Nav: Home

New prognostic test could enable personalised treatment of inflammatory bowel disease

May 02, 2019

Scientists at the University of Cambridge have developed a new test that can reliably predict the future course of inflammatory bowel disease in individuals, transforming treatments for patients and paving the way for a personalised approach.

Ulcerative colitis and Crohn's disease - collectively known as inflammatory bowel disease (IBD) - are chronic conditions that involve inflammation of the gut. Symptoms include abdominal pain, bloody diarrhoea, weight loss and fatigue. There is currently no cure, but there are a growing number of medicines that aim to relieve symptoms and prevent the condition returning; however, the more severe the case of the IBD, the stronger the drugs need to be and the greater the potential side effects.

Researchers at the Department of Medicine, University of Cambridge, and Cambridge University Hospitals NHS Trust previously showed that a genetic signature found in a certain type of immune cell known as a CD8 T-cell could be used to assign patients to one of two groups depending on whether their condition was likely to be mild or severe (requiring repeated treatment). However, isolating CD8 T- cells and obtaining the genetic signature was not straightforward, making the test unlikely to be scaleable and achieve widespread use.

In the latest study, published in the journal Gut, the researchers worked with a cohort of 69 patients with Crohn's disease to see whether it was possible to develop a useful, scaleable test by looking at whole blood samples in conjunction with CD8 T-cells and using widely-available technology.

The team used a combination of machine learning and a whole blood assay known as qPCR - a relatively simple tool used in NHS labs across the country - to identify genetic signatures that re-created the two subgroups from their previous study.

The researchers then validated their findings in 123 IBD patients recruited from clinics in Cambridge, Nottingham, Exeter and London.

"Using simple technology that is available in almost every hospital, our test looks for a biomarker - essentially, a medical signature - to identify which patients are likely to have mild IBD and which ones will have more serious illness," says Dr James Lee, joint first author of the study.

"This is important as it could enable doctors to personalise the treatment that they give to each patient. If an individual is likely to have only mild disease, they don't want to be taking strong drugs with unpleasant side-effects. But similarly, if someone is likely to have a more aggressive form of the disease, then the evidence suggests that the sooner we can start them on the best available treatments, the better we can manage their condition."

The accuracy of the test is comparable to similar biomarkers used in cancer, which have helped transform treatment, say the researchers. They found the new test was 90-100% accurate in correctly identifying patients who did not require multiple treatments.

"IBD can be a very debilitating disease, but this new test could help us transform treatment options, moving away from a 'one size fits all' approach to a personalised approach to treating patients," says Professor Ken Smith, senior author and Head of the Department of Medicine.

The test is now being developed further by PredictImmune, a spinout company co-founded by Professor Smith with support from Cambridge Enterprise, the University's technology transfer arm. The team is involved in a £4.2 million trial to see whether using the biomarker to guide treatment at the time of diagnosis can lead to better outcomes for patients.

The findings have been welcomed by Helen Terry, Director of Research at Crohn's & Colitis UK, which helps fund the research. "It's really exciting that we are moving away from a 'one size fits all' approach for people with Crohn's or Colitis. Dr Lee and his team's latest study is the accumulation of 10 years' worth of research and we're now at the stage where this test will be available in the NHS. This could drastically change the lives of people with Crohn's or Colitis as it means they can be started on the best medication for them sooner."

Additional funding for the research came from Wellcome, the Medical Research Council and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

Later this year, Professor Smith and his team are due to move into the new Cambridge Institute of Therapeutic Immunology and Infectious Disease, to be based in the Jeffrey Cheah Biomedical Centre on the Cambridge Biomedical Campus, the centrepiece of the largest biotech cluster outside the United States.

Case study: Kate Gray, aged 31, Amersham, living with Crohn's

Kate was diagnosed with Crohn's Disease when she was 14 years old having been unwell with symptoms for quite some time.

This meant she needed surgery. "I was told by my consultant I would only need a little bit of a resection and that it's unlikely I would be bothered by symptoms for decades, giving me the impression that was probably the end of it."

Within 9 months of her bowel resection, Kate's symptoms had returned. She tried various medications, including immunosuppressants and steroids but nothing worked, and she kept getting more unwell. She also had some nasty side effects from the drug mercaptopurine, becoming neutropaenic (low on neutrophils), leading to two admissions to hospital.

This pathway continued throughout Kate's secondary education and once on the drug infliximab, it reached the point where Kate couldn't eat solid foods. Her bowel was so strictured and damaged that she was told she needed an ileostomy at the age of 20. In the lead-up to this Kate had a nasal-gastric feeding tube which involved long stints in hospital.

When Kate woke up from her operation, she was told that the damage was much more extensive than thought and she would have a permanent stoma.

Following surgery, Kate was started on the biologic drug, Humira and has been on this weekly ever since. "My stoma's been amazing and bowel wise, my symptoms have been good for the past decade."

Kate could have benefited hugely from a prognostic test, making her more aware of disease course and allowing her to try stronger treatments earlier.

"I do sometimes wonder what would have happened if I knew my disease was going to be more severe and not mild, as I was told. It's likely I would have opted for my ileostomy sooner and would have been keen to try stronger drugs earlier as this might have halted to progression of my Crohn's. It would also have been good to have known what other symptoms I could have expected with more severe Crohn's, including issues with my joints, uveitis and Crohn's on the skin at the site of my surgery scars."
-end-
Reference

Biasci, D and Lee JC, et al. A blood-based prognostic biomarker in inflammatory bowel disease. Gut; April 2019; DOI: 10.1136/gutjnl-2019-318343

University of Cambridge

Related Inflammatory Bowel Disease Articles:

5 major advances in inflammatory bowel disease (IBD) treatment
Summary of five impactful studies to be presented at the Crohn's & Colitis Congress, a partnership of the Crohn's & Colitis Foundation and the American Gastroenterological Association (AGA).
Researchers identify a possible cause and treatment for inflammatory bowel disease
In a study published online in PNAS on Jan. 20, 2020, Prof.
Does inflammatory bowel disease carry certain risks during pregnancy?
Pregnant women with inflammatory bowel disease (IBD) are more likely to undergo delivery by Caesarean section and face certain risks during pregnancy, according to an analysis published in Alimentary Pharmacology & Therapeutics.
Inhibiting a protease could improve the treatment of inflammatory bowel disease
Scientists at the CNIC and CSIC have identified a function of a protease that could be the future target of drugs to treat inflammatory bowel disease.
Inflammatory bowel disease appears to impact risk of Parkinson's disease
Amsterdam, NL, November 14, 2019 - Relatively new research findings indicating that the earliest stages of Parkinson's disease (PD) may occur in the gut have been gaining traction in recent years.
Are steroids used too much for patients with inflammatory bowel disease?
Steroid therapy is commonly used to treat acute attacks of the inflammatory bowel diseases ulcerative colitis and Crohn's disease; however, because it does not provide long-term benefits and it carries a risk of serious side effects, it should not be used to treat inflammatory bowel disease for more than three months.
FODMAPs diet relieves symptoms of inflammatory bowel disease
New research from King's College London has found that a diet low in fermented carbohydrates has improved certain gut symptoms and improved health-related quality of life for sufferers of inflammatory bowel disease (IBD).
The diet-microbiome connection in inflammatory bowel disease
A change in diet is a go-to strategy for treating inflammatory bowel diseases like Crohn's.
Edinburgh is global hotspot for inflammatory bowel disease rates
Edinburgh has some of the highest known rates of inflammatory bowel disease in the world and the figure is expected to rise in the next 10 years.
Medication linked to increased risk of inflammatory bowel disease
Medications that target tumor necrosis factor alpha (TNFα), a protein involved in inflammation, have revolutionized the management of certain autoimmune diseases, but paradoxically, these agents might provoke the development of other autoimmune conditions.
More Inflammatory Bowel Disease News and Inflammatory Bowel Disease Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 3: Shared Immunity
More than a million people have caught Covid-19, and tens of thousands have died. But thousands more have survived and recovered. A week or so ago (aka, what feels like ten years in corona time) producer Molly Webster learned that many of those survivors possess a kind of superpower: antibodies trained to fight the virus. Not only that, they might be able to pass this power on to the people who are sick with corona, and still in the fight. Today we have the story of an experimental treatment that's popping up all over the country: convalescent plasma transfusion, a century-old procedure that some say may become one of our best weapons against this devastating, new disease.   If you have recovered from Covid-19 and want to donate plasma, national and local donation registries are gearing up to collect blood.  To sign up with the American Red Cross, a national organization that works in local communities, head here.  To find out more about the The National COVID-19 Convalescent Plasma Project, which we spoke about in our episode, including information on clinical trials or plasma donation projects in your community, go here.  And if you are in the greater New York City area, and want to donate convalescent plasma, head over to the New York Blood Center to sign up. Or, register with specific NYC hospitals here.   If you are sick with Covid-19, and are interested in participating in a clinical trial, or are looking for a plasma donor match, check in with your local hospital, university, or blood center for more; you can also find more information on trials at The National COVID-19 Convalescent Plasma Project. And lastly, Tatiana Prowell's tweet that tipped us off is here. This episode was reported by Molly Webster and produced by Pat Walters. Special thanks to Drs. Evan Bloch and Tim Byun, as well as the Albert Einstein College of Medicine.  Support Radiolab today at Radiolab.org/donate.