Who should be treated with infliximab during a severe Ulcerative Colitis flare-up?



Acute severe Ulcerative Colitis is life-threatening. If we can identify the people who will respond well to infliximab, we can treat them effectively right from the onset and avoid the need for emergency surgery.

Dr Sree Subramanian
Royal Liverpool and Broadgreen University Hospitals NHS Trust

What is this research looking at? 

Acute severe Ulcerative Colitis (ASUC) is a life-threatening condition that requires urgent treatment with steroids. But, 40% of people do not respond to the steroid treatment and need further rescue treatment with infliximab or cyclosporin to avoid emergency surgery to remove their bowel (colectomy). Unfortunately, 30% of people also fail to respond to infliximab and go on to need an emergency colectomy. Emergency surgery results in more complications and deaths than planned surgery, so if it can be avoided it will result in much better outcomes for the patient.

The way infliximab is absorbed, distributed and excreted from the body, a process known as pharmacokinetics, is different in people with ASUC compared to people with less severe Ulcerative Colitis.

There are a number of reasons for this:

  • There is more inflammation in ASUC - this acts as a sponge to soak up the infliximab and clear it from the body more quickly.
  • More infliximab is lost in the stools due to the ‘leakiness’ of the large bowel caused by the severe inflammation.
  • Infliximab needs to bind to a protein in the blood called albumin and people with ASUC have less albumin in their blood.

This research project will investigate the pharmacokinetics of infliximab in people with ASUC. Researchers will take blood and stool samples and measure the amount of infliximab at different time points after treatment. They will compare this to how severe the patient’s Ulcerative Colitis is by measuring their clinical symptoms and markers of inflammation. This will allow the researchers to find the minimum amount of infliximab that needs to be in the blood to make sure the treatment works. The researchers will use this information to create a new test that can be used in the clinic.

What do researchers think this could mean for people with Colitis? 

Some people with ASUC don’t respond to the first-line treatment of steroids or the second-line treatment of infliximab and need to have an emergency colectomy. Having emergency surgery can be dangerous and leads to more complications after surgery. If doctors had a quick and simple test requiring only a blood sample, they could find out which patients will need more infliximab for the treatment to work. This will lead to a much better outcome for people with ASUC as fewer will go on to need emergency surgery.

Who is leading this research: Dr Sree Subramanian, Royal Liverpool and Broadgreen University Hospitals NHS Trust
Our funding: £87,164
Duration: 36 months
Official title of application: Investigation of infliximab pharmacokinetics in acute severe Ulcerative Colitis (ASUC).