Neanderthals and Biologics, pieces of the puzzle.

Hello, and welcome to today's episode of The Ankylosing Spondylitis Podcast. I'm really glad that you could join me today because we're going to have fun today, we're going to be combining some of my favorite subjects history, modern medicine, and a little bit of speculation mixed in. So stay tuned. This one should be a lot of fun.

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So in today's episode by the title, you saw the word Neanderthal and you go, “What does that have to do with ankylosing spondylitis at all?” Well, I wondered the same thing. And then I was directed towards a few interesting articles and I started reading them and it really was a very interesting hypothesis. So about 30,000 years ago, give or take a few thousand years. What we would know as the modern homosapien came wandering out of the continent of Africa as they were migrating north. And as they got into the colder climates, they walked right into and head on confrontations with an ancestor of theirs that was already living there. But that hadn't changed in the hundreds of thousands of years. The Neanderthal was they got there, what you would expect took place, conflict, fighting, death as one type of species tried to basically conquer the other. Which one was going to win? Well, it ended up obviously being humans, you know,Homo sapiens. But did we walk away with a gift or maybe a curse From Neanderthals? Well, let's look at that. It's an interesting hypothesis or interesting series of debates that had gone on around this. So I was directed to a website called Everyday Battle, where there was an article entitled How a weird fetish among our ancestors led to Ankylosing Spondylitis. And so I started to delve into this article and found it to be really interesting, and I'll have a link down below what the studies are showing where now this is from some information that came out in the 2013, 2012 somewhere back in that area. But it was based upon looking at the DNA of Neanderthals and (modern day)humans and what they found in that and what may have carried over to us as modern humans. Studies suggest that Neanderthal genetics may be responsible for autoimmune diseases in modern humans. The author discusses a documentary called Decoding Neanderthals and in that documentary, they talked about discovering in the ancient DNA of these Neanderthals, the HLA alleles, and one particular HLA, HLA-B27 is the main genetic marker that's used to diagnose Ankylosing Spondylitis. It's found in 95% of the people with AS. Now, that doesn't mean that if you don't have it, you're not going to get Ankylosing Spondylitis or even non radiographic. This is just saying that this gene is found in the predominance of the people that have this disease and as we know, HLA-B27 is an antigen and it helps direct how our white blood cells work. And when you have Ankylosing Spondylitis, that HLA-B27, it malfunctions that it gets messed up and this causes the immune system to basically attack itself. So where does alleles come from? And how did it get to be part of our genetic code? If it can screw some of us up and cause us so much great pain? Why would the body build it? Why historically, why would genetically it come to play to say, Hey, we're going to, we're going to make some people have this great amount of pain, there must be some benefit that it serves, or there must have been some benefit that it served in the past. And the answer may come from being interbred with Neanderthals. Now, this still hasn't been completely documented. And for sure, this is just a “what if”, so please take it with a grain of salt that it's just a what if and I thought it was kind of interesting and a great way to look at the disease from a historical perspective. We know that Neanderthals were the first, you know, one of the first human like species to leave the African continent. And they diverge from what was a common ancestor coming out of Africa around, you know, 600,000 years or so ago, and they had to adapt to a new locale outside of the African continent, and that new locale would be the European area, Russia, Asia, that area, it's cold, they aren't used to the cold in Africa, different types of animals, different types of bacteria in the soil, everything was different than what their ancestors have had to deal with and they had to come about and develop immunities to all that. So in this is where the weird fetish, you know, comes in Neanderthal genetics are, you know, more common in populations of European and Asian descent. So that same population that shows a prevalence of Ankylosing Spondylitis, so it implies that our ancestors were having sex with Neanderthals and do this you know, we got some homosapien walking down the trail, middle of the woods looks over and sees this hot lookin, hairy humanoid, who can't speak with him, but the birds and the bees come into play. And what eight, nine months later, here comes this little baby that's carrying 50% homosapien DNA and 50% Neanderthal DNA. Boom, just lik e that Neanderthal DNA is introduced into the homosapien genetic line and maybe that female is absorbed into the homosapien tribe and that baby grows up looks different than the other Homo sapiens, but breeds with a homosapien. And eventually, the lineage looks more and more homosapien. But that female Neanderthal DNA is still in each one of those ancestors and just a smaller and smaller piece. And if that little bit of DNA encompassed the HLA-B27 gene that the homosapiens coming out of Africa didn't have maybe that's where it came from? Is that we're looking at and why was it developed? What did these HLA-B27 or any of these HLA's benefit the Neanderthals, and that, you know, they wouldn't have had them in the southern part of Africa where the Homo sapiens were developing? Well, let's take a look Neanderthal and Ankylosing Spondylitis? Well, Neanderthal remains have shown evidence of arthritis. They've done genetic sequencing on the remains that they found. And they have shown that Neanderthals had a predisposition to diseases like psoriasis, Crohn's and lupus, though there is currently no direct connection confirming that HLA-B27 in particular is of Neanderthal origin. Inheritance of the HLA alle in our ancestors means that Neanderthal interbreeding could be to blame for your Ankylosing Spondylitis diagnosis. So now how does this help you in our everyday battle against the disease? For one thing, it might explain why certain types of diets are better for reducing flares reducing the symptoms of Ankylosing Spondylitis. You know, if you cut out the carbohydrates, things like the Paleo Diet, Raw Diet, you know, No Starch Diet, No Sugar, you know, all those can have some very beneficial results for people. With ankylosing spondylitis seems no accident that these diets tend to mimic what our ancestors were eating at the time. So if you're at all curious about how much of Neanderthal DNA you may have, you can go out and do a 23andme test, which is where I got my results from it said in my results, I was higher than 66% of everybody else that they had done 23andme tests on, I found that kind of interesting, you know, they'll sequence your DNA, it's really easy. You basically just spit in a little tube, you know, 15 times or so and send it in and, and that's it. And then you'll have scientific proof that you have some or no Neanderthal DNA. 

On to the main portion of today's episode. I hope y'all like that little rundown on Neanderthals. I just thought it was kind of interesting.

So, in looking through some of the forums on Facebook, I've seen a lot of questions either; should I start biologics? I've just Just started biologics, I need to switch a biologic and a lot of what do I expect? Well, it's really dependent upon you, there's no way to say, here's what you're going to expect. And there's not really even a way to generalize what you're going to feel because we all respond to these things differently. But let's kind of look at what the Axial Spondyloarthritis is, and Ankylosing Spondylitis as well as non-radiographic axial spondyloarthritis. But there's some interesting information on biologics for the non-radiographic for the moment we're going to focus on the Ankylosing Spondylitis. So it is a chronic condition. Some categorize it as autoimmune in other spots, you'll see it as auto inflammatory. So it basically is a disease that attacks the joints in your body, for lack of a better term the hips, spine, your knees, your feet, shoulders, it can really attack anywhere. Me personally, mine came on very, very heavy in my hips. When I was a kid, and has now as an adult progressed through my spine, where I know many of you in talking, have told me that it hits your spine yet sore back all the time and has moved to your hips. My mind kind of went in reverse from a lot of people. And this condition can fuse your spine, fuse your hips, be extremely painful cause lack of mobility, and possibly even leading to going on disability where you can't work. In my case, I'm in the United States. And I had both hips replaced by the time I was age 23. And then fast forward by age 40, the left hip worn out had a hip replacement. It was actually supposed to be a revision, I went in for the revision, and he saw the all the extra damage in there that wasn't visible on the X ray and I ended up having to do a hip replacement that didn't take. About three weeks later I went back in for another left hip replacement. So I had two hip replacements done in a matter of a month in 2010. It's now been 10 years since, and I'm still dealing with some issues of sciatic nerve damage, drop foot, things of that nature on my left leg. So it's, it really can affect us all in just numerous ways and some people will get it and have very mild conditions and something like a biologic might not be appropriate or helpful for them at all. So how do I know if a biologic will work for my Ankylosing Spondylitis? Well, you generally don't. But one of the ways they look at it is there's all these different medications that you can start off on that are over the counter medications, like Aleve, ibuprofen, acetaminophen, those may be ways to help how you first start to control. The initial stages are symptoms of Ankylosing Spondylitis, they will knock some of that inflammation down, but eventually for many of us that inflammation rises to a point where the simple over the counter medications just can't work anymore. So maybe they try something like a Celebrex or something a little bit stronger to help that may help you a Sulfasalazine, Meloxicam, Methotrexate. There are a number of different medications that they can try. Well, at that point, your doctor might say to you, I think it's time to look at biologics or if you're in certain countries, they might use a term called biosimilars. And those are a version of the biologic that if you listen back to Episode 51, (link below). When I discuss an interview Michael Mallinson, we talked about axial spondyloarthritis and in there; Michael does a really good discussion on the difference similars and differences of the biologic and the biosimilar. So I would encourage you to go out and listen to Episode 51 for a more detailed explanation of that, but as we go and look at the biologics, I'm going to start off with just the biologics. I won't jump into the biosimilars in this particular piece. But there really are six main names that you'll hear in the biologic world. When you start to discuss them. You'll hear of course, Humira and Enbrel, Cimzia, Simpony, Remicade and Cosentyx. There's another one out now that you hear quite a bit called Taltz and if you listen to Episode 25 that I did back in December (link below) that's titled New Guidelines for Treating Ankylosing Spondylitis. In there I did a discussion on the kind of protocol that they're (Rheumatologists) trying to put in place so that as patients with axial spondyloarthritis, when we go into rheumatologist, we should all get about the same type of treatment, the same type of recommendations now they'll vary because there could be different things the doctor sees that make you A little bit different than others, but it's really just trying to standardize the level of care that we receive as patients. So again, that's Episode 25. (link below). When a doctor is looking at the biologics for you, and how to assist you with feeling better, they're going to kind of look at these five things, as determinations of your ability to use biologics or ability to stay on biologics. And again, as with any type of medication, and treatments. I'm not a doctor, I'm just relaying some very generic things that should be helpful to you to go and have that discussion with your doctor. You may be concerned unsure of where to start even nervous to talk to your doctor and don't be and hopefully an episode like this can help you formulate the questions you want to want to bring up to your doctor.

Number one: Did other medications provide relief? Doctors don't always recommend biologic therapy for everyone with as typically biologics are for people with moderate to severe as in that if they haven't responded to other medications, this makes a next logical step. They're generally not the first line of treatment for this condition. But depending again, on your severity, they may be the medication that your doctor says here, we're going to skip all this other stuff and go right to biologics. That's where the doctor’s discussion and knowledge of you is going to come into play. Some people can improve their symptoms by just making lifestyle changes. These can include you know, being more physically active, which leads to increase joint flexibility, losing weight to reduce pressure on joints, learning to control stress, you know, stress can trigger inflammation in the body. So if some of those have been tried along with maybe over the counter medications or something stronger like Celebrex, and they're not working then The next step is the disease modifying antirheumatic drugs DMARDs that include biologics, and these can help to improve your condition and may very well work for you.

Number two: Can I keep up with scheduled treatments? That's the thing; biologics are not like a pill that you just take once in the morning. There is a usually a shot involved to it and biologic therapy isn't available, you know, as I said, in a pill or oral form. Instead, you'll receive infusions at your doctor's office maybe a few times a year, or you'll give yourself your self administered shots, either using a regular needle syringe, or a almost like an epi pen, a self injector, an auto injector pen. And so these biologic treatments target proteins in your body with the purpose of suppressing your overactive immune system and calming your body's inflammation response to what they think is going on what they think they need to attack. For this therapy to work, you have to keep up with your scheduled injections and/or infusions. If you stop treatment, not only can your symptoms come back, but also that biologic that you were experiencing relief with may not work again for you. You may have to then start going hunting for a new biologic to work for you. So, once you start on, there's something you're going to stay on. And keep in mind that biologics aren't a cure for a AS, there is no cure for this condition. They simply serve to suppress or bring down that immune system and thereby help to hopefully slow and or stop the inflammatory attacks on your joints and making your body deteriorate.

Number three: Will I take other medications with a biologic? Possibly, if you're a candidate for a targeted therapy, your doctor may prescribe only a biologic or you may receive a DMARD to take with your biologic treatment, even though biologics are effective for treating AS, some people don't respond to the treatment alone and need a combination of therapies. You can't take two biologics at the same time, but it is generally safe to combine a biologic with an anti rheumatic drug. So you might take it in combination with a Sulfasalazine or a Celebrex or Methotrexate. There's a number of ways that medications can be combined to help you. I took Celebrex along with Cosentyx for several years and finally had to stop all NSAIDs due to some kidney damage from long-term use and in some cases, abuse of NSAIDs that I did when I was younger to try and relieve pain. So now I'm just strictly on Cosentyx for the AS that I deal with.

Number four: Who shouldn't take a biologic? Well, despite the effectiveness for many people that use the biologics, it's like all medications. It's not right for everyone and your doctor is the person that is going to help you determine if this medication is appropriate for you. Even though biologics aren't like traditional immunosuppressants that suppress the entire immune system, they can compromise your immune system and make you susceptible to illnesses and certain illnesses and infections. It also becomes harder to fight infections while taking biologics. Me personally, I've been on Cosentyx for almost three years now, and I do notice that I get sick less often I get my flu shot every year, and then I really don't get sick. But if I get a cut on my arm or leg or whatever, it takes a long time for that to heal, probably two to three times longer than what I think the average person would take to heal up. So I put some neosporin on maybe a bandaid depending on the type of cut but it really I do notice that cuts and things take a long time for me to heal. Your doctor may not recommend biologic therapy. To you, if you have a weakened immune system for any reason, you know, for instance, if you're being treated for any type of cancer or you've been diagnosed with HIV or Hepatitis C, that may rule out biologic treatments for you at this time completely, the immune suppressing effect of biologics could worsen some of these existing diseases. So therefore, if you have an active infection, you should wait until the infection clears before beginning treatment, and then also, you know, long-term use of biologics may increase the risk of certain cancers. I say this because it is listed as a side effect on the medications. It is only certain cancer not all cancers, and primarily lymphoma. And also there's there's some there's some studies that say that this really may not be the case. But when originally these things were having their warnings written, it was added and taking it off is pretty much impossible. So they've kind of left it out there. But anyway, I'll try to find a link to the studies that talk about really the risk of cancer being very, very low again. But if you have a history of lymphoma, or your family has a history of lymphoma, please let your doctor know before you start taking any biologic. And then after starting a biologic, if you develop a cold or a flu that doesn't improve in a standard, you know, few days, or if you experience other symptoms, such as bruising or weight loss or fatigue, make sure that you call your doctor and let him or her know about that really, really quick. Don't just kind of wait on that.

Number five: What should I know before taking a biologic? Well, that's the question and that's really where this all started at. You'll see people come on and say, “Well, what should I know? What should I be aware of?” I don't know. If you feel like you're not feeling normal. You know, you're feeling off dizzy headaches, whatever after taking it nauseous, that's probably a good time to call your doctor, or many of these medications provide an 800 nurse number. Call that so you don't have to copay for your doctor and talk to them and see if they say no, this is something you need to go to the doctor or the hospital or it should pass in a day or so. So just kind of you know your body, you know what's right and wrong and, and you really want to be just kind of tuned in the first couple of days after you take a shot to see how you're feeling, you know, biologic therapy, it's not a quick fix for inflammation. You know, some people see improvement soon after starting therapies. I started within three shots like within three weeks of starting my Cosentyx shots, I started noticing quite a bit of difference. But now almost three years into it, I've noticed kind of a tail off and I've gone from one pen, two pens to try and keep that same effect going for my body. So does that mean I have another couple years left? Another year? I don't know. I could be on to searching for a new biologic. That's just unfortunately, part of the way these things are right now. There's just no way to know what's going to work and for how long. So if you take one biologic and you don't see an improvement, your symptoms, you know, don't give up. A lot of doctors want you to try it for at least six months, but you don't talk to your doctor three, four months into it. If you're not seeing anything or not feeling anything, talk to your doctor and see if you're a candidate, maybe for another biologic, see what they think is maybe a timeframe that you should be responding. And then even if you find a biologic that works for you, as it could stop working over time, which is kind of what a lot of people run into including myself. In that case, your doctor may switch you to another biologic, or include an anti rheumatic drug with your therapy to try and boost up the effects of that drug.

So finding the right combination of drugs can keep your symptoms you know, under control for a long time, and slow the progression and that's really what we want to do is slow this progression down. And for many of you that have seen the X rays I posted on my back it's a classic bamboo spine completely fused. And if you're not at that section, that's what you want to try to avoid. And that's what you want to work with your doctors to build a treatment plan to try and avoid that. You know, incorporate in and listen to the last episode I did Episode 60 with Jeff Lindsay and Jamie Boder. We discuss their use of yoga to help combat some of the symptoms of Ankylosing Spondylitis. So there's a lot of ways that you can work to try to fight you know, what your body is trying to do to you.

So, again, thank you so much for listening. Thank you to those that have gone out to buy me a coffee calm and help the Ankylosing Spondylitis podcast out. I really appreciate it. And I look forward to hearing from everybody in the future. And also if you want to get a T-shirt or hoodie or facemask with the Ankylosing Spondylitis podcast logo and and show that off, go ahead and hit the link up in the show notes. Everybody have a wonderful week and I look forward to talking to you. And by the way, don't forget to go out to spondee podcast comm and sign up for the newsletter out there. I just sent one out, and I have another one going out probably in the fall sometime. So thanks and everybody, take care.

Neanderthals and Ankylosing Spondylitis - http://www.everydaybattle.com/weird-fetish-among-ancestors-lead-ankylosing-spondylitis/

Will Biologics Work for Me – Healthline - https://www.healthline.com/health/beyond-back-pain-with-as/will-biologics-work#3

Episode 051: Michael Mallinson - Discusson about Axial Spondyloarthritis - https://player.captivate.fm/episode/9c4a5ec1-da27-47e9-aa6f-4b7355a77911

Episode 025: New Guidelines for Treating Ankylosing Spondylitis - https://player.captivate.fm/episode/4519beac-9f38-4560-8301-70e9bf474256

Is there truly a risk of lymphoma from biologic therapies? - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768030/

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