ACR24 SpA Topic Panel Key Discussions on Spondyloarthritis Save

Welcome to our 2020 four ACR recap of axial spondyloarthritis topic. We have a great panel here today. I'm Marina Magre, professor of medicine at Case Western Reserve University, and we're gonna review some highlights about axial spondyloarthritis that were presented at this conference. And we have a great faculty here, and each one of them are going to discuss some key findings from their favorite abstracts about axial spondyloarthritis. Sheila, why don't you go ahead and introduce yourself?

Hello. I'm doctor Sheila Reyes. I'm from The Philippines, and I'm very excited because this is my first year reporting live for RheumNow, and it's I'm very happy to see you all. Great.

We have Doctor. Edder, who is an expert in both psoriatic arthritis and axial SpA.

Hi, everyone. My name is Lily Edder. I'm a clinician scientist and associate professor from the University of Toronto. Very happy to be here.

And our last panelist is Adele Castro. Adele, why don't you go ahead and introduce yourself?

Hi, I'm Adele Castro. I'm a rheumatology clinical assistant professor at here University of Tennessee Memphis, and also very happy to be here.

Wonderful. So tell me what was your favorite abstract?

So my favorite abstract was abstract number eight twenty, and these were the results of the CLASSIC study. So the CLASSIC study was a large and prospective, multicenter study that included over 1,000 patients with back pain, and they were referred to rheumatology for evaluation if they had asthma. Then the patients had to be less than 45 years old and had symptoms more than three months. The primary endpoint of this study was to evaluate the performance of the 2,009 ASA classification criteria for AXPA with an endpoint of assessing specificity more than 90% and sensitivity more than 75%. So the study was divided in different stages.

Stage one was obtaining the history and physical exam. The second stage was additional labs, including CRP and HLA B27. The third stage was obtaining the x rays for SI joints. The fourth stage was the evaluation by local radiologists of the MRI of these patients. And the fifth and last stage was the evaluation of the MRI and all the data from central radiologists that were pertaining to the study in general.

And when there were discordants, they also had an adjudicator, another MRI specialist adjudicating in case there were discordants on these results. So overall, in general, the clinical characteristics of the patients that had asthma were most likely male patients. They most likely had inflammatory back pain. They also had another, the presence of dactylitis, uveitis, peripheral arthritis, elevation on CRP, HLA B27, abnormalities on x rays and MRI. Interestingly, the study did not meet its endpoint of obtaining sensitivity more than 75% and specificity over 90%, which was the plan to optimize the performance for classification on these patients for further clinical trials.

This is going to lead to the revision of these classification criteria. But I think this was important is because we are going to be discussing later on on management and difficult to manage. And it is important to make sure that we are classifying the patients the right way. Something that was very interesting about this study in particular was that local radiologists were overclassifying patients a little bit higher than the central radiology. So that discordance between local radiology and the central radiology was the major differences in attaining the outcome here.

Wonderful, yeah. Our center actually participated in the study. It was a cool study. You know, obviously the 2,009 classification criteria were kind of, you know, landmark for axial SpA classification and research because they actually allowed patients with early diagnosis to be included in the study. However, you know, a lot of people started using these classification criteria, which are meant for research also as diagnostic criteria.

So I think both ASAS and SPARTAN felt the need that we need to refine these criteria further and to increase the specificity of the criteria so that, you know, we are able to recruit right patient into the studies. So the study was, you know, there was actually, I remember, like we would, the PIs, we were blinded to the all the information about the patient. We asked the questionnaire questions which were in the questionnaire about their pain history detail. It was a detailed history. And then at that end of it, we had we had to give on a scale of one to five, we had to say what is our likelihood that this patient has axial SpA just based on history.

We we were blinded to any other information about this patient. And then the second phase would be that then these patients would get blood work done and x rays done. And after the blood work, we would do our second assessment and x-ray and then say, Hey, has the likelihood gone up or likelihood gone down when we included these tests? And then on the third level is when there would be an MRI and then ultimately, we would say whether agree what we feel, whether we moved up on one side of the scale or we went to the downside. So it was a very interesting exercise.

And there were local readers, local radiologist reading the MRIs, and then there were central readers. There was some discordance between the central and the local readers, but not a very major discordance between the two. Overall, they agreed on the findings, what they were. So it is a big study and we're all excited, you know, looking forward to see how these criteria are going to be revised. Yeah.

Anybody else has any input about CLASSIC?

Yes, just emphasizing the difficulty of the diagnosis and the fact that some of the difficult to treat patients may not have the disease. I think it's critical and more education of how to properly read an MRI of the spine by radiologists, but also by rheumatologists maybe could potentially improve things. I think this is coming up again and again of maybe some some sites over reading or over diagnosis, I think may be an issue.

Definitely. And I think there is a larger room for educating radiologists in each center about axial SpA and that may be helpful down the road.

Yeah, that was the conclusion at the end of the presentation, was like, should we need to educate more our local radiologists about the findings for accurate detecting and diagnosing axSpA since we do have valid MRI classification criteria as well that are helpful and validated, and they were also proven in this year ACR.

RUI HYUA, what was your favorite abstract?

So I will be presenting abstract number 2,334, which is the AXIS study, which is a collaboration between GRAPA and ASUS. And this study really addressed the issue of what is axial SpA in PSA or axial involvement in PSA. We do know that there are clinical differences. There are genetic differences between axial involvement in PSA and non PSA patients. And it also came up as whether there is a pathogenic difference that might have implication regarding selection of treatment.

But in studies, people have used different definitions for axial spine. This study really aims to reach a consensus of classification criteria that could be used for research and mostly research, I guess. So this study prospectively collected four zero nine patients with PSA that had symptoms for at least ten years, were not on biologic therapy. All of the patients met Caspar classification criteria. And the patients were evaluated by experts in PSA, and the evaluation included clinical assessment, laboratory assessment, and imaging, both x rays as well as MRI of the spine and SI joints.

And then after that initial assessment and that the imaging was read by local readers, the rheumatologists were asked to decide whether the patients had axial involvement or not. Based on this initial assessment, thirty seven percent of the patients were deemed to have axial involvement. And then the second step was all of the imaging was then evaluated by central readers who were experts in axSpA, as well as by a group of clinicians who evaluated the clinical information. And at that step, there was some modifications of the conclusion of whether there is an imaging involvement of the spine. And the results were then transferred investigator, and they were asked to then reassess their decision based on the evaluation of the experts.

And following that, similar to what we just talked about, there was a drop from thirty seven percent to twenty seven percent of patients that were thought now to have axial involvement in PSA. So I think this is the initial step. The next step will be to, based on these true cases of axial involvement, to define or to develop classification criteria that will help us down the road. But again, we see that there seem to be some overcall in terms of interpretation of imaging by local readers. Then experts reevaluate it.

And these findings were not thought to have. I think axial PSA is complex. We spent a lot of time reading x rays. There is a lot of new bone formations. The patients tend to be older.

They tend to have metabolic abnormalities in dish, and degenerative changes are very frequent in this patient population. So it makes it very difficult. So hopefully, these new classification criteria could help us with research and identify the right patients for treatment.

I definitely agree with you. It was definitely a landmark study, you know, to find out how to classify axial psoriatic arthritis. Over the years, we have been borrowing everything that's for axial SpA and using it for axial PSA, and if you look at this, phenotypically, they are actually a little different. If you look at an x-ray of a patient, spine x-ray of a patient with axial PSA, which has large syndesmophytes, they're not marginal, they're coming from the middle of the vertebra, and the sacroiliitis could be only unilateral. What I was interested in that study was, you know, I wanted to see because there is this belief that patients with axial PSA may not have SI joint involvement and can only have spine involvement.

So that was cool because they say that if you are looking for axial disease in PSA, then do the whole spine and SI joints because in traditional axial spondyloarthritis, we rely on SI joints for making the diagnosis because that's the hallmark of that disease. So I thought if I remember correctly, Lihi, correct me, it was about eighteen percent of the patients who had about only the spine involvement without the SI joints involvement.

Yeah, I can't remember the number, but I remember it wasn't very high. So that's, I guess, in contrast to what we tend to think. Although I personally do order an MRI of the spine in case the patient does have some pain, let's say, in the cervical spine, that may be the predominant, I would extend the MRI. So I think it still has to be individualized based on patient's complaint, because I do have patients that have only spine involvement without sacroiliitis.

Yeah. Have a question, Luis. I'm sorry. So from what I understood, the patients were not on biologic treatments.

So I wonder

what the results would be if they were actually on biologic treatments, because now we're using them more and more for patients with psoriasis and psoriatic arthritis. It will be interesting to see that starting them early in biologics will actually prevent the actual involvement.

These were biologic naive patients because obviously classification, they we wanted to pick up the for the definition in order you wanted those patients that were not treated because that could have masked some of the findings. So we didn't findings had to be original. Excellent. And, Sheila, what did you have? Your favorite topic and I mean, favorite abstract?

K. So one of the hot topics within spondyloarthritis was the gender differences. And the abstract that I liked, abstract fourteen seventy one, was actually by the group of Professor Leahy, where they did a systematic literature review and meta analysis assessing the sex related differences in the efficacy and safety of, or safety endpoints of advanced therapies in axSpA. And they had a total of 79 RCDs that were included. And according to their findings, female patients with XBA were significantly older, they had higher BMIs and higher baseline VASTDI scores, Whereas in contrast, male patients who had AXPA had higher CRPs, they were more prone to have HLA P27 positivity and were more likely to achieve an ASAS40 response.

And this response was significantly observed with the use of the TNF inhibitors and the IL-seventeen inhibitors with numerically noted differences from the IL-seventeen inhibitors. And also interestingly, they found that male patients who had NR axSpA were more likely to achieve efficacy endpoints compared with those with radiographic axSpA. Then, of course, again, the message that gives us, that the study gives us is that there's really the diff, there are differences in gender among patients with axSpA. And I think that's always a recurring theme when we get to see studies, when there are future clinical, even clinical trials. So knowing these differences can, I think, better help us in distinguishing what approach or what types of therapies we could give for our female patients compared to our male patients?

I think Professor Lihue could give more insights about it, but I think it's really an important meta analysis because it gives, it shows us, again, the awareness that although treatment should always be individualized, but I think with the gender differences, particularly with axSpA, we have to be more considerate, we have to be more mindful of what we should give our patients, and how these patients would respond.

Great. Yeah. You know, gender based differences in treatment response was definitely a very hot topic at this ACR convergence meeting this year. There were several abstracts presented about this in different diseases, and, I guess, that's why I think RheumNow has all female panel here today to highlight how we can get do better in our female patients. We our group or fellows also did a similar analysis similar to that.

They actually did they took they did systematically run meta analysis of most of these data were post post hoc analyses from big clinical trials, were already published. And they found the same results that these patients are women actually did not have as robust response as men. And, even the summit other efficacy endpoints were delayed in females, and, they did not have as large responses as men. And HLA B27 obviously was a predictor of response. So males were more likely to have that and, responded better.

Now, what is driving these differences? Is it biologic? Is it, other, you know, contextual factors in females, like central sensitization, pain? Is that what's driving? It needs to be determined.

I think a lot of work is being done by different groups, both at biologic level and seeing how these patients can be better managed. Do you have anything to add, Lihir?

Yeah, I think I can talk about this topic for an hour. Think we don't I have much would just add a few points. I think the findings were not surprising. I think, Marina, right? We've seen this again and again.

Women are doing less well, both in RCTs as well as in observational studies with lower persistence on TNF inhibitors and IL-seventeen inhibitors. What we missed in this particular meta analysis were JAK inhibitors. We were particularly interested in JAK inhibitors because we've shown in PSA that there was no difference in response. So there might be some mode of action differences, and this might suggest that maybe. It's definitely worth exploring.

But unfortunately, the trials on JAK inhibitors in axSpA did not publish the results by sex. We could not include it. That's one of the limitations. And most of the studies don't publish the sex disaggregated results. Second point that I want to make is the fact that we did find more differences in non radiographic axial SpA favoring males compared to radiographic axial SpA, where the differences were minimal.

And that brings up the question of maybe misdiagnosis potentially in non radiographic axial spying females because of maybe some changes in the MRI that could be related to a postpartum or other changes that may have been interpreted as axial or sacroiliitis, and this may not be the case, and therefore they don't respond as good, while in radiographic axial SpA there is more experience and there are more severe changes that therefore, there is maybe less diagnosis. I think the bottom line is that we need to understand the differences, because at this point, we just described the phenomenon that women are doing less well. We don't understand why is that.

Yeah. As you mentioned, interestingly, these differences are seen across all biologics in this disease. And, you know, the session, there was a session for difficult to treat axial SpA led by Doctor. Dennis McGonigal, and his one of the teaching points I learned from take home message from his lecture was this, that if a patient is not responding, please go back to the drawing board and make sure you have the right diagnosis on that patient. This diagnosis is not very easy.

It's a very difficult diagnosis. There was a study that was, it's already published. It was a data from space cohort. They got patients with less than two years of back pain referred to them. And in that cohort, at the end of two years, thirty percent of patients were still not diagnosed, did not have a diagnosis.

So that tells you it's a very difficult diagnosis because we do not have a biomarker like we have in other diseases. So it's all based on a comprehensive history, clinical examination, and then following some, you know, the best we have is MRIs. This is the best that's like been revolutionized and we rely on them. But at the same time, over diagnosis is possibility. And, you know, sometimes in particularly in females who are young, who are postpartum, or athletes who are runners, may see some changes which may mimic axial SpA, but may not be there.

Now

that you mentioned the lecture from Doctor. Dennis McGonagall, I loved that lecture, learned a lot. And one of the things that he did mention that I found interesting that I have not thought about it before was the coexistence of patients with polymyalgia rheumatica that end up becoming axSpA. Do you guys have any experience in these patients? Is that something that you always think about in the PMR patients?

I thought that that was very interesting because sometimes we just see, is this being my PMR? Is this negative RA? And maybe these patients end up having, you know, axSpA that we're missing.

I think that was a very interesting concept. I didn't had not heard about it before that lecture. So I was myself intrigued by that. What does he mean by that? Is it that those patients who are missed all their life and now, because usually PMR is usually seen in patients who are like, you know, who are diagnosis is after age 50 and this disease we're expecting is going to be in a very young patient.

So, or was he trying to tell us that these are the patients who had high CRPs and XPA and they were like PMR like? I didn't quite that's something I think needs to be dealt deeper. That was a very, you know, interesting concept he was alluding to, that PMR, like SPA. So, whether it was that they had elevated markers of inflammation or whether they had some, you know, and the response was better then, because obviously CRP has high elevated CRP is considered to be a good predictor of response and also high, you know, bone marrow edema on an MRI. So, yeah.

So keeping up with that topic, I think there was also an abstract presented by the ASAS group about the consensus definition of difficult to manage XBA. Anybody yeah.

I was actually able to interview Doctor. Padaphni about the criteria, and I think it can help us in such a way that, you know, managing AHPa is already challenging as it is, and then we get to see different subset of patients who are not responding properly to the available treatments that we have. So I think although it may be you know, so that to group our semantics so that to be able to homogenize the patients in terms of what, if you will be guided as to scaling up your treatment, or if you have to follow them more closely. But from a clinical standpoint, I think it also helps because can identify those patients who you think will eventually might have to reconsider treatment or, you know, increase or add other treatments. And I think what the, some, one part there where I also was interested in was that they included in the criteria patients, patients or the physician's decision that if the patient is not improving, either from a patient's perspective or from a physician's perspective, then maybe this is really difficult to treat.

Although it's also a bit strict, I think, the criteria, because you also have to have those three criteria or to meet the criteria to say that it's really difficult to treat. And sometimes it may not translate as such in Yeah. Real world in clinical practice.

I think they included I think they included, like, treatment failure, which they defined as anybody who requires two biologics from two different classes. They also included patients that would have, you know, persistent disease activity high and elevated inflammation like high CRP or an MRI inflammation. And they did take into, they also said that those who have an impaired quality of life. So they were also relying on some subjective symptoms like symptoms, you know, which the both either the patient or the clinician perceived as they were bothersome. So there was some objective data into this definition.

We, you know, before this consensus definition came out, we looked at this, at a real world study, this large database called TriNetX, trying to identify these patients. We defined anybody who had used at least three biologics, two from two different classes. And we saw that this highlighted that the, some of the clinical features, these patients had high BMI's, they had comorbidities like hypertension, they had chronic renal failure, depression, and they tended to have some more extra articular manifestations. So that was interesting. I think this definition is definitely going to allow for more research now.

So, and also let us delve deeper into these patients and figure out why some of them are not responding to patients. Excellent. Great work. Did you have another abstract you thought was great to present?

Yeah. I would like to, present abstract number six zero three. This is a study that was done. Zavada is the first author. It's a poster that asked the question of after failure of first TNF inhibitor, should we switch to a different mode of action or cycle, stay within class of TNF inhibitor?

It's a study from a check registry, and they identified patients with a radiographic axial SpA, a failure of TNF inhibitors, and then they matched by propensity score patients who were cycling within class or a different TNF inhibitor or patients who switched to an IL-seventeen inhibitor. These patients were matched by propensity score, so the baseline characteristics are similar. They had a similar ASTA score at baseline. And they looked at retention as their first primary endpoint. They found that the retention was similar between the TNF and IL-seventeen inhibitors, but there were some differences when it comes to disease activity and safety.

So interestingly, they show that the TNF inhibitors were associated with better reduction in ASTHAS score throughout the course of two years. But on the other hand, the IL-seventeen inhibitors were associated with less adverse effects, including severe adverse effects. So I think, the bottom line for this is that we can still choose one or another TNF or switch to an IL-seventeen inhibitors. The endpoint will probably be the the group level will be the same. But there are some consideration when it comes to maybe safety and efficacy.

And these could be dependent on response. I wonder if this is a primary failure or secondary failure, or if there were some safety issues like infections that might have been higher in the TNF inhibitors in the first period. So until we do have a good biomarker that could inform selection, I think both option at this point are valid, and this is reflecting other studies in PSA and AUXPA that showed the same results.

You know, interestingly, there was another abstract that was presented from the French group, where they looked at the, you know, time to low disease activity for patients who were treated with one, two, or three TNF inhibitors, and then, or treated with the first TNF inhibitor, and then switching to the second TNF inhibitor or IL-17A inhibitor. And they found that time to reach low disease activity was longer in bio naive patients compared to those which had already been treated with the TNF inhibitor. But then they also looked at their durability of this low disease activity, how long they stayed in low disease activity. And they found when a patient switched from a TNF inhibitor to an IL-seventeen, they did not stay for longer in low disease activity, but TNF to TNF, there was not a difference from the first TNF to the second TNF. So I thought the take home message from that abstract was that obviously when patient, when we switch our patients, the response is usually best when we start them on the first drug when they're bio naive biologic.

And then when we are switching them, I think we need to let our patients know that it may take longer now. Mean you, we want to have to be patient. We cannot be cycling these meds, you know, and, moving on from one to another because this second time it may take longer to get to the low disease activity compared to the first time, and we started them.

I agree with Lihi here as well about the reason why we're discontinuing, is it because it's a primary failure or a safety concern? Because if it's definitely a primary failure, I'd be more inclined to switch. If the patient actually responded, but then lost efficacy, then I'm more probably inclined to cycle it. I think knowing that if it's the primary failure versus safety effect, then probably switching will be a little bit better in these cases, as opposed to if it was some sort of response and the patient did well but then lost it, then you can consider possibility of, you know, cycling.

I think

that Go ahead.

And I think it's really important that you we educate our patients. We tell them about the plans and emphasize that it's a shared decision making so that they also understand, you know, why, for example, they will fail one biologic or they will improve with one and then eventually they need to be given another. Just that so that they could also understand and, you know, emphasize that, again, the importance of follow-up and even, you know, understanding the other factors that could drive the lack of treatment response or or complications with the with the options.

Great. I think we if we had time, we could sit here all day. There were so many great abstracts that were presented. There's, like I had some favorites, but I guess we don't know, with respect to our time, I think we may have to stop here, but, it was great chatting with you guys, and, hopefully, you know, this information is gonna help our patients and help us taking care of patients and, advance science. That's all we are all interested in.

Thank you all so much.

Thank you. Thank you. Bye bye.

Bye.