HLA‐DQA1‐HLA‐DRB1 polymorphism is a major predictor of azathioprine‐induced pancreatitis in patients with inflammatory bowel disease. Issue 5 (22nd December 2017)

• Record Type: Journal Article
• Authors: Wilson, A.; Jansen, L. E.; Rose, R. V.; Gregor, J. C.; Ponich, T.; Chande, N.; Khanna, R.; Yan, B.; Jairath, V.; Khanna, N.; Sey, M.; Beaton, M.; McIntosh, K.; Teft, W. A.; Kim, R. B.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 47:Issue 5(2018)
• Page Start: 615
• Page End: 620
• Publication Date: 2017-12-22
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.14483
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Azathioprine (AZA)‐induced pancreatitis is an unpredictable and dose‐independent adverse event affecting 2%‐7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at‐risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine‐induced pancreatitis. Aim: To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles. Methods: A retrospective cohort study evaluated 373 AZA‐exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA‐DQA1*02:01‐HLA‐DRB1*07:01 haplotype and were sub‐divided based on the presence (n = 13) or absence (n = 360) of an AZA‐induced pancreatitis diagnosis. The risk of AZA‐induced pancreatitis was assessed based on rs2647087 genotype. Results: The risk of pancreatitis during AZA‐therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02‐36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80‐145.26, P = 0.0001) for homozygous variant (C/C) patients. Conclusions: The class II HLA region (at rs2647087) is an important marker of AZA‐induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD. Abstract : Linked Content This article is linked to Teich et al and Wilson et al papers. To view these articles visithttps://doi.org/10.1111/apt.14545 andhttps://doi.org/10.1111/apt.14562 .