Drugs

, Volume 66, Issue 16, pp 2059–2065 | Cite as

Anti-Tumour Necrosis Factor Therapy for Ulcerative Colitis

Evidence to Date
  • Chandrashekhar Thukral
  • Adam Cheifetz
  • Mark A. Peppercorn
Leading Article

Abstract

Infliximab, the chimeric monoclonal antibody directed against tumour necrosis factor (TNF)-α, has profoundly changed therapy for Crohn’s disease (CD). However, for ulcerative colitis (UC), before the publication of ACT 1 and ACT 2 (Active Ulcerative Colitis Trials 1 and 2), there were only a few open-label and controlled trials that evaluated the role of infliximab in the treatment of UC. Results from these earlier studies were equivocal and ambiguous. However, the ACT 1 and ACT 2 trials were large, randomised and placebo-controlled, and have shown that infliximab is significantly more efficacious than placebo in treating both corticosteroid-responsive and -refractory moderate to severe UC. Data from these two studies showed that in patients with moderate to severe UC, treatment with infliximab (5 and 10 mg/kg), compared with placebo, led to significantly higher rates of clinical response, clinical remission and mucosal healing. However, a significant proportion of patients who were receiving oral corticosteroids at the start of the trials, remained on corticosteroids despite infliximab therapy. Additionally, the safety profile of the drug was found to be similar to what has been reported in clinical studies of infliximab in patients with CD.

On the basis of currently available data, we use infliximab as a remission-inducing agent in patients who have moderate to severe UC and are either refractory to or intolerant of mesalazine (5-ASA) products and immunomodulators. Moreover, infliximab seems to be a reasonable therapeutic modality for remission maintenance in those patients with UC in whom mesalazine products and immunomodulators have failed. Although data are limited, infliximab may be considered as a remission-inducing agent in patients with moderate to severe UC which is refractory to oral corticosteroids. However, the role of infliximab in the treatment of UC patients who are dependent on oral corticosteroids is still unclear and, therefore, should be considered only in patients who cannot be successfully transitioned to or are intolerant of oral immunomodulators. Furthermore, infliximab may be an alternative to ciclosporin (cyclosporin) in hospitalised patients with severe to moderately severe but not fulminant UC who do not respond to intravenous corticosteroids. At present, there is insufficient evidence to advocate using infliximab as a first-line agent for UC patients with mild or moderate to severe disease. Future randomised, controlled trials with clearly defined patient populations should further help to clarify the definitive role of infliximab in the therapeutic scheme for UC.

Notes

Acknowledgements

Dr Peppercorn is on the speakers’ bureau for Procter & Gamble, TAP and Solvay. Dr Cheifetz is on the speakers’ bureau for Centocor, Procter & Gamble and Salix. Dr Thukral has no conflicts of interest directly relevant to the contents of this review. No sources of funding were used to assist in the preparation of this review.

References

  1. 1.
    Farrell RJ, Banerjee S, Peppercorn MA. Recent advances in inflammatory bowel disease. Crit Rev Clin Lab Sci 2001; 38: 33–108PubMedCrossRefGoogle Scholar
  2. 2.
    Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417–29PubMedCrossRefGoogle Scholar
  3. 3.
    Hanauer S. Medical therapy for ulcerative colitis 2004. Gastroenterology 2004; 126: 1582–92PubMedCrossRefGoogle Scholar
  4. 4.
    Hanauer S, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomized trial. Lancet 2002; 359: 1541–9PubMedCrossRefGoogle Scholar
  5. 5.
    Egan LJ, Sandborn WJ. Advances in the treatment of Crohn’s disease. Gastroenterology 2004; 126: 1574–81PubMedCrossRefGoogle Scholar
  6. 6.
    Murch SH, Lamkin VA, Savage MO, et al. Serum concentrations of tumor necrosis factor in childhood chronic inflammatory bowel disease. Gut 1991; 32: 913–7PubMedCrossRefGoogle Scholar
  7. 7.
    Schurmann G, Betzler M, Post S, et al. Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn’s disease and ulcerative colitis: preoperative levels and postoperative changes in serum concentrations. Digestion 1992; 51: 51–9PubMedCrossRefGoogle Scholar
  8. 8.
    Masuda H, Iwai S, Tanaka T, et al. Expression of IL-8, TNF-alpha and IFN-gamma m-RNA in ulcerative colitis, particularly in patients with inactive phase. J Clin Lab Immunol 1995; 46: 111–23PubMedGoogle Scholar
  9. 9.
    Reinecker HC, Steffen M, Witthoeft T, et al. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn’s disease. Clin Exp Immunol 1993; 94: 174–81PubMedCrossRefGoogle Scholar
  10. 10.
    Watkins PE, Warren BF, Stephens S, et al. Treatment of ulcerative colitis in the cottontop tamarin using antibody to tumour necrosis factor alpha. Gut 1997; 40: 628–33PubMedGoogle Scholar
  11. 11.
    Chey WY. Infliximab for patients with refractory ulcerative colitis. Inflamm Bowel Dis 2001; 7 Suppl. 1: S30–3PubMedCrossRefGoogle Scholar
  12. 12.
    Kaser A, Mairinger T, Vogel W, et al. Infliximab in severe steroid-refractory ulcerative colitis: a pilot study. Wien Klin Wochenschr 2001; 113: 930–3PubMedGoogle Scholar
  13. 13.
    Kohn A, Prantera C, Pera A, et al. Anti-tumour necrosis factor alpha (infliximab) in the treatment of severe ulcerative colitis: result of an open label study on 13 patients. Dig Liv Dis 2002; 34: 626–30CrossRefGoogle Scholar
  14. 14.
    Su C, Salzberg BA, Lewis JD, et al. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol 2002; 97: 2577–84PubMedCrossRefGoogle Scholar
  15. 15.
    Regueiro M, Curtis J, Plevy S. Infliximab for hospitalized patients with severe ulcerative colitis. J Clin Gastroenterol 2006; 40: 476–81PubMedCrossRefGoogle Scholar
  16. 16.
    Ochsenkuhn T, Sackmann M, Goeke B. Infliximab for acute, non steroid refractory ulcerative colitis: a randomized pilot study. Eur J Gastroenterol Hepatol 2004; 16: 1167–71PubMedCrossRefGoogle Scholar
  17. 17.
    Armuzzi A, De Pascalis B, Lupascu P, et al. Infliximab in the treatment of steroid dependant ulcerative colitis. Eur Rev Med Pharmacol Sci 2004; 8: 213–33Google Scholar
  18. 18.
    Armuzzi A, Lupascu P, De Pascalis B, et al. Infliximab in the treatment of glucocorticoid dependant ulcerative colitis: a 54-week randomized methylprednisolone-controlled trial [abstract]. Gastroenterology 2005; 128 Suppl. 2: W1008Google Scholar
  19. 19.
    Probert CS, Hearing SD, Schreiber S, et al. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomized controlled trial. Gut 2003; 52: 998–1002PubMedCrossRefGoogle Scholar
  20. 20.
    Actis GC, Bruno M, Pinna-Pintor M, et al. Infliximab for treatment of steroid-refractory ulcerative colitis. Dig Liver Dis 2002; 34: 631–4PubMedCrossRefGoogle Scholar
  21. 21.
    Sands BE, Tremaine WJ, Sandborn WJ, et al. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm Bowel Dis 2001; 7: 83–8PubMedCrossRefGoogle Scholar
  22. 22.
    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
  23. 23.
    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
  24. 24.
    Fazio VW, Zuv Y, Church JM, et al. Ileal pouch-anal anastomosis: complications and function in 1005 patients. Ann Surg 1995; 222: 120–7PubMedCrossRefGoogle Scholar
  25. 25.
    Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis and treatment. Gastroenterology 1994, 60Google Scholar
  26. 26.
    Shen B, Fazio VW, Remzi FH, et al. Clinical approaches to diseases of ileal pouch-anal anastomosis. Am J Gastroenterol 2005; 100: 2796–807PubMedCrossRefGoogle Scholar
  27. 27.
    Viscido A, Habib FI, Kohn A, et al. Infliximab in refractory pouchitis complicated by fistulae following ileo-anal pouch for ulcerative colitis. Aliment Pharmacol Ther 2003; 17: 1263–71PubMedCrossRefGoogle Scholar
  28. 28.
    Evans RC, Clarke L, Heath P, et al. Treatment of ulcerative colitis with an engineered human anti-TNF alpha antibody CDP571. Aliment Pharmacol Ther 1997; 11: 1031–5PubMedCrossRefGoogle Scholar
  29. 29.
    Iyer S, Kontoyiannis D, Chevrier D, et al. Inhibition of tumor necrosis factor mRNA translation by a rationally designed immunomodulatory peptide. J Biol Chem 2000; 275: 17051–7PubMedCrossRefGoogle Scholar
  30. 30.
    Iyer S, Lahana R, Buelow R. Rational design and development of RDP58. Curr Pharm Des 2002; 8: 2217–29PubMedCrossRefGoogle Scholar
  31. 31.
    Travis S, Yap L, Hawkey CJ. Novel and effective therapy for ulcerative colitis: results of parallel, prospective, placebo-controlled trials [abstract]. Am J Gastroenterol 2003; 98: S239CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Chandrashekhar Thukral
    • 1
  • Adam Cheifetz
    • 1
  • Mark A. Peppercorn
    • 1
  1. 1.Division of Gastroenterology, Center for Inflammatory Bowel Disease, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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