Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the long-term prognosis in cyclosporine A treatment for ulcerative colitis
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Intravenous (IV) cyclosporine A (CSA) is one of the treatments of choice for patients with steroid-refractory severe ulcerative colitis (UC). In this study, we evaluated the overall experience with CSA treatment in UC patients, from their initial response to long-term prognosis.
The medical records of 72 patients admitted to our hospital with a severe UC flare-up and treated with IV CSA between November 1996 and October 2008 were reviewed retrospectively. The initial response to CSA was assessed using a clinical activity index, and colectomy was assigned as the endpoint for the long-term prognosis.
Overall, 53 of 72 (73.6%) patients responded initially to CSA. We could not determine any specific parameters that predicted an initial response. A life-table analysis for all patients revealed that 54.4% of patients required a colectomy within 11 years. The long-term risk of surgery was associated with a shorter disease duration, history of adverse reactions against medications and lack of immunomodulator use. In addition, endoscopic improvement at day 14 was associated with colectomy at 1 year, but not with the long-term prognosis.
Although CSA can exert high initial efficacy for severe attacks of UC, >50% of patients who relapse require a colectomy. Specifically, mucosal healing evaluated by endoscopy was associated with the 1-year colectomy rate. In contrast, a history of adverse drug reactions was correlated with the long-term colectomy rate. Therefore, we propose that treatment of severe UC with CSA requires consideration of both initial remission and long-term maintenance as management goals.
- Wilks S, Moxon W. Lectures on pathological anatomy. 2nd ed. London: J&A Churchill; 1875.
- Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–29. CrossRef
- Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol. 2006;41:10–6. CrossRef
- Sands BE. Immunosuppressive drugs in ulcerative colitis: twisting facts to suit theories? Gut. 2006;55:437–41. CrossRef
- Hanauer SB. Review article: evolving concepts in treatment and disease modification in ulcerative colitis. Aliment Pharmacol Ther. 2008;27(Suppl 1):15–21. CrossRef
- Lichtiger S. Treatment of choice for acute severe steroid-refractory ulcerative colitis is cyclosporine. Inflamm Bowel Dis. 2009;15:141–2. CrossRef
- O’Keefe SJ, Tamura J, Kincaid RL, Tocci MJ, O’Neill EA. FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Nature. 1992;357:692–4. CrossRef
- Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–5. CrossRef
- Cohen RD, Stein R, Hanauer SB. Intravenous cyclosporin in ulcerative colitis: a 5-year experience. Am J Gastroenterol. 1999;94:1587–92. CrossRef
- Moskovitz DN, Van Assche G, Maenhout B, Arts J, Ferrante M, Vermeire S, 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. CrossRef
- Naganuma M, Ichikawa H, Inoue N, Kobayashi T, Okamoto S, Hisamatsu T, et al. Novel endoscopic activity index is useful for choosing treatment in severe active ulcerative colitis patients. J Gastroenterol. 2010 (Epub ahead of print).
- Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006;55:47–53. CrossRef
- 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. CrossRef
- Stack WA, Long RG, Hawkey CJ. Short- and long-term outcome of patients treated with cyclosporin for severe acute ulcerative colitis. Aliment Pharmacol Ther. 1998;12:973–8. CrossRef
- Travis SP, Farrant JM, Ricketts C, Nolan DJ, Mortensen NM, Kettlewell MG, et al. Predicting outcome in severe ulcerative colitis. Gut. 1996;38:905–10. CrossRef
- Benazzato L, D’Inca R, Grigoletto F, Perissinotto E, Medici V, Angriman I, et al. Prognosis of severe attacks in ulcerative colitis: effect of intensive medical treatment. Dig Liver Dis. 2004;36:461–6. CrossRef
- Van Assche G, Vermeire S, Rutgeerts P. Treatment of severe steroid refractory ulcerative colitis. World J Gastroenterol. 2008;14:5508–11. CrossRef
- Cohen RD, Brodsky AL, Hanauer SB. A comparison of the quality of life in patients with severe ulcerative colitis after total colectomy versus medical treatment with intravenous cyclosporin. Inflamm Bowel Dis. 1999;5:1–10. CrossRef
- Cacheux W, Seksik P, Lemann M, Marteau P, Nion-Larmurier I, Afchain P, et al. Predictive factors of response to cyclosporine in steroid-refractory ulcerative colitis. Am J Gastroenterol. 2008;103:637–42. CrossRef
- Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1296–301. CrossRef
- Hibi T, Naganuma M, Kitahora T, Kinjyo F, Shimoyama T. Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis. J Gastroenterol. 2003;38:740–6. CrossRef
- Cassinotti A, Actis GC, Duca P, Massari A, Colombo E, Gai E, et al. Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal. Am J Gastroenterol. 2009;104:2760–7. CrossRef
- Sternthal MB, Murphy SJ, George J, Kornbluth A, Lichtiger S, Present DH. Adverse events associated with the use of cyclosporine in patients with inflammatory bowel disease. Am J Gastroenterol. 2008;103:937–43. CrossRef
- Message L, Bourreille A, Laharie D, Quinton A, Galmiche JP, Lamouliatte H, et al. Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis refractory to steroids. Gastroenterol Clin Biol. 2005;29:231–5. CrossRef
- Campbell S, Travis S, Jewell D. Ciclosporin use in acute ulcerative colitis: a long-term experience. Eur J Gastroenterol Hepatol. 2005;17:79–84. CrossRef
- Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35. CrossRef
- Rapid endoscopic improvement is important for 1-year avoidance of colectomy but not for the long-term prognosis in cyclosporine A treatment for ulcerative colitis
Journal of Gastroenterology
Volume 45, Issue 11 , pp 1129-1137
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Ulcerative colitis
- Cyclosporine A
- Industry Sectors
- Author Affiliations
- 1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan
- 2. Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan