Frequency of use and standards of care for the use of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease: A systematic review of the literature and a survey of Canadian gastroenterologists

OBJECTIVE: To identify the frequency of use and appropriate monitoring guidelines for the adverse effects uf azathioprine and 6-mercaptopurine (6 Mp) in the therapy of patients with inflammatory bowel disease (IBD). METHODS: Surveys were sent to all physician members of the Canadian Association of Gastroenterology. Physicians were asked to describe their monitoring practices for IBD patients receiving azathioprine or 6-MP. A systematic literature search was also performed using MEDLINE for articles published in English between 1966 and 1999 using the MeSH terms 'azathioprine', '6-mercaptopurine', 'inflammatory bowel disease' and 'drug monitoring'. RESULTS: Azathioprine and 6-MP were used to treat an average of 7% of patients - a surprisingly low number given the proven efficacy of these agents. All respondents reported monitoring complete blood counts (CBC), while liver enzyme and pancreatic enzyme levels were monitored by 62% and 29% of respondents, respectively. The most commonly reported initial CBC testing frequencies were weekly (42%), monthly (26%) and biweekly (23%). From the literature, it was determined that severe leukopenia (less than 2.10 g/L) occurs in less than 2% of cases and is sometimes associated with serious outcomes, including death. Most cases of severe leukopenia occurred abruptly, early in treatment. Other reported adverse effects and incidences were pancreatitis (3% to 5%), hepatotoxicity (less than 1%) and hypersensitivity (2 % to 3%). Data concerning an increased risk of non-Hodgkin's lymphoma were equivocal. CONCLUSIONS: Use of azathioprine or 6-MP is low in patients with IBD. A CBC should he performed at weeks 1, 2, 4, 6, 8 and 12, with subsequent testing every eight weeks for the duration of azathioprine or 6-MP treatment. The evidence in support of pancreatic and hepatic monitoring is weak. The risk non-Hodgkin's lymphoma is likely low.