Personalized Medicine will be Central to RA Care – Some Day

March 23, 2016

Mayo Clinic's Timothy Niewold, M.D., speaks with Rheumatology Network about the latest innovations in personalized medicine for rheumatoid arthritis. Scientific advances point to the role of environmental triggers and risk genes.

Oncologists are cracking the genetic code of their patients’ tumors and prescribing medication specific to the cancer they find. Could such a day arrive for rheumatoid arthritis as well? To learn about the latest innovations in personalized medicine for rheumatoid arthritis, Rheumatology Network spoke to Timothy Niewold, M.D., associate professor of medicine and research chair in rheumatology at Mayo Clinic in Rochester, Minnesota. Dr. Niewold recently reviewed the literature on personalized medicine in rheumatoid arthritis for Gene.

Q: Medical treatment for rheumatoid arthritis has progressed rapidly in recent years. What can genetic studies add? [[{"type":"media","view_mode":"media_crop","fid":"47036","attributes":{"alt":"Timothy B. Niewold, M.D.","class":"media-image media-image-right","id":"media_crop_4939628191445","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5504","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"Timothy B. Niewold, M.D.","typeof":"foaf:Image"}}]]

A: The molecules we currently use as treatments are working, but there may be a more elegant way to intervene based on better understanding of the biology. We don’t have many drugs that work in 90 percent of rheumatoid arthritis patients. It’s more in the 40-60 percent range. On the other hand, some people respond really well to particular drugs, but we don’t understand why. Instead of trying something to see if it works and then trying something else if it doesn’t, we would like to have a blood test that could guide us about which treatment will work best in that particular patient. If we better understood how an existing drug targets a particular molecular pathway, it might show us how to target that pathway more precisely - or with fewer side effects or less invasively. I think this work should also shed some light on promising new targets.

Q: How close are you to this kind of personalization?

A: Already with rheumatoid arthritis there are now two established subgroups:  people who have anti-cyclic citrullinated peptide (CCP) antibodies and people who don’t. It seems to be a fundamental distinction that goes all the way back to genetics. The risk genes differ somewhat and outcomes differ somewhat too. The people who have those antibodies tend to have more active disease and tend to have somewhat worse outcomes.

There is not a single way to proceed with that information. You have to take the whole picture into consideration. Rheumatologists are already using that information to personalize treatment to some degree. Someone who is a new patient but has these antibodies will probably need more treatment. You know the patient is at risk for more joint damage and as a physician, you can plan for that.

Q: Is genetic testing useful for treating rheumatoid arthritis?

A: Those findings haven’t translated to the clinic yet. I think that’s where learning some of the biology is really going to help us. There is a bunch of gene variations that we know are linked to rheumatoid arthritis. Genes probably add up together to impact biological pathways and this is true of other auto-immune diseases. One of the big challenges now is to understand how those genetic variations change the immune system and the biology of the person. I think that might lead to more actionable knowledge when we get to that stage.

We have had some findings that look positive and there are other groups working in this area. My guess is that in the end we will probably combine results from a number of successful studies to make a multi-parameter decision-making tool where you could use clinical information and blood test information to get a predictive tool.

Q: What are you learning about the interaction of specific genes with environmental triggers?

A: It’s a little lopsided when you look at the published literature - it looks like it’s all about genes. Some of that has to do with the technology boom we’ve had. The ability to detect risk genes has increased exponentially, so our information about the genetic basis of disease has increased quite a lot. Studying the environment is trickier. It’s hard to track all of the things we’re exposed to in our environment, but we definitely know that genes don’t exist in isolation out in space. There are a lot of gene-environment interactions and efforts are intensifying to work on the other side of the equation.

There is a really nice example:  smoking interacts with one of the risk genes, HLA, really strongly, and you greatly increase your risk of rheumatoid arthritis if you have that particular gene and you also have a significant smoking history. I think that discovery was probably facilitated by the fact that people often know how long they’ve smoked and how many packs a day they smoke. The interaction between the HLA genes and smoking tends to predict who has the CCP antibodies as well. I think that’s really changed some of the understanding of the disease process.

There is also a fairly active field looking at the microbiome in rheumatoid arthritis. The bacteria living within us may interact with our immune system to increase our risk of rheumatoid arthritis.

Q: Could rheumatoid arthritis be treated by removing environmental triggers?

A: We don’t know about other environmental factors, but the smoking example is one where we have some information. In that case, the disease doesn’t seem to go away when you stop smoking, but it does become easier to treat. People who never smoked, or who have stopped smoking, respond better to medication. As we go forward, we hope to make more and more of this kind of information available to clinicians.

 

 

References:

Goulielmos GN, Zervou MI, Myrthianou E, Burska A, Niewold TB, Ponchel F.  “Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients,” Gene. 2016 Feb 8 [Epub ahead of print]