New genetic marker gives hope for faster treatment for severe IBD patients

IBD discovery could lead to earlier access to treatment for patients with severe forms of the disease

Patients with severe inflammatory bowel disease (IBD) may be able to access treatment earlier due to the discovery of a new genetic marker for the condition.

Researchers have identified a combination of genetic variants within the HLA-DRB1 gene – known collectively as HLA-DRB1*01:03 – that is associated with more severe disease in people living with IBD.

The findings, published in The Lancet Gastroenterology and Hepatology, suggest that genetic testing could identify IBD patients at risk of severe disease, meaning they could be monitored more closely and given advanced therapies earlier.

Inflammatory bowel disease (IBD) is an umbrella term used to describe disorders that cause chronic inflammation of the gastrointestinal tract. Between 40,000 and 50,000 people in Ireland live with IBD, which includes Crohn’s disease and ulcerative colitis.

These are painful, debilitating and lifelong conditions with no known cure, which cause ulceration and inflammation in the gut.

Treatments for Crohn’s disease and ulcerative colitis depend on how severe the symptoms are and how much of the gut is affected. Patients are given medicines that reduce inflammation in the gut, including immunosuppressants and monoclonal antibody therapies, and in more severe cases, surgery may also be required.

“We have undertaken the largest genetic study of IBD traits to date, involving data from more than 43,000 patients,” said the study’s first author, Dr Qian Zhang of the Wellcome Sanger Institute.

“With this large cohort we were able to find that a combination of genetic variants known as HLA-DRB1*01:03 is linked to more severe disease, not only in ulcerative colitis patients, but also in those with Crohn’s disease.”

The researchers found that HLA-DRB1*01:03 was present in approximately one-in-20 IBD patients and associated with multiple severe outcomes.

This included the need for removal of part or all of the colon in those with Crohn’s disease and ulcerative colitis as well as individuals with perianal disease – a condition affecting the skin and tissue around the anus. There was also increased need for advanced therapies in patients positive for HLA-DRB1*01:03.

“We found that IBD patients with these genetic variants within the HLA-DRB1 gene had more severe disease, including colon surgeries or advanced treatments, sometimes earlier in their disease progression,” said Dr Laura Fachal, co-senior author at the Wellcome Sanger Institute.

“Genetic testing to see if patients carry these genetic variants may in future help inform treatment decisions, potentially supporting earlier access to advanced treatments. It could also help identify those at a lower risk of severe disease, where conventional treatments might be sufficient.”

Prof James Lee, co-senior author at the Francis Crick Institute, said: “IBD can look very different for different people, and we don’t fully know why. Some patients experience mild symptoms, whereas others develop severe disease and require advanced treatments or surgery.

“This study brings us one step closer to personalised medicine, and to building predictors of disease severity in IBD patients. In the future, patients with increased risk of severe disease could be given advanced treatments earlier, to help improve their quality of life.”

Read the study: HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype–phenotype association study – The Lancet Gastroenterology and Hepatology.