Nr-axSpA: A Different Kind of Inflammatory Spondyloarthritis

Disclaimer (00:00 – 00:20)

This is an educational program sponsored by UCB. The information contained within this podcast is for your educational purposes only and is not intended to be medical advice. The guest speakers have been compensated for the presentation of this educational information. Healthcare providers should exercise their professional judgment when treating their own patients.

Introduction (00:20 – 02:40)

Dr Jeff Stark (00:20)

Welcome. I'd like to introduce to you a new series of podcasts entitled The non-radiographic axSpA Community of Care Podcast Series. This is Dr Jeff Stark. I'm a rheumatologist and head of rheumatology and medical affairs at UCB.

The goal of this podcast is to discuss similarities and differences between non-radiographic axial spondyloarthritis or nr-axSpA and ankylosing spondylitis or AS. Some of the topics that we will cover today include defining non-radiographic axial spondyloarthritis, understanding its epidemiology and demographics, challenging some common misconceptions associated with non-radiographic axSpA, and also exploring how the understanding of this condition by the community and the FDA have evolved over time. 

I'm very pleased to welcome with me today to the podcast a friend and colleague, Dr Victor Sloan. Victor, please say a few words about yourself.

Dr Victor Sloan (01:20)

Thanks, Jeff. As Jeff mentioned, my name is Victor Sloan. I'm the CEO of Sheng Consulting. Formerly, I was the therapeutic area head for immunology at UCB. I spent eight and a half years there, and I continue to be a paid consultant for UCB. 

In addition, I held a faculty appointment at Rutgers Robert Wood Johnson Medical School, where I'm clinical associate professor of medicine in the division of rheumatology. I continue to see patients a half day a week on a voluntary basis. I've been a practicing rheumatologist for 25 years, and I have a special interest in spondyloarthropathy, developed largely through my work at UCB. 

I'd like to talk about a patient I recently saw in clinic. I'd been seeing her for many years for another condition, and she started to complain of back pain. I administered the inflammatory back pain questionnaire, which was positive, and I then went on to order an MRI which was also positive for inflammation. And I want to make this point because the recognition of a patient with potential non-radiographic axSpA requires sensitization to the existence of the condition. And I can honestly say that that sensitization came through my work on this condition at UCB.

Definition of nr-axSpA (02:40 – 04:42)

Dr Jeff Stark (02:40)

As I think about non-radiographic axial spondyloarthritis, one of the greatest barriers today is the general lack of awareness of the condition. And, unfortunately, we see that that lack of awareness contributes significantly to the long delay in diagnosis. That dramatic delay between the onset of disease and an actual diagnosis is, unfortunately, a common experience for patients living with this condition. At the same time, it's important to recognize that non-radiographic axSpA is a real disease and has a substantial burden associated with it. There are negative quality of life implications for patients who live with this disease and, therefore, a reason that we should be aware of it and shorten the path to diagnosis for these patients. 

Victor, I wonder if you could share with us a little bit about how you define non-radiographic axSpA in a clinical context.

Dr Victor Sloan (03:32)

I think of this disease as a member of a larger family of spondyloarthritides, diseases that affect, in some way or another and in some frequency or another, the spine. We think of them as the seronegative spondyloarthritides because, in general, they're negative for rheumatoid factor. We further divide them into diseases that are predominantly peripheral or predominantly axial, so the more peripheral diseases, such as psoriatic arthritis or reactive arthritis, and then the more axial diseases, non-radiographic axSpA and ankylosing spondylitis. So when we refer to nr-axSpA, we're stating that non-radiographic axial spondyloarthritis does not have evidence of structural damage of the sacroiliac joint as seen by X-ray, unlike ankylosing spondylitis, where there is radiographic evidence of structural damage of the SI joint on X-ray. However, nr-axSpA does generally have evidence of inflammation that is sacroiliitis as seen on MRI.

Epidemiology and Demographics (04:42 – 06:00)

Dr Jeff Stark (04:42)

So, Victor, it's very interesting that you mentioned those radiographic and other imaging-type changes associated with the disease. I think it's likely that the absence of X-ray features is one reason why non-radiographic axSpA is underrecognized compared with diseases like AS that do have radiographic features, that and the unfamiliarity with the disease. And yet this is not, as I understand, an uncommon disease but rather one that affects a significant number of people. 

Can you tell us a little bit about the prevalence of non-radiographic axSpA and ankylosing spondylitis?

Dr Victor Sloan (05:16)

That's a really good question. And it's important to recognize that you're absolutely correct. There are about 3.3 million people with axSpA in the United States, which is about 1% of the US population. And that's comparable to that for rheumatoid arthritis. And interestingly, in the patients who have axSpA, it's about a 50/50 split between those who have non-radiographic axSpA and those who have AS. So to your point, those who have non-radiographic axSpA are probably underdiagnosed or underrecognized. So in sum, neither nr-axSpA nor AS is a rare disease. And we should be looking for it and finding it more often.

Common Misconceptions (06:00 – 14:43)

Dr Jeff Stark (06:00)

Very interesting. I think that's not necessarily something that many practicing rheumatologists perceive but perhaps related to the degree to which these patients remain undiagnosed today. 

I think one of the other patterns that is very interesting is non-radiographic axial spondyloarthritis, like AS, is a disease that tends to affect a younger patient population. In fact, the typical age of onset of axSpA is around 28 years, and perhaps that may also have some implications for patients seeking medical care and achieving a diagnosis. Among the other features of non-radiographic axSpA, there are other opportunities, I think, to clear up misconceptions as well. One of those misconceptions, Victor, that we hear frequently from the community is that axial spondyloarthritis is a disease that primarily affects men more than women. 

Any thoughts on that subject?

Dr Victor Sloan (06:55)

Well, that's absolutely true. There's a certain bias in the sense that we were taught for many years that this was the disease that's prevalent in men. I was taught that it was 9:1 men to women. We now know that in AS, it's more like 2:1 men to women and that nr-axSpA is at least as common in women as in men. So we have a situation where patients have a common complaint that is back pain. Most people don't think, "Ooh, back pain, AS." And then if they see a woman, the automatic assumption is it's not spondyloarthritis.

Dr Jeff Stark (07:35)

Wow, that's very interesting, and I think raises the question about the diagnostic delay in women and whether that may even be more pronounced than it is for their male counterparts who have the same disease. 

One of the, I think, patterns that I've read about, Victor, and would love to have you share more about is the way in which non-radiographic axSpA presents in women versus men and whether that actually may be different between the two genders.

Dr Victor Sloan (08:04)

Absolutely. It's pretty clear from a number of studies that the way women experience symptoms from non-radiographic axSpA is different. Women tend to have more widespread pain. They have more subjective disease activity, more fatigue, more peripheral involvement, and more functional impairment. And that when you think about these differences - and some of them are relatively nonspecific - you can see how that can complicate or make more difficult the recognition of non-radiographic axial spondyloarthritis in women. 

It's also interesting that, if you think about those clinical features, there's a significant overlap with those features of fibromyalgia, which can even further confound an accurate diagnosis in women. Interestingly, some studies have shown that the prevalence of nr-axSpA in women diagnosed with fibromyalgia may be up to 10%. Now, it's important to recognize those studies were observational studies without a control group, but nevertheless, the overlap between symptomatology of fibromyalgia and the symptomatology of non-radiographic axSpA makes the diagnosis even more difficult and, to your point, perhaps more delayed. 

So we know, for example, that the average time between onset of symptoms in men is 8.4 years while in women it's 9.8 years.

Dr Jeff Stark (09:42)

So, Victor, that's fascinating information that you share about the diagnostic delay, and while I think we can appreciate that either 8.4 or 9.8 years is indeed too long for a patient to wait for a diagnosis, it's certainly shocking that women experience a longer diagnostic delay than their male counterparts with the same disease. 

You know, in thinking about the gender prevalence differences between ankylosing spondylitis and non-radiographic axSpA, it occurs to me that some of the barriers in understanding of non-radiographic axSpA may be in the tendency to think about it as not different at all from ankylosing spondylitis when, in fact, there are, as you have shared, some very interesting epidemiologic and demographic differences between the two. In speaking with members of the community, I often hear them refer to non-radiographic axSpA as mild AS or early AS. But according to what you've shared, I think we can agree that that's probably inaccurate nomenclature. 

I wonder if you could share your thoughts on the tendency to refer to non-radiographic axSpA as mild ankylosing spondylitis.

Dr Victor Sloan (10:46)

It's an interesting point, Jeff. When you think about it, the only difference is that there's an absence of radiographic findings. Because when we look at the disease burden of nr-axSpA, it's similar to that of not only AS but also rheumatoid arthritis and psoriatic arthritis. 

So for example, if we look at patient-reported outcomes like pain and fatigue, they're comparable between nr-axSpA, AS, RA, and PsA. If you look at the SF-36, both physical and mental components, they're comparable between nr-axSpA, AS, RA, and PsA. And when we compare between nr-axSpA and AS, we look at the functional ability of these patients, which we measure with an instrument called the BASFI; disease activity, which we measure with an instrument called the BASDAI; and the quality of life as measured by SF-36. They're similar for patients with nr-axSpA and patients with AS. 

So what this tells us is the disease burden of non-radiographic axSpA is comparable to that of AS with the sole exception of spinal mobility, which we measure with an instrument called the BASMI. And that's perhaps not a surprise because patients with AS by definition have radiographic changes and, therefore, more limitation of spinal mobility.

When you put all this together, we've gotten an increased understanding of the natural history of the disease. We've got an increased understanding of the significant impact of nr-axSpA on patients. And so the FDA recognizes that nr-axSpA is a condition that is distinct from AS. And it's really important for rheumatologists to understand this because when patients with nr-axSpA are being treated, we want to avoid treatment with either suboptimal or inappropriate therapies like opioids, corticosteroids, or small molecules like methotrexate.

Dr Jeff Stark (12:56)

Hmm, that's really interesting, Victor. As I think about our perspective as rheumatologists, we recognize the burdensome nature of diseases like rheumatoid arthritis and psoriatic arthritis and ankylosing spondylitis. And so these data that you're sharing that demonstrate that non-radiographic axSpA is equally severe in almost every way as these diseases we see day in and day out in clinic is an important reminder and, I think, clearly helps us to understand that “mild” is a mischaracterization when it comes to non-radiographic axSpA. The other perhaps mischaracterization that we hear sometimes is this term of early or even identifying non-radiographic axSpA as "early AS." 

Any thoughts on that particular nomenclature?

Dr Victor Sloan (13:44)

Absolutely. That's another one that's pretty clearly wrong. We know that a small fraction of patients with non-radiographic axSpA may develop AS. So over a period of 2 years, one study showed that 10% of patients with nr-axSpA developed AS, and followed out to 10 years, 40% developed AS, but what that tells you is that 60% did not. And those 60% of patients continued to have non-radiographic axSpA, and they continued to have that significant and similar burden of disease and incidence of extraspinal manifestations over time. 

Closing (14:43 – 16:14)

Dr Jeff Stark (14:43)

An important reminder for us. Thank you. So, Victor, in closing, I'd really like to thank you for joining us today and contributing your insights to this discussion. The information and data that you've shared are truly valuable.

Dr Victor Sloan (14:54)

Thanks for the invitation, Jeff. I really enjoyed it.

Dr Jeff Stark (14:58)

I'd also like to thank our listeners for tuning in and joining this podcast today. In closing, I'd like to provide some of the key points from this podcast that we hope everyone walks away with. One of those is that non-radiographic axSpA is an inflammatory disease that is common and, in fact, affects many individuals in the United States today. 

Although there are many misconceptions about the disease, we hope that the information we've shared with you today clears some of those up. 

We want everyone to remember that non-radiographic axSpA affects males and females nearly equally. In terms of severity, non-radiographic axSpA is not only comparable to ankylosing spondylitis but also to many other rheumatic diseases that we see in our clinics day in and day out. 

It's also important to remember that non-radiographic axSpA does not always convert to ankylosing spondylitis over time. In fact, many of these patients never convert, but yet they still experience significant and comparable disease burden that merits an intentional and appropriate approach to treatment. 

We hope that this discussion and the information we've shared with you today proves useful in your clinical practice as you take care of these patients day to day. And we hope that you'll join us for future episodes of this podcast. Thanks, and goodbye.

Dr Victor Sloan (16:13)

Thanks, Jeff. Bye-bye.