Understanding Axial Spondyloarthritis, Its Diagnosis & Treatment Options: Interview with MD Newsline

I recently joined MD Newsline for a discussion of the complexities of axial spondyloarthritis. We covered the common and uncommon symptoms, the pathway to a diagnosis and various treatment options for this often-missed diagnosis.

Video Transcript:

On this episode of our Key Opinion Leaders series, we speak to Dr. Jill Weintraub. Dr. Jill Weintraub is a double board-certified Integrative Rheumatologist in New York. She graduated from the Albert Einstein College of Medicine with Honors, finished her Internal Medicine Residency at The Mount Sinai Medical Center, and completed her Rheumatology subspecialty training at The Hospital for Joint Disease at NYU. She is the Andrew Lowell fellowship recipient for the study of Integrative Medicine with Dr. Andrew Weil.  She was the Chief of Rheumatology at a large multi-specialty group for over 10 years and was named one of New York’s best doctors. Dr.  Weintraub is an active member of the American College of Rheumatology and the primary investigator for several studies on the use of complementary therapies in autoimmune diseases.

Esther Ikoro:
Dr. Weintraub, thank you so much for joining us on MD Newsline podcast. Can you please introduce yourself to our audience?

Dr. Jill Weintraub:
Sure, and thank you so much for inviting me. My name is Dr. Jill Weintraub. I am an integrative rheumatologist, which means that I am a conventional rheumatologist, but I have additional training in integrative medicine, so I combine both in my practice and with the way that I treat patients, and I'm the founder and chief rheumatologist at Integrative Rheumatology Consultants.

Esther Ikoro:
And we're going to be talking about spondyloarthritis. Can you please define it a little bit for us? There's so many people who haven't heard of it, so please just tell us a little bit about the umbrella term as a whole, and then some of the subtypes clinicians should distinguish between.

Dr. Jill Weintraub:
Sure. So axial spondyloarthritis is a form of inflammatory arthritis that typically involves the spine. However, it can involve really almost any joint, and it typically also involves what we call entheses, which are tendons and connective tissue. So a classic example of that would be something like the Achilles tendon. They are indolent and progressive diseases that usually require treatment and they can be hard to diagnose.

Today we divide them generally into two categories. One is called radiographic and that used to be called ankylosing spondylitis, and that was the classic syndrome that was originally diagnosed in young men, where they have a progressive inflammation and fusion of the spine, starting at the base of the spine in the sacroiliac joints, and working its way up.

Today, we make a distinction, and we recognize that there is another group that is called non-radiographic axial spondyloarthritis, and these are people who also present with inflammatory back pain, but we don't usually pick it up on the initial X-ray, so they require additional advanced imaging to make the diagnosis, and today we use MRI for that. So those are the two basic categories of axial spondyloarthritis.

I would say that within that family, there are other conditions as well that may share some of the features or be related. And those would include things like psoriatic arthritis, the arthritis associated with inflammatory bowel disease, and also reactive arthritis.

Esther Ikoro:
Interesting. Tell me a little bit about what the demographic distribution of this disease is, and are there sex differences? Are there age differences? You mentioned a little bit about younger men with ankylosing spondylitis. So tell me a little bit about who tends to get this disease and when it shows up.

Dr. Jill Weintraub:
Well, you know, that's a really good question, because we have definitely changed the way that we think about this. We originally thought of this as a condition that primarily affected young men. Now we recognize that it could affect just about anyone, and we see this all over the world. And in fact, I recently learned that in Japan and Southeast Asia, this is the most common form of inflammatory arthritis, but we see it equally in men and women.

In women, typically it takes longer to diagnose, and that's because it may not present as typically or it may take longer to come to medical attention. But hence the reclassification now, including the non-radiographic variants, that is helping us capture more of the women as well, who don't typically present with the radiographic findings.

Esther Ikoro:
When you talk about the presentation in women and it not necessarily presenting as typically, what is the typical kind of road to diagnosis, and how might it differ between men and women?

Dr. Jill Weintraub:
So the hallmark, classic clinical feature that we see in axial spondyloarthritis is what we call inflammatory back pain. And of course, back pain is incredibly common, and if you ask any primary care provider, it's probably a good proportion of their day is dealing with back pain, and most of it is not inflammatory.

So inflammatory back pain has some very key features to it. It typically starts in patients who are younger than 40. It typically presents with stiffness in the morning and pain in the morning that gets better with exercise and movement, which is really the opposite of what we see in mechanical back pain or back pain from a slipped disc or a strained muscle, which usually is okay when you wake up in the morning, but by the end of the day, is very painful. And the other hallmark of inflammatory back pain is that it tends to get better with anti-inflammatory type medications. So that is a pretty universal feature of anyone with axial spondyloarthritis.

Having said that, in women, they may not have the more typical presentation. It may not sound exactly like how I described and very commonly in women and in men, but more so in women, they get what's called a central sensitization of pain, and what that is, is it's involvement of the nervous system. So in that case, we're not just dealing with inflammatory type back pain, but when you have central sensitization of pain, what that implies is that the nerves that sense pain have been sensing pain for so long that they've been up-regulated and they are now firing on their own, meaning that the nervous system has laid down new tracks for pain, and so that can look like pain in the cervical spine, or pain elsewhere, or pain everywhere, and not just the inflammatory back pain.

And when that is present, that can really be the forefront of what the patient is talking about, which can delay diagnosis. So it's very important to remember, particularly with women, when you're considering this diagnosis, that they may not look like a textbook because the nervous system is more involved, and that muddies the presentation.

Esther Ikoro:
So when you have that kind of referred pain or kind of distributed pain, what's the thought process or what have you seen people go through to finally get to a correct diagnosis?

Dr. Jill Weintraub:
Yeah, that's a really good question. And I think the average time for a diagnosis of axial spondyloarthritis is five years. But I could tell you from my own personal experience, for several people, it takes longer than that, and I think part of the problem is that it's unfortunate that their pain is not taken more seriously.

I think that patients also, though, really do need to advocate for themselves, and even if they are told that what they are experiencing may not be inflammatory, or it may be, you know, they pulled something, or they lifted something, if that does not feel right, to really keep going until you find yourself somebody who can listen to you or get yourself into the right specialty where they're used to dealing with this.

Esther Ikoro:
So when we talk about things like axial spondyloarthritis, a lot of these types of things are described as this interplay between genetics, microbiome, immune activity. Can you tell me a little bit about how all of those things might interplay amongst each other when it comes to disease presentation and maybe people developing this in the first place?

Dr. Jill Weintraub:
Sure. So that's a model that we can think about for a lot of different inflammatory syndromes. But yeah, generally, we think that you should have some genetics in place. So the classically described genetic allele for axial spondyloarthritis is HLA-B27, which was described in young men in Minnesota. The axial spondyloarthritis that occurs throughout the world is often not associated with HLA-B27 and frequently in my practice, I see people who have axial spondyloarthritis who do not have this particular gene, but they probably have a gene that we either cannot readily test or has not been described yet.

But that's not enough. So a lot of people, actually, I believe it's 5% of the US population, has HLA-B27 and most of those people do not have axial spondyloarthritis. So the gene needs to be activated by certain triggers. And there's a lot of research and attention looking at mucosal surfaces, particularly the gut for axial spondyloarthritis.

So the gut is a mucosal surface that is incredibly large, and on top of that mucosal surface is a collection of bacteria and viruses and fungi and other organisms that are basically living with us and that are immunologically active, meaning they influence our immune system. And there's been a lot of research and time spent looking into what are the disruptions in the gut microbiome that might lead to a disruption in the mucosal surface, and that's important because on the other side of the mucosal surface of the gut and other mucosal surfaces are large aggregates of your immune system, and so when the immune system is abnormally stimulated by possibly an abnormal gut microbiome signature or a disruption to the lining of the mucosal surface, those signals over time can then become generalized to involve other structures away from the gut, including the joints, the spine, the tendons or entheses.

And of course, we know with axial spondyloarthritis that its cousin is inflammatory bowel disease-associated arthritis, where there is clearly bowel inflammation and clearly disruption to the gut microbiome.

So I don't think we know exactly the organisms at play yet. In rheumatoid arthritis, we're starting to understand that a little bit more with organisms like Prevotella copri, which has been described in early RA. We don't have that kind of information yet for axial spondyloarthritis, but hopefully we will soon, and hopefully that will open up some new treatment targets.

Esther Ikoro:
Are there any emerging biomarkers or molecular signatures under investigation that you find particularly interesting when it comes to stratifying patients?

Dr. Jill Weintraub:
So not that are available, or at least readily available in clinical practice. I do find that one thing that can be useful is calculating what's called a BASDAI score, which is actually not based on laboratory information, but it's really based on clinical information, and it's clinical information that you obtain from the patient.

So it's a series of six questions, where you ask about morning stiffness, you ask about generalized pain, you ask about joint pain, and it gives you a score, which you can then follow as you're treating the patient to see how impactful your treatments are, which I find getting that kind of more objective evidence at every visit can provide a little bit more information about if we're doing a good job or not.

It's probably as close as we get to a treat-to-target approach, which is something that's been described more in rheumatoid arthritis and now in lupus, where we're really trying to make sure that we're not just relying on our gut or our gestalt of how well we're doing at treating people, that we have some clinical data that we can follow.

Esther Ikoro:
On the diagnostic side, what are the diagnostic criteria and imaging modalities that you consider most reliable in identifying spondyloarthritis early, especially in non-radiographic disease?

Dr. Jill Weintraub:
So I think really taking a careful history about the pain and stiffness and what makes it better is probably the most important thing. We do have diagnostic criteria for this, but this is still largely a clinical disease. Blood work can be helpful. So if someone is HLA-B27 positive, that can be helpful. But I find a lot of people are not.

You know, looking at levels of inflammation, so a CRP and a sed rate can also be helpful, but certainly a lot of people with very active disease do not elicit those types of responses. And again, I often find this backfires in clinical practice, because those people may be told that nothing is wrong with them and it's really just that the parts of the immune system that are involved here don't elicit a sed rate or a CRP.

So I think it's useful to look but it's not useful to rely on those. I would say that when those are present, those do portend a more aggressive disease course, a higher likelihood of joint fusion, and they also actually predict a better response to medication.

But I think doing a good history and a good clinical exam is really still the basis for making this diagnosis, and I think also really trying to understand the source of the pain and whether it's coming entirely from the back, or whether we think that there is secondary nervous system involvement as well, is not only helpful in trying to make the diagnosis, but helpful in trying to craft a treatment, because we would treat those types of involvement separately.

Esther Ikoro:
And are there any pitfalls clinicians should be aware of, in your opinion, especially when it comes to things like MRI, which are increasingly central in diagnosis? How can they avoid pitfalls like as far as maybe interpreting things like subtle findings on MRIs?

Dr. Jill Weintraub:
That's a really good question, because first, I think you have to order the right MRI. So the MRI of choice when we're trying to make a diagnosis of axial spondyloarthritis is an MRI of the pelvis without contrast. So when we use contrast, we get a really good look at the pelvic organs, but when we're trying to diagnose axial spondyloarthritis, that's not so much what we're interested in. We actually don't want the contrast, and we want to use what's called a STIR sequence so we can actually get a better look at the bone marrow.

I work in New York City, so I have the luxury of working with bone radiologists who can help me in interpreting this. Not everybody has that available to them, and it can get difficult, because a lot of the readings you get, I think, are very dependent on the experience of either yourself, if you're reading it, or the radiologist who's reading it. And there certainly can be subtle findings that suggest sacroiliitis, which is really what we're looking here for, other than just erosions and fusions, which are late findings.

Esther Ikoro:
And can you comment at all on the recent development of standardized disease activity measures like ASDAS and BASDAI and their roles in guiding therapy today?

Dr. Jill Weintraub:
Yeah, so I find using BASDAI scores are very helpful, particularly in grayer areas. So it's not that hard to know when someone is really flaring, and it's not that hard to know when someone is in a clinical remission, meaning they really have no symptoms of stiffness or pain. But I would say there's a lot of gray area in between, and using a BASDAI, which you can calculate with the patient in the office, or you can print out and put on a worksheet and have them fill out in the waiting room before they get to the office, can be very helpful in comparison in making those determinations about whether we're doing a good enough job with our therapy.

Esther Ikoro:
With so many biologic and targeted synthetic options available, what principles guide your selection between TNF inhibitors and IL-17 inhibitors and even JAK inhibitors?

Dr. Jill Weintraub:
So we really have to step back and look at the whole patient. So the nice thing about TNF inhibitors is that they've been around now for more than 25 years. We have a lot of safety data established for them. They have had a good role for a long time in preventing the radiographic change with axial spondyloarthritis, which is really what we want to do with our therapy, meaning we want to make people feel better, but we also want to know that we're preventing progression of the disease that we might see on X-rays or MRIs. So we know that TNF inhibitors do a good job of doing that.

However, TNF inhibitors do increase the risk of infection pretty considerably. So in someone who has other risk factors for infection, like diabetes, or if they have a long smoking history and they're set up for pneumonia, I might think twice about using that class.

Luckily, we do have other options today, so IL-17A inhibitors are generally less immunosuppressive, so I might use that in someone who I'm worried about infectious risk. The caveat with that is they do increase the risk of viral reactivation type infections, so namely, shingles. So we really encourage people, regardless of their age, to get vaccinated for shingles, and at least to get the first dose before we start treatment.

JAK inhibitors would be a second-line therapy, meaning after someone has failed a TNF inhibitor or an IL-17A or combined IL-17 A and F inhibitor, we would think about using a JAK inhibitor. I would say the pros of using a JAK inhibitor is that it's an oral medication, so the patient does not have to do an injection. I would say the cons are that they are more immunosuppressive. They have more malignancy risk long term, and they increase what is called the incidence of MACE. So that would be major adverse cardiovascular events, heart attacks and strokes and venous thromboembolism.

So they are contraindicated in people who are over 50 and who smoke, which you know leaves out a lot of people, but often in younger people, they can be useful. And another interesting thing about JAK inhibitors is because they inhibit the cytokine cascade much, much earlier. So they're inhibiting actually several cytokines. They can be very useful for people with just generalized pain, so sometimes in people who are having a lot of disease activity but are also having a lot of central sensitization of pain, I lean toward using one of those to try and get some of the pain mediators as well.

Esther Ikoro:
How do you integrate non-pharmacologic interventions like exercise, physical therapy or patient education into disease management?

Dr. Jill Weintraub:
So exercise and physical therapy are really part of the treatment. They're just as important as medication, and we really encourage people to do something with a lot of range of motion. So swimming and yoga are really the most evidence-based, but there are a lot of other exercises as well that are really part of the treatment for this.

And I would say, certainly in my practice, I have several master swimmers, I have several yoga teachers, and those are the people who I find really do the best with this long term. So that is really part of conventional treatment is exercise and physical therapy, and that really needs to be lifelong.

I would also say that, you know, in the world of integrative medicine and in functional medicine, there are other modalities that we look at to help relieve pain, and some of those might be supplements, some of those could be dietary changes, and those are generally very useful. I think the caveat is that none of those types of treatments are disease modifying, so they are adjunctive treatments. They are not instead of medical treatments.

And unfortunately, I can say that I've seen several patients who, for very valid reasons, did not want to pursue conventional treatment and sought to control their symptoms solely with diet and supplements. And while they did feel better, you know, X-raying and doing MRIs later did reveal that the disease did progress, and it was somewhat masked by these treatments. So I really encourage people that if they want to seek ultra alternative type treatments, that they can be very useful, but they're not a substitute for conventional treatment, and that these things need to be integrated together.

Esther Ikoro:
And what are your thoughts on patients that have overlapping extra-articular manifestations, like uveitis, psoriasis, IBD? How do you coordinate care and treatment selection across specialties in these cases?

Dr. Jill Weintraub:
Yeah, so very often our patients will have uveitis or psoriasis or hidradenitis suppurativa, you know, Crohn's disease. All these things exist on a continuum together, and when we're picking a treatment, we really try to pick a treatment that will cover more than one entity.

So, you know, HUMIRA or adalimumab would be a good choice for someone who also has hidradenitis suppurativa or who also has Crohn's disease. An IL-17A inhibitor would not be a good choice in someone who also has inflammatory bowel disease or possibly uveitis. So when we're making a treatment selection, we really try to look at the whole patient and the other types of manifestations that they have along this spectrum, and we try to choose a treatment that will cover more than one.

Esther Ikoro:
What are the most common misconceptions among patients or even clinicians when it comes to chronic back pain and spinal arthritis recognition?

Dr. Jill Weintraub:
I think that a lot of patients get missed just because mechanical sources of back pain are so much more common. They are so common, as opposed to inflammatory sources. But I think that when we're seeing particularly young people, young men and women, we really need to keep it in the back of our heads that this could be inflammatory, and that picking it up early and treating early can really change the life of the patient, meaning that if we treat before there is any chronic damage, or if we treat before the nervous system has had a chance to adapt to the chronic pain and lay down these new tracks to sense it, people do so much better.

So I think just having an awareness that these conditions are more common than we have previously appreciated, and that picking them up early really is impactful and changes the natural history of what this can look like, can change diagnosing practices.

Esther Ikoro:
Are there any ongoing clinical trials or areas of research that you're excited to see focused on in the future that you hope people continue to look into?

Dr. Jill Weintraub:
I'm really excited about the gut microbiome research that's going on at several institutions. I think it's a fascinating concept that these tiny microbes that live with us in our GI tract, that are helping us digest our food, can play such a role in the development of a pathologic process, and that perhaps by modulating the gut microbiome, which I understand, is easier said than done, but that this might open up new treatment pathways, or at least open up avenues where the medications we have can be more impactful. I'm very excited to see where all this research lands. Hopefully within the next 10 years, we should know.

Esther Ikoro:
Wonderful! Well, this has been an amazing conversation. Thank you so much for joining us on MD Newsline podcast.

Dr. Jill Weintraub:
Thank you for having me.