Historically, in the 1950s, the introduction of simple, old-fashioned steroids resulted in a significant drop in mortality and hence offered for the first time a real therapeutic option for patients with inflammatory bowel disease. However, as we are all aware of, steroids are no option for maintenance of remission. This review will provide an overview of the available data on the current role of azathioprine in the therapy of Crohn's disease. Based on several controlled trials, the place of azathioprine for maintenance of remission is indisputable. Data from a pediatric cohort suggested that early introduction of azathioprine is beneficial for the disease course. Two recent studies aimed at reproducing these data in adult populations and failed. Hence indicating that azathioprine should only be introduced for maintenance of remission in a step-up-wise approach. An additional role for azathioprine in combo therapy with TNF antibodies has been indicated by several trials revealing a substantial benefit on response. This is partly attributed to the gain in the therapeutic effect by azathioprine itself and possibly through reduction of anti-drug antibody development. In summary, the current role of azathioprine in the therapy of Crohn's disease is manifold and still has an impact in times of targeted therapy.

1.
Truelove SC, Witts LJ: Cortisone in ulcerative colitis: final report on a therapeutic trial. Br Med J 1955;2:1041-1048.
2.
Colombel JF, et al: Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology 2007;132:52-65.
3.
Hanauer SB, et al; ACCENT I Study Group: Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359:1541-1549.
4.
Sandborn WJ, et al; GEMINI 2 Study Group: Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med 2013;3697:11-21.
5.
Chande N, Tsoulis DJ, MacDonald JK: Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2013;4:CD000545.
6.
Prefontaine E, Macdonald JK, Sutherland LR: Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2010;6:CD000545.
7.
O'Donoghue DP, et al: Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease. Lancet 1978;2:955-957.
8.
Candy S, et al: A controlled double blind study of azathioprine in the management of Crohn's disease. Gut 1995;37:674-678.
9.
Vilien M, et al: Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year. Aliment Pharmacol Ther 2004;19:1147-1152.
10.
Lémann M, et al: A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine. Gastroenterology 2005;128:1812-1818.
11.
Camus M, et al: Long-term outcome of patients with Crohn's disease who respond to azathioprine. Clin Gastroenterol Hepatol 2013;11:389-394.
12.
Markowitz J, et al: A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology 2000;119:895-902.
13.
Panés J, et al: Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn's disease. Gastroenterology 2013;145:766-774.e1.
14.
Cosnes J, et al; Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID): Early administration of azathioprine vs conventional management of Crohn's disease: a randomized controlled trial. Gastroenterology 2013;145:758-765.e2; quiz e14-e15.
15.
D'Haens G, et al; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 2008;371:660-667.
16.
Lemann M, et al; Groupe d'Etude Therapeutique des Affections Inflammatoires du Tube Digestif (GETAID): Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. Gastroenterology 2006;130:1054-1061.
17.
Colombel JF, et al; SONIC Study Group: Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010;362:1383-1395.
18.
Ben-Horin S, Chowers Y: Review article: loss of response to anti-TNF treatments in Crohn's disease. Aliment Pharmacol Ther 2011;33:987-995.
19.
Louis E, et al; Groupe d'Etudes Thérapeutiques Des Affections Inflammatoires Digestives: Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology 2012;142:63-70.e5; quiz e31.
20.
Satsangi J, et al: How to apply for and secure EU funding for collaborative IBD research projects. J Crohns Colitis 2016;10:363-370.
21.
Lehmann PF, White LO: Acquired immunity to Aspergillus fumigatus. Infect Immun 1976;13:1296-1298.
22.
Sachar DB, et al: Risk factors for postoperative recurrence of Crohn's disease. Gastroenterology 1983;85:917-921.
23.
Sutherland LR, et al: Effect of cigarette smoking on recurrence of Crohn's disease. Gastroenterology 1990;98(5 pt 1):1123-1128.
24.
D'Haens GR, et al: Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's disease: a controlled randomized trial. Gastroenterology 2008;135:1123-1129.
25.
De Cruz P, et al: Crohn's disease management after intestinal resection: a randomised trial. Lancet 2015;385:1406-1417.
26.
Teich N, et al; German IBD Study Group: Azathioprine-induced acute pancreatitis in patients with inflammatory bowel diseases - a prospective study on incidence and severity. J Crohns Colitis 2016;10:61-68.
27.
Beaugerie L, et al; CESAME Study Group: Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009;374:1617-1625.
28.
Peyrin-Biroulet L, et al; Cesame Study Group: Increased risk for nonmelanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology 2011;141:1621-1628.e1-e5.
29.
Beaugerie L, et al; CESAME Study Group: Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease. Gastroenterology 2013;145:166-175.e8.
You do not currently have access to this content.