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Personalised ibd treatment - new research results

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Posted 5/21/2019 11:21 PM (GMT 0)
Personalised ibd treatment - new research results
https://www.cam.ac.uk/research/news/new-prognostic-test-could-enable-personalised-treatment-of-inflammatory-bowel-disease
Posted 5/22/2019 12:13 AM (GMT 0)
Wow now that's pretty cool.

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.
Posted 5/22/2019 3:07 PM (GMT 0)
I saw several large take-aways in looking at the underlying article, and some prior work by the authors.

1) A number of innovative techniques to group thousands of genes (groups=signatures) and correlate these groups with markers of disease activity (e.g., serum blood levels of inflammation markers or tissue damage) as well as clinical outcomes (i.e., long remissions or short remissions) were needed. Also newer innovative machine learning algorithms were needed. This level of massaging the data argues for caution in approaching results - but this looks to be 1st class work on the forefront on new methods in medicine.

2) The signature that predicted long remission and low severity had to do with CD8 T-cells. People whose genetic makeup favored quick downregulation (exhaustion) of CD8 T-cell response stopped flaring sooner and had longer remissions.

3) Unfortunately these same people who did better for chronic autoimmune do worse for fighting viral infections and cancer. Exhaustion was good for stopping autoimmune. But an immune system that did not get exhausted was better for fighting viral infections and some types of cancer.

4) They also found that they could manipulate the downregulation of DC8 T-cells (quicken or slow exhaustion) by stimulating CD4 T-cells that more or less send the signals to CD8 cells to ramp up or slow down. This means that not only does the signature they found predict who will be more prone to relapse and disease progression, but they also have a target (the CD4 signaling) for new drugs to use in treatment.

The challenge is to turn off the CD8 to get long remission without making the patient lose immune function needed to fight viruses and cancers. This is a general challenge in medicines for immune related disease. You want the therapy to be very targeted on the bad response without messing up any of the good responses.
Posted 5/22/2019 4:57 PM (GMT 0)
DB....makes sense.
q
Posted 5/22/2019 6:17 PM (GMT 0)
Thanks for the synopsis DB! The main question that came to my mind which wasn't mentioned in the article was how long were they following patients for? Presumably you'd need decades of records to assess what someone's ibd does over the long term.
Posted 5/22/2019 10:36 PM (GMT 0)
I went back to look. The key figure is https://www.nature.com/articles/nature14468/figures/2

They looked at 3 autoimmune disease. 1) antibody-associated vasculitis (AAV) in 44 patients, 2) systemic lupus erythematosus (SLE) in 23 patients, and IBD (mix of CD and UC). I did not see the exact number with IBD, but if you count the dots in the red and blue groups in the figure panel i., it is about 44 people with 22 in the short remission group and 22 inthe long remission (CD8 exhausted group).

The appear to have followed the AAV and SLE patients for over 2000 days (more than 5.5 years) but looks like the IBD group was only followed for 800 days (just over 2 years) based on figure panel k.

You can see in panel i. that similar numbers of people (13 acute and 12 exhausted) had relapses - but more people had no relapse in the exhausted group Look at how many blue dots are on the bottom axis versus only 8 red dots on the bottom axis.

So, the UC was likely only about 25 people followed for only 2.2 years. Hopefully the continue to follow them and also do this work at larger scale. Now that they have a cheap test that can be easily administered to group people, we can expect to see more extended reports of IBD relapse rates in future research.

Post Edited (DBwithUC) : 5/25/2019 12:26:33 PM (GMT-6)

Posted 5/24/2019 8:45 PM (GMT 0)
Thanks for the research! I would have thought 800 days isn't long enough to get a clear picture for how your ibd will develop, but I guess this is a good start.
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