A. Wilson1, Q. Wang2, J. Gregor1, N. Chande1, M. Beaton1, T. Ponich1, M. Sey1, B. Yan1, R. Kim1
1London Health Sciences Centre, Medicine, London, Canada, 2Western University, Medicine, London, Canada
Background
Genetic variation in the HLADQA1-HLADRB1*07:01 haplotype is strongly associated with azathioprine (AZA)-induced pancreatitis in inflammatory bowel disease (IBD). We aimed to evaluate the utility of pre-emptive HLA DQA1-HLADRB1*07:01 screening to reduce the risk of AZA-induced pancreatitis in an IBD population.
Methods
A prospective cohort study is ongoing in IBD patients being considered for AZA therapy who are assigned to pre-treatment HLA DQA1-HLADRB1*07:01 (rs2647087) screening (n = 372 currently recruited) and compared with historical controls who have received AZA standard of care (n = 373). Participants in the pre-emptively screened group found to be variant carriers (AC or CC) are excluded from AZA treatment while wild type carriers (AA) received standard dosing. The incidence of clinically diagnosed pancreatitis (lipase >3 times the upper limit of normal and one of abdominal pain or imaging findings suggestive of pancreatitis) occurring within 3 months in all participants with AZA exposure is being compared between the prospective and historic populations.
Results
The minor allele frequency of HLADQA1-HLADRB1*07:01 is 29%. To date, 194 participants (AA genotype) in the pre-emptively-screened cohort have received AZA therapy and completed the 3-month follow-up period. An additional 136 individuals with AA genotype are needed to obtain the target sample size (n = 330). Thus far, fewer cases of AZA-induced pancreatitis are seen in the pre-emptively screened population (pre-emptive cohort, 1/194 vs. historical controls, 13/373; odds ratio = 7.01, 95%CI = 0.91–53.98, p = 0.04).
Conclusion
Pre-emptive HLA DQA1-HLADRB1*07:01 screening may reduce the risk of pancreatitis during AZA treatment in patients with IBD. Completion of this study will help define whether HLA DQA1-HLADRB1*07:01 screening is a clinically-actionable and relevant tool for the safe use of AZA therapy in IBD.
