Long term evolution of corticodependant and corticoresistant Crohn’s disease patients treated by azzathioprine

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Sami Karoui
Asma Hamrouni
Norsaf Bibani
Meriem Serghini
Jalel Boubaker
Azza Filali

Abstract

Background: Immunosupressors, particularly azathioprine, represents the therapeutic alternative in patients with corticodependant or corticoresistant Crohn’s disease. The prescription of azathioprine in Tunisia is common, but there is not Tunisian studies evaluating the long term results of this drug in Crohn’s disease patients.
Aims : To evaluate the long term results of azathioprine treatment with determination of rates of relapses, surgery and need to corticosteroids in patients with corticodependant or corticoresistant Crohn’s disease, and to look for predictive factors to theses events.
Methods: A retrospective study on 12 years including all patients treated by azathioprine for corticodependant or corticoresistant Crohn’s disease. We excluded the cases of follow up less than 6 months.
Results: We studied 56 patients (46 corticodependant and 10 corticoresistant). Induction of remission was obtained in 89% of the cases. Concerning the long term results, the relapse rate was 60% of patients treated with azathioprine, with actuarial rates of 38% at one year, 65% at 5 years and 75% at 10 years. Need for corticosteroid treatment was estimated at 42% and need for surgical treatment was estimated at 24%. The only predictive factor for relapse was duration of treatment by azathioprine more than 36 months, with sensitivity of 93% and specificity of 50%.
Conclusion: Although an excellent result of azathioprine in induction remission, long term results showed deterioration of results of treatment. Physicians must be followed up Crohn’s disease patients in order to rapidly detect and treat the clinical relapses of the disease.

Keywords:

Crohn's disease, Azathioprine

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References

  1. Benchimol EI, Seow CH, Steinhart AH, Griffith AM. Traditional corticosteroids for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2008;2:CD006792.
  2. Rutgeerts P. The limitations of corticosteroid therapy in Crohn's disease. Aliment Pharmacol Ther 2001;15:1515-25.
  3. Faubion WA Jr, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 2001;121:255-60.
  4. Karoui S, Ben Yaghlène L, Fekih M, Boubaker J, Filali A. Corticodépendance et corticorésistance au cours de la maladie de Crohn: Prévalence et facteurs prédictifs. Tunis Med 2003 ;81 :15- 19.
  5. Modigliani R, Mary JY, Simon JF, Gender JP, and the GETAID. Clinical, biological and endoscopic picture of attacks of Crohn's disease: evolution on prednisolone. Gastroenterology 1990; 98:811-8.
  6. Lemann M, Bonhome P, Bitoun A. Traitement de la maladie de Crohn par l'azathioprine ou la 6-mercaptopurine : Etude rétrospective chez 126 malades. Gastroenterol Clinic Biol 1990;14: 548-54.
  7. Pearson DC, May GR, Fick GH, Sutherland LR. Azathioprine and 6-mercaptopurine in Crohn's disease: a meta-analysis. Ann Intern Med 1995;123:132-42.
  8. Dubinsky MC. Azathioprine, 6-Mercaptopurine in Inflammatory Bowel Disease: Pharmacology, efficacy and safety. Clin Gastroenterol Hepatol 2004;2:731-43.
  9. Candy S, Wright J, Gerber M. A Controlled double blind study of azathioprine in the management of Crohn's disease, Gut 1995;37:674-78.
  10. Bouhnik Y, Lemann M, Mary JY. Long term follow -up pf patients with Crohn's disease treated with azathioprine or 6- mercaptopurine. Lancet 1996;347:215-9.
  11. Prefontaine E, Sutherland LR, MacDonald JK. Azathioprine or 6- mercaptopurine for maintenance of remission in Crohn's disease Cochrane Database Syst Review 2009;21 CD000067. Review.
  12. Pinto AL, Chebli LA, Ribeiro MS. Azathioprine therapy in steroid- dependent patients with Crohn's disease: results of a 10- year longitudinal follow-up study. Med Sci Monit 2009;15:119- 26.
  13. Gisbert JP, Nino P, Cara C. Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term,follow- up study of 394 patients. Aliment Pharmacol Ther2008; 28: 228-38.
  14. Chebli J M, Gaburri P D, Flavio A. Long term results with azathioprine therapy in patients corticosteroid_dependent Crohn's disease: open-label prospective study Gastroenterology 2007;22:268-74.
  15. Peter S, Kim MD, Zlatanic J. Optimum duration of treatment with 6-mercaptopurine for Crohn's disease. Am J Gastroenterol 1999;94: 3255-57.
  16. Lemann M, Mary JY, Colombel JF (GETAID). A Randomized, double blind, controlled withdrawal Trial in Crohn's disease patients in long -term remission on azathioprine. Gastroenterology 2005;128:1812-18.
  17. Fraser AG, Orchard TR, Jewell DP .The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002; 50: 485-89.