In the Journals

Genetic predictor helps IBD patients avoid drug-induced pancreatitis

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.

Richard B. 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.

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.

Richard B. 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.

    See more from Ulcerative Colitis Resource Center