Expert opinion: experience with 6-mercaptopurine in the treatment of inflammatory bowel disease.

Arbitrarily, modern day treatment of inflammatory bowel disease begins with the introduction of immunosuppressives for ulcerative colitis. Clinical improvement with sulfasalazine had been meaningful but modest. Treatment with adrenocorticotropic hormone and corticosteroids led to clinical responses never before realized but it took much too long to recognize that they were not capable of maintaining remission, that adverse reactions were subtle but potentially devastating and that some other agent would be necessary to capitalize on their transient advantage. This of course was true in the treatment of Crohn's disease as well. Not much was ever made of the role of sulfasalazine for Crohn's disease, but with the severing of the diazobond and the elimination of the sulphur component, the 5-aminosalacylic acid (5-ASA) products clearly led to clinical improvement, especially in cases of Crohn's colitis and those with ileitis where the 5-ASA product was released in the terminal ileum and more proximal in the small bowel as well as in ulcerative colitis. The induction of remission was first demonstrated by 6-mercaptopurine (6-MP) with case reports and uncontrolled trials in patients with ulcerative colitis, but its placebo controlled trial for Crohn's disease firmly established its role in inducing remission. No subsequent trial has confirmed its similar role for ulcerative colitis, but nevertheless clinicians know well that 6-MP works at least as well and probably more effectively for ulcerative colitis than for Crohn's disease. What changes have taken place utilizing 6-MP in the management of inflammatory bowel disease since its introduction in the 1960's and 1970's and its trial for Crohn's disease published in the New England Journal of Medicine in 1980?