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Helping clinicians make an informed choice about the best biological drug treatment.
2016
Identification of accurate predictors of response prior to commencing therapy will minimize time spent with active disease and enable the clinician to make an informed decision to commence the treatment to which the patient is most likely to respond to.
Dr Sreedhar Subramanian, University of Liverpool
Biologic medicines can be used to treat Ulcerative Colitis. The main types of biologic medicines used are anti-TNF medicines, such as infliximab, adalimumab and golimumab, and gut selective integrin blockers, such as vedolizumab.
But every person with Ulcerative Colitis responds to these medicines differently. And some people to do not respond to biologic medicines at all.
There is currently little way of predicting which medicine will work best for an individual. This means the choice of medicine used is arbitrary. If researchers could find a way of predicting which drug type would work best, then the person being treated could start to feel better much sooner. Unwanted side effects may also be avoided.
Currently, one of the few ways of predicting how a person will respond to anti-TNF drugs is to look at the genetics expressed in the lining of the bowel. But studying genes from the lining of the bowel involves using endoscopy to get biopsies, and this is an invasive procedure. Also, there have been no studies yet looking at how a person’s genetics may affect how they respond to vedolizumab.
Other research studies have shown that by looking at gene expression in blood samples, doctors may be able to predict the pattern and course of Inflammatory Bowel Disease in individuals.
The researchers of this study aimed to use a similar idea. They are working towards developing a blood test which could help work out how people with Ulcerative Colitis would respond to biologic medicines based on the gene expression in the blood.
The researchers studied blood samples from 39 people with Ulcerative Colitis in total. Of these people, 18 were having an anti-TNF medicine for the first time, and 21 people were having vedolizumab for the first time. The researchers further separated the study participants into:
They then studied blood samples of the different groups of people to see if there were differences in their genetics. They specifically looked at the genes expressed in T-cells, a type of immune cell involved in inflammation.
In people taking vedolizumab:
The researchers found 58 genes that were more switched on in people who responded to vedolizumab. In particular, genes expressing something called FLI1 transcriptor factor binding motif were more common in people that responded to vedolizumab. This was of interest to the researchers, as another research study also noticed that this transcription factor seemed to be linked to controlling T cell activity. They also identified another 62 genes that were more switched on in people who did not respond to vedolizumab.
In people taking anti-TNFs:
When comparing the genetics of anti-TNF responders to non-responders, the researchers found no significant differences in the genes expressed in their T-cells. However, the genes involved in allograft rejection and glucocorticoid pathways were significantly more switched on in non-responders.
In summary, the researchers identified several genes that may be linked to whether someone with Ulcerative Colitis responds to vedolizumab or anti-TNF medicines.
What do the researchers think this could mean for people with IBD?
These results are important as they will help us move closer towards tailored medicine. This means doctors may be able to use someone’s genetics to predict more accurately whether a medicine will work for them or not. This could save the person with Ulcerative Colitis going through multiple medicines before finding one that’s right for them.
The findings from this study could also help the development of new targeted medicines, giving people with Colitis more treatment options.
Who is leading this research?: Dr Sreedhar Subramanian, University of Liverpool
Our Funding: £49,579
Duration: 24 months
Official title of application: Peripheral blood gene expression profiling as predictors of response to biological therapy in Ulcerative Colitis
Tags: Biologics
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