A genetic polymorphism was a major predictor of azathioprine-induced pancreatitis in patients with inflammatory bowel disease, according to a study published in Alimentary Pharmacology & Therapeutics.
Kim, MD, of the division of clinical pharmacology in the department of medicine at Western University in London, Ontario, Canada, and colleagues said they wanted to test the findings of a recent genome wide association study that found a strong association between the Class II HLA region polymorphism and azathioprine (AZA)-induced pancreatitis in an IBD cohort.
“The aim of our study was to validate the findings in a large and independent cohort of patients with IBD and to further delineate an IBD AZA treatment algorithm based on pharmacogenomic principles,” they wrote.
Researchers conducted a retrospective cohort study comprising 373 patients with IBD who were on AZA for at least 6 months. Overall, 13 received a diagnosis of AZA-induced pancreatitis.
Investigators used genotypic analysis to identify the presence of wild-type (A/A) or variant alleles (heterozygous, A/C; homozygous, C/C) in the class II HLA gene region at rs2647087. In addition to testing the 13 patients with AZA-induced pancreatitis, researchers conducted a genotypic analysis on the 360 other patients to use as a control group.
The data showed a strong association between carriers of the variant C allele and AZA-induced pancreatitis (OR = 5.63; 95% CI, 2.41-13.15).
“Our finding suggests the pancreatitis risk is in fact much higher, 4- and 15-fold for rs2647087 A/C or C/C compared to those who are A/A,” the researchers wrote.
According to the study, payers across the country require patients to try and fail low-cost immunomodulators, like AZA, before they can use more effective, but costlier, biological therapies. The researchers noted that costs for acute pancreatitis can be quite high, more than $10,000 for hospitalization costs alone.
To avoid these exorbitant costs, as well as the painful symptoms of AZA-induced pancreatitis, the investigators proposed a genotype-guided algorithm for the treatment of patients with IBD with AZA that takes each individual’s genetic makeup into account.
Patients with an A/A genotype could proceed with AZA treatment. Individuals with an A/C genotype could proceed with AZA therapy if no other treatment was feasible, whereas patients with C/C genotypes should receive advice to select alternative treatment because of their higher risk for pancreatitis.
“The marked increase in risk for pancreatitis among carriers of the variant allele provides a strong rationale for a companion diagnostic approach for patients who are to be prescribed AZA, similar to what is already the case for medications such as abacavir,” the researchers wrote, adding that cost-benefit analyses would help to further clarify the usefulness of their proposed clinical practice. – by Alex Young
Disclosures: The authors report no relevant financial disclosures.