Cumulative experience with short- and long-term toxicity to 6-mercaptopurine in the treatment of Crohn's disease and ulcerative colitis.

BACKGROUND AND AIMS

The efficacy of 6-mercaptopurine (6-MP) in the treatment and long-term maintenance of remission of inflammatory bowel disease and prevention of recurrence after resection in Crohn's disease have been established. Concern about 6-MP toxicity remains, especially the development of neoplasm. The aim of this study is to determine the incidence of all short- and long-term toxicity by follow-up of all patients with inflammatory bowel disease treated with 6-MP over a 20-year period.

MATERIALS AND METHODS

We reviewed the office and hospital records and also determined the recent status of 410 patients with inflammatory bowel disease treated with 6-MP from 1980 to 1999. All toxicity was recorded.

RESULTS

There was a low incidence of early drug-related allergic reactions (3.9%) and pancreatitis (1.2%). Desensitization to either 6-MP or azathioprine is often successful with the same or the other drug. Significant leukopenia (<or=3500) was observed in 11.5%. In some cases, this was caused purposefully. Infectious complications occurred at different times during treatment with 6-MP in 14%, including pneumonia in 3.9% and herpes zoster in 3%. We now establish diabetes as a 6-MP-related complication. No significant difference in the incidence of neoplasm was seen from our earlier study or from patients not treated with 6-MP. We have now seen three lymphomas and two leukemias, again not greater in incidence than the overall inflammatory bowel disease population.

CONCLUSIONS

Our data support the long-term safety of 6-MP in the management of patients with inflammatory bowel disease. Earlier development of a neoplasm in a patient predisposed, without a change in incidence, remains possible.