Examining the Relationship Between Axial Spondyloarthritis and Inflammatory Bowel Disease

Disclaimer (00:00 – 00:24)

• 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 (00:25 – 02:32)

Dr Stark
Welcome and thank you for joining our podcast today, examining the relationship between axial spondyloarthritis and inflammatory bowel disease.

The goals of our podcast are several and include providing an overview of axial spondyloarthritis and inflammatory bowel disease, examining the influence the gut microbiome has on the pathogenesis of axial spondyloarthritis and reviewing the potential role of magnetic resonance enterography in identifying patients with axial spondyloarthritis.

I'm happy to join you as your host today. My name is Dr. Jeff Stark. I'm head of medical immunology at UCB and a rheumatologist at UCB. I lead our medical and scientific teams in areas of inflammatory disease, including rheumatology, gastroenterology, and dermatology. During our podcast today, we'll focus on several important topics. These include axial spondyloarthritis, peripheral spondyloarthritis, and some of the other systemic manifestations patients with these diseases may experience, like uveitis and psoriasis. We'll also talk about inflammatory bowel disease and some of the extra-intestinal manifestations associated with these diseases.

And finally, we'll talk about inflammatory bowel disease and the potential role that magnetic resonance enterography may play in the early diagnosis of sacroiliitis. I'm particularly happy today to be joined by Dr. Fardina Malik.

Dr. Malik is an assistant professor for the New York University Grossman School of Medicine at NYU Langone Health. Before joining NYU Langone Health, she earned her medical degree from Chittagong Medical College in Bangladesh and completed her medical residency at Baylor College of Medicine, followed by a rheumatology fellowship at the hospital for special surgery at Weill Cornell Medical College. Currently, Dr. Malik is a clinical rheumatologist with several research interests, including inflammatory bowel disease related arthritis, axial spondyloarthritis, and psoriatic arthritis.

Welcome, Dr. Malik. Thanks for joining us today.

Dr Malik

Thank you, Dr. Stark. It is my pleasure to be here.

Overview of axSpA and peripheral SpA (02:33 – 06:49)

Dr Stark

So as we begin our discussion today, let's talk first about spondyloarthritis. As our listeners may know, spondyloarthritis is something of an umbrella term that encompasses, really, a spectrum of related inflammatory diseases that may have overlapping clinical features involving the axial skeleton but also peripheral joints as well as additional SpA manifestations. And we know that within this larger category of spondyloarthritis, patients are often classified according to their most prominent symptoms, as either axial or peripheral spondyloarthritis.

Dr. Malik, I wonder if you could tell us a little bit more about axial spondyloarthritis in particular.

Dr Malik

Sure. Axial spondyloarthritis is a subtype of spondyloarthritis. As you mentioned, that is an umbrella term of some related diseases with similar immuno pathogenesis. So axial spondyloarthritis is an inflammatory disease of the axial skeleton, where there is inflammation of the sacroiliac joint as well as other parts of the spine. The most common symptoms that these patients present with are inflammatory back pain, stiffness of their back, fatigue, etc. I should mention that about half of these patients with axial spondyloarthritis are called non-radiographic axial spondyloarthritis when there is no SI joint changes on the plain X-ray. And about half of these patients are ankylosing spondylitis, where patients have radiographic changes in their SI joint X-ray or syndesmophytes on their L spine xray.

It is associated with peripheral spondyloarthritis as well as many other extraarticular manifestation. It is estimated that 3.3 million individuals have axial spondyloarthritis, and the disease affects younger population, and the mean age is around mid-20s.

Dr Stark

Very interesting. And the numbers you mentioned suggest maybe that axial spondyloarthritis is much more common than many of us realize or intuitively feel. In addition to the inflammatory back pain that these patients experience, patients with axial spondyloarthritis can also have extra-spinal manifestations outside of their spine. I wonder if you could tell us a little bit about the most common extra-spinal manifestations these patients experience.

Dr Malik

Absolutely. These patients have many extra-spinal manifestations and the most common being peripheral arthritis or peripheral spondyloarthritis, enthesitis, dactylitis, and other extraarticular manifestations such as psoriasis, uveitis, inflammatory bowel disease, and subclinical gut inflammation. I would like to mention that about 5 to 10 percent of the patients with SpA have IBD. And on the other end, about 42% of the individuals with SpA have subclinical gut inflammation.

Dr Stark

So that number really catches my attention, the 42% of patients who may have subclinical bowel inflammation or subclinical IBD. I wonder if you could tell us a little bit more about what subclinical IBD may actually mean.

Dr Malik

Sure. Subclinical, the term by itself, means that these patients tend not to have overt GI symptoms of inflammatory bowel disease. There were a series of elegant studies that were done in Europe where patients were prospectively enrolled in these studies, and they had the diagnosis of axial or peripheral spondyloarthritis. They underwent colonoscopy and random ileal or colonic biopsy, and some studies also did capsule endoscopy.

And interestingly, a large percentage of patients, close to half of these patients, had evidence of inflammation on their capsule endoscopy or on random biopsy that showed either acute or chronic inflammation, and these patients actually did not have any overt GI symptoms that would raise a concern for a clinical presentation of inflammatory bowel disease.

Dr Stark

Well, that's so interesting. What a great insight for us as rheumatologists to be aware of as we take care of patients with axSpA and think about how we monitor them for bowel symptoms over time or even think about what medications we may choose to treat them with.

Dr Malik

Yes, I agree

IBD and EIMs (06:50 – 09:00)

Dr Stark

So as we think about the relationship between spondyloarthritis and inflammatory bowel disease, it seems like for some patients, these two conditions can almost be two sides of the same coin. And as we talked about patients with axSpA having extraspinal manifestations, in a similar way, patients who have inflammatory bowel disease can also have inflammation outside of their gastrointestinal tract, or what we call extraintestinal manifestations. Dr. Malik, I wonder if you can tell us a little bit about inflammatory bowel disease in general?

Dr Malik

Yeah, so inflammatory bowel disease, as the name suggests, is chronic inflammatory disease of the gastrointestinal tract. It primarily includes Crohn's disease and ulcerative colitis. A small fraction of patients also have indeterminate colitis. These patients present with signs of GI inflammation such as diarrhea, abdominal pain, bloody stool, rectal bleeding, weight loss, fatigue, etc. About 1.6 million people in the US have either Crohn's disease or ulcerative colitis. Again, similar to spondyloarthritis, this disease tends to affect younger population, and the mean age of diagnosis is usually younger than 35 years of age.

Dr Stark

Very interesting. And interesting as well for us to note that these patients with inflammatory bowel disease may have inflammation outside of their gastrointestinal tract. The extraintestinal manifestations that we see in these patients are many and can include conditions like uveitis, hepatobiliary disease, skin manifestations, and also musculoskeletal inflammation either in the peripheral joints or in the axial skeleton. And these patients who have axial inflammation may present even as a patient with ankylosing spondylitis or non-radiographic axial spondyloarthritis. And among these extraintestinal manifestations, spondyloarthritis is actually quite frequent. Up to 45% of individuals with inflammatory bowel disease may develop some form of spondyloarthritis.
Influence of the gut microbiome on the pathogenesis of axSpA (09:01 – 13:29)

Dr Malik

Absolutely. I think it is very well established now that the inflammation of the gut is strongly associated with spondyloarthritis, and hence the term gut-joint axis. There are several reasons for that. Number one, there is very high prevalence of IBD, as we just discussed, and a much higher prevalence of subclinical gut inflammation in our SpA patients, although this is much better established in European cohorts, not so much in Asian cohorts. Then there are also similarities, not only in the immuno pathogenesis of the SpA and IBD at the site of inflammation but also how successful targeted therapies are in both SpA and IBD. There are somewhat similar in nature.

Furthermore, we have a genome-wide association study that also showed risk alleles that are common in both AS and IBD. We also know that presence of gut inflammation correlates with early age of disease onset, severity of the disease in SpA and intensity of bone marrow edema on SI joint MRI.

Dr Stark

Well, very interesting. And I think perhaps mechanistically, some of the insights that you just discussed help us to understand why this overlap, this high prevalence of axial spondyloarthritis is seen in patients with inflammatory bowel disease. In some literature, we've seen that up to 50% of individuals with Crohn's disease may have evidence of axial inflammation, although some of them, in fact, many of them are asymptomatic. I wonder if you could tell us a little bit about studies that have looked at this overlap of IBD in patients with axial spondyloarthritis

Dr Malik

Sure. There are several epidemiological studies, so I'll try to summarize as best that I can. But we should also understand that the prevalence of axial SpA that are describing the IBD literature varies widely, and it actually depends on how axial SpA was defined in a given clinical study, such as was it based on X-ray, was it based on MRI, or was it based on just a clinical arm of the ASAS classification criteria of axial SpA? So the 50% or the 45% that we had just mentioned could be an overestimation.

For example, and also in terms of prevalence of SpA in IBD population, one of the cohort from southeastern Norway, called Ipsen Cohort, which studied beautifully these patients over the years, interestingly, it shows that patients with inflammatory bowel disease have a very high prevalence of inflammatory back pain, and not necessarily spondyloarthritis per se. But about 6% of these patients actually have non-radiographic axial SpA, and about 5% has enclosing spondylitis. And these figures are primarily for Crohn's disease, and the prevalence is slightly lower for patients who have ulcerative colitis. And so similarly, for inflammatory back pain, about 10% of these patients have inflammatory back pain, and only 2% have non-radiographic axial SpA, and about 4% have ankylosing spondylitis.

And these studies have also shown that chronic persistent or relapsing IBD activity was also associated with higher prevalence of axial SpA. The other end of the story when we look at the prevalence of IBD or subclinical gut inflammation, the numbers are quite striking. About half of the patients with SpA with GI symptoms had evidence of small bowel inflammation, and about one third had small bowel inflammation despite absence of symptoms.

There was another prospective study that showed about two thirds of SpA patient had GI inflammation at baseline at the time that they were diagnosed. And when these patients were followed over the next two years, 7% developed frank IBD.

Dr Stark

Thanks, Dr. Malik, for that great review of the literature. It is really intriguing to see in these real-world studies some of the actual clinical overlap between these conditions, although I think your review also highlighted for us that there's definitely a need in the future for larger and more diverse studies to help us understand this overlap in the future.

Dr Malik

Absolutely. Cannot agree more.

MRE evidence of IBD & sacroilitis (13:30 – 16:07)

Dr Stark

So as we turn to our final topic and begin to think about imaging and the role that it may play in evaluating these patients with overlapping conditions, it's interesting and fun, perhaps, to talk about magnetic resonance enterography, a topic that I know is near and dear to your own heart.

MRE is an important imaging modality in the assessment of Crohn's disease, and there are several reasons for that. As an imaging modality, it's noninvasive. It provides superior soft tissue contrast and, of course, involves no exposure to ionizing radiation. Intriguingly, though, when magnetic resonance enterography is used to image the bowel, it may also capture pelvic images, which give an opportunity to detect sacroiliitis. So that inflammation, not only in the gastrointestinal tract but also in the musculoskeletal system, may be evaluated.

I wonder, Dr. Malik, if you could tell us a little bit about your own work and some of the learnings regarding magnetic resonance enterography in identifying patients who have axial spondyloarthritis.

Dr Malik

Sure, Dr. Stark. So we published our own study where we looked at the MR enterography that was done in about 258 Crohn's patients in our institution. As you mentioned, MR enterography is a great study for all the reasons that you described. But for us, we took advantage of the pelvic side of the MR enterography and wanted to look at the sacroiliac joint and whether these patients have evidence of sacroiliitis or not.

What we found was about 17% of these patients with Crohn's disease had actually evidence of sacroiliitis on this MR enterography, meaning that they either had evidence of bone marrow edema or structural lesions, such as erosion, ankylosis, fat metaplasia, etc.

In addition, we also found that upper GI involvement was significantly associated with structural changes. And on our univariate analysis, what we also found was that it was slightly more prevalent in females compared to men, and these patients actually reported back pain to their gastroenterologists around the time that MR enterography was obtained.

But most importantly, what we found was that only one third of these patients who had evidence of sacroiliitis on MR enterography were ever seen by a rheumatologist, meaning that about two thirds of these patients were never assessed by rheumatologists for presence of axial spondyloarthritis.

Summary (16:08 – 18:44)

Dr Stark

So as we come to the end of our session today, I'd like to revisit some of the key takeaways from today's discussion. First of all, axial spondyloarthritis is a systemic inflammatory disease that may be accompanied by extra-musculoskeletal or extra-spinal manifestations. Similarly, inflammatory bowel disease is also a systemic and inflammatory disease that may have extra-intestinal manifestations, and we see that there can be overlap of these two conditions in the same patient. And finally, we've had the opportunity to visit magnetic resonance enterography as an imaging modality and see that it can be used to assess inflammatory disease activity in both the bowel and in the musculoskeletal system so that patients with IBD may be screened for evidence of axial spondyloarthritis as well. Dr. Malik, I'd like to see if you have any final thoughts to share with our listeners on the management of patients with axial spondyloarthritis.

Dr Malik

Sure. I just wanted to briefly say that axial spondyloarthritis is not uncommon. It affects about 1% of our population. And there is actually a delay of about 7 to 10 years in the diagnosis of these patients.

And as we mentioned before, these patients are young. So a delay in the diagnosis and treatment initiation can cause chronic fatigue and pain, and that can impact their quality of life and productivity.

And the diagnosis can be even more delayed in IBD patients and, hence, we can probably utilize some of these imaging modalities that we discussed. And one final thought is that I wanted to say that physicians and other providers caring for our patients with back pain should consider axial spondyloarthritis in their differentials. In addition, the fact that spondyloarthritis is associated with other extra-articular manifestations such as uveitis, inflammatory bowel disease, and psoriasis would actually allow an opportunity for ophthalmologists, gastroenterologists, and dermatologists to capture these patients early in their disease process and refer them to rheumatologists for further evaluation and, possibly, earlier initiation of treatment.

Dr Stark

Great reminders for our audience today. Thank you. I'd like to say a thank you to our listeners for joining us for this podcast today. We hope this discussion has been insightful and informative for you.

I'd also like to extend a special thanks to Dr. Malik for joining us today and, particularly, for sharing her passion and her expertise on this important topic.

Dr Malik

Thank you, Dr. Stark. Thanks for having me.