Predicting Inflammatory Bowel Disease

14 May 2019

Interview with 

Ken Smith, James Lee, University of Cambridge

HUMAN-ABDOMEN

Human abdomen cartoon, showing liver, stomach and intestines

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Inflammatory bowel disease can cause severe pain and serious issues in those who deal with it every day. But what does it mean for those who suffer from it, and how might we improve their lives? Adam Murphy spoke to Ken Smith and James Lee from Cambridge University about a new test they've developed, which can predict the future severity for inflammatory bowel disease in those who suffer with it. But first, we heard from IBD patient Kate, who has been coping with the condition for many years...

Kate - I was diagnosed with Crohn's at 14 and there was no indication that things were going to be so severe in the long run. I was told by my consultant at the time that I would need to have some bowel removed but that there was no reason to think that that wouldn’t be the end of it for a long time. Unfortunately though, within nine months I was unwell again and for the next few years I went through a series of drugs,  all of which caused quite serious side effects, but did little to stop the progress of the disease. Eventually, my large bowel became too badly damaged to save and after a few months with a feeding tube to try and get my weight up before surgery, I was told I would need to have a permanent colostomy bag.

Adam - That is Kate. As you heard, she suffers from Crohn's disease, an inflammatory bowel disease or IBD. But what is going on in the bodies people like her? I spoke to James Lee, a gastroenterologist at the University of Cambridge.

James - IBD is an umbrella term. It stands for inflammatory bowel disease and it encompasses Crohn's disease and ulcerative colitis which are two different diseases. But essentially in both diseases what happens is your immune system gets its wires crossed, the immune system actually attacks the bowel, and the result of that is it can cause ulceration and inflammation within the bowel, and that can lead to quite nasty symptoms where you get bleeding and abdominal pain. These are incurable, lifelong diseases and one of the big problems is that some patients will get a very severe and aggressive form of the disease, other people with the same disease can actually have a very mild disease course. And so one of the biggest challenges for treating patients with ulcerative colitis and Crohn's disease right now is identifying which patients need the more aggressive treatment approach because their disease is going to be that much more aggressive, and which patients actually would do very well with relatively minimal therapy.

Adam - And how do you do that? Ken Smith, Head of the Department of Medicine at Cambridge University took me through it...

Ken - We started about 12 years ago. We were interested in working out what factors drove different long-term outcomes for patients with diseases like inflammatory bowel disease. So we started off by recruiting a lot of patients at diagnosis, measuring the expression of genes in their blood at that day, and then comparing the patterns of expression of those genes, so-called signatures, comparing that with their long-term clinical outcomes, so this study's taken many years to do.

What we found was a signature that correlated very strongly with how well people did in the long term. We then took that signature, and in a complex process, developed a test that worked on whole blood that recreated the effect of that signature allowing us to divide patients into two groups that had very different long-term outcomes.

Adam - And the signature you found, what was that?

Ken - It was a signature in things called CD8 T cells, which are a subset of white blood cell, and it essentially was a measure of something that's called T cell exhaustion. So if you have a tendency to have exhausted T cells you tend to have very good long-term outcome, whereas if you don't have exhaustion you have the opposite, you tend to have more aggressive disease course. So we do understand the biological pathways that sort of underpin this observation in this test.

Adam -  And what could this mean for patients? Back to James...

James - This could really be a game changer for treating patients with IBD. At the moment, most patients receive what is ostensibly a 'one size fits all' approach to their treatment and that's because we simply haven't had good ways of identifying the patients who need the more aggressive treatment from those who don't. So, at the moment, everybody in the UK and in many other parts of the world will be started on an initial treatment. If their disease continues to flare up frequently, they'll go on to something stronger, and if it continues to flare up they'll go on to something stronger still, and that incremental increase in treatment keeps going until we finally get to the treatment they need.

For the patients who have the most agressive disease that might not be until they get onto their fourth of fifth line treatment and, in the meantime, they've been exposed to sometimes years of persistently active disease with all the risks of the complications that go along with that. Conversely we know that actually if we were able to give the most effective treatments upfront to those sort of patients, those are the patients who stand the most to gain by getting their disease into control early.

So for a long time in inflammatory bowel disease and, for that matter, in other fields of medicine people have been looking for ways to match the right treatment to the right patient, so if you have something that enables you to personalise treatment in that way it could completely change how we treat patients in the future.

Adam - And finally, what could it mean for people like Kate?

Kate - For me, Crohn's has always been a disease that's constantly trying to gain ground. In the years after my diagnosis, failing my way through drugs of varying strength, I lost ground that I might never have had to give up if the people in charge of my care had a tool that allowed them to see a clearer picture of what I needed to stay well. It's incredible to think what a test like this could spare people.

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