Research Update - Personalised medicines for Crohn's & Colitis

What has been happening so far?

When we used a microscope to look at biopsy samples from people with Crohn’s or Colitis, we found that different cells and molecules were involved in inflammation in different people. This shows that bowel inflammation is individual to each person. But medicines are often prescribed in a ‘one-size-fits-all’ way, without considering the individual characteristics of the person’s bowel inflammation. To overcome this, and tailor medication to individuals, we are investigating two approaches.

1. We’re looking at biopsy samples from people with Crohn’s or Colitis under a microscope. We hope to work out how the pattern of inflammation we can see relates to how well the person responds to a particular medicine. So far, we’ve collected over 300 biopsy samples from people at seven different hospitals in the UK. We’ve also collected the medical history of each person, so we have information on how well the most common Crohn’s or Colitis medicines worked for them. We’re now preparing digital scans of the samples so we can analyse them to look for features that might predict how an individual person might respond to a particular medicine. This analysis will be carried out using Artificial Intelligence (computers that can process large amounts of data much faster and more accurately than humans can).
2. We will also be looking at the genes and proteins in the biopsy samples, to see if we can find any patterns that help predict whether or not a person will respond to a particular medicine. This pattern of genes or proteins is called a ‘molecular signature’. We have collected over 300 biopsy samples within the first 6 months. Soon we will start to analyse them.

When are medicines needed for Crohn’s or Colitis?

There is currently no cure for Crohn’s or Colitis. People living with the conditions usually have some periods when their condition is active, known as flare-ups, and other periods of good health, known as remission. Flare-ups can have a big impact on people’s quality of life, mental health, and wellbeing. During a flare-up, people might have symptoms like abdominal pain or diarrhoea. Treatment aims to control flare-ups and help keep people in remission.

During a flare-up, people usually have tests to find out how bad the inflammation is and what parts of their gut are affected. These may include blood tests, faecal calprotectin tests, symptom scores and colonoscopy.

The choice of medicine depends on many things. This includes how bad the inflammation is, where it is, and how well other medicines have worked in the past. Medicines are often effective, but they don’t work for everyone. Sometimes it can take a while to find a medicine that work, and some people may need surgery, or choose to have surgery, to remove inflamed parts of the bowel.

Current medicines for Crohn’s and Colitis

Here Harinder, our Crohn’s & Colitis UK Research Champion, briefly describes the most common medicines used to treat Crohn’s and Colitis. You can find more detail here.

• Steroids dampen down the immune system. They help reduce inflammation quickly. They’re often used to get flare-ups under control, but they’re not suitable for long-term use.
• 5-ASAs, like sulphasalazine and mesalazine, are related to aspirin. They reduce inflammation in the lining of the bowel. They may be used in people with mild inflammation.
• Thiopurines, like azathioprine and mercaptopurine, dampen down the immune system. This helps reduce inflammation. They can be given alongside steroids or biologics.

Advanced medicines for Crohn’s and Colitis block particular proteins involved in the inflammatory response. They aim to reduce bowel inflammation and symptoms quickly and keep them under control. There are two main types of advanced medicines: biologic medicines and small molecule medicines. Biologic medicines are made by living cells in a lab. Small molecule medicines are made using chemical processes.

Biologic medicines for Crohn’s and Colitis include:

• Adalimumab, infliximab and golimumab. These all target a protein called TNF-alpha. TNF-alpha is involved in the body’s inflammatory response. The medicines block TNF-alpha, which reduces inflammation.
• This targets a protein called α4β7 integrin. White blood cells use this protein to help them move from the blood stream into the lining of the gut, where they can cause inflammation. Vedolizumab blocks the protein, which stops the white blood cells moving into the gut and reduces gut inflammation.
• This blocks two proteins, called IL-12 and IL-23. These proteins are involved in the body’s inflammatory response. Ustekinumab blocks the proteins, which reduces inflammation.

Small molecule medicines for Crohn’s and Colitis include:

• Filgotinib, tofacitinib and upadacitinib. These are small molecule medicines. They all target proteins called Janus kinases, or JAKs. JAKs are involved in activating the body’s immune response, which can cause inflammation. Blocking JAKs helps to reduce the inflammatory response in the body, and the gut. Small molecule medicines usually start to work more quickly than biologics.

Lived experiences with medicines in Crohn’s and Colitis