Immunomodulator therapy in inflammatory bowel disease

Abstract

6-Mercaptopurine and its prodrug counterpart, azathioprine, have proven efficacy in the induction and maintenance of remission, fistula closure, and steroid sparing in patients with Crohn's disease. Long-term follow-up has demonstrated the safety of the purine analogues, with no increased risk of malignancy. For patients with Crohn's disease intolerant or unresponsive to azathioprine or 6-mercaptopurine, methotrexate has emerged as an effective alternative. In patients with severe ulcerative colitis, intravenous cyclosporine is highly efficacious in the short term, and with the addition of azathioprine or 6-mercaptopurine to oral cyclosporine, long-term remission rates of 60% to 70% can be achieved. Azathioprine or 6-mercaptopurine therapy is effective in patients with steroid-dependent or steroid-refractory colitis and is valuable in maintaining remission. Neither methotrexate nor cyclosporine has been shown to be effective for maintenance therapy in patients with ulcerative colitis. Current data are insufficient to recommend routine use of genetic or enzymatic testing of thiopurine methyltransferase or measurements of blood 6-thioguanine metabolites to guide 6-mercaptopurine or azathioprine dosing.

Purine analogues as a risk factor of postoperative complications in abdominal surgery for Crohn’s disease

“…Włączenie ich do terapii pozwala na znaczne ograniczenie dawek steroidów u 65% leczonych pacjentów. Poza steroidozależną postacią choroby Leśniowskiego-Crohna [7,8] wskazaniami do ich stosowania są także: częste nawroty choroby niemożliwe do opanowania dotychczasowym leczeniem, pojawienie się oporności na steroidy [9,10], obecność przetok jelitowych [11] oraz podtrzymanie remisji, zarówno tej wyindukowanej zachowawczo, jak i operacyjnie.…”

Refractory inflammatory bowel disease

“…Though the use of intravenous corticosteroids and cyclosporine currently remains the mainstay of therapy for fulminant colitis, a variety of alternative medications have been used both to enhance clinical response rates and to achieve and maintain steroid-independent remission [8••] Immunomodulating medications such as azathioprine and 6-mercaptopurine are used extensively in therapy for patients with refractory colitis, and their efficacy has been confirmed in several large controlled studies [9]. Azathioprine and 6-mercaptopurine generally are considered to be first-line agents in treatment of patients with steroid-resistant ulcerative colitis, steroiddependent ulcerative colitis, or Crohn's disease (see the accompanying article by Legnani and Kornbluth [10], which also covers methotrexate). In addition, azathioprine maintains remission induced by cyclosporin A in patients with severe ulcerative colitis.…”