To Örebro University

Background: Studies have shown an association between use of azathioprine and acute pancreatitis in adult inflammatory bowel disease. However, whether there is an association among pediatric patients isnot known.

Objectives: To investigate if there is an association between use of azathioprine and the risk of acute pancreatitis in pediatric inflammatory bowel disease (pIBD) patients.

Methods: We conducted a nationwide Swedish cohort study based on health care register data, 2006‐2014. From a cohort of all pediatric patients (<18 years) with IBD (n = 4631), we included 1477 episodes of new azathioprine use and 1477 episodes of no use in propensity score‐matched (1:1 ratio) analyses. The propensity score included patient characteristics, comorbidities, previous treatment, indicators of disease severity and health care utilization. Incident cases of acute pancreatitis occurring in the primary risk period of 90 days following treatment initiation were identified through outpatient and inpatient hospital records. A sensitivity analysis was restricted to inpatient cases alone. A secondary risk period of 91‐365 days following treatment initiation was also assessed. Cox proportional hazards models were used to estimate hazard ratios (HRs).

Results: Among azathioprine‐exposed, mean age was 14.3 (SD 3.2) years, 56.5% were male, and 56.1% had Crohn's disease and 43.9% had ulcerative colitis or IBD‐unclassified. During the first 90 days following azathioprine initiation, 23 patients (1.6%) experienced acute pancreatitis compared with 5 patients (0.3%) in the no use group; corresponding incidence rates were 65 and 16 per 1000 person‐years. The risk was significantly higher in patients with azathioprine use, HR = 4.21 (95% CI 1.60‐11.08). The HR was similar when only considering acute pancreatitis events in inpatient care (4.82 [1.65‐14.03]) and there was no increased risk during the period 91‐365 days following treatment initiation (0.36 [0.03‐4.01]).

Conclusions: Use of azathioprine was associated with an increased risk of acute pancreatitis in pIBD during the first 90 days of use but not later. The finding suggests that the risk of acute pancreatitis needs to be considered when deciding on optimal treatment strategy in pIBD. Additional analyses also including nationwide Danish data are ongoing and will be presented at the conference.