Immunosuppressive drugs in Crohn's disease

We review clinical experience with the immunosuppressive drugs 6-mercaptopurine (6-MP) and azathioprine, cyclosporine, and methotrexate in the management of patients with Crohn's disease. 6-MP and azathioprine are closely related structurally. Their exact mechanism of action is unknown, but both cause immunosuppression by interfering with nucleic acid metabolism in the immunological sequence that follows antigenic stimulation. 6-MP and azathioprine have proved most useful for two indications: reducing steroid requirements and healing fistulas. Among patients who are dependent on steroids for control of active inflammatory Crohn's disease, approximately 50% can be completely weaned from prednisone, and an additional 25% can tolerate a substantial dose reduction when treated with 6-MP or azathioprine. Likewise, 6-MP is effective in closing fistulas in approximately one third of patients and in reducing fistula drainage in an additional one third. However, the onset of action is slow and the results may be dose dependent. Cyclosporine, a selective immunosuppressant drug, inhibits T lymphocytes by inhibiting expression of interleukin-2 and its receptors. Its principal usefulness may be in patients with disabling fistulas or active steroid-refractory colitis who cannot tolerate the several months required for a remission induced by 6-MP or azathioprine. Methotrexate, a dihydrofolate reductase inhibitor, has antimetabolite and antiinflammatory properties. Methotrexate is only slightly, if at all, faster acting than 6-MP or azathioprine. Its principal usefulness may therefore be in cases when these other drugs have not been tolerated or are ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)