ACR20 - Day 4.3 Save

This is the RheumNow podcast, and you're listening to highlights from the ACR twenty twenty virtual meeting. Our faculty reporters have been doing videos and recordings so that you could stay up to date. Hope you enjoy these and our panel discussions.

Hello. I'm Anthony Chan. I'm consultant rheumatologist in Reading, United Kingdom, and I'm reporting here from ACR20. There have been a lot more interesting posters and abstracts today in the conference, and I wanted to share with you some of the abstracts which I thought were really interesting, especially in the field of axial spondyloarthritis. Now, as you know, the treatment in axial spondyloarthritis has expanded.

We have seen new modes of action including IL-seventeen and also JAK inhibitors. Today, want to concentrate on the new data that's available in the field of axial spondyloarthritis, particularly in the mode of action, which is from IL-seventeen inhibition. Now we know IL-seventeen can form as a homodimer or an heterodimer. So it can bind IL-seventeen in terms of IL-17A and IL-17F sub types. And in the area of IL-17A, there are two agents that we currently use in our clinical practice.

And there are some up to date data from the conference today. Firstly, in abstract number thirteen sixty six, there is a study looking at the use of secukinumab, which is an IL-17A inhibitor. And they've studied this in the non radiographic axial spondyloarthritis group. As you know, there are two groups, the non radiographic and also the radiographic what we know of as ankylosing spondylitis. In the non radiographic group from the PREVENT study, they have now looked into a bit more detail.

And what they've done, they categorized the patients according to their MRI and CRP results. And what they found is that patients were either positive for both MRI and CRP01, and they found that they were in fact, the treatment worked across all groups, but the treatment was most effective in the MRI positive and CRP positive or the double positive group and they were, they looked at outcome measures such as ASAS forty and also other outcome measures such as the BEST I 50, ASAS partial remission and also STAS inactive disease. In the ASAS 40 group, the double positive group achieved an ASAS 40 of fifty four percent versus twenty one percent in the placebo group and very similar results in the other groups where they were single positive. So I think this is a really encouraging result, a signal that we can see in a non radiographic group. The other agent that's being used is called isekizumab.

Now this is another IL-17A agent and the study is called COS X and in poster number thirteen sixty seven, they looked at the aspect of a defect of IL-17A inhibition on work. Now work is a big issue for our patients. There's a lot of absenteeism or presenteeism and how we can look at these two aspects of the work in patients with axial SpA. And they found that IL-17A inhibition with his ezacuzumab improve productivity and also activity impairment and also presenteeism and reduce absenteeism with treatment. So again, it's good to see that beyond our traditional measures of efficacy such as ASAS forty and PASTI, there's also improvement in some of the patient reported outcomes such as work and productivity.

So that's again a very positive signal. Now, if you look at the IL-seventeen, there's also the subtype L17F, and there is a report today and poster thirteen sixty four, which looks at bimekizumab. Now bimekizumab inhibits both IL-17A and F. So it's a combined dual inhibition of IL-17A and F. And they looked at the outcome measures and the study is called B Agile.

And what they had done is they looked at the extension study beyond forty eight weeks. So in the first part of the study, they had people, patients going up to forty eight weeks. And what we saw in the first forty eight weeks, there was a rapid response Within twelve weeks patients had already starting to respond to the treatment. Eighty seven of these percent of the patients carried on beyond forty eight weeks and they went on to ninety six weeks. And when we looked at the non responder imputation results of the ASAS forty, sixty five percent of patients maintained ASAS forty at week ninety six.

The ASAS partial remission was thirty six percent and the SDES inactive disease was twenty eight percent. So this again shows the benefit of IL-seventeen ANF inhibition. All these studies tell us that the mode of action of IL-seventeen inhibition is again increasing our choice of treatment and also the mode of action beyond the other treatments. And this is really a encouraging sign for us as we see of our patients and they vary and they have different clinical features and it's important for us to have choice when we make some of the treatment decisions that we have in our clinic. I'm Anthony Chan reporting from ACR20, thank you.

Hi everyone. I'm Nicola del Beath from Auckland, New Zealand. Talking about some more gout abstracts from the ACR twenty twenty meeting. So I was really interested in a couple of abstracts today related to comorbidities and gout. The first is abstract fourteen sixty six, which describes multimorbidity in various rheumatic diseases, including rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and gout.

So this is a study from the RISE Registry, so a rheumatology clinic based registry really assessing the burden of multimorbidity in various rheumatic diseases. And in this study, people with gout within rheumatology clinics had the highest rates of multimorbidity. And not surprisingly, I think the most common comorbidities observed were metabolic and cardiac risk categories. So I think this certainly gels with what we see in the Rheumatology clinic. Often patients with comorbidities such as severe heart failure, kidney disease are more likely to come to our clinics because management of gout is more complex.

But I think this really does raise quite a lot of challenges for us in rheumatology clinics. And I think, given that we have a lot of focus at the moment on The role of comorbidities and outcomes related to covert I think that this is a particularly important area for people with gout and we haven't really seen a lot of data on outcomes for people with gout related to covert nineteen infection. The other thing that's been really important this year has been within the medical literature has been a number of clinical trials reporting outcomes of common gout medications for other comorbidities. So I'm particularly thinking about a couple of allopurinol trials. The Pearl trial and also CKD fixed trial which tested the role of allopurinol for prevention of CKD progression, both of which were negative And also the Colcott studies and Lodoco2 study, which reported improved cardiovascular outcomes in people treated with colchicine.

Now in both the allopurinol studies and also the colchicine studies, this didn't specifically include people with gout, but I think certainly this again raises the possibility that some of the medications that we use for gout, particularly medicines colchicine, may also have some benefits for comorbidities such as cardiovascular disease. The issue around kidney disease with allopurinol, I think, is probably less clear, and in fact, there may not be benefit. Related to this, there's also been a really interesting abstract, Abstract six sixty, which reports on the risk of gout with SGLT2 inhibitors. So of course, these are drugs that are used increasingly for people with type two diabetes and a number of studies have reported that SGLT2 inhibitors are urate lowering and can also prevent the risk of gout. This is a very interesting abstract because it suggests that some of the SGLT2 inhibitors may have a preferential effect on gout risk using the THIN registry.

So I think that these are important abstracts. They really highlight the importance of thinking about comorbidities for people with gout in our clinics and also suggest that some therapies that we use for treatment of gout may have benefits for comorbidities and also vice versa. Some medications used for comorbidities may be useful for prevention of gout as well. Thanks.

Hi, this is Doctor. Eric Dine from Baltimore, Maryland checking in with RheumNow at ACR Convergence. This is day three of abstracts. And today I'm going to talk about this morning at the poster sessions, there's great poster series on variety of different issues with regards to cardiovascular risks with rheumatoid arthritis. I'm going to talk in particular about abstract zero, I'm sorry, abstract eleven eighty nine.

That's a poster by Doctor. Husni at the Cleveland Clinic. And they looked at patients to as part of the precision biomarker study to try to get a sense of what risk factors we can use to best predict cardiovascular event in rheumatoid arthritis and osteoarthritis. They looked at in particular, high sensitivity cardiac troponin as well as high sensitivity CRP, C reactive protein to predict MACE major adverse cardiac events in these patients. The PRECISION study, it's a large biomarker study looking at a large number of patients with RA and OA.

They had six thirty six patients in RA and over six thousand OA patients in the subset that were having this analysis. And again, the primary outcome was the MACE events. What they did was they enrolled these patients prospectively looking to see which patients had this outcome comparing to their initial high sensitivity biomarkers. The patient population, the mean age was about 64 years old. It was slightly female, fifty eight percent predominant, eighty percent Caucasian, thirty three percent were seropositive with CCP antibodies eighteen percent had known CAD thirty six percent had diabetes eighty percent pretty high number with hypertension.

So this was a population with some pretty good risk factors to go on to have MACE events. When they looked at it, they found that the high sensitivity cardiac troponin was slightly higher in the osteoarthritis group. And they found that it was predictive of having MACE events. They had a fair number of events that were captured in it. And they did find a predictive value in both the rheumatoid arthritis group as well as the osteoarthritis.

High sensitivity troponin had an odds ratio of one point six increased risk for RA one point two in osteoarthritis. The prediction value of the high sensitivity CRP was not quite as good. Was just barely met statistical significance in the RA group at one point three and did not show any any predictive value in osteoarthritis. So this is an interesting study for me in a couple ways. One is that we don't, the high sensitivity troponin is not something that we're clinically following right now.

It's rare that we see a patient that comes in with a baseline elevated troponin on a normal troponin exam that we'll capture in the office. But this might be an early indicator. We do think a lot about the high sensitivity CRPs. We think about the overall inflammation, which we would capture with the CRP. And that did not show to be quite as predictive and in osteoarthritis, not predictive at all.

But thinking about patients that may have some mild evidence of cardiac damage or some cardiac inflammation, or maybe some early cardiomyopathy that we may be able to capture with this high sensitivity troponin is important. I think generally, as you look at the posters in this session, there's really a lot of information about various risk factors that are important for us to be aware of. I'll talk elsewhere about the role of subclinical coronary calcification on CT angiogram studies, as well as carotid atherosclerosis that could be picked up on ultrasound. I think it's been incorporated more that rheumatologists should be thinking about lipid panels, and statin initiation for rheumatoid arthritis. But I think this is really indicating that we should go beyond that.

We often expect primary care to be the ones to carry this torch, but they don't recognize that all of these factors, atherosclerosis and inflammation are all higher in our patients, and they're at a higher risk that the PCPs may underappreciate. And I think that's an indication that we should be driving this conversation and we should be thinking about what further workup we may need to do or how we want to best involve preventative cardiology and at what stage for our patients. So I think there's a lot more left to learn and to work in the future. But I thought all these posters that are collected in the Sunday morning poster collection were phenomenal resources and great things to generate thoughts. This is Doctor.

Dine with RheumNow and looking forward to our final Monday session tomorrow and I'll be checking in periodically with more information.

Hello, I'm Anthony Chen. I'm consultant rheumatologist in Reading, United Kingdom, and I'm here reporting from the ACR twenty. There are interesting abstracts again today in the spec of spondyloarthritis. And I wanted to share with you some of the latest data from the study shown. Now, one of the challenges that we face globally is the delays to diagnosis in axial spondyloarthritis.

Despite our many interventions and the average delays to diagnosis, certainly across many countries can be somewhere between eight and a half to ten years for ankylosing spondylitis. And there are a lot of new initiatives worldwide, certainly in The UK, we have just launched our new drive to reduce the delays to diagnosis. And when we looked at what happens on a ground level, often see patients with undifferentiated chronic back pain and we try to distinguish whether they have mechanical back pain or inflammatory back pain. There exists quite a few criteria for inflammatory back pain, such as the Kaling Criteria, the Berlin Criteria, the ASUS Criteria. In poster thirteen oh three Weber and colleagues very nicely studied the sensitivity and specificity of the various different inflammatory back pain criteria.

What they did was from the suspect study, they looked at patients with undifferentiated back pain who are less than 45 years of age and had features of inflammatory back pain for three months or more. Now these patients had either anterior uveitis, psoriasis or inflammatory bowel disease, so they had an extra articular feature of axial spondyloarthritis, and when they had the presence of inflammatory back pain together with these extraticular manifestations. They then used the different criteria to see which had the highest specificity and sensitivity of eventually having a diagnosis made by a rheumatologist as to having a diagnosis of Axial's bar. And they found that in the psoriasis patient, they've detected forty five percent of patients, a new diagnosis of Axial SpA, sixty two percent in the uveitis group, and forty percent in the inflammatory bowel disease group. When they looked at all the different criteria, it appeared that the criteria that worked best in terms of sensitivity and specificity was the ASUS modification of the original Berlin criteria.

What is the ASAS modification or the Berlin criteria? This is when inflammatory back pain is no longer the mandatory feature of the criteria and inflammatory back pain becomes an SPA feature in the criteria, as opposed to the original Berlin criteria where IBP is the mandatory feature. When the ASOS modification is made to the Berlin criteria, the sensitivity is about 76% and specificity 77.3%. Now this works quite well compared to some of the other criteria that they used in the study. So again, I think when we try to reduce the delays to diagnosis, we perhaps should be thinking about which criteria we use, how we use it in our clinical practice and which groups of patients we would target.

Another interesting study thinking in terms of delays to diagnosis and how we can reduce that is poster number thirteen oh six, where they looked at patients who presented to the ophthalmologist with acute anterior uveitis with chronic back pain. They found that fifty three percent of these patients who had uveitis had inflammatory back pain and the HLA B27 positivity was about fifty six percent. And when they looked to these patients and they had investigations and also they were looking for excess spondyloarthritis, at the end of the study, twenty three percent of the patients who presented had definite diagnosis of excess spondyloarthritis. So twenty three percent of patients who with uveitis presenting to the ophthalmologist were eventually diagnosed by the rheumatologist as having Axial Spondyloarthritis. But interestingly, forty one percent also were not diagnosed at the time, but probably had probable axial and would then require some follow-up.

So in total, sixty four percent of the patients who presented with anterior uveitis had features of either definite or probable altogether axial spondyloarthritis and the delay from the onset of the back pain was ten years. So I think these studies today, these two posters perhaps will shape our kind of thinking about how we can reduce the delays to diagnosis. Firstly, having sensitive and specific criteria so that we are sure about who we should go on to investigate further, and maybe secondly, thinking about how we can work together with our ophthalmologists, our dermatologists and also gastroenterologists to kind of work together to ensure that these patients who present in another specialty could then be referred or screened to ensure that we can pick them up as they may have excess spondyloarthritis, first presenting with an extra articular manifestation. So hopefully we can pick some of these points up and then try to bring it back to our clinical practice to reduce the delays to diagnosis. I'm Anthony Chan, thank you very much for listening.

I hope you enjoy the conference.

Hi. David Lou from Melbourne Australia for RheumNow for ACR twenty twenty. And I wanted to tell you a little bit more about some of the Geacter data. I know we've been talking about this for the last few years, now we've got continuation data. And what we're doing is actually getting some really interesting data coming out of this about questions that we have about GCA and about tocilizumab treated patients in GCA, which is proving really useful now that tocilizumab is close to being or is standard of care in GCA if and when it's available.

So the first bit, two abstracts presented by Spasson Unazzoni at this meeting. The first one related to the nature of flares on tocilizumab. And I think there had been some concern previously that tocilizumab might be pushing down a part of the GCA response, but their interferon gamma part of their response. The bit that might be actually concerning as far as intravascular events are concerned might actually be particularly a problem. So looking at the flares from for patients on tocilizumab, are we seeing a whole bunch of patients with visual manifestations or strokes?

Well, thankfully not. Visual manifestations very rare in the JAKTA cohort as far as flares on tocilizumab are concerned. The other question, of course, is tocilizumab takes away classically takes away your CRP and ESR. Are we seeing elevations in ESR and CRP in these patients who are already being treated with tocilizumab and have flares of their giant cell arteritis, which we're detecting in other ways? Hopefully, if you take the ESI and CRP combined, three quarters of patients have a raise in their ESR and CRP during a flare of their GCA,

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least as was defined by the clinician, when they were on tocilizumab. Now, having said that, a lot of the contribution there is from the ESR. So we're talking seventy one percent of the new onset GCA and sixty percent of the relapsing GCA had the increase in ESR and CRP was much less. So thirty five percent in the new onset GCA and then forty percent in the relapsing GCA. So really, the question is, do we have anything else that can help us with trying to a biomarker that can help us to try and detect flares in GCA patients who are treated with tocilizumab.

The next bit was that they looked at a few patients using some quite nice technology really, using mass spec but with tandem mass tag technology, with a multiplexed, 11 plexed tandem mass tag. But basically to try and pick up the proteins that were getting increased in these patients with GCA relapses, comparing to the times when they weren't, labeling them, indexing them, and try and understand where all these candidate proteins might sit. So they ended up looking seeing 344 candidate proteins and then ranking them. And right at the top of the list was haptoglobin. Now that's something which we can use, which we can order right now.

And that's something that was going back to the 1980s. Sarah Mackie has pointed out to me some of the literature regarding this, that in fact there are descriptions of haptoglobin being really useful when conventional inflammatory markers ESR and CRP weren't elevated. Now, of course, we want to see this in prospective study. We want to validate this in different cohorts. But it certainly raises the prospect that there probably are biomarkers out there that can help us when patients are receiving tocilizumab.

Now, should say as well, they took a bundle. If you take the top 10 and you put them together, you get really nice test performance. You get really nice AUC on this. But really, I think looking at haptoglobin, that's something simple, and that might be something which might be at your clinic bedside soon. For more on vasculitis and on everything that's on ACR twenty twenty, head long to rheumnow.com.

Hi, ACR twenty twenty. This is Doctor. Robert Chow coming to you live from RheumNow. I'm joined today by Doctor. Monica Guma.

I'd like to first start off by letting you introduce yourself, Doctor. Guma.

Hi, hi Robert. I'm Monica Guma and I'm a rheumatologist at UCSD and doing research in rheumatoid arthritis and diet.

Great, great. Yeah. So the reason why we have you on today is I saw you had a very interesting talk on the trial of diet to impact rheumatoid arthritis and gut microbiome. So obviously a lot of questions. I'm going to start off with the most important question.

What should we be eating and what should my patients be eating? And please tell me it's more hamburgers.

Not hamburgers, I'm sure. No hamburgers in the diet. I think there are like a lot of data already and actually I'll talk about websites, even some rheumatology websites, that they also have ideas and advices for the patient. So it's true that we sometimes don't know how to answer that question. But if you Google, you go to these foundations, they already give a lot of information.

And we know what kind of diet they need to eat. There is a more classical Mediterranean kind of diet or more like a plant based diet we know. And there are some data about that. I think that the only difference now is that we can't really focus more on the mechanism. But the advice to the patients, I think it's easy to give this kind of advice and not hamburgers, not red meat.

That's for sure. The first thing hamper for meat actually is a red meat.

I can say I tried and asked when my team asked me. So, you know, I went through the study and I saw your diet, you know, the one that you tested on, was I think it's feasible. Did you find any issues with adherence, especially long term adherence?

So the trial that we will present in our presentation tomorrow, it was really like a pilot trial. So we actually wanted to see if the patients, they were more also adherent to the whole trial itself because we wanted stool samples, blood samples, that sometimes is difficult. So the test, the trial was only between two, three weeks. So it was a short trial. And we have no problems for adherence in this short term trial.

When we build the diet, we build the diet with the feedback, helping feedback from other patients. So we already put the right schedule, right instructions to help a more higher number of patients to be able to follow the diet. So I think this diet is really feasible is easy to be adherent. What I think is difficult at long term is not to take the things that are forbidden. So for our patients, was easy for them for two or three weeks to stop drinking soda or to stop eating hamburgers.

But if you want to do a long term diet, some of these things you need to be more flexible because there is no way a real patient will be able to follow so strict and so kind of like the diet. But that's okay because if you change 80% of your diet is of course much better than 0%. Even if you once in a while, you are going to do a transgression and probably you will feel that day maybe some pain or some swelling is our own decision to say, okay, but the rest of the time you are eating different and you are changing these, we don't know if microbiome or metabolites or both that helps the inflammation.

Got it, got it. Yeah,

well, since you mentioned, it was a two to three week study. As far as the results, I think I saw very interesting results. Would you comment on that? And do you think it was surprising to you or was this what you expected?

So the thing that was surprising to me was actually the fatigue. So the patients, when we saw them two or three weeks later, but we gave them the questionnaires so they could really give some feedback in between. So then at the end of the trial, after the three weeks when they came back to our clinics, we collected the questionnaires and we asked them their feedback. And one of the most important things or things that we didn't expect is that very, very, very shortly, like maybe in three, four, five days, they noticed a decrease of the fatigue and increased the energy and feeling better overall. It doesn't mean that that was specifically the joints.

I'm talking about general improvement. That was quite homogeneous. Then another thing that was also interesting is that, of course, we don't have placebo, it's very limiting how we interpret the results. But it was obvious that some patients, the improvement was really striking, like a really swelling when gone, literally gone. Okay?

And other patients that they didn't respond so well. And in the analysis, we cannot blame that to the adherence because most of them, the adherence was quite Okay. So we have to think that or to interpret that is something intrinsic, that even if changing the diet in the same way, not everybody was responding the same. So again, short term, we don't know if the patients that didn't respond, they would respond in a longer trial. Or the ones that they responded, it was only like a short term, who knows?

Maybe then at the end. So that's why we are now doing a longer trial. But that was the feedback that we were getting from the patients. Overall, very good in terms of fatigue, energy, well-being. But then when we went specifically with the joint and swollen, I mean, tender joints, swollen joints, the result was like a fiftyfifty of like a super good response or only very like a moderate or no response.

Yeah.

I still think it's very surprising to even see a fiftyfifty swollen joint count improvement in three weeks with diet change. Do you have any information on where these diet changes from someone, let's say, who was on a very bad diet or were they already quote unquote on a healthy diet and now they're on a healthier diet?

So we know that the patients that they do respond better, they were already on a healthier diet. That we know. That's why we think that maybe some patients, they need more time to respond. So patients that they already are taking, eating a lot of vegetables and they were overall having what we name, like a diet score because we had to score the diet somehow. So they were already on a better diet score, they responded better.

That's what we know. Then the adherence after all was very similar. But going back to what you said about it's surprising to respond too quick. And that again is because it's short term so that you have to be limited. You know that our patients, when sometimes they come to our clinics and you ask, how have you been doing in the last three months?

They say overall well, but they had a couple of weeks that I felt really bad. So it's true that sometimes the disease has some flares that it can be environmental and we don't know, and that they get very well controlled. So I think that some of these things that people don't realize or they do sometimes, they tell me, I had a bad week, but that week I was traveling and I was eating a lot of junk food. They actually, they realize it. They don't know the ingredients that they realize.

So I think that you can actually like having, you can potentially be taking something that you don't know, that is actually inflammatory in your diet that you don't know, and then you remove that thing and you feel better. So that thing is not the same for all the patients. That's why you have to change the diet overall. But maybe that patient is only the gluten, you know what I mean? Or maybe it's the milk.

That is the next step, try to be more personalized. But yes, I think that's the situation. That's why they do respond. Yeah.

Right. And I think the second part of your study that was very interesting, commented on the gut microbiome. I think that's a big topic again this year. And I think, also many ACRs in the past. Can you comment on what you found as far as gut microbiome, the diets, and of course, in relation with our diseases?

So we know that the microbiome, there is dysbiosis in arthritis. We don't know if that's the cause or the consequence. So that's very important. Know there is a lot of data, but we still know very little, okay? Because it's very different.

It has a consequence of being sick. And of course you will have changes and they are not related to the disease or really these are the cause. So more data about that. But in terms of a diet, it's already known that diet is not the most important factor that changes the microbiome, especially in an adult person. So an adult person has a history of tons of factors that is actually shaping the microbiome.

And the microbiome is robust. So maybe you can shift the microbiome a little bit, but it will go back to what it was before. So the microbiome overall, we don't see big changes. What we are analyzing in detail now is maybe as a specific bacteria, maybe that is the one that you are changing. So we were not detecting big changes.

There is a lot of ways to interpret the microbiome, it's called, it's kind of like a diversity, okay? How diverse is your microbiome? We didn't see much changes on that. We saw that the patients that they do respond, they have like a better, larger diversity that correlates sometimes with healthier diet, okay? But it didn't change much.

But we are now seeing if some specific microbe actually was changing and that maybe it can be causal and not consequence, we still don't know, okay? So that thing. On the other hand, we are and I'm not really an expert on microbiome. I analyze microbiome because it's a way to interpret the metabolites. That's what I'm very interested.

So circulating metabolites makes sense that they can be also pro or anti inflammatories. And that is the product between diet and microbiome. So maybe the microbiome doesn't change much, but because you're changing the diet, you are changing the final product, which is all the metabolites, the circulating metabolites. That probably 60%, percent, they depend on the diet. So those metabolites are the ones that we are analyzing in detail to see if some of them are actually correlated strongly with improving after diet.

That would be a little bit the conclusions of our trial. Again, limited for the time and the design, but that's how we are building the next trial to try to answer questions.

Great.

Well, thank you so much for your input and you're explaining for everything to us in detail. Definitely very fascinating topic. We look forward to your upcoming trials and the longer studies from RheumNow. This is Doctor. Robert Chao and Doctor.

Monica Guma. Thank you for tuning in and for full coverage. Continue to follow RheumNow and follow me on Twitter at Doctor. RBC. Thank you.

Thank you.