IBD treatments safer with new genetic test
New genetic research has uncovered a gene mutation that will allow practitioners to identify Crohn's disease and ulcerative colitis patients who are at risk for potentially deadly drug side effects, allowing clinicians to tailor alternative treatments to these individuals.
The research, which published yesterday in the Journal of the American Medical Association, looked at genetic variants associated with thiopurine-induced myelosuppression (TIM) among patients with Crohn's disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD). They conducted genome-wide association studies (GWAS) and exome-wide association studies (EWAS) for 491 patients affected by TIM and 679 unaffected patients from 89 international sites between March 2012 and November 2015.
Crohn's disease and ulcerative colitis are incurable lifelong conditions, with IBD affecting more than 3 million of U.S. adults, according to the Centers for Disease Control and Prevention. The main symptoms are urgent diarrhea, often with rectal bleeding, abdominal pain, profound fatigue, and weight loss.
Drugs to suppress the immune system are the common method of treatment, however many patients with Crohn's Disease or ulcerative colitis will require surgery. The lifetime medical costs associated with IBD are similar to the costs of treating diabetes or cancer, researchers say.
About a third of patients with IBD are treated with a thiopurine drug. However, approximately 7 percent of patients develop an adverse reaction to the drug known as bone marrow suppression, which makes the body’s immune system less able to fight infection and the patient at risk of sepsis.
According to an announcement made by the University of Exeter Medical School in the U.K., whose research team led the investigation, previous studies have identified mutations in a gene known as TPMT, which predisposes patients to thiopurine-induced bone marrow suppression. Clinicians either adjust the dose or avoid thiopurines altogether if routine tests show that patients are likely to carry faulty versions of the TPMT gene. However, only a quarter of patients who suffer from bone-marrow suppression have abnormalities in TPMT, suggesting that other genes may be involved.
DNA from patients with IBD that suffered thiopurine-induced bone marrow suppression and patients who had received thiopurines and had no history of bone marrow suppression were analyzed to identify genes possibly associated with this adverse drug reaction. Among the patients studied, analyses confirmed association between mutations in genes called NUDT15 and bone marrow suppression, finding three different variants in NUDT15 that were associated with bone marrow suppression.
"In the largest genetic analysis into the side effects of thiopurine drugs, we've discovered variation in a gene that can help us identify who is susceptible to thiopurine-induced bone marrow suppression,” said Tariq Ahmad, PhD, chief investigator and faculty at the University of Exeter Medical School, in the statement. “In line with the [goal] to increase personalized medicine, testing for this genetic abnormality prior to prescribing thiopurine drugs will reduce the risks to patients, and costs associated with this potentially serious drug side effect.”