Predicting who will respond well to specific biologic medicines

What this research is looking at

Biologic medicines like adalimumab and ustekinumab are an important treatment option for people with Crohn’s Disease or Ulcerative Colitis. Biologic medicines are usually prescribed for people with moderate to severe Crohn's or Colitis when other treatments have not worked.

Adalimumab and ustekinumab are effective in improving gut symptoms, and in bringing about and maintaining remission (preventing flares). But they don’t work for everyone, and for some people, they stop working after some time.

Because they suppress parts of the immune system, these biologic medicines may carry an increased risk of infections. Very rarely, more serious side-effects are also reported.

We know from clinical trials that both adalimumab and ustekinumab are effective treatment options for Crohn’s and Colitis. However, we don’t know whether an individual will respond well to either adalimumab or ustekinumab before they start taking them. This means some people may potentially take a biologic medicine for many months – with the associated side effects and risks – before they know that the medicine isn't working for them. They then have to do the same again with another biologic medicine.

Professor Satsangi and the research team in Oxford have been working with researchers in Europe. They are interested in personalising care to individuals who are starting on biological medicines. During this project, the research team will look for genetic markers, known as biomarkers, in blood samples from people with Crohn’s and Colitis. They will compare biomarkers in people who responded well to adalimumab or ustekinumab with people who did not respond to these medicines.

Firstly, they will use anonymised data and DNA samples from people with Crohn’s or Colitis who had been recruited into the UK IBD Bioresource. They will create a panel of biomarkers that can predict whether someone is likely to respond or not to adalimumab or ustekinumab.

Next they will check these findings in a second phase of experiments. They will look to confirm this panel of biomarkers in people who are starting treatment with these medicines in the clinic in Oxford. The researchers will follow up to see whether the biomarkers were successful and accurate in predicting how well people respond to these medicines.

The researchers plan to use the data from these studies to create a simple and rapid test for each medicine that can look for this panel of biomarkers in a hospital setting. This test could be used in any hospital setting, including developing nations.

What researchers think this could mean for people with Crohn's and Colitis 

The biomarker test developed during this research project will allow a patient and their doctor to easily and quickly find out whether they are likely to respond well to adalimumab or ustekinumab. This information is vital in helping them make an informed decision on their treatment options.

Taking a biologic medicine does carry some risks, so it’s important to know whether someone is likely to respond well or not before they start the treatment. It can be difficult for people with Crohn’s and Colitis to go through the trial and error process of starting treatments and those treatments not working for them. Additionally, biologic medicines are expensive. So being able to better target their use in people who are likely to respond well will also save the NHS money.

Who is leading this research: Professor Jack Satsangi, University of Oxford

Our funding: £95,082 

Duration: 12 months 

Official title of application: Discovery and validation of epigenetic biomarkers of response to biological therapies in inflammatory bowel disease.