HLA association with azathioprine-induced pancreatitis in patients with inflammatory bowel disease: A case series.

Background: Azathioprine (AZA)-induced pancreatitis is a significant adverse event affecting patients with inflammatory bowel disease (IBD). A genetic association with HLA-DRB1*07 and HLA-DQA1*02 alleles polymorphisms has been reported, but its prevalence and impact on Asian patients with IBD remain unclear.

Methods: A retrospective review of a prospectively maintained database of patients with IBD was done from January 2005 till December 2024. Patients who developed pancreatitis were tested for HLA association with HLA class II-DRB1*07 and HLA-DQA1*02 alleles. Duration of AZA, dose of AZA and other risk factors such as smoking, alcohol intake, steroid administration, previous history of pancreatitis and any other risk factors for pancreatitis were noted. These patients were compared with a matched control group of non-IBD patients undergoing human leukocyte antigen (HLA) typing for other indications.

Results: Of 1751 patients with IBD, 441 (25.1%) were exposed to AZA 12/441 (2.7%) developed azathioprine-induced pancreatitis. Patients with pancreatitis had a significantly higher prevalence of the HLA-DRB1*07 and HLA-DQA1*02 haplotype compared to controls (8/12; 66.6% vs. 1877/7361; 25.4% p = 0.001089). The onset of pancreatitis occurred within a median of 15 days of initiation of AZA, with all cases being mild in severity. Rechallenge confirmed causality in one patient.

Conclusion: Azathioprine-induced pancreatitis occurred in 2.7% patients. The class-II HLA-DRB1*07 and HLA-DQA1*02 is an important marker for AZA-induced pancreatitis risk. Rechallenge should be avoided in patients with this HLA antigen. More data is required for pre-emptive HLA testing prior to initiation of azathioprine.