van Deventer SJ, et al. Successful treatment of metastatic Crohn disease with infliximab. J Pediatr Gastroenterol Nutr 2002; 34: 420–3PubMedCrossRefGoogle Scholar
  97. 97.
    Sierra C, Barco A, Luis DR. Treatment of metastatic Crohn disease [letter]. J Pediatr Gastroenterol Nutr 2002; 35: 708PubMedCrossRefGoogle Scholar
  98. 98.
    Hommes D, Baert F, van Assche G, et al. Management of recent onset Crohn’s Disease: a controlled, randomized trial comparing step-up and top-down therapy [abstract]. Gastroenterology 2005; 129: 371CrossRefGoogle Scholar
  99. 99.
    Löwenberg M, Peppelenbosch M, Hommes D. Biological therapy in the management of recent-onset Crohn’s disease: why, when and how? Drugs 2006; 66: 1431–9PubMedCrossRefGoogle Scholar
  100. 100.
    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: 601–8PubMedCrossRefGoogle Scholar
  101. 101.
    Farrell RJ, Alsahli M, Jeen YT, et al. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn disease: a randomized controlled trial. Gastroenterology 2003; 124: 917–24PubMedCrossRefGoogle Scholar
  102. 102.
    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: 32–9PubMedCrossRefGoogle Scholar
  103. 103.
    Cheifetz A, Smedley M, Martin S. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol 2003; 98: 1315–24PubMedCrossRefGoogle Scholar
  104. 104.
    Persley KM. Infliximab infusion reactions: desensitizing ourselves to the danger. Inflamm Bowel Dis 2004; 10: 62–3PubMedCrossRefGoogle Scholar
  105. 105.
    Stephens MC, Shepanski MA, Mamula P, et al. Safety and corticosteroid-sparing experience using infliximab for Crohn disease at a pediatric inflammatory bowel disease center. Am J Gastroenterol 2003; 98: 104–11PubMedCrossRefGoogle Scholar
  106. 106.
    Cohen RD. Efficacy and safety of repeated infliximab infusions for Crohn disease: 1-year clinical experience. Inflamm Bowel Dis 2001;7 Suppl. 1: S17–22PubMedCrossRefGoogle Scholar
  107. 107.
    Cohen RD, Tsang JF, Hanauer SB. Infliximab in Crohn disease: first anniversary clinical experience. Am J Gastroenterol 2000; 95: 3469–77PubMedCrossRefGoogle Scholar
  108. 108.
    Miele E, Markowitz JE, Mamula P, et al. Human antichimeric antibody in children and young adults with inflammatory bowel disease receiving infliximab. J Pediatr Gastroenterol Nutr 2004; 38: 502–8PubMedCrossRefGoogle Scholar
  109. 109.
    Kugathasan S, Levy MB, Saeian K, et al. Infliximab retreatment in adults and children with Crohn disease: risk factors for the development of delayed severe systemic reaction. Am J Gastroenterol 2002; 97: 1408–14PubMedCrossRefGoogle Scholar
  110. 110.
    Sandborn WJ. What’s new: innovative concepts in inflammatory bowel disease. Colorectal Dis 2006; 8 Suppl. 1: 3–9PubMedCrossRefGoogle Scholar
  111. 111.
    Sandborn WJ, Faubion WA. Biologics in inflammatory bowel disease: how much progress have we made? Gut 2004; 53: 1366–73PubMedCrossRefGoogle Scholar
  112. 112.
    Sandborn WJ. Preventing antibodies to infliximab in patients with Crohn disease: optimize not immunize. Gastroenterology 2003; 124: 1140–5PubMedCrossRefGoogle Scholar
  113. 113.
    Jacobstein DA, Markowitz JE, Kirschner BS, et al. Premedication and infusion reactions with infliximab: results from a pediatric inflammatory bowel disease consortium. Inflamm Bowel Dis 2005; 11: 442–6PubMedCrossRefGoogle Scholar
  114. 114.
    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: 265–9PubMedCrossRefGoogle Scholar
  115. 115.
    Han PD, Cohen RD, Motamedi F, et al. Infliximab infusion reactions: the influence of sex and drugs. Gastroenterology 2002; 122 Suppl. 4: A612Google Scholar
  116. 116.
    Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005; 123: 903–12PubMedCrossRefGoogle Scholar
  117. 117.
    Garcia-Planella E, Domenech E, Esteve-Comas M, et al. Development of antinuclear antibodies and its clinical impact in patients with Crohn disease treated with chimeric monoclonal anti-TNFalpha antibodies (infliximab). Eur J Gastroenterol Hepatol 2003; 15: 351–4PubMedCrossRefGoogle Scholar
  118. 118.
    McIlwain L, Carter JD, Bin-Sagheer S, et al. Hypersensitivity vasculitis with leukocytoclastic vasculitis secondary to infliximab. J Clin Gastroenterol 2003; 36: 411–3PubMedCrossRefGoogle Scholar
  119. 119.
    Crandall WV, Mackner LM. Infusion reactions to infliximab in children and adolescents: frequency, outcome and a predictive model. Aliment Pharmacol Ther 2003; 17: 75–84PubMedCrossRefGoogle Scholar
  120. 120.
    Puchner TC, Kugathasan S, Kelly KJ, et al. Successful desensitization and therapeutic use of infliximab in adult and pediatric Crohn’s disease patients with prior anaphylactic reaction. Inflamm Bowel Dis 2001; 7: 34–7PubMedCrossRefGoogle Scholar
  121. 121.
    Marino MW, Dunn A, Grail D, et al. Characterization of tumor necrosis factor-deficient mice. Proc Natl Acad Sci U S A 1997; 94: 8093–8PubMedCrossRefGoogle Scholar
  122. 122.
    Colombel JF, Loftus Jr EV, Tremaine WJ, et al. The safety profile of infliximab in patients with Crohn disease: the Mayo clinic experience in 500 patients. Gastroenterology 2004; 126: 19–31PubMedCrossRefGoogle Scholar
  123. 123.
    Kamath BM, Mamula P, Baldassano RN, et al. Listeria meningitis after treatment with infliximab. J Pediatr Gastroenterol Nutr 2002; 34: 410–2PubMedCrossRefGoogle Scholar
  124. 124.
    Gupta G, Gelfand JM, Lewis JD. Increased risk for demyelinating diseases in patients with inflammatory bowel disease. Gastroenterology 2005; 129: 819–26PubMedCrossRefGoogle Scholar
  125. 125.
    Behnam SM, Behnam SE, Koo JY. TNF-alpha inhibitors and congestive heart failure. Skinmed 2005; 4: 363–8PubMedCrossRefGoogle Scholar
  126. 126.
    Reichardt P, Dahnert I, Tiller G, et al. Possible activation of an intramyocardial inflammatory process (Staphylococcus aureus) after treatment with infliximab in a boy with Crohn disease. Eur J Paed 2002; 161: 281–3CrossRefGoogle Scholar
  127. 127.
    Armbrust W, Kamphuis SS, Wolfs TW, et al. Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology 2004; 43: 527–9PubMedCrossRefGoogle Scholar
  128. 128.
    Myers A, Clark J, Foster H. Tuberculosis and treatment with infliximab. N Engl J Med 2002; 346: 623–6PubMedCrossRefGoogle Scholar
  129. 129.
    Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345: 1098–104PubMedCrossRefGoogle Scholar
  130. 130.
    Winthrop KL. Risk and prevention of tuberculosis and other serious opportunistic infections associated with the inhibition of tumor necrosis factor. Nat Clin Pract Rheumatol 2006; 2: 602–10PubMedCrossRefGoogle Scholar
  131. 131.
    Mow WS, Abreu-Martin MT, Papadakis KA, et al. High incidence of anergy in inflammatory bowel disease patients limits the usefulness of PPD screening before infliximab therapy. Clin Gastroenterol Hepatol 2004; 2: 309–13PubMedCrossRefGoogle Scholar
  132. 132.
    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: 621–30PubMedCrossRefGoogle Scholar
  133. 133.
    Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006; 295: 2275–85PubMedCrossRefGoogle Scholar
  134. 134.
    Navarro JT, Ribera JM, Mate JL, et al. Hepatosplenic T-gammadelta lymphoma in a patient with Crohn’s disease treated with azathioprine. Leuk Lymphoma 2003; 44: 531–3PubMedCrossRefGoogle Scholar
  135. 135.
    Biancone L, Orlando A, Kohn A, et al. Infliximab and newly diagnosed neoplasia in Crohn’s disease: a multicentre matched pair study. Gut 2006; 55: 228–33PubMedCrossRefGoogle Scholar
  136. 136.
    Siegel CA, Hur C, Korzenik JR. Risks and benefits of infliximab for the treatment of Crohn’s disease. Clin Gastroenterol Hepatol 2006; 4: 1017–24PubMedCrossRefGoogle Scholar
  137. 137.
    Thayu M, Markowitz JE, Mamula P, et al. Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. J Pediatr Gastroenterol Nutr 2005; 40: 220–2PubMedCrossRefGoogle Scholar
  138. 138.
    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: 265–7PubMedCrossRefGoogle Scholar
  139. 139.
    Condino AA, Fidanza S, Hoffenberg EJ. A home infliximab infusion program. J Pediatr Gastroenterol Nutr 2005; 40: 67–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Gabor Veres
    • 1
  • Robert N. Baldassano
    • 2
  • Petar Mamula
    • 2
  1. 1.First Department of PediatricsSemmelweis UniversityBudapestHungary
  2. 2.Division of Gastroenterology, Hepatology, and Nutrition, Center for Pediatric Inflammatory Bowel DiseaseThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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