A new jigsaw piece to potentially improve personalised treatment for Crohn’s Disease

Earlier this year a UK wide collaboration led by the University of Exeter and the Royal Devon & Exeter NHS Foundation, and funded by Guts UK, revealed that early personalised treatment could help people with Crohn’s disease to get a more effective therapy¹.

The immune system (our natural defensive mechanism) does not function properly in people with Crohn’s disease. They produce a molecule, called TNF (anti-tumour necrosis factor) that drives persistent gut inflammation. The use of drugs that interfere with TNF (anti-TNF drugs called Infliximab and Adalimumab) has greatly advanced the treatment of Crohn’s disease. They are commonly used to treat people when other medicines are not working. However only half of patients show any benefit, and for some the effect of the drugs decrease over time.

Until now, there has been no way of predicting how people with Crohn’s disease would respond to these treatments. One reason patients lose response is because their body recognises the drug as a threat, and they produce antibodies (soldiers of our immune system) to attach to it. As a result, the treatment can’t work properly.

“Without the initial funding from Guts UK, this study probably wouldn’t have happened. Thank you to Guts UK for your support”

– Claire Bewshea, a member of the research team.

In an important study funded by Guts UK and published in the journal Gastroenterology² this week, Dr Ahmad and colleagues from Exeter have confirmed that these antibodies against anti-TNF drugs are an important cause of treatment failure. For the first time, they have also shown that these antibodies are more common amongst patients with a variation in a specific region of the DNA (the cell’s instruction manual), called HLA-DQA1*05. This variation is present in 40 percent of the European population and people carrying it are twice likely to produce these antibodies. Ultimately, this suggests that for those carrying HLA-DQA1*05, anti-TNF drugs may not be the first-choice drug. These findings will help identifying the right drug for the right patient first time.

“At Guts UK we are delighted to have supported this ground-breaking study. This is an important step towards the goal of personalised medicine for those with Crohn’s disease or colitis (which is around 1 in 200 people). 

We will need a further trial to confirm genetic testing before we can begin treating those with Crohn’s and colitis with more effective and personalised treatments”