Current Gastroenterology Reports

, Volume 3, Issue 6, pp 471–476

Evolving medical therapies for crohn’s disease

  • Uma Mahadevan
  • William J. Sandborn
Article

Abstract

Medical therapy for Crohn’s disease has changed dramatically over the past few years. Physicians have become increasingly willing to use traditional immunosuppressive agents such as azathioprine/6-mercaptopurine (6-MP) and methotrexate as well as new biologic therapies such as infliximab. Azathioprine, 6-MP, and methotrexate have demonstrated efficacy in induction and maintenance of remission in Crohn’s disease. 6-MP has also demonstrated efficacy in the pediatric population and possibly as first-line therapy. As use of the purine metabolites grows, therapeutic drug monitoring for efficacy and toxicity will become an emerging area of interest. With respect to the biologic therapies, infliximab is increasingly used to treat patients with difficult disease; however, knowledge is still evolving regarding optimal dosing schedules and the significance of immune reactions to the compound. A humanized anti-tumor necrosis factor antibody, CDP571, may be less immunogenic. Interleukin-10 did not consistently demonstrate benefit in Crohn’s disease. Similarly, antisense to intracellular adhesion molecule 1 (ISIS 2302) was not efficacious when administered either subcutaneously or intravenously. Finally, growth hormone has shown promising results in a small trial.

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References and Recommended Reading

  1. 1.
    Pearson DC, May GR, Fick GH, Sutherland LR: Azathioprine and 6-mercaptopurine in Crohn disease: a meta-analysis. Ann Intern Med 1995, 123:132–142. Meta-analysis of multiple trials of purine analogues.PubMedGoogle Scholar
  2. 2.
    Markowitz J, McKinley M, Kahn E, et al.: Endoscopic screening for dysplasia and mucosal aneuploidy in adolescents and young adults with childhood onset colitis. Am J Gastroenterol 1997, 92:2001–2006. First prospective trial of purine analogues in children and adolescents.PubMedGoogle Scholar
  3. 3.
    Dubinsky MC, Lamothe S, Yang HY, et al.: Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000, 118:705–713. Study of various types of therapeutic drug monitoring and pharmacogenetic assessment of response to and toxicity from 6-MP.PubMedCrossRefGoogle Scholar
  4. 4.
    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, 332:292–297.PubMedCrossRefGoogle Scholar
  5. 5.
    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, 342:1627–1632. This report demonstrates the benefit of methotrexate for maintenance of remission.PubMedCrossRefGoogle Scholar
  6. 6.
    Te HS, Schiano TD, Kuan SF, et al.: Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease. Am J Gastroenterol 2000, 95:3150–3156.PubMedCrossRefGoogle Scholar
  7. 7.
    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’s disease: Crohn’s Disease cA2 Study Group. N Engl J Med 1997, 337:1029–1035. Landmark paper on the use of anti-TNF therapy in Crohn’s disease.PubMedCrossRefGoogle Scholar
  8. 8.
    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, 340:1398–405.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanauer SLG, Columbel JF, Linchtenstein, GR et al.: Maintenance infliximab (Remicade) is safe, effective and steroidsparing in Crohn’s disease: preliminary results of the Accent I trial. Gastroenterology2001, 120(suppl):A21.CrossRefGoogle Scholar
  10. 10.
    Remicade (infliximab): prescribing information. In Physician’s Desk Reference, edn 55. Montvale, NJ; Medical Economics:1085–1088.Google Scholar
  11. 11.
    Farrell RJ, Alsah M, Falchuk P, et al.: Human anti-chimeric antibody levels correlate with lack of response and infusion reactions following infliximab therapy [abstract]. Gastroenterology 2001, 120:A69.CrossRefGoogle Scholar
  12. 12.
    Bickston SJ, Lichtenstein GR, Arseneau KO, et al.: The relationship between infliximab treatment and lymphoma in Crohn’s disease. Gastroenterology 1999, 117:1433–1437.PubMedCrossRefGoogle Scholar
  13. 13.
    Sandborn WJ, Feagan BG, Hanauer SB: An engineered human antibody to TNF (CDP571) for active Crohn’s disease: a randomized double-blind placebo-controlled trial. Gastroenterology 2001, 120:1330–1338.PubMedCrossRefGoogle Scholar
  14. 14.
    Feagan BG, Baker JP, Feagan BG, Sandborn WJ, Baker JP, et al.: A randomized, double-blind, placebo-controlled, multi-center trial of the engineered human antibody to TNF (CDP571) for steroid sparing and maintenance of remission in patients with steroid-dependent Crohns disease [abstract]. Gastroenterology 2000, 118(suppl 2):A655.CrossRefGoogle Scholar
  15. 15.
    van DeventerSJ, Elson CO, Fedorak RN: Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Crohn’s Disease Study Group. Gastroenterology 1997, 113:383–389. Only trial of IL-10 to demonstrate significant benefit over placebo.PubMedCrossRefGoogle Scholar
  16. 16.
    Schreiber S, Fedorak RN, Nielsen OH, et al.: Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn’s disease. Gastroenterology 2000, 119:1461–1472.PubMedCrossRefGoogle Scholar
  17. 17.
    Fedorak RN, Gangl A, Elson CO, et al.: Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease. Gastroenterology 2000, 119:1473–1482.PubMedCrossRefGoogle Scholar
  18. 18.
    Fedorak RN, Nielson DH, Williams NC, et al.: Human recombinant interleukin-10 is safe and well tolerated but does not induce remission in steroid dependent Crohn’s disease.Gastroenterology 2001, 120(suppl 1):A681.Google Scholar
  19. 19.
    Yacyshyn BR, Bowen-Yacyshyn MB, Jewell L, et al.: A placebocontrolled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn’s disease. Gastroenterology 1998, 114:1133–1142.PubMedCrossRefGoogle Scholar
  20. 20.
    Yacyshyn BR, Chey Wy, Goff J, et al.: Double-blinded, randomized, placebo-controlled trial of the remission inducing and steroid sparing properties of two schedules of ISIS 2302 (ICAM-1 Antisense) in active, steroid-dependent Crohn’s disease. Gastroenterology2000, 118(suppl):A570.Google Scholar
  21. 21.
    SchreiberS, Nickolaus S, Malchow H, et al.: Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn’s disease. Gastroenterology 2001, 120:1339–1346. This is a novel therapeutic modality, although results are disappointing.PubMedCrossRefGoogle Scholar
  22. 22.
    Sartor RB: New therapeutic approaches to Crohn’s disease. N Engl J Med 2000, 342:1664–1666.PubMedCrossRefGoogle Scholar
  23. 23.
    Slonim AE, Bulone L, Damore MB, et al.: A preliminary study of growth hormone therapy for Crohn’s disease. N Engl J Med 2000, 342:1633–1637.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • Uma Mahadevan
    • 1
  • William J. Sandborn
    • 1
  1. 1.Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA

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