Immunosuppressant therapy of inflammatory bowel disease. Pharmacologic and clinical aspects.

Abstract

The history of immunosuppressant drug use, both azathioprine (Aza) and 6-mercaptopurine (6-MP), in inflammatory bowel disease (IBD) over the past 20 years is briefly reviewed. The two drugs appear identical in their pharmacologic and biologic effects. Azathioprine is converted to 6-MP while in the body. Conflicting reports on the effectiveness of Aza have been published. The major National Cooperative Crohn's Disease Study (NCCDS) has found no advantage in Aza over placebo. In contrast, 6-MP was found to be effective in a large randomized trial. The shortcomings of the NCCDS reports are discussed with possible explanations for their negative findings. Our own studies, dating from 1968, are reviewed with 38 patients having been treated for up to 18 years, always in combination with small doses of steroids. Our results with Aza are similar to those of Present and Korelitz with 6-MP; about 70% of previously intractable patients improved substantially. Both Aza and 6-MP bring about healing and closure of most fistulas. Side effects can be serious but are usually manageable and, to some extent, preventable by appropriate dosage schedules. Since Aza has been approved for another benign, presumably autoimmune disease--rheumatoid arthritis--and because of its extensive use in other autoimmune diseases, we prefer to use Aza in selected patients with Crohn's disease who have failed to respond to more conventional modes of therapy. The use of immunosuppressants in ulcerative colitis is less clearly indicated.