Treatment of Ulcerative Colitis with Antimetabolites

Ulcerative colitis is a disease of widely varying severity. The course in any patient is difficult to predict. In this community repeated episodes commonly lead to a chronic active stage, in which the sufferer becomes an invalid unless the process is relieved by colectomy. In this phase exacerbations and com plications are common, and not infrequently lead to death. It is with patients in this group that the present trial has been concerned. While ulcerative colitis as representative of an autoimmune disorder fails to fill all the criteria enumerated by McKay and Burnet (1963) for autoimmune disease, there remains strong evidence for immunological disturbance. This evidence has been reviewed by Kirsner (1961). I do not propose to discuss at length whether this disturbance represents a normal response to modified tissue or a defect of the immune mechanism. I consider the action of antimetabolites, together with observa tions made during this therapy, supports the view of primary tissue damage or modification. With the exception of steroid hormones, the most powerful suppressants of the immune response, as measured by failure of graft rejection, are all agents developed for the treatment of cancer. These agents may be considered in their main groupings?nitrogen mustard and its derivatives, the sulphur mustards, the antimetabolites, and antibiotics. There is prob ably some selectivity of action of these agents, antagonism occurring between the antimetabolites, mercaptopurine, and the folic-acid antagonists. In our early trials we used the anti metabolites mercaptopurine and 6-thioguanine. More recently the sulphur mustard busulphan has been employed.