Considerations in Recognizing and Diagnosing nr-axSpA Part 2: Imaging

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
• Healthcareprovidersshouldexercisetheirprofessionaljudgmentwhentreatingtheir own patients

Introduction (00:24 –02:33)                                                                                                              

Dr Jeff Stark (00:24)

Welcome and thank you for joining us today. I'd like to welcome you to the fifth and final episode in the Non-radiographic AxSpA Community of Care podcast series. The goal of our episode today is to focus on imaging, recognizing the role that imaging can play in a diagnosis of patients who have non-radiographic axial spondyloarthritis or nr-axSpA. My name is Dr Jeff Stark. I'm the head of Immunology Medical Affairs at UCB. I'm delighted to welcome you to this episode today.

We have a great agenda that will focus on topics related to imaging, including recognizing the differences between X-ray and magnetic resonance imaging findings in patients with non-radiographic axSpA. We will also focus on the challenges in interpreting some of these imaging results, as well as the key features that are necessary in an appropriate order for patient imaging when screening for non-radiographic axSpA. I'm especially delighted today to be joined by someone who has real expertise in rheumatology and in caring for patients with non-radiographic axSpA, as well as particular expertise to share in the area of imaging of this disease state.

I'd like to welcome Dr Xenofon Baraliakos and invite him to say a few words about himself.

Dr Xenofon Baraliakos (01:40)

Yes. Thank you very much, Jeff. My name is Xenofon Baraliakos, as you just mentioned. I work in Germany in a large tertiary hospital seeing patients with axial spondyloarthritis. We do have as a team some data that have contributed to the diagnosis of axial spondyloarthritis by using imaging. Obviously, that's our biggest expertise, and what I think is also very important is that not only us but also the entire community nowadays focuses more on imaging, not only for diagnosing axSpA but also for excluding wrong diagnosis by either clarifying the reasons for having back pain similar to axSpA and also for avoiding over-treatment. So I'm really happy to take part in this discussion today, and thanks for the invitation.

X-ray and MRI Findings (02:33 –07:10)                                                                                            

Dr Jeff Stark (02:33)

Thank you, Dr Baraliakos. I think that as we think about the non-radiographic axSpA patients, one of the things that stands out about this patient group is the complexity of diagnosing them and, I think because of that, sometimes the long journey that they have to diagnosis. And that complexity, I think, has to do with the fact that clinical features are important, such as the symptomatology that they have. Laboratory assays may be helpful and certainly pertinent to our discussion today. Imaging findings are important in diagnosis as well. Could you tell us a little bit about non-radiographic axSpA and how it fits into the broader family of spondyloarthritis diseases? And also maybe describe some of the imaging findings that may be seen in patients with non-radiographic axSpA.

Dr Xenofon Baraliakos (03:23)

Imaging is part of the tools that we have for the diagnosis. And when we talk about diagnosis, we talk about the whole family of spondyloarthritides, and non-radiographic axSpA is a member of this family, together with ankylosing spondylitis. And MRI is one important tool for the imaging parts or for diagnosing spondyloarthritis simply because it shows very nicely the most important findings that we know that are characteristic with this disease, and this is inflammation. This means bone marrow edema. We know that bone marrow edema is the starting point of pathological lesions of spondyloarthritis. Obviously, also in terms of non-radiographic axial spondyloarthritis since the X-ray findings or the X-ray changes will not yet be visible in that part.

And next to inflammation, we also know that once this is becoming chronic, which means it's there for already longer times, that might also be what we call tissue metaplasia, which is being seen as either fatty lesions, fat metaplasia where inflammation has been before or erosions or even sclerosis. So altogether, these are the imaging findings we would expect to see on MRI. So for the non-radiographic axial spondyloarthritis, I would expect to see mainly inflammation, bone marrow edema, which is seen in specific areas, close to the joint and so on.

Dr Jeff Stark (04:49)

Great. That's very helpful. And are there ways that those MRI changes of inflammation can be quantified or measured?

Dr Xenofon Baraliakos (04:56)

Yes. All of them can be quantified and measured. Speaking about inflammation, we have different scoring systems that have been published by different teams. We had published many years ago the score for inflammation AS Spinal MRI-A is called, for the spine where we do measure inflammation based on the extent of the signal in the spinal areas, in the brittle areas. There is also the score from

North America, which is called the SPARCC. It works similarly, having also additional items for the depth of the signal and the density. However, there the quantification works a little bit different. It doesn't count the extent of the signal but whether or not it's present. For the sacroiliac joints, we have the so-called Berlin score, which covers all the features that we know that are important. This means inflammation, fat lesions, erosions, sclerosis, and ankylosis. Similarly, we also have the SPARCC part for sacroiliac joints, which also covers inflammation. And there is also another score system called SSS triple S, which also covers fat and erosions and sclerosis and ankylosis.

I think the additional question that comes up is which score may be better. We have done this analysis years ago within an OMERACT initiative project, and we've seen that, in fact, whichever score you may be using, there's no big differences in terms of outcomes. This means, when it comes to the follow-up of the patients and looking at whether or not they see an efficacy, for example, by treatment, all scores that are available are appropriate. The two that I just mentioned, the AS Spinal MRI-A or Berlin score and the SPARCC are obviously the most well-fitted, and they're also the mostly used ones.

Dr Jeff Stark (06:40)

And I imagine these measures are important parts of clinical trials in this disease space.

Dr Xenofon Baraliakos (06:45)

Yes. This is absolutely correct. We're using them for clinical trials, and we're using them to show whether or not treatments are working in a way that we reduce inflammation. For daily practice, we are not using this scores because they're also time-consuming. But for the clinical trials, yes, we need to quantify the lesions, and we need to see the course of the disease in the MRI. This is exactly where we're using this course.

Interpretation of MRI (07:10 –12:21)                                                                                               

Dr Jeff Stark (7:10)

So coming back to this concept of the complexity of diagnosis for patients with non-radiographic axSpA, I think we recognize that imaging can't stand alone as the sole diagnostic test, that other features are important. Yet, at the same time, we recognize that imaging does play an important role overall in diagnosis. Some of those features that we see on imaging that you've alluded to, Dr Baraliakos, like bone marrow edema, for example, and the sacroiliac joint, can be helpful. But at the same time, I've seen some recent data – and would love your thoughts about it – on that feature not necessarily being unique to patients with non-radiographic axSpA. So for example, recent publications have highlighted that bone marrow edema has been seen in patients with non-specific back pain or even healthy individuals without back pain. I wonder if you could tell us a little bit your thoughts about the potential for false-positive results on magnetic resonance imaging.

Dr Xenofon Baraliakos (08:08)

Yes. Well, all these findings that you already mentioned are, I would also call it, the problem or the challenging part of the interpretation of MRI, especially because we do know that this very sensitive tool may – due to its sensitivity – may be not so specific sometimes. So we do have issues when we interpret MRI images, especially when it comes to different experience. So there might be lack of agreement between the people who may see that.

And we also know now, from more than two or three studies that have been just published, that not only athletes – this means those individuals who are exposed to bone stress - but also healthy persons, they may also show – I wouldn't call it now inflammation, but bone marrow edema. Which, again, comes and goes. The most recent data that were just published were from a large number of people below 45 years of age from the general population who never suffered from back pain, and there we found that 20% of them, so ever fifth, has bone marrow edema which might be misinterpreted as a spondyloarthritis positive.

Similarly for the spine, we found that about 50% of these individuals may have either inflammation or bone marrow edema and fatty lesions, and other groups from the Netherlands, from Belgium, and others have shown similar numbers. So these false-positive findings may be an issue. This is the challenging part of the MRI interpretation, and this is why we also always say that MRI is a tool, it's not the diagnosis. It has to be combined with the symptoms that the patients have, and then the interpretation has to come out by putting all pieces of the puzzle together.

Dr Jeff Stark (09:54)

Sure. So I hear in what you say that there are some important limitations of MRI that we need to be aware of, and in particular perhaps a lack of specificity when it comes to these changings. That's helpful for us to keep in mind. I know, however, that MRI remains an important part of the diagnostic workup for these patients. Are there certain features of bone marrow edema that would give you greater confidence in them as reflecting true disease or suggest that those changes are less likely to represent a false-positive imaging result?

Dr Xenofon Baraliakos (10:28)

Yes, there are. And these have been also published by ASAS in an international collaboration with rheumatologists and radiologists. And these are especially findings that deal with the localization of these lesions. This means for the sacroiliac joint, we do know that both the inflammatory lesions and the structural lesions should rather be localized very close to the joint, to the sacroiliac joint. This means they should be very articulately located. They should have a distinct border to the remainder of the bone marrow. And they should not be just spread around, spread around in the, in the bone. So let's say, the more condensed area, or the more condensed lesion is the more spondyloarthritis-like, at least considered as such, and not so much the diffused lesion that may be seen even in, again, either healthy individuals or, for example, also elderly people.

For the spine, on the other hand, we do know that the lesions that are more spondyloarthritis-related should be located at the edges of the vertebral bodies, not so much in the endplate area. And together with that, we expect those findings - if we consider them SpA-like - to be associated with a more or less healthy intervertebral disk. This means the disk has to have a normal height, not be dehydrated or even have a prolapse or something else that is more of a degenerative finding. So overall, these are the areas or the lesion types or the lesion morphology we would be expecting, and this can be found mainly in the patients with spondyloarthritis and not so much in those without the disease.

Dr Jeff Stark (12:09)

Those are very practical points, I think, that you mentioned and great for us to be aware of as rheumatologists but perhaps equally if not more important for our radiology colleagues also to be aware of.

Key Features in an order for Patient Imaging (12:21 –18:36)                                                          

Dr Jeff Stark (12:21)

So Dr Baraliakos, I'd like to come back to this concept of a close partnership between rheumatologists and radiologists. Because I think that's so key as we address this topic. When ordering an MRI, I think that there are many things that can be helpful for the rheumatology community to be aware of. Some of those are quite simple, of course, like communicating a suspected diagnosis or relevant aspects of the patient's medical history. But some of those other important things that we can communicate to our radiology colleagues are more technical in nature, such as requesting them to focus on certain parts of anatomy, like the sacroiliac joint, and use certain angling of the imaging to emphasize the importance of T1 windows or STIR sequences that really highlight inflammation, for example, in this disease state.

I frequently hear from the rheumatology community that there's some misunderstanding about the necessity of contrast and a belief that contrast is necessary to highlight inflammation when, in fact, that is not actually the case for magnetic resonance imaging in axSpA.

Some of the, I think, very practical things that we have the opportunity to address in these patients who frequently have significant back pain is how they can be positioned to maximize their safety and their comfort for a test that oftentimes may be quite lengthy for them. But all of these facets of ordering an MRI are not necessarily something that the rheumatology community is intimately familiar with. I wonder if you would take us through, from your viewpoint, what are those best practices in ordering an MRI and how do you communicate with your radiology colleagues to ensure that's the best experience for the patient as well as providing the best diagnostic results.

Dr Xenofon Baraliakos (14:10)

Yes. This is a lot of information that we can indeed discuss with a radiologist. I will try to make it as simple and clinically-related as possible. And what I would start with would be that I always prefer and also suggest and advise is to work with particular radiologists only, not because the others may not be good enough but because then those who you work with regularly, they also know your needs. And then you can also learn with each other, from each other. This means, have standard protocols that may be used when patients are being referred from the rheumatologist to the radiologist. Because we have to acknowledge that, of course, rheumatology's not the biggest discipline that they would be serving. So obviously, this is something that I would start with always.

We know that there are specific sequences that are preferred in rheumatology and especially when it comes to diagnosing spondyloarthritis or they're suspicious of non-radiographic or radiographic axSpA. Those sequences are the D1 sequence in combination with the STIR sequence. We want with this to capture both the structural damage and the inflammatory lesions respectively. This is why we have said that these are the standard sequences that we advise to do.

When it comes to the position of the patient, the goal is that there will be a use or difference of other technical aspects. That's for the radiologists to consider. However, I think, one thing that we can communicate with them upfront is how thick the slices should be. Because this might also influence the sensitivity and the specificity of the images. And there we have said that the international standard is

three to four millimeters. This is the part that I would expect the rheumatologist to communicate with the radiologist.

Now for the other thing, for the other aspect that you mentioned, whether or not we would be using gadolinium or any kind of contrast agent, there's a clear no to this for using contrast agents. We do not need them. We know that bone marrow edema, this means osteitis, is similarly well-detected in the simple STIR images. So we do save time. We do save costs. And, of course, not using a contrast agent is less dangerous for in order to avoid adverse events by using gadolinium.

Dr Jeff Stark (16:30)

That's really helpful to remember. So recognizing how important that communication is, one of the things that we've recently done as UCB is to make some educational material regarding this topic available. And so we prepared an axSpA clinical resource toolkit that, among other resources, has a section on MRI best practices and even a sample protocol of what a detailed MRI order for diagnosing axSpA might look like. Is there any other information, Dr Baraliakos, that you would share or that radiologists should know when they're performing an MRI in patients suspected of having nr-axSpA?

Dr Xenofon Baraliakos (17:12)

Well, first of all, I have to say that exactly these actions are extremely important. Because we do not only need to diagnose the patient but need to spread the message about what chronic or inflammatory back pain is. One thing that I believe is also important is to know whether or not we should be screening patients who are at their, right age – this means based on the cutoff that we have set below 45 years of age - when they come in for clarification of any kind of chronic back pain those patients who complain about chronic back pain, independent of whether or not this is inflammatory or non-inflammatory, and they're below 45 years of age – most of the times, obviously, the imaging that will be performed on MRI will be the one of the lumbar spine. And there we suggest or advise to, together with the lumbar spine images, also do a very short image of the sacroiliac joints in the coronal view in order to also capture the sacroiliac joints there and see if there is any suspicion of inflammatory lesions. It might be patients who just don't have anything yet in their lumbar spine, but this screening method for sacroiliac joints is important where there might be things that can be captured. And then the radiologist and any other physician who has asked for the images can consult the rheumatologist in order to go on with the imaging procedures and maybe also diagnose or even exclude the diagnosis of spondyloarthritis.

Conclusion (18:36 – 20:08)

Dr Jeff Stark (18:36)

That's wonderful. Thank you for sharing your wisdom with us on that topic. So Dr Baraliakos, it's hard to believe that our time is coming to an end. This has been a great discussion today. I think that we've really had the opportunity to cover some key points around the concept of imaging and non- radiographic axSpA, including things like the X-ray and MRI findings and how those may differ, some of the pros and cons with regards to MRI, and some of the watch-outs that we can have to guard against over-interpretation of MRI diagnostic findings, as well as - I think very helpfully and practically – some great information about how to maximize the efficiency and outcomes of our imaging through close collaboration with our radiology colleagues. I'd just like to thank you so much for joining today. This has been a fantastic discussion.

Dr Xenofon Baraliakos (19:28)

Yes. Thank you very much also from my side. Thanks for all the questions. They were, I believe, extremely to-the-point. Thanks also for listening, to everyone who has listened. I hope that these kind of actions will indeed help to improve the discussions with radiologists and also improve our diagnoses in daily practice. So I'm really happy to see the further development in this area, imaging, clinical diagnosis, avoiding over-diagnosis, and – of course – right and early treatment.

Dr Jeff Stark (19:58)

Thanks again, Dr Baraliakos.