Nonrad AxSpA and the Disease Burden on the Patient

Dr Bittar educates the listeners on the core differences and similarities between ankylosing spondylitis and axial spondyloarthritis; and provides guidance on diagnosing and monitoring/ treating patients with various forms of axial diseases.

Mohamad Bittar, MD, is an assistant professor of medicine at the University of Tennessee Health Science Center in the rheumatology division of connective tissue disease.

TRANSCRIPT:

Priyam Vora:
Welcome to this podcast from the Rheumatologist and Arthritis Learning Network. I'm your host, Priyam Vora, and today we are talking with Dr. Mohammad Bittar. Dr. Bittar is assistant professor of medicine at the University of Tennessee Health Science Center in the rheumatology division of connective tissue disease. Today he's going to talk to us about axial spondyloarthritis or axSpA, more specifically non-radiographic axSpA and the disease burden on the patient. And more on identifying and treating the different axial diseases.

Thank you for joining us today, Dr. Bittar. Would you begin by giving our listeners a basic overview of axial diseases? For instance, what is the difference between Ankylosing spondylitis and axial spondyloarthritis?

Dr. Bittar:
Thank you so much for inviting me and thank you for having me. I'm happy to be talking to you today about this topic. So this is a great question. Axial spondyloarthritis is a condition that affects the axial skeleton, which is the sacroiliac joint and the spine and the axial skeleton of the body. It can cause inflammatory chronic inflammation, which can be very debilitating and it can lead to different complications if patients are untreated in a timely fashion. That's why what we would like to do is we would like to raise awareness about the subject. We would like providers to know more about the condition so we can diagnose it and catch it early on so that we can treat patients as early as possible. Back to your question, it's very important to know the difference between ankylosing spondylitis and non-radiographic disease. So axial spondyloarthritis is the umbrella term of the condition.

It contains both ankylosing spondylitis and non-radiographic axial spondyloarthritis. Both cause inflammation in the spine. Both are, if you want to think about it as both are spectrum of the same condition. Usually it starts as non radiographic disease and it moves on, in certain percentages of the patients it moves on to ankylosing spondylitis. So both non radiographic axial spondyloarthritis and and ankylosing spondylitis are both within the axial spondyloarthritis conditions. The difference between them is that early on the disease is usually not detected on an X-ray of sacroiliac joint and actually studies have shown that it can take up to 10 years for inflammation to appear on an X-ray. So for us to see an objective evidence of damage on an X-ray, it can take up to 10 years and of course we do not want to wait for 10 years to make the diagnosis.

We want to catch it as early as possible. In the early stages when patients have symptoms of the condition of axial spondyloarthritis, if we check X-ray it might be a negative where it might show very early changes. Those changes are usually not enough to call the condition ankylosing spondylitis. If you want to think about the definitions per the modified New York criteria, the definitions of ankylosing spondylitis, patients have to meet either grade two or more of sacroiliitis on an X-ray to meet that definition, and if we are catching it early on, patients might not meet those definitions. So the researchers in axial spondyloarthritis introduce the MRI to the field in around mid early two thousands and they saw that a big percentage of the patients who do not have X-ray findings, but they have a typical symptoms of the condition, they can have MRI findings of a disease.

So if we do MRI pelvis on those patients, we might see bone marrow edema, inflammation, certain findings of inflammation or damages in the MRI, in the sacroiliac joints and so on. So in those patients who we do not have advanced X-ray findings, but they have typical type of symptoms and they have MRI findings, we call them non-radiographic axial spondyloarthritis. So this is basically the difference between them and I want to very briefly speak about the symptoms of axial spondyloarthritis because this is something that we want to providers to be aware of so they can catch the disease as early as possible. Most patients with axial spondyloarthritis, they have what we call inflammatory back pain, is a spinal pain that starts in the low back at the level of the sacroiliac joints. It can be also at different levels of the spine.

 We call it inflammatory because it has inflammatory features such as it wakes up patients at the second portion of their sleep at night. They have a lot of stiffness in the morning in the spine. It takes when they move, when they exercise, it gets a little bit better if they rest or if they stay still for some time, they get more stiff and they have more symptoms. All these type of course, different other types of symptoms, they contribute to what we call inflammatory type of back pain. Also, patients can have inflammatory arthritis in different joints such as swollen joints and so on. Even peripheral joints such as the knee, the elbow, the wrist and so on. Patients can have other systemic manifestations such as psoriasis in the skin, uveitis, which is inflammation in the eye, and also inflammatory bowel disease or inflammation of the bowels such as Crohn's disease or ulcerative colitis. Those are briefly some of the symptoms that patients have. Of course, there are much more that we can talk about.

Priyam Vora:
That's wonderful. Okay, thank you. Do these diseases present more often in men or women or in any other subpopulations? How about the age of onset? Are there any variances there?

Dr. Bittar:
Thank you for this excellent question. This is again, very important point that we need to talk about.

Initially, in the past, it used to be thought that this condition happens more in men compared to women. If you want to think about ankylosing spondylitis, which by definition is the advanced radiographic condition, it is more common in men, the ratio is three to one. So for every three men, there is one woman that can be affected with ankylosing spondylitis, but with the new terminology of non-radiographic disease, non-radiographic axial spondyloarthritis, actually the ratio is now one to one. It's 50-50 between men and women. This is very important because we want the providers to know that this disease can happen equally in men and women because we want to catch the condition as early as possible in everyone without any delay in diagnosis. Regarding other subpopulations as per the question.

Also, one of the thing that it was thought in the past that this condition happens mainly in white or Caucasian population. If this is not correct, because we see this condition happen in everyone regardless of race or ethnicity. Of course, epidemiology. Epidemiology by definition is the study of frequency and distribution in population. If we want to talk epidemiology, yes, the condition is more prevalent or more common in Caucasian or white population, but that does not mean it does not happen in other races or ethnicities. We see it often in African Americans, in Hispanics, in Asians. So the condition can happen in everyone. That's why it's important for the provider to ask all the questions needed to make a diagnosis because this condition can happen in everyone.

Regarding the age of onset, this condition, and it's important to think about it as age of onset. When do the symptoms start? The age of onset is usually younger than 45 years of age. Sometimes we can see a patient who is 60 years old, but they tell us that the symptoms started 30 years ago when they were 30 years old. So the age of onset is very important by definitions that we have right now. The age of onset is younger than 45 years of age. It happens in the pediatric population. It's called juvenile spondyloarthritis.

Most commonly it's between the ages of 18 and 45.

Priyam Vora:
Other than the fact that AS or ankylosing spondyloarthritis and axSpA, they show signs on imaging imaging and non rad axSpA does not, other than the symptoms and the markers, does the diagnosis rely solely on imaging?

Dr. Bittar:
So actually not. The diagnosis is much more complex than only imaging alone. We always say that we need to combine the clinical picture with the imaging finding and with what we have on labs or laboratory finding. So in order to make a diagnosis, we need to combine all the features together because one of the causes of over diagnosis of the disease is if providers rely only on imaging on its own. Recent studies have shown that sometimes X-ray or MRI findings can be not very specific to one condition. Of course, now it's evolving. The definitions of what axial spondyloarthritis on an MRI is evolving with dying. This spondyloarthritis community always meets to redefine what do they think is consistent of axial spondyloarthritis on an imaging. So for example, if we see one location that has edema or swelling on an MRI, this is not enough to make a diagnosis.

We need to meet specific criteria on imaging in addition to the clinical picture and the laboratory findings regarding laboratory findings. Sometimes those might not be helpful because inflammatory markers, they might be negative in certain percentage of axial spondyloarthritis patients. Same for HLA-B27, which is a genetic marker that can be seen with this condition. It does not see in all the time. In a lot of patients, we do not have HLA-B27 positive, so sometimes the laboratory findings might not be helpful or they might be negative. That's why it's very important to go back to the patient because we always treat a patient, we treat the clinical manifestations to see what symptoms do they have. We need to be able to correlate the clinical symptoms with the imaging so we can make a diagnosis.

Priyam Vora:
So moving on to treatment, what kinds of treatment are available today for these conditions?

Dr. Bittar:
Perfect. The happy thing is that we have more treatments than before. So if you think about before 2000, there were not many treatments for this condition, but thankfully over the last two decades we have more and more treatments. So per the guidelines that we have, the ACR-Spartan-SAA guidelines that were published last in 2019, and I hope to see an update of the guidelines soon. The first line treatment is anti-inflammatory NSAIDs, non-steroidal anti-inflammatory agents. This is first line treatment.

If patients do not have any contraindications, of course, if patients have chronic kidney disease or any type of kidney disease, they cannot be on an NSAID because that's a contraindication. If they have an active GI ulcer, if they have heart disease, different types of contraindications in those patients, we cannot use NSAIDs because it's contraindicated. So if they have contraindication to NSAIDs or if they do not respond fully to NSAIDs, we need to jump to what we call it a second line treatment.

The second line treatment is usually Tumor Necrosis Factor inhibitors, TNF inhibitors. Those are biologic treatments. TNF inhibitors, again, in the absence of contraindications, what all the contraindications do? They are different type of contraindications, but mainly demyelinating diseases such as multiple sclerosis or advanced heart failure. Those type of conditions can be contraindications.

Of course, any type of infections such as tuberculosis, active hepatitis, things like that can be contraindications. Definitely. We do not want to start anyone on a biologic treatment. If they have an active infection, the infection has to be treated. So again, with all of those type of classes, we need to make sure patients do not have contraindications before we can start them on the medication. So if they do not have a contraindication, then TNF inhibitors will be the second line treatment. If they have any contraindications or if they do not respond fully to TNF inhibitors, then we move to what we call third line treatment, which is interleukin 17 inhibitor, which is again, it's a biologic treatment, interleukin 17 inhibitor as well. They have their own contraindications. For example, active inflammatory bowel disease would be a contraindication for interleukin 17 inhibitor infections as well, and so on.

A newly and recently the Janus kinase inhibitors were approved. This class was approved for the treatment of axial spondyloarthritis. At this point in time, per the 2019 guidelines, they were not approved at that point in 2019, so they were put after the third line treatment or with the third line treatment after patients, if they failed interleukin 17 or they have contraindications. At this point in time, we do not know where will it be their position on the treatment guidelines. We hope to see it soon when the treatment guidelines are updated. We hope to see where the position of Janus kinase inhibitors will be. In the practice usually Janus kinase inhibitors, axial spondyloarthritis are used.

If patients fail or have contraindications to TNF inhibitors or interleukin 17 inhibitors, you might want to ask me, what is the role of methotrexate or the, what we call them, synthetic DMARDs. Those medications do not play a role in axial disease treatment, spinal disease, those medications do not work on spine, but those medications can help. If patients have peripheral arthritis or for example, if they have uveitis, methotrexate might help and so on.

Priyam Vora:
That was good to know. Would you monitor a patient with non rad axSpA differently from a patient with AS or radiographic axSpA?

Dr. Bittar:
No, so actually what I would like the speakers to know is that we think about non radiographic disease and ankylosing spondylitis as a spectrum of the same condition, so we monitor a similar way. We treat them in a very similar way. They have a little bit of differences between them, but mainly they are both. They belong to the same condition. That's why the monitoring is very, very similar. The treatment is very, very similar, and also the studies have shown that the burden of the disease, it can be very similar between ankylosing spondylitis and non radiographic disease.

So patients will have very similar type of symptoms, very similar burden of the disease, very similar functional disability or functional impairment, if I want to say, or pain symptoms and so on, and ankylosing spondylitis because they have more advanced radiographic changes. Usually they have a little bit worse functional impairments, a little bit worse measurements on exam and so on, but the burden of the disease is very similar between both entities.

Priyam Vora:
What advice would you have for fellow rheumatologists who are trying to make a definitive diagnosis and then choose a treatment for these patients?

Dr. Bittar:
Perfect, so my main advice is please, please help us as much as possible to make the diagnosis as early as possible. Again, there is a lot of delay in diagnosis in this field in specific in the field of axial spondyloarthritis studied studies have shown that on average to be global, the global studies, the average delay in diagnosis is around 6-7 years from the onset of symptoms to diagnosis.

Imagine patients can be suffering from the condition for around six or seven years on average before they can get a diagnosis and before they can get treated. This can lead to a lot of debilitating symptoms to progression of disease and complications, and we do not want that. That's why I want my fellow dermatologist to please help us as much as possible to diagnose and catch this condition early so we can help patients as much as possible.

So the most important thing is to know the manifestations of the disease, to read more about the condition, to know how patients present. By appreciating the presentations of the condition, it'll be easier for us to think about it so we can make a diagnosis for it. I always say that if you are in doubt, always ask for help. Ask for support, especially for primary, special primary care providers and so on. If they have a question they are not sure about what's going on, please ask the rheumatologist. Please refer to your patients because we want to see the patients. We want to catch them, catch the condition as early as possible so we can treat as early as possible. One of the most difficult things to do is to make the diagnosis. This is very tricky because again, it's not very easy to make this diagnosis, so when patients are getting evaluated and getting work up to make a diagnosis, we want support as much as possible.

If the rheumatologist is also in doubt, please try to reach out to one of the expert rheumatologists in the field. To run the case by them to see what do they think, because we want to help you to make a diagnosis and reach this diagnosis. When it comes to treatment, thankfully we have the treatment guidelines which guide the providers and rheumatologists on how to proceed. It's not a complicated guideline. It's pretty straightforward.

Mainly we need to know what manifestations patients have. If they have, is it purely musculoskeletal disease or is it affecting other parts like the eye, uveitis or inflammatory bowel disease or psoriasis and so on. We will know what manifestations patients have. We will think about what comorbidities they have. Do they have heart problems? Do they have kidney problems, and so on. We need to collect all these information, and then based on that, we can choose whatever the appropriate treatment is for the patient. If the rheumatologist reaches a position where they tried different type of medications, patients are not responding and they would have liked to see a response. At that point, we advised the rheumatologist to rethink about the diagnosis.

Are we dealing with the correct diagnosis or are we dealing with a mimic of the condition? Of course, we always need to think about this. Even especially at the beginning when we see the patients, when we make a diagnosis, we want to make sure we're not dealing with a mimic. We want to make sure that we are trying to reach the correct diagnosis as much as possible, so after that, of course, patients will be put on a treatment. If at some point the patients are not responding as the physician would like to, at every stage, the rheumatologist will have to rethink about the diagnosis to make sure that they arrive to a correct diagnosis.

Again, if they are in doubt that they have some questions that they cannot answer, I would recommend that they should always reach out to an expert in the field to see if they can get some help in trying to think about the condition, about the presentation of patient to get some help and support.

Priyam Vora:
Thank you for taking the time to talk to us once again for our listeners. That was Dr. Mohammad Bittar speaking about the disease burden of the different axial disease on the patient and the different ways to combat them. Thank you, Dr. Bittar.

Dr. Bittar:
Thank you so much and have a great day.