Update on the Management of Ulcerative Colitis

  • Sahar Taba Taba Vakili Department of Internal Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Mohammad Taher Department of Internal Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  • Nasser Ebrahimi Daryani Department of Gastroenterology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Keywords:
Ulcerative Colitis, Inflammatory bowel diseases, Therapeutics

Abstract

The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid- dependent or steroid- refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid- refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who have moderately to severely active UC with an inadequate response to conventional agents such as aminosalicylates, corticosteroids, or immunomodulators. Other anti-TNF agents and biologic therapies are undergoing evaluation in clinical trials for their efficacy in IBD. Most patients who start biologics should continue treatment for the foreseeable future and potential consequences of discontinuation should be discussed with individual patients. Currently, data do not exist to administer biologics as first-line therapy in UC. Emerging data suggest that biologics may have the potential to prevent complications and limit disease progression. If such benefits are proven, biologics may be used in the future to modulate subclinical inflammation and to prevent the development of clinical disease.

References

Adibi P, Mollakhalili P, Fallah Z, Daryani NE, Ajdarkosh H, Khedmat H, Derakhshan F, Karbassi A, Ashkzari M, Tavakkoli H. Promising effect of infliximab on the extent

Mehrjardi A, Saber Afsharian M, Mirskandari M, Ebrahimi Daryani N, Faghihi A, Iranikhah T. Comparison of fecal calprotectin level in inflammatory bowel disease and irritable bowel syndrome. Govaresh 2010:14(4):275-8.

D’Haens G. Risks and benefits of biologic therapy for inflammatory bowel diseases. Gut 2007;56(5):725-32.

de Zoeten E, Mamula P. What are the guidelines for using biologics in pediatric patients? Inflamm Bowel Dis 2008;14 Suppl 2:S259-61.

Daryani NE, Bashashati M, Aram S, Hashtroudi AA, Shakiba M, Sayyah A, Nayer-Habibi A. Pattern of relapses in Iranian patients with ulcerative colitis. A prospective study. J Gastrointestin Liver Dis 2006;15(4):355-8.

Lees CW, Heys D, Ho GT, Noble CL, Shand AG, Mowat C, Boulton-Jones R, Williams A, Church N, Satsangi J, Arnott ID; Scottish Society of Gastroenterology Infliximab Group. A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis. Aliment Pharmacol Ther 2007;26(3):411-9.

Bianchi Porro G, Cassinotti A, Ferrara E, Maconi G, Ardizzone S. Review article: the management of steroid dependency in ulcerative colitis. Aliment Pharmacol Ther 2007;26(6):779-94.

Carter M, Lobo A, Travis S. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004;53(suppl 5):V1-V16.

Lawson MM, Thomas AG, Akobeng AK. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2006;(3):CD005112.

Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002;50(4):485-9.

Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial ofazathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut 2006;55(1): 47-53.

Gisbert JP, Linares PM, McNicholl AG, Maté J, Gomollón F. Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis. Aliment Pharmacol Ther 2009;30(2):126-37.

Talley NJ, Abreu MT, Achkar JP, Bernstein CN, Dubinsky MC, Hanauer SB, Kane SV, Sandborn WJ, Ullman TA, Moayyedi P; American College of Gastroenterology IBD Task Force. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol 2011;106 Suppl 1:S2- 25; quiz S26.

Khan KJ, Dubinsky MC, Ford AC, Ullman TA, Talley NJ, Moayyedi P. Efficacy of immunosuppressive therapy for inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 2011;106(4):630-42.

Gisbert JP, Niño P, Cara C, Rodrigo L. Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients. Aliment Pharmacol Ther 2008;28(2):228-38.

Mantzaris GJ, Sfakianakis M, Archavlis E, Petraki K, Christidou A, Karagiannidis A, Triadaphyllou G. A prospective randomized observer-blind 2-year trial of azathioprine monotherapy versus azathioprine and olsalazine for the maintenance of remission of steroiddependent ulcerative colitis. Am J Gastroenterol 2004;99(6):1122-8.

Gearry RB, Barclay ML. Azathioprine and 6- mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. J Gastroenterol Hepatol 2005;20(8):1149-57.

Ban H, Andoh A, Imaeda H, Kobori A, Bamba S, Tsujikawa T, Sasaki M, Saito Y, Fujiyama Y. The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease. J Gastroenterol 2010;45(10):1014-21.

Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6- mercaptopurine. Gut 2005;54(8):1121-5.

Durai D, Hawthorne AB. Review article: how and when to use ciclosporin in ulcerative colitis. Aliment Pharmacol Ther 2005;22(10):907-16.

Loftus CG, Loftus EV Jr, Sandborn WJ. Cyclosporin for refractory ulcerative colitis. Gut 2003;52(2):172-3.

Sandborn W. A critical review of cyclosporin therapy in inflammatory bowel disease. Inflamm Bowel Dis 1995;1:48-63.

Actis GC, Ottobrelli A, Pera A, Barletti C, Ponti V, Pinna-Pintor M, Verme G. Continuously infused cyclosporine at low dose is sufficient to avoid emergency colectomy in acute attacks of ulcerative colitis without theneed for high-dose steroids. J Clin Gastroenterol 1993;17(1):10-3.

Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994;330(26):1841-5.

D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, Peeters M, Vermeire S, Penninckx F, Nevens F, Hiele M, Rutgeerts P. Intravenous cyclosporine versus intravenous corticosteroids as singletherapy for severe attacks of ulcerative colitis. Gastroenterology 2001;120(6):1323-9.

Lichtenstein GR, Abreu MT, Cohen R, Tremaine W; American Gastroenterological Association. American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006;130(3):940-87.

Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, Arts J, D'Hoore A, Penninckx F, Rutgeerts P. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology 2003;125(4):1025-31.

Actis GC, Fadda M, David E, Sapino A. Colectomy rate in steroid-refractory colitis initially responsive to cyclosporin: a long-term retrospective cohort study. BMC Gastroenterol 2007;7:13.

Fernández-Bañares F, Bertrán X, Esteve-Comas M, Cabré E, Menacho M, Humbert P, Planas R, Gassull MA. Azathioprine is useful in maintaining long-term remission induced by intravenous cyclosporine in steroid-refractory severe ulcerative colitis. Am J Gastroenterol 1996;91(12):2498-9.

Message L, Bourreille A, Laharie D, Quinton A, Galmiche JP, Lamouliatte H, Alamdari A, Zerbib F. Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids. Gastroenterol Clin Biol 2005;29(3):231-5.

Bamba S, Tsujikawa T, Inatomi O, Nakahara T, Koizumi Y, Saitoh Y, Sasaki M, Fujiyama Y, Andoh A. Factors affecting the efficacy of cyclosporin A therapy for refractory ulcerative colitis. J Gastroenterol Hepatol 2010;25(3):494-8.

Kornbluth A, Present DH, Lichtiger S, Hanauer S. Cyclosporin for severe ulcerative colitis: a user's guide. Am J Gastroenterol 1997;92(9):1424-8.

Aberra FN, Lichtenstein GR. Review article: monitoring of immunomodulators in inflammatory bowel disease. Aliment Pharmacol Ther 2005;21(4):307-19.

Cheifetz AS, Stern J, Garud S, Goldstein E, Malter L, Moss AC, Present DH. Cyclosporine is safe and effective in patients with severe ulcerative colitis. J Clin Gastroenterol 2011;45(2):107-12.

Järnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlén P, Grännö C, Vilien M, Ström M, Danielsson A, Verbaan H, Hellström PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 2005;128(7):1805-11.

Fellermann K, Tanko Z, Herrlinger KR, Witthoeft T, Homann N, Bruening A, Ludwig D, Stange EF. Response of refractory colitis to intravenous or oral tacrolimus (FK506). Inflamm Bowel Dis 2002;8(5):317-24.

Ogata H, Matsui T, Nakamura M, Iida M, Takazoe M, Suzuki Y, Hibi T. A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006;55(9):1255-62.

Baumgart DC, Macdonald JK, Feagan B. Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis. Cochrane Database Syst Rev 2008;(3):CD007216.

Baumgart DC, Pintoffl JP, Sturm A, Wiedenmann B, Dignass AU. Tacrolimus is safe and effective in patients with severe steroid-refractory or steroid-dependent inflammatory bowel disease: a long-term follow-up. Am J Gastroenterol 2006;101(5):1048-56.

Yamamoto S, Nakase H, Mikami S, Inoue S, Yoshino T, Takeda Y, Kasahara K, Ueno S, Uza N, Kitamura H, Tamaki H, Matsuura M, Inui K, Chiba T. Long-term effect of tacrolimus therapy in patients with refractory ulcerative colitis. Aliment Pharmacol Ther 2008; 28(5):589-97.

Naganuma M, Fujii T, Watanabe M. The use of traditional and newer calcineurin inhibitors in inflammatory bowel disease. J Gastroenterol 2011;46(2):129-37.

Patel V, Macdonald JK, McDonald JW, Chande N. Methotrexate for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev 2009;(4): CD006884.

Kozarek RA, Patterson DJ, Gelfand MD, Botoman VA, Ball TJ, Wilske KR. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 1989;110(5):353-6.

Maté-Jiménez J, Hermida C, Cantero-Perona J, Moreno- Otero R. 6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroiddependent inflammatory bowel disease. Eur J Gastroenterol Hepatol 2000;12(11):1227-33.

Paoluzi OA, Pica R, Marcheggiano A, Crispino P, IacopiniF, Iannoni C, Rivera M, Paoluzi P. Azathioprine or methotrexate in the treatment of patients with steroiddependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission. Aliment Pharmacol Ther 2002;16(10):1751-9.

Wahed M, Louis-Auguste JR, Baxter LM, Limdi JK, McCartney SA, Lindsay JO, Bloom SL. Efficacy of methotrexate in Crohn's disease and ulcerative colitis patients unresponsive or intolerant to azathioprine/ mercaptopurine. Aliment Pharmacol Ther 2009; 30(6):614-20.

Searles G, McKendry RJ. Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol 1987;14(6):1164-71.

Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 2009;68(7):1100-4.

Behrend M. A review of clinical experience with the novel immunosuppressive drug mycophenolate mofetil in renaltransplantation. Clin Nephrol 1996;45(5):336-41.

Ford AC, Towler RJ, Moayyedi P, Chalmers DM, Axon AT. Mycophenolate mofetil in refractory inflammatory bowel disease. Aliment Pharmacol Ther 2003;17(11):1365-9.

Palaniappan S, Ford AC, Greer D, Everett SM, Chalmers DM, Axon AT, Hamlin PJ. Mycophenolate mofetil therapy for refractory inflammatory bowel disease. Inflamm Bowel Dis 2007;13(12):1488-92.

Orth T, Peters M, Schlaak JF, Krummenauer F, Wanitschke R, Mayet WJ, Galle PR, Neurath MF. Mycophenolate mofetil versus azathioprine in patients with chronic active ulcerative colitis: a 12-month pilot study. Am J Gastroenterol 2000;95(5):1201-7.

Tan T, Lawrance IC. Use of mycophenolate mofetil in inflammatory bowel disease. World J Gastroenterol 2009;15(13):1594-9.

Owczarek D, Cibor D, Szczepanek M, Mach T. Biological therapy of inflammatory bowel disease. Pol Arch Med Wewn 2009;119(1-2):84-8.

Yanai H, Hanauer SB. Assessing response and loss of response to biological therapies in IBD. Am J Gastroenterol 2011;106(4):685-98.

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, Mayer L, Regueiro C, Rutgeerts P, Sandborn WJ, Sands BE, Schreiber S, Targan S, Travis S, Vermeire S. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21- 23, 2006. Gastroenterology 2007;133(1):312-39.

Blonski W, Buchner AM, Lichtenstein GR. Inflammatory bowel disease therapy: current state-of-the-art. Curr Opin Gastroenterol 2011;27(4):346-57.

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353(23):2462-76.

Su C, Salzberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, Stein RB, Adler DR, Lichtenstein GR. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol 2002;97(10):2577-84.

Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Aliment Pharmacol Ther 2003;18(2):175-81.

Chey WY, Hussain A, Ryan C, Potter GD, Shah A. Infliximab for refractory ulcerative colitis. Am J Gastroenterol 2001;96(8):2373-81.

Chey WY. Infliximab for patients with refractory ulcerative colitis. Inflamm Bowel Dis 2001;7 Suppl 1:S30-3.

Kaser A, Mairinger T, Vogel W, Tilg H. Infliximab in severe steroid-refractory ulcerative colitis: a pilot study. Wien Klin Wochenschr 2001;113(23-24):930-3.

Actis GC, Bruno M, Pinna-Pintor M, Rossini FP, Rizzetto M. Infliximab for treatment of steroid-refractory ulcerative colitis. Dig Liver Dis 2002;34(9):631-4.

Kohn A, Prantera C, Pera A, Cosintino R, Sostegni R, Daperno M. Anti-tumour necrosis factor alpha (infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients. Dig Liver Dis 2002;34(9):626-30.

Ochesenkuhn T, Sackmann M, Geoke B. Infliximab for acute severe ulcerative colitis: a randomized pilot study in non steroid refractory patients. Gastroenterology 2003;124(4 Suppl 1):A62.

Plevy SE, Targan SR. Future therapeutic approaches for inflammatory bowel diseases. Gastroenterology 2011;140(6):1838-46.

Probert CS, Hearing SD, Schreiber S, Kühbacher T, Ghosh S, Arnott ID, Forbes A. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a ran83domised controlled trial. Gut 2003;52(7):998-1002.

Sands BE, Tremaine WJ, Sandborn WJ, Rutgeerts PJ, Hanauer SB, Mayer L, Targan SR, Podolsky DK.Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm Bowel Dis 2001;7(2):83-8.

D'Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, Hanauer SB, Herfarth H, Hommes DW, Kamm M, Löfberg R, Quary A, Sands B, Sood A, Watermeyer G, et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol 2011;106(2):199-212; quiz 213.

How to Cite
1.
Taba Taba Vakili S, Taher M, Ebrahimi Daryani N. Update on the Management of Ulcerative Colitis. Acta Med Iran. 50(6):363-372.
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