Skip to main content
SpringerLink
Log in

Cyclosporine for Ulcerative Colitis

  • Chapter
  • First Online:
Medical Therapy of Ulcerative Colitis

  • 1235 Accesses

Abstract

Ulcerative colitis (UC) is an idiopathic inflammatory disorder of unknown etiology that affects the mucosa and the submucosa of the colon. The inflamed epithelium extends continuously from the rectum and involves part or all (pancolitis) of the colon. Symptomatically, patients exhibit increased, bloody, bowel movements with fecal urgency, diarrhea, abdominal cramping, abdominal pain, hematochezia, and fever. These characteristics can have a gradual or an acute onset with variable durations of flare and remission. Population cohort studies have shown that during the lifetime of their disease, 10–40 % of patients with ulcerative colitis will ultimately require a colectomy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Farmer RG, Easley KA, Rankin GB. Clinical patterns, natural history, and progression of ulcerative colitis. A long-term follow-up of 1116 patients. Dig Dis Sci. 1993;38:1137–46.

    Article  CAS  PubMed  Google Scholar 

  2. Doherty GA, Cheifetz AS. Management of acute severe ulcerative colitis. Expert Rev Gastroenterol Hepatol. 2009;3:395–405.

    Article  PubMed  Google Scholar 

  3. Solberg IC, Lygren I, Jahnsen J, et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol. 2009;44:431–40.

    Article  PubMed  Google Scholar 

  4. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54.e42. quiz e30. doi:10.1053/j.gastro.2011.10.001. Epub 2011 Oct 14.

    Article  PubMed  Google Scholar 

  5. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12 Suppl 1:3–9.

    Article  Google Scholar 

  6. Lichtenstein GR. Inflammatory bowel disease. In: Goldman L, Schafer AI, editors. Goldman’s Cecil medicine. 24th ed. Philadelphia, PA: Elsevier; 2012. p. 913–21.

    Chapter  Google Scholar 

  7. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–24. doi:10.1038/nature11582.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Kerner C, Lichtenstein GR. Digestive Diseases Self-Education Program (DDSEP). 2014. 7.

    Google Scholar 

  9. Pham CQD, Efros CB, Berardi RR. Cyclosporine for severe ulcerative colitis. Ann Pharmacother. 2006;41(1):96–101.

    Google Scholar 

  10. Hart AL, Al-Hassi HO, Rigby RJ, et al. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology. 2005;129(1):50–65.

    Article  CAS  PubMed  Google Scholar 

  11. Biancone L, Monteleone G, Marasco R, Pallone F. Autoimmunity to tropomyosin isoforms in ulcerative colitis (UC) patients and unaffected relatives. Clin Exp Immunol. 1998;113(2):198–205.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1756–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Lichtenstein GR, Kamm MA, Boddu P, et al. Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2007;5:95–102.

    Article  CAS  PubMed  Google Scholar 

  14. La Nauze RJ, Sparrow MP. Thiopurine immunomodulators in ulcerative colitis: moving forward with current evidence. Curr Drug Targets. 2011;12(10):1406–12.

    Article  PubMed  Google Scholar 

  15. Dickinson RJ, Ashton MG, Axon AT, et al. Controlled trial of intravenous hyperalimentation and total bowel rest as an adjunct to the routine therapy of acute colitis. Gastroenterology. 1980;79:1199–204.

    CAS  PubMed  Google Scholar 

  16. McIntyre PB, Powell-Tuck J, Wood SR, et al. Controlled trial of bowel rest in the treatment of severe acute colitis. Gut. 1986;27:481–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; preliminary report on a therapeutic trial. Br Med J. 1954;2:375–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2:1041–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501–23. doi:10.1038/ajg.2009.727. quiz 524.

    Article  PubMed  Google Scholar 

  20. D’Haens G, Lemmens L, Geboes K, et al. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001;120(6):1323–9.

    Article  PubMed  Google Scholar 

  21. Martínez-Martínez S, Redondo JM. Inhibitors of the calcineurin/NFAT pathway. Curr Med Chem. 2004;11(8):997–1007.

    Article  PubMed  Google Scholar 

  22. Borel JF, Kis ZL. The discovery and development of cyclosporine (Sandimmune). Transplant Proc. 1991;23(2):1867–74.

    CAS  PubMed  Google Scholar 

  23. Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev. 2005;1, CD004277.

    PubMed  Google Scholar 

  24. Von Wartburg A, Traber R. Cyclosporins, fungal metabolites with immunosuppressive activities. Prog Med Chem. 1988;25:1–33.

    Article  Google Scholar 

  25. Kapturczak MH, Meier-Kriesche HU, Kaplan B. Pharmacology of calcineurin antagonists. Transplant Proc. 2004;36(2 Suppl):25S–32.

    Article  CAS  PubMed  Google Scholar 

  26. Venkataramanan R, Starzl TE, Yang S, et al. Biliary excretion of cyclosporine in liver transplant patients. Transplant Proc. 1985;17(1):286–9.

    PubMed Central  PubMed  Google Scholar 

  27. Kovarik JM, Mueller EA, van Bree JB, et al. Reduced inter- and intraindividual variability in cyclosporine pharmacokinetics from a microemulsion formulation. J Pharm Sci. 1994;83(3):444–6.

    Article  CAS  PubMed  Google Scholar 

  28. Friman S, Bäckman L. A new microemulsion formulation of cyclosporin: pharmacokinetic and clinical features. Clin Pharmacokinet. 1996;30(3):181–93.

    Article  CAS  PubMed  Google Scholar 

  29. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–5.

    Article  CAS  PubMed  Google Scholar 

  30. Van Assche G, D'Haens G, Noman M, et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003;125:1025–31.

    Article  PubMed  Google Scholar 

  31. Moskovitz DN, Van Assche G, Maenhout B, et al. Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis. Clin Gastroenterol Hepatol. 2006;4:760–5.

    Article  CAS  PubMed  Google Scholar 

  32. Cohen RD, Stein R, Hanauer SB. Intravenous cyclosporin in ulcerative colitis: a five-year experience. Am J Gastroenterol. 1999;94:1587–92.

    Article  CAS  PubMed  Google Scholar 

  33. Chang KH, Burke JP, Coffey JC. Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis. Int J Colorectal Dis. 2013;28:287–93.

    Article  PubMed  Google Scholar 

  34. Laharie D, Bourreille A, Branche J, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 2012;380:1909–15.

    Article  CAS  PubMed  Google Scholar 

  35. Maser EA, Deconda D, Lichtiger S, et al. Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis. Clin Gastroenterol Hepatol. 2008;6:1112–6.

    Article  CAS  PubMed  Google Scholar 

  36. Croft A, Walsh A, Doecke J. Outcomes of salvage therapy for steroid-refractory acute severe ulcerative colitis: ciclosporin vs infliximab. Aliment Pharmacol Ther. 2013;38:294–302.

    Article  CAS  PubMed  Google Scholar 

  37. Nelson R, Liao C, Fichera A, et al. Rescue therapy with cyclosporine or infliximab is not associated with an increased risk for postoperative complications in patients hospitalized for severe steroid-refractory ulcerative colitis. Inflamm Bowel Dis. 2014;20:14–20.

    Article  PubMed  Google Scholar 

  38. Garcia-Lopez S, Gomollon-Garcia F, Perez-Gisbert J. Cyclosporine in the treatment of severe attack of ulcerative colitis: a systematic review. Gastroenterol Hepatol. 2005;28:607–14.

    Article  CAS  PubMed  Google Scholar 

  39. Rolny P, Vatn M. Cyclosporine in patients with severe steroid refractory ulcerative colitis in the era of infliximab. Scand J Gastroenterol. 2013;48:131–5.

    Article  CAS  PubMed  Google Scholar 

  40. Campbell S, Travis S, Jewell D. Ciclosporin use in acute ulcerative colitis: a long-term experience. Eur J Gastroenterol Hepatol. 2005;17:79–84.

    Article  CAS  PubMed  Google Scholar 

  41. Sharkey L, Bredin F, Nightingale A, et al. The use of Cyclosporin A in acute steroid-refractory ulcerative colitis: long term outcomes. J Crohns Colitis. 2011;5:91–4.

    Article  PubMed  Google Scholar 

  42. Actis GC, Lagget M, Rizzetto M, et al. Long-term efficacy of oral microemulsion cyclosporin for refractory ulcerative colitis. Minerva Med. 2004;95:65–70.

    CAS  PubMed  Google Scholar 

  43. Actis GC, Pinna-Pintor M. An audit of the immunosuppressive management of ulcerative colitis. A retrospective chart review from a referral Day-Hospital of Gastroenterology. Minerva Gastroenterol Dietol. 2002;48:115–20.

    CAS  PubMed  Google Scholar 

  44. Carbonnel F, Boruchowicz A, Duclos B, et al. Intravenous cyclosporine in attacks of ulcerative colitis: short-term and long-term responses. Dig Dis Sci. 1996;41:2471–6.

    Article  CAS  PubMed  Google Scholar 

  45. Hyde GM, Thillainayagam AV, Jewell DP. Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal? Eur J Gastroenterol Hepatol. 1998;10:411–3.

    Article  CAS  PubMed  Google Scholar 

  46. McCormack G, McCormick PA, Hyland JM, et al. Cyclosporin therapy in severe ulcerative colitis: is it worth the effort? Dis Colon Rectum. 2002;45:1200–5.

    Article  PubMed  Google Scholar 

  47. Actis GC, Aimo G, Priolo G, et al. Efficacy and efficiency of oral microemulsion cyclosporin versus intravenous and soft gelatin capsule cyclosporin in the treatment of severe steroid-refractory ulcerative colitis: an open-label retrospective trial. Inflamm Bowel Dis. 1998;4:276–9.

    CAS  PubMed  Google Scholar 

  48. Sandborn WJ, Strong RM, Forland SC, et al. The pharmacokinetics and colonic tissue concentrations of cyclosporine after i.v., oral, and enema administration. J Clin Pharmacol. 1991;31:76–80.

    Article  CAS  PubMed  Google Scholar 

  49. Sandborn WJ, Tremaine WJ, Schroeder KW, et al. Cyclosporine enemas for treatment-resistant, mildly to moderately active, left-sided ulcerative colitis. Am J Gastroenterol. 1993;88:640–5.

    CAS  PubMed  Google Scholar 

  50. Winter TA, Dalton HR, Merrett MN, et al. Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'. Scand J Gastroenterol. 1993;28:701–4.

    Article  CAS  PubMed  Google Scholar 

  51. Sandborn WJ, Tremaine WJ, Schroeder KW, et al. A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis. Gastroenterology. 1994;106:1429–35.

    CAS  PubMed  Google Scholar 

  52. de Saussure P, Lavergne-Slove A, Mazeron MC, et al. A prospective assessment of cytomegalovirus infection in active inflammatory bowel disease. Aliment Pharmacol Ther. 2004;20:1323–7.

    Article  PubMed  Google Scholar 

  53. Takahashi Y, Tange T. Prevalence of cytomegalovirus infection in inflammatory bowel disease patients. Dis Colon Rectum. 2004;47:722–6.

    Article  PubMed  Google Scholar 

  54. Issa M, Vijayapal A, Graham MB, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5:345–51.

    Article  PubMed  Google Scholar 

  55. Schneeweiss S, Korzenik J, Solomon DH, et al. Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections. Aliment Pharmacol Ther. 2009;30:253–64.

    Article  CAS  PubMed  Google Scholar 

  56. Nguyen GC, Kaplan GG, Harris ML, Brant SR. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol. 2008;103:1443–50.

    Article  PubMed  Google Scholar 

  57. Minami M, Ohta M, Ohkura T, et al. Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan. World J Gastroenterol. 2007;13(5):754–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Melmed GY. Vaccination strategies for patients with inflammatory bowel disease on immunomodulators and biologics. Inflamm Bowel Dis. 2009;15:1410–6.

    Article  PubMed  Google Scholar 

  59. Melmed GY, Agarwal N, Frenck RW, et al. Immunosuppression impairs response to pneumococcal polysaccharide vaccination in patients with inflammatory bowel disease. Am J Gastroenterol. 2010;105:148–54.

    Article  PubMed  Google Scholar 

  60. Sands BE, Cuffari C, Katz J, et al. Guidelines for immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:677–92. 485.

    Article  PubMed  Google Scholar 

  61. Esteve M, Saro C, Gonzalez-Huix F, et al. Chronic hepatitis B reactivation following infliximab therapy in Crohn’s disease patients: need for primary prophylaxis. Gut. 2004;53:1363–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Cheifetz AS, Stern J, Garud S, et al. Cyclosporine is safe and effective in patients with severe ulcerative colitis. J Clin Gastroenterol. 2011;45:107–12.

    Article  CAS  PubMed  Google Scholar 

  63. Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without. J Immunol. 2013;191(12):5785–91. doi:10.4049/jimmunol.1390055.

    Article  CAS  PubMed  Google Scholar 

  64. Heisel O, Heisel R, Balshaw R, Keown P. New onset diabetes mellitus in patients receiving calcineurin inhibitors: a systematic review and meta-analysis. Am J Transplant. 2004;4(4):583–95. doi:10.1046/j.1600-6143.2003.00372.x.

    Article  PubMed  Google Scholar 

  65. Yoshimura N, Nakai I, Ohmori Y, et al. Effect of cyclosporine on the endocrine and exocrine pancreas in kidney transplant recipients. Am J Kidney Dis. 1998;12(1):11–7.

    Article  Google Scholar 

  66. Demozay D, Tsunekawa S, Briaud I, et al. Specific glucose-induced control of insulin receptor substrate-2 expression is mediated via Ca2+-dependent calcineurin/NFAT signaling in primary pancreatic islet β-cells. Diabetes. 2011;60(11):2892–902. doi:10.2337/db11-034.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Weir MR, Fink JC. Risk for posttransplant diabetes mellitus with current immunosuppressive medications. Am J Kidney Dis. 1999;34(1):1–13. doi:10.1053/AJKD03400001.

    Article  CAS  PubMed  Google Scholar 

  68. Hahn HJ, Dunger A, Laube F, et al. Reversibility of the acute toxic effect of cyclosporin A on pancreatic B cells of Wistar rats. Diabetologia. 1986;29(8):489–94.

    Article  CAS  PubMed  Google Scholar 

  69. Arnette D, Gibson TB, Lawrence MC, et al. Regulation of ERK1 and ERK2 by glucose and peptide hormones in pancreatic beta cells. J Biol Chem. 2003;278(35):32517–25. doi:10.1074/jbc.M301174200.

    Article  CAS  PubMed  Google Scholar 

  70. Nielsen JH, Mandrup-Poulsen T, Nerup J. Direct effects of cyclosporin A on human pancreatic beta-cells. Diabetes. 1986;35(9):1049–52.

    Article  CAS  PubMed  Google Scholar 

  71. Wijdicks EF, Wiesner RH, Krom RA. Neurotoxicity in liver transplant recipients with cyclosporine immunosuppression. Neurology. 1995;45(11):1962–4.

    Article  CAS  PubMed  Google Scholar 

  72. Miller LW. Cyclosporine-associated neurotoxicity: the need for a better guide for immunosuppressive therapy. Circulation. 1996;94(6):1209–11. doi:10.1161/01.CIR.94.6.1209.

    Article  CAS  PubMed  Google Scholar 

  73. Sternthal MB, Murphy SJ, George J, et al. Adverse events associated with the use of cyclosporine in patients with inflammatory bowel disease. Am J Gastroenterol. 2008;103:937–43.

    Article  CAS  PubMed  Google Scholar 

  74. Kubo M, Kiyohara Y, Kato I, et al. Risk factors for renal glomerular and vascular changes in an autopsy-based population survey: the Hisayama study. Kidney Int. 2003;63:1508–15.

    Article  PubMed  Google Scholar 

  75. Bleck JS, Thiesemann C, Kliem V, et al. Diltiazem increases blood concentrations of cyclized cyclosporine metabolites resulting in different cyclosporine metabolite patterns in stable male and female renal allograft recipients. Br J Clin Pharmacol. 1996;41(6):551–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Krentz AJ, Dousset B, Mayer D, et al. Metabolic effects of cyclosporin A and FK 506 in liver transplant recipients. Diabetes. 1993;42(12):1753–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  78. Fernandez-Banares F, Bertran X, Esteve-Comas M, et al. Azathioprine is useful in maintaining long-term remission induced by intravenous cyclosporine in steroid-refractory severe ulcerative colitis. Am J Gastroenterol. 1996;91:2498–9.

    CAS  PubMed  Google Scholar 

  79. Maser EA, Deconda D, Lichtiger S, et al. Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis. Clin Gastroenterol Hepatol. 2008;6(10):1112–6.

    Article  CAS  PubMed  Google Scholar 

  80. Siegel CA, Schwartz LM, Woloshin S, et al. When should ulcerative colitis patients undergo colectomy for dysplasia? Mismatch between patient preferences and physician recommendations. Inflamm Bowel Dis. 2010;16(10):1658–62. doi:10.1002/ibd.21233.

    Article  PubMed Central  PubMed  Google Scholar 

  81. Kaplan GG, Seow CH, Ghosh S, et al. Decreasing colectomy rates for ulcerative colitis: a population-based time trend study. Am J Gastroenterol. 2012;107(12):1879–87. doi:10.1038/ajg.2012.333.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, 950 Biomedical Research Building II/III, Philadelphia, PA, 19104, USA

    Gregory P. Botta M.D., Ph.D.

  2. Internal Medicine, United Health Services, Wilson Memorial Center, 33-57 Harrison St., Picciano Building 4th Floor, Johnson City, NY, 13790, USA

    Wojciech Blonski M.D., Ph.D.

  3. Division of Gastroenterology, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, 3400 Spruce Street 3rd Floor, Philadelphia, PA, 19104, USA

    Gary R. Lichtenstein M.D., F.A.C.P., F.A.C.G., A.G.A.F.

Authors
  1. Gregory P. Botta M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wojciech Blonski M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gary R. Lichtenstein M.D., F.A.C.P., F.A.C.G., A.G.A.F.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregory P. Botta M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    Gary R. Lichtenstein

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Botta, G.P., Blonski, W., Lichtenstein, G.R. (2014). Cyclosporine for Ulcerative Colitis. In: Lichtenstein, G. (eds) Medical Therapy of Ulcerative Colitis. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1677-1_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1677-1_13

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1676-4

  • Online ISBN: 978-1-4939-1677-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation