Considerations in Recognizing and Diagnosing nr-axSpA Part 1: Manifestations of Disease

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 – 02:06)

Dr Jeff Stark (00:20)
Welcome to the fourth installment in the non-radiographic axSpA, a Community of Care podcast series. This is Dr Jeff Stark at UCB. I'm head of medical affairs for rheumatology and delighted that you can join us for this ongoing discussion. The podcast you're joining today is the first in a twofold discussion on considerations when diagnosing non-radiographic axial spondyloarthritis or non-radiographic axSpA. The goal of this podcast is to explore the clinical manifestations of non-radiographic axSpA when diagnosing patients with this disease. 

We'll cover some important topics today and these will include some of the current challenges that limit the recognition and diagnosis of patients with non-radiographic axSpA. We'll also talk about how to approach a clinical diagnosis of such a patient as well as the role that other specialties play in helping to recognize patients and refer them to rheumatology practices. 

I'm very delighted today to be joined by Dr Anthony Turkiewicz, someone who brings some extensive experience in this area through the practice of rheumatology, and also specifically in caring for patients with non-radiographic axSpA. 

Anthony, please, tell us a little bit about yourself.

Dr Anthony Turkiewicz (01:31)
Thanks, Jeff. Yes, my name is Anthony Turkiewicz. I'm director of the Clinical Research Unit and partner here at Rheumatology Associates in Birmingham, Alabama. My focus in research-- I mean, my clinical practice has been in the spondyloarthropathies having developed a consortium for early spondyloarthropathy patients during my time at Georgetown University and at the NIH 18 years ago. As a member of SPARTAN and GRAPPA, I've participated as principal investigator in a number of the spondyloarthropathy clinical trials focusing on treatment as well as early detection and diagnoses of the diseases.

Diagnostic Journey (02:06 – 04:47)

Dr Jeff Stark (02:06)
Thanks, Dr Turkiewicz. So glad you can join us today. As I think about patients with this condition, one thing that always stands out to me is the dramatic delay that the typical patient has between the onset of their symptoms and when they are correctly diagnosed with non-radiographic axSpA. 

And when you look at the data in this area, although we as a community are improving a little bit over time, the latest data still tell us that a diagnosis of axSpA takes five to eight years on average.

It's amazing to think of a patient suffering with the disease in the absence of a diagnosis for that length of time. I wondered, Dr Turkiewicz, with your extensive clinical experience in this area, if you could share a story of a patient, maybe, who experienced a long delay of diagnosis. Someone maybe who had inflammatory back pain but was mistaken for having back pain of a more mechanical cause.

Dr Antony Turkiewicz (02:58)
Sure, Jeff. So I've seen in my clinic a number of examples. One patient in particular that exemplifies this often-frustrating journey to diagnosis, it was a 32-year-old Caucasian female and it was a teacher here at a local college. And she had complaints for just about nine years of chronic low back pain. And she had talked to her primary care physician about the pain, really no antecedent trauma, no sciatica type symptoms but it was peculiarly, exceptionally painful late at night. Required her to ambulate, get out of the bed. Activity improved her pain. She had lumbar imaging that ended up revealing some small disc bulging at L4-L5 and it was felt that she had degenerative lumbar disc disease.

She underwent subsequent evaluation by a chiropractor, a physical therapist, pain management, and then she was going to be referred onto neurosurgery. Pain management had performed two lumbar epidurals really without much success. She felt the NSAIDs had done just as well, and there was consideration for even surgery. Five months ago, she had her first episode of right eye uveitis that was diagnosed and evaluated by a local ophthalmology. When asked about her comorbid conditions by ophthalmology, she revealed her 10-year history of back pain, and the ophthalmologist then consulted me. So when I saw her here in the clinic, she gave that classic inflammatory back pain history. And while her X-ray showed no significant sacroiliitis, and that her HLA-B27 was negative, her MRI showed some fairly classic bone marrow edema in the SI joints, which was strongly suggestive of non-radiographic axSpA.

Challenges with Diagnosis (04:47 – 07:22)

Dr Jeff Stark (04:47)
That's really an amazing story, unfortunate for the patient, but great for our audience I think in terms of how many learning points really there are there. And as I hear you describe that patient's history, some of the red flags and opportunities where she could have been caught earlier, and had an earlier diagnosis with some of those back pain features, for example, that she experienced, and ultimately that episode of uveitis that unlocked that mystery for her. 

But although this patient story seems very dramatic in the retelling, it's unfortunately, I think very common among patients with this disease and what they typically experience before they achieve diagnosis and arrive in a proper care setting.

Dr Anthony Turkiewicz (05:29)
Yeah. Absolutely. Yeah. And again, this is one example of many of the cases we see here.

Dr Jeff Stark (05:35)
Dr Turkiewicz, as I think about that clinical story that you shared from your practice that unfortunately, is all too common, it causes me to think about the reason behind that story and why it is that so many of these patients with non-radiographic axSpA take so long to be diagnosed. Any thoughts about why that might be?

Dr Anthony Turkiewicz (05:53)
Yes, Jeff. In general, I think there still is this general lack of awareness of non-radiographic axSpA. I think hopefully with endeavors such as these, healthcare community will become better educated. This being said, it's not just the primary care physicians or the chiropractors or the orthopedist who may be missing some of these patients. Patients with undiagnosed non-radiographic axSpA can also be found in our own rheumatology practices. 

There was a study, the prevalence of axial spondyloarthritis study, the PROSpA study, that was a multi-center study conducted at US rheumatology centers, and we had participated in that study. In that analysis, the patients were required to have chronic back pain for three months beginning at less than 45 years of age, no prior SpA diagnosis, and have at least one of three spondyloarthropathy features. 

Overall, among the existing rheumatology patients, axSpA was diagnosed in just under 40% of patients. And of the 348 patients who met ASAS criteria for axSpA, 68% were characterized as having non-radiographic axSpA. And so what we see from this is that as rheumatologists, we are missing some of these patients as well. And also worth pointing out I think challenging to some is the lack of a specific ICD-9 or 10 code for non-radiographic axSpA.

Clinical Diagnosis of nr-axSpA (07:22 – 14:06)

Dr Jeff Stark (07:22)
Those data are so interesting, especially the observation about 68% of those patients diagnosed as axSpA had non-radiographic axSpA. It actually makes one wonder if the diagnostic barriers are even greater for non-radiographic axSpA patients than for AS patients. 

One of the questions that I'm often asked in having conversations with the rheumatology community about non-radiographic axSpA is whether there are diagnostic criteria that would help to make this an easier process for the clinical community. And unfortunately, although we do have classification criteria for non-radiographic axSpA and for axSpA in general, we don't have validated diagnostic criteria that are widely used across the rheumatology community. 

As we think about those two kinds of criteria, I think it's important for us to understand the difference. Classification criteria are used to create a well-defined relatively homogeneous cohort, primarily for purposes of clinical trials. And because that is the purpose of classification criteria, they have high specificity, but unfortunately what's sacrificed in maximizing specificity is sensitivity. And what that means is that classification criteria may miss individuals who truly have the disease.

That's different than diagnostic criteria, which are used to identify as many patients as possible with the condition and in doing so they maximize sensitivity. Unfortunately, we recognize that without widely adopted diagnostic criteria, there are patients with non-radiographic axSpA who will remain unrecognized and undiagnosed in the healthcare community. Dr Turkiewicz, as we think about this complex issue of diagnosis, I wonder if you could share with us a little bit of your own clinical perspective about how you might approach the diagnosis of a patient with non-radiographic axSpA in your own clinical practice.

Dr Anthony Turkiewicz (09:20)
Sure, Jeff. As we had discussed the clinical diagnosis of non-radiographic axSpA can be challenging. And the first step in approaching a patient with chronic back pain is to determine whether that back pain is mechanical or inflammatory. Among patients with chronic back pain, approximately 5% are likely to have axSpA, but if you make that back pain inflammatory, the probability increases approximately three-fold, just under 15%, right? About 14%.

Dr Jeff Stark (09:51)
So it seems like this concept of inflammatory back pain is an important one. As I think back to the patient case that you shared, I remember that that patient exhibited some of these inflammatory back pain features. 

I wonder if you can tell us a little bit about what those features of inflammatory back pain are and why they're important.

Dr Anthony Turkiewicz (10:08)
Sure. More than any other measure we discussed, that description of a patient's back pain which again is simply obtained by thorough history, it's so pivotal to the workup of these patients. 

So characteristic symptoms of inflammatory back pain and axial spondyloarthritis include an age of onset of less than 40 years old, it's an insidious onset, there's improvement with exercise and no improvement with rest. In fact, rest can exacerbate the pain. And characteristically, the pain is at night and improves as the patient gets up. For those patients that have this inflammatory back pain, we then evaluate for the presence of additional spondyloarthritis features. The presence of additional features can increase the probability of axSpA.

Dr Jeff Stark (10:57)
So this is very interesting. It almost seems that there is a step-wise approach to the evaluation of these patients that maybe allows us to have increasing confidence as we go along and find additional elements of evidence to support a diagnosis. These spondyloarthritis clinical features that you've mentioned I think are an important part of that and data that I've seen suggest that having one or two of those clinical features actually increases the probability of an axSpA diagnosis to somewhere between 35% to 70%. 

I wonder if you could share with us a little more specific information about what those features are and, in particular, some of those features that clinicians should be aware of in these patients.

Dr Anthony Turkiewicz (11:38)
When we think about the additional features beyond the inflammatory back pain in spondyloarthritis, we think about enthesitis, dactylitis, uveitis, family history of spondyloarthritis, Crohn's disease, psoriasis, alternating buttock pain, and asymmetric peripheral arthritis. There's a positive response to NSAIDs. And you can also have elevated levels of the acute-phase reactants, mainly, sed rate and CRP. So in the patients that possess some of these spondyloarthritis features, HLA-B27 positivity further increases the probability of axSpA to 80%, 90%.

Dr Jeff Stark (12:21)
Awesome. This allows us really to have, I think, a fairly high degree of confidence in a diagnosis once a patient begins to exhibit some of these clinical features. 

As I think back again to the patient case that you shared, I remember that one of the final elements that made that diagnosis for that patient was imaging evidence of sacroiliac inflammation. And although as rheumatologists, we love to have that objective evidence that really allows us to feel confident in our diagnosis.

I wonder if you could give us a sense of the role that imaging actually plays in the diagnosis of a patient with non-radiographic axSpA.

Dr Anthony Turkiewicz (12:58)
When combined with a clinical suspicion of axSpA, imaging can help distinguish patients with ankylosing spondylitis from those with non-radiographic axSpA. So as you know, patients with ankylosing spondylitis, they have definite evidence of sacroiliitis visible by plain radiograph. But it's important to note that patients with non-radiographic axSpA may have inflammation actively visible by an MRI.

Dr Jeff Stark (13:25)
So as important as that imaging evidence can be in cinching a diagnosis for this type of patient, are there still patients who can have negative imaging and still carry a diagnosis of non-radiographic axSpA?

Dr Anthony Turkiewicz (13:37)
And, Jeff, I think that's one of the key elements of this discussion would cause that-- while we like that objective measure, that MRI, active inflammation, there is a population of patients with non-radiographic axSpA who have negative MRIs. It's in those very cases where the clinical symptoms, which again include inflammatory back pain and other objective signs of inflammation such as an elevated CRP, that can help support the diagnosis of non-radiographic axSpA.

The Role of Other Specialties (14:06 – 16:24)

Dr Jeff Stark (14:06)
Dr Turkiewicz, in our discussion today I think we've had some great highlights about what some of the barriers to diagnosis are for these patients and ways that we can evolve in order to help them overcome those barriers. 

But one of the things I think about is a closer collaboration between rheumatologists and various other specialists who may encounter these patients somewhere along their early journey. We've had the ability to look at this a little bit in the literature and have seen that the non-radiographic patient often times ends up in a variety of care settings prior to coming to the attention of a rheumatologist, and those include radiology, pain medicine, physical medicine and rehab, anesthesiology or pain medicine, neurology, orthopedic surgery. And I think even your patient that you described landed in some of those settings on her way to ultimately arriving in your clinic. 

But can you give us some thoughts about those other specialties and the degree to which perhaps they should be made aware of axial spondyloarthritis and the inflammatory back pain features that characterize it?

Dr Anthony Turkiewicz (15:14)
Absolutely, Jeff. And, again, a key part to educating the healthcare community. The example I'd provided I think she actually had been to pretty much every one of those and it's not uncommon. I think one thing to educate those specialists about, as well as primary care physician, is again, going back to the features of an inflammatory back pain and then pointing out some of those key spondyloarthritis features. And that really should trigger a referral to come see rheumatology. When you talk about inflammatory back pain, again that's that pain at night that improves upon waking up, gets better with exercise. HLA-B27 positivity, definitely a helpful part of the puzzle, not required, not essential, but definitely part of the puzzle. And those that do possess HLA-B27 positivity, elevated inflammatory markers such as seg rate or CRP, and again history of inflammatory manifestations including uveitis, Crohn's or psoriasis. All these features really should trigger a referral over to rheumatology.

Conclusions (16:24 – 17:57)

Dr Jeff Stark (16:24)
So, Dr Turkiewicz, I'd like to thank you very much for joining this discussion today. I think we've had a really great conversation about the diagnosis of non-radiographic axSpA.

Dr Anthony Turkiewicz (16:33)
I appreciate the invitation, Jeff. Such an important discussion, hopefully enhancing and getting the word out on the diagnosis of non-radiographic axSpA. So, again, appreciate the invite.

Dr Jeff Stark (16:47)
Absolutely. I'd also like to thank our audience for joining us today, we're delighted that you've been able to join us for this great conversation as well. 

And as we wrap up our time, a couple of key points stand out in my mind from our conversation today. One of those is that the path to diagnosis of non-radiographic axSpA is, unfortunately, a complicated and protracted one for many patients. This is due to several diagnostic challenges that those patients experience along the way, including the absence of diagnostic criteria, as well as the absence of an ICD-10 code for this condition. 

However, we know that proper identification of inflammatory back pain, as well as clinical features of spondyloarthritis and objective signs of inflammation like laboratory tests and imaging findings, can help to inform the diagnosis and move patients past these barriers in their diagnostic journey. 

Once again I'd like to thank our listeners for joining us today, we hope that you have enjoyed this conversation and we hope that you will join us again for our next and final episode in this series of podcasts focused on non-radiographic axial spondyloarthritis.