Drug-induced acute pancreatitis due to medications used for inflammatory bowel disease: A VigiBase pharmacovigilance database study

Abstract

Background: Nearly all medications used for inflammatory bowel disease (IBD) have been reported as causes of acute pancreatitis (AP), with the thiopurines being among the most frequently described. However, with the development of newer medications, thiopurine monotherapy has largely been replaced by newer immunosuppressive drugs. There are few data on the association between AP and biologic/small molecule agents.

Methods: VigiBase, the World Health Organization's Global Individual Case Safety Report database, was used to assess the association between AP and common IBD medications. A case/non-case disproportionality analysis was performed and disproportionality signals were reported as a reporting odds ratio (ROR) with 95% confidence intervals (CIs).

Results: A total of 4,223 AP episodes were identified for common IBD medications. Azathioprine (ROR 19.18, 95% CI 18.21-20.20), 6-mercaptopurine (ROR 13.30, 95% CI 11.73-15.07), and 5-aminosalicylic acid (ROR 17.44, 95% CI 16.24-18.72) all had strong associations with AP, while the biologic/small molecule agents showed weaker or no disproportionality. The association with AP was much higher for thiopurines when used for Crohn's disease (ROR 34.61, 95% CI 30.95-38.70) compared to ulcerative colitis (ROR 8.94, 95% CI 7.47-10.71) or rheumatologic conditions (ROR 18.87, 95% CI 14.72-24.19).

Conclusions: We report the largest real-world database study investigating the association between common IBD medications and AP. Among commonly used IBD medications including biologic/small molecule agents, only thiopurines and 5-aminosalicylic acid are strongly associated with AP. The association between thiopurines and AP is much stronger when the drug is used for Crohn's disease compared to ulcerative colitis and rheumatologic conditions.

Keywords: Drug-induced acute pancreatitis; Inflammatory bowel disease; Pharmacovigilance; Vigibase.