Jayson:

Welcome to this week's episode of The Ankylosing Spondylitis Podcast. I'm very lucky today to have on Dr. David Fox. Dr. Fox is one of the co-chairs of the University of Michigan's Autoimmune Center of Excellence. Dr. Fox has been a rheumatologist for a number of years, a member of the medical school faculty since 1985, Dr. Foxx is a professor of Internal Medicine, and from 1990 to 2018 was the chief of the Division of Rheumatology with the University of Michigan's medical school. You've gotten your undergrad from Massachusetts Institute of Technology and your Doctorate from Harvard Medical School. So fantastic training as you then jumped up to University of Michigan, Where you work through all the different wonderful areas that the University of Michigan's medical school has to offer. So, Dr. Fox, glad to have you here and welcome.

Dr. Fox:

Jayson, thank you very much. I'm very pleased to be chatting with you this morning.

Jayson:

Something that I find very interesting that you’re involved in is this Autoimmunity Center of Excellence. As we discussed prior to the conversation, there's about 12 or 11 of those centers around the US at different universities and hospitals. And what is the basic premise of an Autoimmunity Center of Excellence?

Dr. Fox:

It's a group of investigators that are conducting research in the treatment of autoimmune diseases and also trying to understand causes of autoimmune diseases. And these include forms of arthritis, other rheumatologic diseases like Lupus and Scleroderma, and autoimmune diseases that are in other areas of medicine, like for instance, Multiple Sclerosis, which affects the brain. Different centers have specific projects and clinical trials that they're working on. But a very important part of this Autoimmunity Center of Excellence or Ace program, as it's called, is that the different centers have a chance to meet a few times a year and interact with each other and have what are called collaborative projects where we get to work together with an experts at other institutions and benefit from their knowledge and hopefully they benefit from ours.

Jayson:

Now what I find interesting and these Autoimmunity Centers of Excellence, the ones we're talking about that you're involved with are all in the United States. Is there cross-country collaboration, like do you as doctors and researchers work with folks say in England or Australia or Canada, anything of that nature?

Dr. Fox:

Yes, we do. Not necessarily directly within the framework of this Ace program, but in other aspects of our research. We certainly work with physicians in other countries. One way that that occurs is in some of the clinical trials, particularly in our scleroderma program. Many of these trials are international trials. It's a rare disease. So we may need quite a few centers to Join up in a clinical trial to recruit the number of patients needed for you know, useful study. So we have collaborations with our colleagues in Europe and in Canada and occasionally other parts of the world.

Jayson:

Interesting. Your background, I know you've really focused on Rheumatoid Arthritis and the Scleroderma. 

Dr. Fox:

Yes. 

Jayson:

When we look at those diseases, how do they cross over into fields of say, like research for Ankylosing Spondylitis? Or can something that happens in Rheumatoid Arthritis say; oh, wow, this may or may not work for AS let's try it on AS patients.

Dr. Fox:

Yes. So there are similarities and also differences between these various diseases and sometimes we find out more about where the similarities and differences are by trying new treatments and seeing what works. So for instance, if you look at TNF blockers, so these are biologics that inhibit the action of a molecule called TNF (tumor necrosis factor) Those TNF blockers are useful not only in Rheumatoid Arthritis, but in Ankylosing Spondylitis as well. There are other biologics that may be useful in RA but not in Ankylosing Spondylitis or vice versa more useful in Ankylosing Spondylitis, but not RA. Both of these forms of arthritis are considered autoimmune in that cells of the immune system are inside the joint linings or instructors adjacent to joints and causing inflammation and eventually damage in those areas. And these are locations where the immune system generally does not take precedence. But the details of what's going wrong are somewhat different if you compare these two forms of arthritis and that leads to areas of difference in terms of whether some treatments work in one versus the other disease.

Jayson:

Oh, interesting. I use myself as an example because I've dealt so long with Ankylosing Spondylitis, the general rule from the best I can see is that it's thought of as a disease that primarily affects the spine. In me the spine was really a secondary area that was affected. Mine really attacked my hips when I was really young and resulted in multiple hip replacements in my early 20s, just because it had so gone after the cartilage around the hips so bad 

Dr. Fox:

Well, it can certainly do that. And we think of Ankylosing Spondylitis and most patients as being worse than what we call the axial skeletal joint the joints that are near the center of the body like the spine or the hips. In some patients with Ankylosing Spondylitis you can get involvement of the hands and feet as you do in Rheumatoid Arthritis. In Rheumatoid Arthritis, the spine can be involved but only the cervical spine. In other words, the neck the lower parts of the spine are not involved by Rheumatoid Arthritis, but are frequently involved by enclosing spines So, one really interesting feature of these different forms of arthritis is that they have an intrinsic kind of map to them as to which locations they go to and and which they avoid. And that's one of many things that we'd like to understand better, but yet have only, I would say, very fragmentary clues as to what's going on.

Jayson:

Yeah, I've talked with my Rheumatologist who has since retired Dr. Morton, and it was really interesting. Again, when I was diagnosed, there really wasn't any biologics, and it wasn't until the early 2010’s that I was offered and tried out my first biologic, which at the time was Enbrel had short success with it just not long term. So like many the Rheumatologist I was seeing moved me to Humira kind of the same thing and neither worked long term for me but I did feel some relief while using them both for maybe six months to a year on each medication and then stopped. I stayed on Celebrex, which I had been on since it's basically was rolled out. And it wasn't until 2017 that I tried Cosentyx and to me that was a game changer. I had never felt better than when I took that Cosentyx. And I just found it really interesting that my body reacted really well to that I IL-17 blocker. Whereas the TNF didn't do much for me long term and it's one of those mysteries with biologics, you just have to trial and error.

Dr. Fox:

Well, to a great extent that's true. And we wish we had a more reliable and systematic way of picking the best remedy for each patient on an individualized basis right at the start, and we need to do that is improvement in what are called biomarkers. In other words, things that we can test or image or measure that will tell us this patient is going to respond to a TNF blocker better but the other patient is going to respond to an IL-17 blocker better. And so we will individualize that treatment in that way, to a large extent this biomarker based selection of treatment has already come into play in cancer treatment, not yet very much in rheumatic diseases. But I think that's going to happen over the next five to 10 years. And so treatment will become more systematic and not just a matter of trial and error. 

Jayson:

Well, Dr. Fox, how do you do that biomarker testing? Is it just through a blood test? Or is it more indept in that I'm not sure how that's done?

Dr. Fox:

Well, there there are many kinds of biomarkers ideally, for practical purposes, you would be able to do it through blood tests or urine test or or x-rays or other kinds of imaging in the cancer area. Of course, the frequently the actual tumor tissue is available and the biomarker tests are often done on the on the cancer itself. In the case of arthritic diseases, sometimes we have joint flow or sometimes we can take a biopsy from the inside of the joint. But we don't typically have a large piece of tissue, as the oncologist do to do all sorts of tests on so hopefully we will get some biomarker tests that can be done through the blood that reflect the specific pathways that are going on in the inflammation in that patient's joint tissue and then based treatment on that. And so the NIH has organized an initiative called the AMP that stands for Accelerated Medicines Partnership, and that's funded in collaboration with a number of pharmaceutical companies and they initially focused on Rheumatoid Arthritis and Lupus and have come up with some pretty interesting results about immune mechanisms and those diseases that can be measured through biomarker tests and that may be guides in the future to new kinds of treatment and personalized individualized treatment. And so there's discussion about the next phase perhaps, of this and collaborative and that type of approach, I think is is going to move the needle and get us more towards where we'd like to be in terms of picking the right treatment for the right patient. 

Jayson:

Any breakthrough in Rheumatoid or any of those can potentially lead to breakthroughs in the other forms of autoimmune issues. So it's great to hear that as a patient, it might not seem like much is happening, but behind the scenes, it sounds like there's quite a bit

Dr. Fox:

There is quite a bit and there's another branch of the NIH called the FNIH, Foundation for the NIH and this is a branch of the government that is undertaking research that is funded not by taxpayer dollars, but by contributions from pharma companies and philanthropic contributions and one of the programs in the NIH is a biomarkers program and within that program, there is a sub program about immune mediated diseases and in fact, there's a project being organized through that program specifically to come up with biomarkers in Ankylosing Spondylitis and Spondyloarthropathy. And that's in collaboration with the patient organizations that are involved and invested in Ankylosing Spondylitis research. So they're at the table on on this also, along with some academic centers that work very hard in the Ankylosing Spondylitis area. So you'll be pleased to know that we're soon hoping to launch a specific new biomarkers initiative in Ankylosing Spondylitis.

Jayson:

Oh, interesting. Oh, yeah, we'll definitely keep an eye out for that. Another area that you really focus on, I believe, if I understood this right was autoimmune eye diseases.

Dr. Fox:

Well, we've done some work in autoimmune eye diseases as well. There are several kinds some involve the retina which is the back of the eye. Some are called Uvitis which means inflammation of the inner structures of the eye but in front of the retina, many patients with inflammatory arthritis or other systemic autoimmune diseases like Rheumatoid Arthritis or Ankylosing Spondylitis, they can get eye inflammation Also, sometimes it can be pretty serious and the eye is a special zone in the body that normally is protected from immune attack, but in some diseases, something happens to break down the barrier that defends the eye and the immune system can get in there and inflame the structures of the eye. It's a very important aspect of autoimmunity and yes, we are interested in that.

Jayson:

Uvitis/iritis is very common in people that have Ankylosing Spondylitis? Yeah, I haven't had a bout of it in a while. But I've noticed that like many things, the older I get, the longer it takes me to fight it and get rid of it with the last bout being around for a good six months.

Dr. Fox:

Yeah, six months and and the iritis is quite painful as well. So you know, it's a significant problem.

Jayson:

Yeah, my first bout of Iritis, nobody knew what it was, was treated as pinkeye. And you know what happens three, four days later, it's not cleared up. And it's only substantially worse, I happen to go to an emergency room. And luckily there was a Ophthalmologist there and he came walking in, he looked at that, and he says, Oh, you got a hot one there. He said, you're not gonna like the treatment that I got to do to fix this, but we're going to get it under control. So we did everything that was done. This was in the early 90s. And it's been a few bouts since but I try to tell everybody from a patient side, even if you've never had I read us or uveitis to make sure you get a good Ophthalmologist on speed dial that understands that if you call them it's an emergency that you need to be fit into their schedule.

Dr. Fox:

Yes, we need specialized pathologic care for these kinds of eye diseases. They have the equipment to exam the eye properly and the knowledge to ask assess what's going on at least in ankylosing spondylitis, you know when your eyes inflamed because it's bright red and very painful. But uveitis can be sneaky and be deeper in the eye and not as painful and not as red but very dangerous. So patients with juvenile forms of arthritis, they frequently have Uvitis that has no symptoms, but can cause blindness and so children with that kind of arthritis where there's a risk of that kind of up if they have to see the Ophthalmologist every three months. That's how dangerous this condition can be. So yes, the eyes are a very important target organ and we definitely pay attention to that. 

Jayson:

Wow and see again, I was not even aware that it could be that severe. I mean, I knew it could be severe but I didn't understand kids because I never had to affect me and nor did I know anybody that it could be that intense that directed where a doctor needs to be seen that often. So that's that's really interesting. 

Dr. Fox:

The eyes are such complex organs.

Jayson:

Amazing. Yeah. Well, Dr. Fox, I really appreciate the time you've given to me and to the listeners to talk about some of the things going on behind the scenes. So many times when we go to rheumatologists for our visit, you can sometimes feel like maybe didn't get all your questions answered. I encourage folks to always write down and give your rheumatologist any specific questions, but to get from you a better understanding what's going on behind the scenes. I really just, I can't thank you enough.

Dr. Fox:

Well, Jayson, you're very welcome. It's really my pleasure to convey some of the excitement and progress that we have in our field. And you know how far we've come in the past 30 years or so. But I like to tell my students we're not quite there yet. Maybe we're halfway there. But for any disease, we want to do more than partially understand it and we want to do more than, you know, partially treated, we really need to aim for understanding the cause the cure, and eventually the prevention of these diseases. And hopefully in the next 30 years, that's where we get

Jayson:

Well, again, I thank you, I think you're being overly modest. And for the listeners, something that's really unique that Dr. Fox, the University of Michigan has established what they call a professorship in Rheumatology, named after Dr. David a Fox. And this is something that in the show notes, I'll have a link to if you should be more interest in it, or want to make a donation to it, leaving doctors coming up future doctors in Rheumatology will be able to apply for and get the David A. Fox Professorship in Rheumatology, I think you're very modest, you know, you're very well liked by what I can read from the colleagues and the information that you have is just from a rheumatology patient.  I can't thank you enough for what you're doing behind the scenes. I look forward to see what future sufferers who have AS will benefit from the research that you're doing today.

Dr. Fox:

Well, thank you very much. That's certainly our hope.

Jayson:

Thank you again. I appreciate your time and you have a wonderful day

Dr. Fox:

You too and be healthy. Thank you. Thank you. Bye

https://medicine.umich.edu/dept/intmed/david-fox-md-professorship-rheumatology-update

https://labblog.uofmhealth.org/lab-report/exploring-new-treatments-for-autoimmune-diseases

http://www.autoimmunitycenters.org/index.php

https://www.ncbi.nlm.nih.gov/pubmed/31436036

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