Der Gastroenterologe

, Volume 8, Issue 3, pp 205–210 | Cite as

Therapie der CED bei Steroidversagen

Immunsuppressiva oder Biologika?
Schwerpunkt

Zusammenfassung

Trotz oftmals erfolgreichem Einsatz von systemischen Steroiden in der Behandlung von Patienten mit aktiver chronisch-entzündlicher Darmerkrankung (CED) sind Limitationen vorhanden aufgrund von primärem Nichtansprechen, Steroidabhängigkeit sowie Steroidresistenz. Eine Langzeittherapie mit Steroiden ist im Hinblick auf die bekannten Nebenwirkungen zu vermeiden. Dieser Artikel erläutert Indikationen für den Einsatz von Immunmodulatoren (Azathioprin, 6-Mercaptopurin, Methotrexat), Medikamenten gegen Tumornekrosefaktor (Anti-TNF-Therapie) sowie Calcineurininhibitoren (Ciclosporin, Tacrolimus) bei Steroidresistenz.

Schlüsselwörter

Morbus Crohn Colitis ulcerosa Steroidresistenz Immunmodulatoren Anti-TNF-Therapie 

Therapy of steroid resistant inflammatory bowel disease

Immunomodulators or biologicals?

Abstract

Although systemic corticosteroids are often successfully applied for induction of clinical response and remission of inflammatory bowel disease (IBD) patients presenting with a flare, a proportion of these treated patients present with a primary non-response to steroids, resistance or steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided given the high frequency of adverse treatment effects. This article highlights the indications for the use of immunomodulators (e.g. azathioprine, 6-mercaptopurine and methotrexate), drugs directed against tumor necrosis factor (anti-TNF) as well as calcineurin inhibitors (e.g. cyclosporine and tacrolimus).

Keywords

Crohn’s disease Ulcerative colitis Steroid resistance Immunomodulators Anti-TNF therapy 

Notes

Interessenkonflikt

Der korrespondierende Autor weist für sich und seinen Koautor auf folgende Beziehungen hin: Beraterhonorare von Abbott Schweiz, MSD Schweiz, UCB Schweiz.

Literatur

  1. 1.
    Alfadhli AA, Mcdonald JW, Feagan BG (2005) Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev: CD003459Google Scholar
  2. 2.
    Barnes PJ, Adcock IM (2009) Glucocorticoid resistance in inflammatory diseases. Lancet 373: 1905–1917PubMedCrossRefGoogle Scholar
  3. 3.
    Bossa F, Fiorella S, Caruso N et al (2007) Continuous infusion versus bolus administration of steroids in severe attacks of ulcerative colitis: a randomized, double-blind trial. Am J Gastroenterol 102: 601–608PubMedCrossRefGoogle Scholar
  4. 4.
    Caprilli R, Gassull MA, Escher JC et al (2006) European evidence based consensus on the diagnosis and management of Crohn’s disease: special situations. Gut 55(Suppl 1): i36–i158PubMedCrossRefGoogle Scholar
  5. 5.
    Chouchana L, Narjoz C, Beaune P et al (2012) Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease. Aliment Pharmacol Ther 35: 15–36PubMedCrossRefGoogle Scholar
  6. 6.
    Colombel JF, Sandborn WJ, Reinisch W et al (2010) Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 362: 1383–1395PubMedCrossRefGoogle Scholar
  7. 7.
    Colombel JF, Sandborn WJ, Rutgeerts P et al (2007) Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 132: 52–65PubMedCrossRefGoogle Scholar
  8. 8.
    Creed TJ, Probert CS (2007) Review article: steroid resistance in inflammatory bowel disease – mechanisms and therapeutic strategies. Aliment Pharmacol Ther 25: 111–122PubMedCrossRefGoogle Scholar
  9. 9.
    D’haens G, Sandborn WJ, Feagan BG et al (2007) A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology 132: 763–786CrossRefGoogle Scholar
  10. 10.
    Dignass A ER, Magro F, Maaser CH (2012) Second EUROPEAN evidence-based Consensus onthe diagnosis and management of ulcerative colitis: definitions and diagnosis. J Crohns Colitis. http://dx.doi.org/10.1016/j.crohns.2012.09.003Google Scholar
  11. 11.
    Dignass A LJ, Sturm A (2012) Second European evidence-based Consensus on the diagnosis and management of ulcerative colitis: current management. J Crohns Colitis http://dx.doi.org/10.1016/j.crohns.2012.09.002Google Scholar
  12. 12.
    Dignass A, Preiss JC, Aust DE et al (2011) Updated German guideline on diagnosis and treatment of ulcerative colitis, 2011. Z Gastroenterol 49: 1276–1341PubMedCrossRefGoogle Scholar
  13. 13.
    Dignass A, Van Assche G, Lindsay JO et al (2010) The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 4: 28–62PubMedCrossRefGoogle Scholar
  14. 14.
    Faubion WA Jr, Loftus EV Jr, Harmsen WS et al (2001) The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 121: 255–260PubMedCrossRefGoogle Scholar
  15. 15.
    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 591PubMedCrossRefGoogle Scholar
  16. 16.
    Lemann M, Mary JY, Duclos B et al (2006) Infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial. Gastroenterology 130: 1054–1061PubMedCrossRefGoogle Scholar
  17. 17.
    Lichtenstein GR, Abreu MT, Cohen R et al (2006) American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 130: 940–987PubMedCrossRefGoogle Scholar
  18. 18.
    Manz M, Michetti P, Seibold F et al (2011) Treatment algorithm for moderate to severe ulcerative colitis. Swiss Med Wkly 141: w13235PubMedGoogle Scholar
  19. 19.
    Mowat C, Cole A, Windsor A et al (2011) Guidelines for the management of inflammatory bowel disease in adults. Gut 60: 571–607PubMedCrossRefGoogle Scholar
  20. 20.
    Munkholm P, Langholz E, Davidsen M et al (1994) Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut 35: 360–362PubMedCrossRefGoogle Scholar
  21. 21.
    Patel V, Macdonald JK, Mcdonald JW et al (2009) Methotrexate for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev: CD006884Google Scholar
  22. 22.
    Pola S, Patel D, Ramamoorthy S et al (2012) Strategies for the care of adults hospitalized for active ulcerative colitis. Clin Gastroenterol Hepatol 10: 1315–1325 e1314PubMedCrossRefGoogle Scholar
  23. 23.
    Prefontaine E, Macdonald JK, Sutherland LR (2010) Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev: CD000545Google Scholar
  24. 24.
    Prefontaine E, Sutherland LR, Macdonald JK et al (2009) Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev: CD000067Google Scholar
  25. 25.
    Reinisch W, Sandborn WJ, Rutgeerts P et al (2012) Long-term infliximab maintenance therapy for ulcerative colitis: the ACT-1 and -2 extension studies. Inflamm Bowel Dis 18: 201–211PubMedCrossRefGoogle Scholar
  26. 26.
    Rutgeerts P, Sandborn WJ, Feagan BG et al (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353: 2462–2476PubMedCrossRefGoogle Scholar
  27. 27.
    Sandborn WJ, Van Assche G, Reinisch W et al (2012) Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 142: 257–265 e251–e253PubMedCrossRefGoogle Scholar
  28. 28.
    Schreiber S, Khaliq-Kareemi M, Lawrance IC et al (2007) Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med 357: 239–250PubMedCrossRefGoogle Scholar
  29. 29.
    Stange EF, Travis SP, Vermeire S et al (2006) European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. Gut 55 (Suppl 1): i1–i15PubMedCrossRefGoogle Scholar
  30. 30.
    Steinhart AH, Ewe K, Griffiths AM et al (2003) Corticosteroids for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev: CD000301Google Scholar
  31. 31.
    Taylor KM, Irving PM (2011) Optimization of conventional therapy in patients with IBD. Nature reviews. Gastroenterol Hepatol 8: 646–656Google Scholar
  32. 32.
    Travis SP, Stange EF, Lemann M et al (2006) European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut 55 (Suppl 1): i16–i35PubMedCrossRefGoogle Scholar
  33. 33.
    Turner D, Walsh CM, Steinhart AH et al (2007) Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol 5: 103–110PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Abteilung für Gastroenterologie und HepatologieClaraspitalBaselSchweiz
  2. 2.Division de Gastroentérologie et d’HépatologieCentre Hospitalier Universitaire Vaudois/CHUVLausanneSchweiz

Personalised recommendations