Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is the collective term used to describe ulcerative colitis and Crohn’s disease. These conditions cause diarrhea, rectal bleeding, fatigue, weight loss, and rectal bleeding. These symptoms can significantly affect the quality of life of patients.
Unfortunately, there has yet to be a cure found for either form of IBD. However, there are treatments. Patents are typically prescribed drugs that work to suppress the body’s immune system. For about a third of patients, this drug is a thiopurine. Many patients also require surgery.
IBD manifests differently in different patients, depending on what genes are affected. This means that patients will respond to different treatment regimes in various ways. Some patients can have severe side effects to treatments, which ultimately can be life threatening.
Thankfully, researchers at the University of Exeter have recently discovered a new way to test which patients may have an adverse reaction to thiopurines. Once physicians have this information they can either adjust doses or prescribe an entirely new treatment regime if needed.
The Study
7% of IBD patients treated with thiopurine experience bone marrow suppression. This is a series side effect that impairs the body’s immune system making it much more difficult for the patient to fight off infection. Patients who develop bone marrow suppression are at risk of developing sepsis.
Previously, researchers were able to uncover that mutations in the TPMT can cause bone marrow suppression. If clinicians know that it is likely that their patient has mutations in this gene (as indicated in routine testing), they will alter treatment accordingly. But unfortunately, this mutation is only the cause of bone marrow suppression for a quarter of IBD patients. That means for three-quarters of patients theres truly been no way to know if they may develop this extremely serious side effect until it happens.
This new study aimed to uncover what other gene mutations may cause the reaction. If these genes are uncovered, physicians can monitor them specifically, and potentially drastically improve patient outcomes.
Patients in the study were recruited from the UK, the Netherlands, New Zealand, Australia, Sweden, Canada, Malta, South Africa, and the United States in addition to various other countries. In total, 500 IBD patients who dealt with bone marrow suppression and 680 controls (who were defined as IBD patients who had been given thiopurines but had not experienced bone marrow suppression) were included in the study. This was the largest study of its kind to date.
Results
Researchers were successful in uncovering another gene which can cause bone marrow suppression. It’s called NUDT15. Actually, they had previously understood this gene could impact it, but they thought it could only affect patients of East Asian descent. In fact there are actually three different kinds of mutations of this one gene which can result in bone marrow suppression in patients of European descent.
The findings of this study were published in JAMA on February 26, 2019.
Looking Forward
The researchers who conducted this study hope that it will lead to the standard use of a blood test which can detect NUDT15 mutations. This will allow physicians to personalize their patient’s treatment. Side effects can truly be just as dangerous as the symptoms patients are dealing with. Ultimately, this discovery, and a simple blood test, could save patient lives.
You can read more about this discovery here.
