Monatsschrift Kinderheilkunde

, Volume 155, Issue 2, pp 118–126 | Cite as

Biologische Therapie chronisch entzündlicher Darmerkrankungen

Leitthema
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Zusammenfassung

Infliximab ist derzeit die einzige nachgewiesen wirksame bzw. kommerziell verfügbare Substanz aus der Gruppe der Biologika für die Behandlung von chronisch entzündlichen Darmerkrankungen. Certolizumab und Adalimumab stehen im Moment einer Zulassung am nächsten. Andere Biologika haben hingegen die in sie gesetzten hohen Erwartungen nicht erfüllt. Die Auswahl geeigneter Patientenkollektive lässt ebenso noch Fragen offen wie Aspekte der Anwendungssicherheit und mögliche Langzeitnebenwirkungen.

Schlüsselwörter

Biologika Chronisch entzündliche Darmerkrankung Morbus Crohn Colitis ulcerosa Infliximab 

Biological therapy for chronic inflammatory bowel disease

Abstract

At present, infliximab is the only proven and available biological agent for treating patients with inflammatory bowel disease. Approval for certolizumab and adalimumab may be expected in the near future. Other biologicals have not fulfilled their high expectations. Unresolved issues with infliximab and other emerging biological agents include the selection of appropriate patients for treatment, monitoring of therapy and long-term safety.

Keywords

Biologicals Inflammatory bowel disease Crohn’s disease Ulcerative colitis Infliximab 

Notes

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Literatur

  1. 1.
    Akobeng AK, Zachos M (2004) Tumor necrosis factor-alpha antibody for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 2004: CD003574Google Scholar
  2. 2.
    Baldassano R, Braegger CP, Escher JC et al. (2003) Infliximab (REMICADE) therapy in the treatment of pediatric Crohn’s disease. Am J Gastroenterol 98: 833–838CrossRefPubMedGoogle Scholar
  3. 3.
    Baumgart DC, Wiedenmann B, Dignass AU (2003) [Biologic therapy of inflammatory bowel disease]. Z Gastroenterol 41: 1017–1032CrossRefPubMedGoogle Scholar
  4. 4.
    Blonski W, Lichtenstein GR (2006) Complications of biological therapy for inflammatory bowel diseases. Curr Opin Gastroenterol 22: 30–43CrossRefPubMedGoogle Scholar
  5. 5.
    Bousvaros A, Guandalini S, Baldassano RN et al. (2005) 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 11: 833–839CrossRefPubMedGoogle Scholar
  6. 6.
    Chapman TM, Plosker GL, Figgitt DP (2006) VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs 66: 1371–1387CrossRefPubMedGoogle Scholar
  7. 7.
    Derkx B, Taminiau J, Radema S et al. (1993) Tumour-necrosis-factor antibody treatment in Crohn’s disease. Lancet 342: 173–174CrossRefGoogle Scholar
  8. 8.
    Hanauer SB, Feagan BG, Lichtenstein GR et al. (2002) Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 359: 1541–1549CrossRefPubMedGoogle Scholar
  9. 9.
    Hanauer SB, Sandborn WJ, Rutgeerts P et al. (2006) Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology 130: 323–333; quiz 591CrossRefPubMedGoogle Scholar
  10. 10.
    Hommes DW, Oldenburg B, Van Bodegraven AA et al. (2006) Guidelines for treatment with infliximab for Crohn’s disease. Neth J Med 64: 219–229PubMedGoogle Scholar
  11. 11.
    Hyams JS, Markowitz JF (2005) Can we alter the natural history of Crohn disease in children? J Pediatr Gastroenterol Nutr 40: 262–272CrossRefPubMedGoogle Scholar
  12. 12.
    Isaacs KL, Lewis JD, Sandborn WJ et al. (2005) State of the art: IBD therapy and clinical trials in IBD. Inflamm Bowel Dis [Suppl 1] 11: S3–12Google Scholar
  13. 13.
    Jarnerot G, Hertervig E, Friis-Liby I et al. (2005) Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 128: 1805–1811CrossRefPubMedGoogle Scholar
  14. 14.
    Korzenik JR, Dieckgraefe BK, Valentine JF et al. (2005) Sargramostim for active Crohn’s disease. N Engl J Med 352: 2193–2201CrossRefPubMedGoogle Scholar
  15. 15.
    Korzenik JR, Podolsky DK (2006) Evolving knowledge and therapy of inflammatory bowel disease. Nat Rev Drug Discov 5: 197–209CrossRefPubMedGoogle Scholar
  16. 16.
    Kugathasan S, Werlin SL, Martinez A et al. (2000) Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease. Am J Gastroenterol 95: 3189–3194CrossRefPubMedGoogle Scholar
  17. 17.
    Lamireau T, Cezard JP, Dabadie A et al. (2004) Efficacy and tolerance of infliximab in children and adolescents with Crohn’s disease. Inflamm Bowel Dis 10: 745–750CrossRefPubMedGoogle Scholar
  18. 18.
    Lichtenstein GR, Feagan BG, Cohen RD et al. (2006) Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol 4: 621–630CrossRefPubMedGoogle Scholar
  19. 19.
    Lichtenstein GR, Olson A, Travers S et al. (2006) Factors associated with the development of intestinal strictures or obstructions in patients with Crohn’s disease. Am J Gastroenterol 101: 1030–1038CrossRefPubMedGoogle Scholar
  20. 20.
    Lindsay JO, Whelan K, Stagg AJ et al. (2006) Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn’s disease. Gut 55: 348–355CrossRefPubMedGoogle Scholar
  21. 21.
    Lionetti P, Bronzini F, Salvestrini C et al. (2003) Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment Pharmacol Ther 18: 425–431CrossRefPubMedGoogle Scholar
  22. 22.
    Lowenberg M, Peppelenbosch M, Hommes D (2006) Biological therapy in the management of recent-onset Crohn’s disease: why, when and how? Drugs 66: 1431–1439CrossRefPubMedGoogle Scholar
  23. 23.
    Mamula P, Cohen SA, Ferry GD et al. (2004) CDP571, a humanized anti-tumor necrosis factor-alpha monoclonal antibody in pediatric Crohn’s disease. Inflamm Bowel Dis 10: 723–730CrossRefPubMedGoogle Scholar
  24. 24.
    Mannon PJ, Fuss IJ, Mayer L et al. (2004) Anti-interleukin-12 antibody for active Crohn’s disease. N Engl J Med 351: 2069–2079CrossRefPubMedGoogle Scholar
  25. 25.
    Markowitz J, Hyams J, Mack D et al. (2006) Corticosteroid therapy in the age of infliximab: acute and 1-year outcomes in newly diagnosed children with Crohn’s disease. Clin Gastroenterol Hepatol 4: 1124–1129CrossRefPubMedGoogle Scholar
  26. 26.
    Miner PB Jr, Wedel MK, Xia S et al. (2006) Safety and efficacy of two dose formulations of alicaforsen enema compared with mesalazine enema for treatment of mild to moderate left-sided ulcerative colitis: a randomized, double-blind, active-controlled trial. Aliment Pharmacol Ther 23: 1403–1413CrossRefPubMedGoogle Scholar
  27. 27.
    Nancey S, Blanvillain E, Parmentier B et al. (2005) Infliximab treatment does not induce organ-specific or nonorgan-specific autoantibodies other than antinuclear and anti-double-stranded DNA autoantibodies in Crohn’s disease. Inflamm Bowel Dis 11: 986–991CrossRefPubMedGoogle Scholar
  28. 28.
    Panaccione R, Ferraz JG, Beck P (2005) Advances in medical therapy of inflammatory bowel disease. Curr Opin Pharmacol 5: 566–572PubMedGoogle Scholar
  29. 29.
    Rioux KP, Fedorak RN (2006) Probiotics in the treatment of inflammatory bowel disease. J Clin Gastroenterol 40: 260–263CrossRefPubMedGoogle Scholar
  30. 30.
    Rutgeerts P, Sandborn WJ, Feagan BG et al. (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353: 2462–2476CrossRefPubMedGoogle Scholar
  31. 31.
    Rutgeerts P, Diamond RH, Bala M et al. (2006) Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn’s disease. Gastrointest Endosc 63: 433–442; quiz 464CrossRefPubMedGoogle Scholar
  32. 32.
    Rutgeerts P, Van Assche G, Vermeire S (2006) Review article: infliximab therapy for inflammatory bowel disease – seven years on. Aliment Pharmacol Ther 23: 451–463CrossRefPubMedGoogle Scholar
  33. 33.
    Sandborn WJ, Targan SR (2002) Biologic therapy of inflammatory bowel disease. Gastroenterology 122: 1592–1608CrossRefPubMedGoogle Scholar
  34. 34.
    Sandborn WJ, Faubion WA (2004) Biologics in inflammatory bowel disease: how much progress have we made? Gut 53: 1366–1373CrossRefPubMedGoogle Scholar
  35. 35.
    Sandborn WJ, Feagan BG, Radford-Smith G et al. (2004) CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn’s disease: a randomised, double blind, placebo controlled trial. Gut 53: 1485–1493CrossRefPubMedGoogle Scholar
  36. 36.
    Sandborn WJ, Colombel JF, Enns R et al. (2005) Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med 353: 1912–1925CrossRefPubMedGoogle Scholar
  37. 37.
    Sands BE, Anderson FH, Bernstein CN et al. (2004) Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 350: 876–885CrossRefPubMedGoogle Scholar
  38. 38.
    Sartor RB (2005) Probiotic therapy of intestinal inflammation and infections. Curr Opin Gastroenterol 21: 44–50PubMedGoogle Scholar
  39. 39.
    Schreiber S, Rutgeerts P, Fedorak RN et al. (2005) A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology 129: 807–818CrossRefPubMedGoogle Scholar
  40. 40.
    Sinha A, Nightingale J, West KP et al. (2003) Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N Engl J Med 349: 350–357CrossRefPubMedGoogle Scholar
  41. 41.
    Soderlin M, Blomkvist C, Dahl P et al. (2005) [Increased risk of infection with biological immunomodifying antirheumatic agents. Clear guidelines are necessary as shown by case reports]. Lakartidningen 102: 3794–3796, 3799–3800PubMedGoogle Scholar
  42. 42.
    Stephens MC, Shepanski MA, Mamula et al. (2003) Safety and steroid-sparing experience using infliximab for Crohn’s disease at a pediatric inflammatory bowel disease center. Am J Gastroenterol 98: 104–111CrossRefPubMedGoogle Scholar
  43. 43.
    Summers RW, Elliott DE, Urban JF Jr et al. (2005) Trichuris suis therapy in Crohn’s disease. Gut 54: 87–90CrossRefPubMedGoogle Scholar
  44. 44.
    Summers RW, Elliott DE, Urban JF Jr et al. (2005) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128: 825–832CrossRefPubMedGoogle Scholar
  45. 45.
    Van Assche G, Rutgeerts P (2005) Physiological basis for novel drug therapies used to treat the inflammatory bowel diseases. I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 288: G169–174CrossRefPubMedGoogle Scholar
  46. 46.
    Van Deventer SJ, Wedel MK, Baker BFet al. (2006) A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis. Aliment Pharmacol Ther 23: 1415–1425CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2007

Authors and Affiliations

  1. 1.Zentrum für KinderheilkundeUniversitätsklinikum BonnBonnDeutschland

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