Risk of acute pancreatitis in users of azathioprine: a population-based case-control study

OBJECTIVE: Azathioprine has been linked to subsequent acute pancreatitis in several case reports and small case series. We examined the risk for acute pancreatitis in users of azathioprine in North Jutland County, Denmark, with about 490,000 inhabitants.

METHODS: We identified patients with incident cases of acute pancreatitis from the Hospital Discharge Registry of the county from 1991-2000, and selected 10 controls per case, matched by age and sex, from the Central Personal Registry using incidence density sampling technique. All prescriptions of azathioprine within 90 days before admission were likewise collected from the population-based North Jutland Prescription Database. Data on potential confounders were extracted from registries. We used conditional logistic regression to adjust for confounding.

RESULTS: A total of 1,388 patients and 13,836 controls were included in the study. We found that 1,317 persons in the entire population redeemed a total of 15,811 prescriptions of azathioprine in the county. The incidence rate for acute pancreatitis among all users of azathioprine was one per 659 treatment year. The crude OR of having redeemed prescriptions for azathioprine within 90 days before admission for acute pancreatitis was 7.5 (95% CI = 2.6-21.6). After adjustment for gallstone disease, alcohol-related diseases, inflammatory bowel disease, and use of glucocorticoids, the OR increased to 8.4 (95% CI = 2.4-29.4). The population-attributable risk, which measures the proportion of all cases of pancreatitis that are attributable to the use of azathioprine in our study population, was 0.4%.

CONCLUSIONS: There was a substantially increased relative risk of acute pancreatitis in users of azathioprine.