Predicting treatment response in rheumatoid arthritis

Recently, I published some work from my PhD in which I identified a small section of DNA which could potentially be used to predict which patients with rheumatoid arthritis are likely to respond to etanercept, a biologic drug.

First of all, for those who are new to the world of epigenetics, I will explain a bit about this. Epigenetics is the study of modifications of the DNA which do not change the DNA sequence, but which can change how the DNA is used (which genes are switched ‘on’ or ‘off’). While there are a lot of different types of epigenetic changes, the most studied modification is called DNA methylation. Your DNA methylation profile changes as you get older, can be influenced by your environment (for example, smoking), and can be changed in disease. DNA methylation is also different in different tissues of your body, such as blood, skin or brain. This is how you can have one genome throughout your body, but lots of different methylation profiles, resulting in lots of different types of cells.

In the paper, we measured the levels of DNA methylation at around half a million methylation sites (called CpGs) in 72 patients with rheumatoid arthritis. All these patients were treated with a biologic therapy called etanercept, and were split into two groups who either responded very well to etanercept (36 patients) or didn’t respond at all (36 patients). By comparing the methylation of the two groups, we found a small segment of a gene (called LRPAP1), which has a different methylation pattern in people with rheumatoid arthritis who respond to etanercept, compared to people who don’t.  This is a relatively small study, and needs to be repeated in a much larger number of patients; however this is a very exciting finding which indicates that DNA methylation could be used in the future to predict which therapies a patient with rheumatoid arthritis is most likely to respond to. This would vastly improve the quality of life of patients with rheumatoid arthritis, as it would decrease the time taken to identify the right drug for a particular patient when they are diagnosed, in a ‘stratified medicine’ approach to treatment.

Stratified medicine is an approach to treatment in which patients are split into smaller subgroups based on their likelihood of responding to particular therapies. This means that instead of a ‘one drug fits all’ model, each patient would be assessed to identify which treatment strategy is most likely to be effective for them. Different characteristics can split patients into these groups, such as genetic or epigenetic tests or other biological markers. While the UK is on the forefront of personalised medicine research, there is still a long way to go before it can be used in everyday medicine.

If you are interested in reading the original article, you can access it here: http://www.ncbi.nlm.nih.gov/pubmed/26814849

If you are interested in reading more about biologic therapies, there is some great information on the arthritis research UK website: arthritisresearchuk.org

If you are interested in reading more about the basics of epigenetics (after all, who isn’t?!), there was a great article in the guardian, and for more detail try: the-scientist.com

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