Optimizing biologic therapies for inflammatory bowel disease (ulcerative colitis and crohn’s disease)

  • Marc Ferrante
  • Geert D’Haens
  • Paul Rutgeerts
  • Séverine Vermeire
  • Gert Van Assche
Article

Abstract

The introduction of biologic agents and particularly of anti-tumor necrosis factor antibodies dramatically changed the therapeutic algorithm in patients with inflammatory bowel diseases. Although the efficacy of these agents has been demonstrated clearly, optimal treatment strategies are debated. Recent trials advocate the introduction of biologic agents at an early stage to prevent debilitating complications. However, significant adverse events have led to careful selection of patients who will benefit most from long-term treatment with biologic agents. Once on biologic therapy, scheduled maintenance therapy is recommended to minimize the risk of loss of response. Nevertheless, treatment adaptation is frequently necessary in patients who lose response. Interventions encompass strategies to increase drug exposure by increasing the dose or decreasing the dosing interval, or by changing to another biologic agent. Finally, it remains unclear if and when a biologic agent can be stopped in patients with long-standing remission.

References and Recommended Reading

  1. 1.
    Sandborn WJ: Current directions in IBD therapy: what goals are feasible with biological modifiers? Gastroenterology 2008, 135:1442–1447.CrossRefPubMedGoogle Scholar
  2. 2.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al.: Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002, 359:1541–1549.CrossRefPubMedGoogle Scholar
  3. 3.
    Hanauer SB, Sandborn WJ, Rutgeerts P, et al.: Human antitumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology 2006, 130:323–333.CrossRefPubMedGoogle Scholar
  4. 4.
    Sandborn WJ, Feagan BG, Stoinov S, et al.: Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med 2007, 357:228–238.CrossRefPubMedGoogle Scholar
  5. 5.
    Colombel JF, Sandborn WJ, Rutgeerts P, et al.: Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 2007, 132:52–65.CrossRefPubMedGoogle Scholar
  6. 6.
    Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al.: Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med 2007, 357:239–250.CrossRefPubMedGoogle Scholar
  7. 7.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al.: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005, 353:2462–2476.CrossRefPubMedGoogle Scholar
  8. 8.
    Baert F, Noman M, Vermeire S, et al.: Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 2003, 348:601–608.CrossRefPubMedGoogle Scholar
  9. 9.
    Sandborn WJ, Rutgeerts P, Enns R, et al.: Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med 2007, 146:829–838.PubMedGoogle Scholar
  10. 10.
    Sandborn WJ, Colombel JF, Enns R, et al.: Natalizumab induction and maintenance therapy for Crohn’s disease. N Engl J Med 2005, 353:1912–1925.CrossRefPubMedGoogle Scholar
  11. 11.
    Van Assche G, Van Ranst M, Sciot R, et al.: Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 2005, 353:362–368.CrossRefPubMedGoogle Scholar
  12. 12.
    Su C, Lichtenstein GR: Are there predictors of remicade treatment success or failure? Adv Drug Deliv Rev 2005, 57:237–245.CrossRefPubMedGoogle Scholar
  13. 13.
    Cosnes J, Cattan S, Blain A, et al.: Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis 2002, 8:244–250.CrossRefPubMedGoogle Scholar
  14. 14.
    D’Haens G, Baert F, van Assche G, et al.: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial. Lancet 2008, 371:660–667.CrossRefPubMedGoogle Scholar
  15. 15.
    Colombel JF, Rutgeerts P, Reinisch W, et al.: SONIC: a randomized, double-blind, controlled trial comparing infliximab and infliximab plus azathioprine to azathioprine in patients with Crohn’s disease naive to immunomodulators and biological therapy. Gut 2009, 57:A1.Google Scholar
  16. 16.
    Sandborn WJ, Rutgeerts PJ, Reinisch W, et al.: One year data from the Sonic study: a randomized, double-blind trial comparing infliximab and infliximab plus azathioprine to azathioprine in patients with Crohn’s disease naive to immunomodulators and biologic therapy. Gastroenterology 2009, 136:A116.Google Scholar
  17. 17.
    Targan SR, Feagan BG, Fedorak RN, et al.: Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE Trial. Gastroenterology 2007, 132:1672–1683.CrossRefPubMedGoogle Scholar
  18. 18.
    Schreiber S, Rutgeerts P, Fedorak RN, et al.: A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology 2005, 129:807–818.CrossRefPubMedGoogle Scholar
  19. 19.
    Maser EA, Villela R, Silverberg MS, Greenberg GR: Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin.Gastroenterol.Hepatol. 2006, 4:1248–1254.CrossRefPubMedGoogle Scholar
  20. 20.
    Farrell RJ, Alsahli M, Jeen YT, et al.: Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 2003, 124:917–924.CrossRefPubMedGoogle Scholar
  21. 21.
    Hanauer SB, Wagner CL, Bala M, et al.: Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2004, 2:542–553.CrossRefPubMedGoogle Scholar
  22. 22.
    Vermeire S, Noman M, Van Assche G, et al.: Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut 2007, 56:1226–1231.CrossRefPubMedGoogle Scholar
  23. 23.
    Karmiris K, Paintaud G, Degenne D, et al.: Antibodies against adalimumab in Crohn’s disease patients who failed infliximab treatment: correlation with clinical response and trough serum levels. Gut 2008, 57:A67.Google Scholar
  24. 24.
    Sandborn WJ, Hanauer SB, Rutgeerts P, et al.: Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut 2007, 56:1232–1239.CrossRefPubMedGoogle Scholar
  25. 25.
    Schnitzler F, Fidder H, Ferrante M, et al.: Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut 2009, 58:492–500.CrossRefPubMedGoogle Scholar
  26. 26.
    Sands BE, Anderson FH, Bernstein CN, et al.: Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004, 350:876–885.CrossRefPubMedGoogle Scholar
  27. 27.
    Afif W, Loftus EV, Faubion WA, et al.: Clinical utility of measuring infliximab and human anti-chimeric antibody levels in patients with inflammatory bowel disease. Gastroenterology 2009, 136:A147.CrossRefGoogle Scholar
  28. 28.
    Van Assche G, Magdelaine-Beuzelin C, D’Haens G, et al.: Withdrawal of immunosuppression in Crohn’s disease treated with scheduled infliximab maintenance: a randomized trial. Gastroenterology 2008, 134:1861–1868.CrossRefPubMedGoogle Scholar
  29. 29.
    Lemann M, Mary JY, Duclos B, et al.: Infliximab plus azathioprine for steroid-dependent Crohn’s disease patients: a randomized placebo-controlled trial. Gastroenterology 2006, 130:1054–1061.CrossRefPubMedGoogle Scholar
  30. 30.
    Louis E, Vernier-Massouille G, Grimaud JC, et al.: Infliximab discontinuation in Crohn’s disease patients in stable remission on combined therapy with immunosuppressors: a prospective ongoing cohort study. Gastroenterology 2009, 136:A146.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Marc Ferrante
  • Geert D’Haens
  • Paul Rutgeerts
  • Séverine Vermeire
  • Gert Van Assche
    • 1
  1. 1.Department of GastroenterologyUniversity Hospital GasthuisbergLeuvenBelgium

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