Azathioprine treatment in inflammatory bowel disease patients: type and time of onset of side effects

Azathioprine (AZA) and 6-mercaptopurine (6-MP), purine analogues, are the immunosuppressant drugs most frequently used for inducing and maintaining remission in inflammatory bowel disease (IBD). The occurrence of adverse effects is a major drawback in the use of these drugs, and short- and long-term toxicity represent a major limitation to their use.

The present study investigated the prevalence, type and time of onset of AZA-related adverse events, in a cohort of IBD patients in a single referral Centre.

The records of consecutive IBD outpatients, referred to our Institution between 1987-2009, were retrospectively evaluated.

We reviewed 2014 patients, in whom AZA was prescribed in 302 of them, 139 (46%) with ulcerative colitis (UC) and 163 (54%) with Crohn's disease (CD). Side-effects were complained by 98 (32.4%) out of 302 patients, 50 UC and 48 CD, (36% UC vs 29.4% CD, p = 0.26). In 20 (20.4%) patients, 11 UC and 9 CD, side-effects recovered after dosage reduction whilst in 78 (79.6%), 39 UC and 39 CD, the treatment was discontinued (dose-dependent side-effects in 42 patients and dose-independent in 36). Overall, side-effects were observed after a mean period of 14.5 ± 7.8 months (range 0.5-123) of AZA treatment. The majority (76%) of the dose-dependent adverse events were reported between 12-18 months after the beginning of treatment.

The prevalence of side effects leading to withdrawal of AZA treatment, in our series of Italian patients, was higher respect to data reported in the literature (25.8%).