ACR2018 RheumNow Roundtables Save

Hi. You are listening to ACR two thousand eighteen podcast. I'm Jack Cush, executive editor of RheumNow. This is a compilation of podcasts from the ACR two thousand eighteen meeting in Chicago wherein you'll hear daily reports from the experts, the KOLs, and people making the news. Hope you enjoy the recording.

Hi. I'm Kathy Calbrace. I'm here in Chicago at ACR twenty eighteen, and I am pleased to have a few days like Elvries and Jack Cush to talk about vaccinations in patients with rheumatic diseases. Starting with this morning, there was an abstract episode I certainly can see some coverage issues getting paid for, but what do you guys think about that, Jack?

Well, I I I sort of start off with some of the issues in trial design. You know, it's a very large trial. It was done over started 2016, twenty sixteen-seventeen season, twenty seventeen-eighteen season, not this year. They had a large number of patients and the trial design was basically everybody was on methotrexate and then they had groups based on what drugs you were on and I had no problem with the groups except for the last group which was the rituximab abatacep group with or without methotrexate or a DMARD and I don't see adding those. Mean rituximab by itself makes sense, but, and they said that it was because it was before the data was known fully about Avatacep, that's why they included that that group.

That was one thing. The other thing is, you know, I understand this is all RA patients and you have really no information about how active or bad they are or whatever, but it's mainly getting used in the elderly population and that's where it seems to be pushed and they're asking for it. In the general population, I don't know that it really has applicability unless it's really gonna be that much more effective in a regular RA patient. So question is, is the data good enough or compelling enough that we should be pushing in RA patients?

I was very impressed and I think the the effect sizes were not trivial. No. These were threefold levels in mean geometric means and protective levels of antibodies. And I mean I really was moved by that data. Yeah, there's a lot of issues in trials and I but we've been talking about this for a couple years now.

I wonder what would happen. Well, actually did the trial and the results were trivial. I would change my practice based on this if I could get this.

That's the key issue because I don't think enough rheumatologists are pushing their patients. It's hard enough to get them vaccinated. We're really bad at getting them vaccinated, period. But then to push them to get the high dose, which is generally not available in the clinic in most places, it's gonna have to it's gonna be a substantial change in practice. Does the data merit it?

Think it does. It's it is very strong data. Changing practice is gonna be hard.

We'll hear if you guys know what the best difference is between high dose and traditional.

She said she said $10 for traditional, you know, versus, like, over a $100. But I I think it I I looked it up on Hippocrates. I saw 40. So basically, four to 10 times higher would probably be

a reasonable estimate. If you gotta pay out a bucket. Right.

Yeah. That's a very good point. We certainly do carry the items vaccine in our department. We run out of it very closely. They have the state's police.

It's gonna cover that

I give them credit for studying vaccines Absolutely. In a vulnerable population.

That's an important result. I think it's a we need to have a discussion amongst our amongst our colleagues about how to best vaccinate patients. This is the season, and putting information out there is really important. So I might be starting.

You know, this is a vaccine that everybody knows is highly efficacious. It's been studied in virtually the same identical fashion as live vaccine. You know that it is a preferred in the general population. We have an abundance of caution about this vaccine. I am concerned and disappointed that we know so little about Shingrix in patients with significant immune related adverse events on aggressive therapy.

So I have an abundance of caution from it. Yes, I've used it on a few patients. I've had people because of our discussions contact me over the country with anecdotes of you know, asking me whether flares of rheumatoid arthritis or lupus were related to it. I said, I don't know.

Yeah, my experience has been kind of interesting in that learning from the master and talking about this with Lenny and and there is concerns about how our immune driven populations are going to respond to this and we'll be the same response and I believe the company should have the obligation to study this. But you know the feeling is because an active vaccine therefore it should be safe as other inactive vaccines are and while this has come up a lot in my practice the amazing observation is way way way more patients are getting this without my knowledge or consent. Hi, I'm Jack Cush with RheumNow. I'm here in the RheumNow booth at ACR twenty eighteen in Chicago. Been a great meeting so far.

So far, I've convened a panel of friends to talk about what's hot in rheumatoid arthritis. I'm joined by Doctor. Jeff Sparks from Boston and Doctor. Artie Cavanaugh from San Diego and I'm Jack Cush, as you know. Gentlemen, today, we've a few things I want to go down on the list to discuss, but let's start off with what you have seen that you think is really a highlight in RA so far, or maybe something you're gonna see in the next few days.

I'll start out the data with the JAK inhibitors. Maybe not new, but really there's so much more of it now that we're seeing, of course, longer term data with tofacitinib, additional data with baricitinib, a lot of data with upicitinib, and further data with filgotinib. So I think it's exciting that we may see, are these all gonna be the same? Is there really anything to the putative in vitro differences in terms of their cell activity? I think we've adopted them in the clinic and I think that's gonna increase.

I'm going to get back to Jackson in a second. Jeff, so far?

I think the thing that stood out for me from an epidemiologic perspective for rheumatoid arthritis is looking at interstitial lung disease risk factors. In particular, the MUC5B SNP, is associated clearly with rheumatoid arthritis, it's interstitial lung disease. And the fact that this is related to interstitial pulmonary fibrosis, may may mean that these drugs that are used for IPF could be used in RA ILD and those trials are ongoing. Obviously, rheumatologists take care of patients before the ILD develops and our work and others are looking at things that happen for rheumatologists. So disease activity being the things that we did show that active disease did increase risk for interstitial lung disease within RheumNow.

So the the snip was presented today as a plenary session and that that was new and information surprising. I do want to talk about some of your posters that you had. Sort getting to drug safety and whatnot, but still safety I should say or comorbidity issues and that's the ILD story, which we know ILD and lung disease is a very bad player in rheumatoid arthritis, which I think is what has gotten you into this and you had a few presentations here, a podium presentation on disease activity and another one looking at rheumatoid factor negative versus factor positive. Can you sort of summarize those results?

Well sure, the first is the disease activity. We look very carefully to look at dynamic measures of disease activity and to see whether active disease was related to subsequent risk of incident interstitial lung disease. And we did in fact find that high and moderate disease activity were put you at a two to three fold increased risk. As rheumatologists, we really think about the risk mostly within the seropositive subset, particularly CCP positive. However, some of our work also shows that you can get interstitial lung disease, you can get bronchiectasis even within the seronegative population.

So this is something that, should be on rheumatologists' minds, as far as serostatus and, obviously treat to target might have other downstream ramifications of, decreasing, interstitial lung disease.

Yeah. The the the seronegative story is really interesting in that you've found in the population that you looked at, you know, it was like fifteen, sixteen percent in seronegative. Mhmm. But it was almost the same number in seronegative. Right.

Which I find found really surprising and changes my my thinking. Yeah. Your your finding of disease activity driving it, you know, moderate to high disease activity led to a two to three fold increased risk, I guess. But the number of patients that qualified as having ILD in your follow-up period was still quite low. So, how are going to answer the question of which of the high disease activity patients are the ones who are going to get into having ILD downstream?

Yeah. Well, clearly further work has to be done to identify other risk factors you could use in clinic. Doubtful

that

this new SNP they found, the MUC5B, is something that would be useful in clinical care, and whether there's, understanding the natural history, you know, what's going on underneath the surface before patients get symptoms, how big of a problem really is this, are things getting better because we're treating treating patients better as well? So I think there's still a lot of work that needs to be done as far as, understanding risk stratification, things we can use in clinic to really go after the people that are most likely to benefit.

So as it as it I think is one of the ways that translates environmental signals to what we see in our patients epigenomics. So though it's still in its infancy may be an important factor with with interstitial lung disease. It's hard to see how it wouldn't be. Don't I think we understand enough of it, as you said, the genetics alone aren't gonna explain it. The seropositivity and negativity aren't gonna explain it, but there's an additional thing.

Maybe it's an epigenetic factor that we can identify indicating the history of exposures.

So, Artie, you brought the issue of the JAKs here and they are sort of front and center. We've got some data about, you know, baricitinib extension studies showing good data when you continue on barrier switch from TNF inhibitor to Barrie and whatnot. We've got new TNF inhibitors that are in development, some pretty close, some pretty far. How what's the lessons that the new JAKs can take from the old JAKs in drug development and where they're gonna sort of grow this brand or or or get greater respect for JAKs in in treating RA patients?

Well, one thing is the dosing. I think across the jacking into what we see is that the companies can often find two doses that can be effective. The lower dose generally has a little bit better safety signal. And as we found out today, we had a session I moderated with the FDA, we're kind enough to come. And they pay a lot of attention to safety as we all know.

And they're very keen on that. So I think how best to how to look at the optimal dosing. I think as rheumatologists, we'd love to play around. We'd love to have many doses and tailor the therapy, but the FDA is very concerned about safety with these new molecules. So I think one of the things that I think may come is as we get additional safety data, maybe we'll see additional dosing options for each of the jackups.

You know, the the issue is are they going to affect care and will they be taken up well? It was obviously hard for the first one tofacitinib to grow the respect and comfort with rheumatologists. But, you know, we're gonna we may have one next year. I mean, it's one there after. We got upadacitinib and filgotinib and what's the other one doctor Pepcitinib.

Pepcitinib was presented at this meeting. And there are others still. Jeff, do you think that this is they're gonna become more acceptable as they get more in the marketplace or what what might be the the tipping point for rheumatologists and having comfort with JAK inhibitors?

Yeah. Well, mean, I think obviously it's really good news for both patients and providers that there's a long list of approved medications for RA. And obviously the new kid on the block is gonna be sort of at the, bottom of the line. But I feel like the, the convenience factor both from a patient is moving up the JAK class. The other thing is the longer they've been approved and no new safety signals are coming out and actually several abstracts here showing fear about DVT.

PE may not be founded in the sort of real world clinical use. And as it's being used in other diseases, I think it's only gaining traction as far as people are becoming more comfortable as far as moving this up as far as the line of succession.

The last thing I want to just bring up things that there's a few things here like find that seem to be an overwhelming recurring theme. There's a lot on biosimilars, there's a lot about weaning therapy, but the new thing that was surprising to me was this issue of seroconversion. Patients, you know, are factor positive, CCP positive, patients who become seronegative or drop their titers over time. A lot of reports here about that and the question is, are rheumatologists doing this and then what are they doing with the data? So, Artie, you look at some of this.

What what's the is there a message right now about serial converters? Does it mean anything?

I think that the bottom line message is that it doesn't mean anything to the individual patient in your clinic when you go back to clinic on Friday or next Monday. You shouldn't necessarily worry if they don't seroconvert. If they do, that's maybe a good thing, but it certainly doesn't seem to be a strong enough signal that it's worth pursuing as a target. Meaning, I'm gonna keep changing therapy until you see or convert. And, you know, you think back to rheumatologists older than us who chased rheumatoid factor for years.

And the hope was that if you decrease the titer that that would not only be a biomarker, but that would be a goal of treatment. I don't think it's that case. Certainly not an individual patient.

Yeah. Remains to be seen whether clearly not all drugs can will do this. And and the other issue is if you do see it, is there really an association there whether you have better outcome or or or no effect on outcome? How do you consider this when you're talking about factor? Do you do you recommend repeating it in patients?

Or

I think we have clear already goals of target that are already underutilized. To add CCP in the mix where it's questionable that the number needed to treat are ever going to be cost effective. Certainly it's interesting from a research perspective, but how are you going to understand when you're treating a patient whether it's noise, you repeat the same assay two times, you're going to get the same a different result. Is it really going down or is it just noise of the assay? Not ready for prime time.

Such sage advice from such a young rheumatologist. Arty, we should worry.

Yeah. No, you think the you think back of of you kind of alluded to there are probably drugs that change rheumatoid factor like Dilantin. There are people on Dilantin whose rheumatoid factor would go away of course had absolutely no clinical relevance so there may be a dissociation between that and I think Jeff hit it on the head that is it cost effective? Is it worth doing that next patient you see in the clinic? Alright,

I want to thank my friends Jeff and Arty for joining us on his RA panel. See you at the meeting. Hi, I'm Jack Cush with RheumNow. We're here in the booth at ACR twenty eighteen in Chicago. I've gathered a group of friends, experts in the field of ankylosing spondylitis and spondyloarthritis to talk about what's happening here at the meeting.

I'm joined by Doctor. Jose Cher, Doctor. John from New York, Doctor. John Rivell from Houston, Doctor. Mohamed Azim Khan from Cleveland, and Doctor.

York Ehrman from Boston to tell us their impressions of the meeting. Why don't we just sort of go down the line and talk about maybe what either what you've seen so far or what you're looking forward to because there are a bunch of spondylitis presentations this afternoon and a few tomorrow and whatnot. So Jose, is there something you're looking forward to?

I am looking forward to seeing the data on Sertolizumab in non radiographic axial SpA. Wow. That's a hot topic. It appears that the data is robust. I am looking forward to the 17 class in AS and the ICSI data.

And I'm looking forward to a few data sets that look at ways of referring spondyloarthritis earlier, particularly from the German group. And those are the hot topics that I can think of.

John, you were involved in the abstract selections. You only have about 1,700 that are on your mind.

Right. Although one of the ones that I was most excited by was a plenary session yesterday, which is a presentation from doctor Matthew Brown's group, where they looked at approximately 6,600 European derived Caucasians, as well as a similar 6,001 Chinese, approximately 800 Turks, and 600 Iranians, and to generate a panel of snips, single nucleotide polymorphisms that taken in a sort of a a when looked at together, provides very significant predictive value to make a diagnosis of axial of ankylosing spondylitis in the clinical setting. It's a it's a large panel of SNPs, and what was ironic and so the the the discovery cohort were, of course, the the 6,000 so European derived whites and the 6,001 East Asians, primarily Chinese. The replication course, of course, the Turks and the Iranians. And it was shocking to to see that this panel of single nucleotide polymorphisms, a panel that costs about $50 performed equally as well as MRI in establishing a diagnosis in an individual patient.

Obviously, applying at a population based level is a bit more problematic. But given the problems we have making a diagnosis in the clinic, when you have a clinical suspicion, this panel may potentially be of important use. And, of course, similar, movements are being done in other rheumatic diseases and probably is a good sign of where the future is going and how genetics can be applied to diagnosis.

So, Doctor. Khan, you know, it's not just B27 now. So, what's your thinking about this advance?

Well, you can tell me whether how much better it is than just typing for b twenty seven.

Significantly better, but but b twenty seven needs to be put into mix. If you look at the in individual snips, like 23 and me use, for example, the specificity is only about 53%. But but the specificity for this, is 90 one well, ninety one percent in whites, ninety five percent if you look at Asians. And you compare that and the sensitivity of course is eighty three percent. MAP actually performs much better than the current ASSIS criteria.

So in African Americans, fifty percent of the patients lag E27.

Actually forty percent. That's published a couple days ago. Have a paper in Arthritis Animal Jamax Disease.

Hard to keep up with his papers.

So over there, how can any test be helpful? The what? They don't have b twenty seven.

Well, it it obviously has not been validated. When what we found looking in African Americans, what was shocking was that HLA b twenty seven is significantly down in frequency like we saw in the Chinese and like we saw in the whites. Of course B27 is present in sixty percent just like you described in 1978. We also found similar impact of MAC class two genes such as especially with the HLA DP locus and this was seen in whites and blacks.

But let me rephrase the question. B27 test is helpful but then it doesn't help when somebody has the disease in the absence of B27. Has developed or has Matt developed some kind of genetic profile that can predict the

yes. Can you

rephrase this question again?

He wanted to know about how this applies to making a diagnosis in the B27 negative patient And the answer is it works well. Obviously if you throw in B27, you lose some specificity at that point the best specificity is seen when you include B27 in the process. But that said, you know how many false diagnosis polychloride you get in B27 positive individuals in the clinical setting.

So Jorg, what's your comment on this?

Yeah, actually have also a question because I think that there's still a lot of work that needs to be done in terms of validating prospectively. My question is how is this going to perform in patients with the wider diagnosis of axial spondyloarthritis, not the narrow diagnosis of ankylosing spondylosis?

Wow. Okay. You know there's a publication that came from the same group. This is a study that was commissioned by OSIS. They looked at the top five SNPs, ERAP1, IL-twenty three receptor, the chromosome 2P gene desert, which is seen in every ethnic group.

They looked at all those and the answer was they didn't. They looked at approximately four hundred patients and they did not perform very well. But there were a lot of reasons because there was a lot of heterogeneity between the groups that were referring patients with axial SpA, number one. Some, for example, only referred to B27 positives, others looked at other criteria for referral. Secondly, and most importantly, it was vastly underpowered.

Most of these SNPs require patient sample sizes of up to a thousand and more because we're dealing with odds ratios of 1.1, 1.2 before you really see the association. So with a panel with three fifty patients, it's not surprising that you're not going to have the power to really see this. I I I think it was a combination of heterogeneity in the axSpA group as well as power that that caused it not to perform very well. And I think to make this this the users panel, it's gonna have to be refined a bit more before we can get to the non radiographic axial spot peak.

So I want to get to Jorg, tell us what thing you're looking forward to at this meeting and same thing Doctor. Khan, just tell us what you're looking forward, what you've seen so far that excites you.

Yeah, so I think something that I would highlight is an effort that was discussed yesterday in the spondyloarthritis study section. And that is a study that's going to start next year called classic. And that's a combined effort of Spartan and ASUS. And this study the goal of this study is to validate the existing classification criteria for axial spondyloarthritis in a thousand patients worldwide. This will generate a lot of data.

If the criteria are not good enough, this will also provide a lot of data to improve them in the future and I think that's very important.

This is like the ideal use of a study group and bring coming together at the ACR. Doctor Khan, is there anything you're looking forward My

main interest is to see how we can prevent syndesmophyte formation and ultimate ankylosing. The data on insulin seventeen inhibitor, executive new map, looked pretty good. Four years, they were eighty percent of the patients did not show progression. Jose and I are interested in exactly RheumAb also. So my hope is that now that we can control inflammation pretty well, we hope to prevent Roni Fusen.

Right. And that flexibility retention will improve functional abilities of the patient. So that's the next hurdle we have to

So two things I want to end with. One is a discussion of IL-seventeen and where we are, and two, to go back to the non radiographic axial Spock. But first, IL-seventeen and where we are, we're going to have the three year extension data on the secukinumab study in AS. That's going to be presented today. And we're also going to hear about ixekizumab, another IL-seventeen inhibitor in ankylosing spondylitis, that's going to be presented today.

And an axial spot.

And an axial spot.

And axial non radiographic, yes. Right.

So where are we with this? This is all very encouraging. Is it changing the paradigm? And what's the hope for IL-seventeen inhibition going forward? Jose?

I'm not so sure it's changing the paradigm. This is what we expected based on prior data. I think what's changing is, to summarize the discussion, going as early as possible on the treatment of these conditions where we can not only predict who is going to develop but have actionable therapeutic strategies. The question is who amongst those that are currently classified as non radiographic axial SpAF are the ones that will eventually go on the OsteoProdeferative pathway.

I'm interested in the fact that prebiotics, probiotics, antibiotics don't yet have any clinical role, but what would be your protection since you are working on gut microbiome? Would there be a way to handle that aspect of trigger or control inflammation at early stage?

Well, there's a very interesting presentation today on trafficking of cells from the gut to the joint.

That's our session.

Yes. So that's going to be really exciting. Just give a preview of that.

The fundamental question of whether or not modulation of the gut microbes can prevent or delay the appearance of systemic inflammation. That's a challenging one. The field is also moving towards something called pharmaco microbiomics. Can we use our gut microbes to predict or modulate our current therapies so we can improve outcomes at the time where we can also prevent adverse events. That's fascinating and it's coming this afternoon.

But I think one thing that I think is important to point out that we've learned only recently is that the the actual microbes that are associated with disease tends to vary a great deal from center to center, from ethnic group to ethnic group. And probably it's not the issue of the bug, but the pathway that the the what is actually happening.

It is about the enzymatic capabilities of the bugs that could be exactly the same with a different name on the bug.

Different bug. Yeah.

Different bug,

same Same mechanism. Same mechanism.

So I wanna end with the story about non radiographic axial SpA accepted nomenclature by all you experts just not have to not necessarily popular in America as it is in Europe and outside of America and it failed as an indication with two companies go in front of the FDA a few years ago, but one company has taken it forward and they have a study today on non radiographic axial SpA. My question is, is America ready to actually start using the term and treating patients as such as opposed to what they've been doing which is probably what we call creative coding, calling it something else.

Well, she wants to make America great again. Right? Right.

In 1985, I described this entity, I called it Spondylitic Disease without Radiographic Evidence of Sacroiliacs. Right. So the word spondylitis is actually better than spondylitis or spondyloarthritis. Just like rheumatoid arthritis, we call it rheumatoid disease. The disease has wider spectrum, not just musculoskeletal, but extra skeletal as well.

So that particular entity is now called we call it non radiographic axial spondylosis, but it is a very wide spectrum. Maybe most of the people with non external auditory may not develop sacroiliac. Right. And just like lupus, many have a ANA positive, they may get thrombocytopenia, but they may never develop. So the whole field of non radiographic textures, there's so much heterogeneity that it is a big problem for FDA to really readily approve that indication.

But we'll see, but I think it's important about you know the studies that are done that's important. You come from Germany where obviously it's very well accepted. What's your impressions of how we consider non regressive active spa here?

My personal opinion is I think that Axiosporone Arthritis is something that's a valuable category. I'm not so sure about the category of non radiographic because this is a very difficult term that is very confusing the difference between non radiographic disease and radiographic disease is very blurry. I think that still needs some discussion whether we should use that qualifier non radiographic just say Tell

me both on it for now.

Yes, the fact of the matter is that only if you look at insurance databases, fourteen percent of people with chronic back pain in The United States ever see a rheumatologist. If you look at those with onset between the ages of 20 and 29 years, it's nine percent. So the problem here is that low back pain affects nineteen point four percent according to NHANES of The US population in the ages of 20 and 70. These people, if you look at the concept of axial spondyloarthritis, it is virtually unknown outside of the rheumatology community. And these people aren't getting to rheumatologists.

So this is probably represents one of the biggest challenges and unmet needs that we face in this country is dealing with the issue of chronic back pain, inflammatory back pain, which occurs in seven percent of the population, and axial spondyloarthritis.

The point being also that if we did this right, we'd be diagnosed with people earlier, and we, as experts, wouldn't be seeing people at the supermarket or in the airport who have spondylitis who've never been diagnosed. Jose?

The counterargument to that is the pharmacoeconomics. How many people that will never develop true inflammatory, osteoporosis, axial spondyloarthritis will see biologic therapies that are only skyrocket?

And how many of the indirect costs given the back is the leading cause of disability in The United States would we be saving by diagnosing those people earlier?

Obviously, challenges ahead. Thanks for tuning to this panel on spondylitis. I wanna thank my panel for their expert opinions. Enjoy the meeting.

Thank you. Alright.

Hi, I'm Jack Cush with RheumNow. We're here in the RheumNow booth at ACR twenty eighteen in Chicago. Exciting meeting. More exciting is I've been able to gather up the gout mavens and bring them together have a discussion about what's happening in gout here at ACR twenty eighteen. Thankfully, I'm joined by Naomi Schlesinger from New Jersey, Ken Saag from Alabama, and Nicola Dalvez from New Zealand.

And we'll start off by saying thank you and welcome. And I'd like to know from each of you what is the one thing at this meeting that you've seen or looking forward to seeing that you want to bring up so that we can maybe have a little discussion. Let's start with Naomi.

Wow, so there are too many to name. I'm going to actually start with the new treatments from the different uricases, the oral uricase, peglodecase and the new immunogenicity abstracts and the select actually posters, one that's going to be presented today showing inflammation reduction when using uricase.

Let me add to Naomi what you're saying because I think this is really an important area. For those of us particularly in academic centers we see very severe gout. See people that come in with deposits and the use of uricase has really been a salvage therapy that we look forward to having available. The major problem is immunogenicity. You can't take it forever.

People develop immunogenicity and it loses its effectiveness. So the idea about administering either co therapy with methotrexate, is the poster that I think you were referencing and other approaches, very exciting, more data is needed. But it's certainly one of the things that we look forward to I've understanding more

seen a series of posters and actually one of the really interesting things is that it seems that this preparation with rapamycin and apigylated uricase may well have anti inflammatory effects through the effects of the Rapamycin actually. So there's co administration and then inhibition of IL-one release and reduction of flares. That's really, that is very exciting,

agree. I think the

real question for me is what is the right immunomodulatory therapy to use? I'm not sure we really know and it may turn out that one size fits none. And we may need other options. We may be rapamycin, methotrexate, we're looking at mycophenolate in a small study we're doing. So we've got to understand this better and figure out for the patient depending on their comorbidities what the optimal thing to give with peglodecase and how safe is it to do that ultimately?

So for the audience, again the issue here is that peglodecase may be limited by its immunogenicity against PEG, even your case in different forms may have immunogenic response as well and how do you limit that to get the most out of the drug. The combination of uricase with rapamycin is interesting because you eliminate immunogenicity as you mentioned and also be better but then if you're using peglodecase then what's the drug that you use? Why don't we start off by talking about Jeff Peterson's abstract about methotrexate? Anybody want to give us some of that result?

Sure, basically nine patients given methotrexate as I mentioned before starting peglodecase infusions and throughout their time on peglodecase somewhere between sixteen and weeks. And this is showing that none surprisingly of these patients actually had infusion reactions or any other problems with using peglodecase. So this is actually very promising here. Methotrexate, the rheumatologists who are very comfortable using it. Right.

Fifty milligrams. For in these very severe patients with gout.

Let me add two caveats that I think are important. One is that methotrexate, appealing because rheumatologists have a lot of experience and knowledge with it, may not be optimal in our gout patients because a lot of them also unfortunately drink. And so that's a concern. Moreover, there may be some drug interactions with other things they're doing and the need to titrate up. So we don't really know for sure whether that's going to work.

This is all predicated on a series of transplant patients who have had protracted efficacy of uricase therapies in combination with their use of immunosuppressive therapies and in some cases actually have had an increase in urate levels when they stop their drugs transiently such as

using Imurane, azathioprine. So that's my next question. This experiment is with nine patients, pretty interesting and it all responses, no untoward effects, but as you say, that may not be the right drug. What are the other options? You have a trial that's going be starting.

What are the other options that are out there?

We're looking at Mycophenolate in part because there's less interaction with other drugs. One of the concerns is that if you're treating people with gout, sometimes there's other doctors involved and they may for example decide to start Allopurinol even and in it's conceivable that if you were to say use Imuran there might be a problem with drug drug interactions there. So that was one of the reasons when we polled doctors that they were enthusiastic about Mycophenolate but it's not to say that it's the only reasonable therapeutic option. I think Rapamycin is interesting, I think Methotrexate is interesting, and obviously Azathioprine is the other one that has gained some traction here.

So I'd like to pause back a bit and talk about what I found interesting, which is really kind of not this group of people, small group of people with very severe disease, but actually the bigger gout population. And for me, of the really interesting data has been that's been presented by in this meeting is a is a abstract from Poojikana who in the oral concurrent session presented this a a very large survey of people with gout and asked them about, you know, in the community ask them about actually the number of flares that they had reported to their doctor versus the number of flares that they had actually experienced over that period. And what was really striking to me was that the number of patients that were or the number of flares that patients were experiencing was in the order of, what, six per year, something like that, and reporting, you know, two or fewer. And so I think this really speaks to the sort of broader issue around gout management where we see and we see again, seeing lots of posters today of, you know, very and we've seen this for the last decade, maybe even longer, probably longer, is, you know, these these are these reports of very low use of allopurinol, this kind of, you know, this philosophical issue with different groups of medical professionals saying actually, you know, who should be getting allopurinol?

You know, the patients that are treated by the rheumatologists are different to the patients treated in primary care. And actually, I think we're releasing some data to say actually we're substantially underestimating the flare burden and burden of disease if we're only looking at what the patient tells us in our office.

It underscores the under management of gout. Have a Twitter poll out right now that says, what is your max dose on Allopurinol? It's overwhelmingly 800mg. Who uses 800mg? Even rheumatology and it's shocking.

There are two reports, one just in Lancet about a nurse run gout clinic and one here about pharmacist run gout clinics. Do you think of that?

Well actually my colleague Jeff Curtis and a collaborator Ted Michaels were involved with the pharmacist led approach within the Kaiser system. I think this is the strategy we've got to move towards. We've got to figure out how to unburden the busy clinician and to bring in arthritis health professionals that can help be it nurses, pharmacists, health system approaches to improve quality in this area. I want to come back to the flare thing because I think it's really interesting. You've talked about the clinical ramifications.

The other problem with flares is in our clinical trials. We're not doing a good job of capturing We've got to come up with better ways to be able to assess disease activity in an episode is that occurring mostly at home and is subject to a lot of recall. That's probably a big part of the problem with detecting this in studies of new therapeutics. Got a lot of noise in the There's got to be new approaches.

I'd like to add another that here we

see inflammation being common, inflammation being a major problem in gout patients,

inflammation contributing to cardiovascular disease kidney disease, and yet we're not treating it because we don't know about it. And I think this is where education is important, both for patients and for physicians. We need to treat that better.

Absolutely. And so there's a report here and it's kind of out there right now in the literature and at the regulatory agencies about Xanthine oxidase inhibitors and cardiovascular events. There's a report here about Allopurinol versus Fabixisstat and we're seeing more with Fabixisstat. Where is this going in

your Yeah, well I can comment on that. I was part of that study and regrettably I think that the bottom line is it raises more questions than it provides answers. There was a very high dropout rate. The primary endpoint, which was non inferiority of a combined cardiovascular safety signal, non inferior, yet we saw this increase in all cause mortality and cardiovascular mortality. We're just frankly not quite sure what to make of it.

There's another study that's being done in Europe that will read out and that will be very important. There's a recent one done presented at a European cardiology meeting this year called the Fried study, where in patients with hyperuricemia but not with gout, febuxostat actually looked cardioprotective. So I don't know that we really know. In an active comparator study where you're looking at two xanthine oxidase inhibitors, it just makes it very difficult to disentangle whether we're actually seeing a safety signal or we're just seeing a difference possibly due to chance or possibly due to one drug being a little more protective than the other.

Yeah, agree, but I also think actually we can take some things out of it. Actually, there's

been this huge fear about allopurinol dosing.

If you look at the protocol in the Cares trial, people with CKD had allopurinol dose escalation up to four hundred.

Those who had normal kidney function, allopurinol up to

600. And at least as good outcomes as with fevoxacet. So I think this is actually reassuring at least that dose escalation of allopurinol is safe and effective. That's really what

we should do.

And that's really been a great contribution of you and Lisa to the field of showing us that the old handy criteria really are not very evidence based and that we probably, if we start low and go slow, we can get away with a better dose of our xanthine oxidase inhibitors, even with CKD.

One of the points in the study there is no placebo arm could be that actually allopurin is protective and fungicide is not so bad. Had you had the placebo arm, you may

have done some the free

exercise. So I think the word is not out yet. I think this is not the final end for febuxostat. I think we still need to see further studies comparing

Well, it's still around in full flair. Yes. I wanna thank the panel for an interesting discussion.

Well, thanks for your

interest in

gout. We're glad

we got some party here in AR this year. Eight point three million people in United States.

We got a bit more

attention to it.

And many more over the world. Yes.

Alright. It's growing, unfortunately. Yeah.

As we are growing. Yes.

Alright. Thank you. Alright. Bye. Thank you.

Hi. I'm Jack Cush with RheumNow. We're here in the RheumNow booth at ACR two thousand eighteen in Chicago. Exciting meeting. More exciting is I've been able to gather up the Gout Mavens and bring them together to have a discussion about what's happening in Gout here at ACR twenty eighteen.

Thankfully, I'm joined by Naomi Schlesinger from New Jersey, Ken Sag from Alabama, and Nicola Dalvath from New Zealand. And we'll start off by saying thank you and welcome. And I'd like to know from each of you what is the one thing at this that you've seen or looking forward to seeing that you want to bring up so that we can maybe have a little discussion. Let's start with Naomi.

Wow, so there are too many to name. I'm going to actually start with the new treatments from the different uricases, the oral uricase, peglodecase and the new immunogenicity abstracts and the selectin actually posters that one that's going be presented today showing inflammation reduction when using uricase.

Add to Naomi what you're saying because I think this is really an important area. For those of us particularly in academic centers we see very severe gout. See people that come in with topaceous deposits and the use of uricase has really been a salvage therapy that we look forward to available. The major problem is immunogenicity. You can't take it forever.

People develop immunogenicity and it loses its effectiveness. Idea about administering either co therapy with methotrexate which is the poster that I think you were referencing and other approaches, very exciting, more data is needed. It's certainly one of the things that we look forward to understanding I've more

seen a series of posters and actually one of the really interesting things is that seems that this preparation with rapamycin and a pegylated uricase may well have anti inflammatory effects through the effects of the rapamycin actually. So there's co administration and then addition of IL-one release and reduction of flares. That's really, that is very exciting,

I I

think the real question for me is what is the right immunomodulatory therapy to use? I'm not sure we really know and it may turn out that one size fits none. We may need other options. We may be rapamycin, methotrexate, we're looking at mycophenolate in a small study we're doing. We've got to understand this better and figure out for the patient depending on their co morbidities what's the optimal thing to give with peglodecase and how safe is it to do that ultimately?

So for the audience, again the issue here is that peglodecase may be limited by its immunogenicity against PEG, even your case in different forms may have immunogenic responses as well and how do you limit that to get the most out of the drug. The combination of uricase with rapamycin is interesting because you eliminate immunogenicity as you mentioned and also be better but then if you're using peglodecase then what's the drug that you use? Why don't we start off by talking about Jeff Peterson's abstract about methotrexate? Anybody want to give some of that result?

Sure, basically nine patients given methotrexate that I mentioned before starting peglodecase infusions and throughout their time on peglodecase somewhere between six to nine weeks. And this is showing that none surprisingly of these patients actually had infusion reactions or any other problems with using peglodecase. This is actually very promising here. Methotrexate, the rheumatologists who are very comfortable using.

Right. Fifty milligrams per

For in these very severe Let patients with

me add two caveats that I think are important. One is that methotrexate, appealing because rheumatologists have a lot of experience and knowledge with it, may not be optimal in our gout patients because a lot of them also unfortunately drink. So that's a concern. Moreover, there may be some potential for drug interactions with other things they're doing and the need to titrate up. So we don't really know for sure whether that's going to work.

This is all predicated on a series of transplant patients who have had protracted efficacy of uricase therapies in combination with their use of immunosuppressive therapies and in some cases actually have had an increase in urate levels when they stop their drugs transiently such as using Imuran, azathioprine.

So that's my next question. This experiment is with nine patients, pretty interesting and it all responses, no untoward effects, but as you say, it may not be the right drug. What are the other options? You have a trial that's going to be starting. What are the other options that are out there?

Well, we're looking at mycophenolate in part because there's less interaction with other drugs. One of the concerns is that if you're treating people with gout, sometimes there's other doctors involved and they may, for example, decide to start Allopurinol even in a patient on peglodecase. It's conceivable that if you were to use Imuran there might be a problem with drug drug interactions there. That was one of the reasons when we polled doctors that they were enthusiastic about Mycophenolate but it's not to say that it's the only therapeutic option. I think Raphamycin is interesting, think Methotrexate is interesting, and obviously Azathioprine is the other one that has gained some traction here.

So I'd like to pull us back a bit and talk about what I found interesting, which is really not this group of people, small group of people with very severe disease, but actually the bigger gout population. For me, some of the really interesting data has been presented in this meeting is an abstract from Poojikana, who in the oral concurrent session presented as a a very large survey of people with gout and asked them about, you know, in the community, them about actually the number of flares that they had reported to their doctor versus the number of flares that they had actually experienced over that period. And what was really striking to me was that the number of patients that were or the number of flares that patients were experiencing was in the order of, what, six per year, something like that, and reporting, you know, two or fewer. And so I think this really speaks to the sort of broader issue around gout management where we see, and we see, again, seeing lots of posters today of, you know, very and we've seen this for the last decade, maybe even longer, probably longer, is, you know, these these are these reports of very low use of allopurinol, this kind of, you know, this philosophical issue with different groups of medical professionals saying actually, you know, who should be getting allopurinol, know, the patients that are treated by the rheumatologists are different to the patients treated in primary care.

And actually, think we're releasing some data to say actually we're substantially underestimating the flare burden and burden of disease if we're only looking at what the patient tells us in

our office. Underscores the under management of gout. Have a Twitter poll out right now that says, what is your max dose on allopurinol? It's overwhelmingly eight hundred milligrams. Who uses eight Even 100 rheumatology.

And it's shocking. There are two reports, one just in Lancet about a nurse run gout clinic and one here about run What gout do you think of that?

Well actually my colleague Jeff Curtis and a collaborator Ted Michaels were involved with the pharmacist led approach within the Kaiser system. I think this is a strategy we've got to move towards. We've to figure out how to unburden the busy clinician and to bring in arthritis health professionals that can help be it nurses, pharmacists, health system approaches to improve quality in this area. I want to come back to the flare thing because I think it's really interesting. You've talked about the clinical ramifications.

The problem with flares is in our clinical trials. We're not doing a good job of capturing We've got to come up with better ways to be able to assess disease activity in an episode that is occurring mostly at home and is subject to a lot of recall. That's probably a big part of the problem with detecting this in studies of new therapeutics. Got a lot of noise in the There's got to be new approaches.

I'd like to add another point

that here we see inflammation being common, being a major problem

in gout patients, inflammation contributing to cardiovascular disease and kidney disease and yet we're not treating it because we don't know about it. And I think this is where education is important both for patients and for physicians. We need to treat that better.

Absolutely. And so there's a report here and it's kind of out there right now in the literature and at the regulatory agencies about Xanthine oxidase inhibitors and cardiovascular events. And there's a report here about Allopurinol versus Fabulcastat and we're seeing more with Fabulcastat. Where is this going in your Yeah,

well I can comment on that. Was part of that study and Regrettably, I think the bottom line is it raises more questions than it provides answers. There was a very high dropout rate. The primary endpoint, which was non inferiority of a combined cardiovascular safety signal, was non inferior, yet we saw this increase in all cause mortality and cardiovascular mortality. And we're just frankly not quite sure what to make of it.

There's another study that's being done in Europe that will read out and that will be very important. There's a recent one done presented at a European Cardiology meeting this year called the FREED study where in patients with hyperuricemia but not with gout, febuxostat actually looked cardio protective. So I don't know that we really know. In an active comparator study where you're looking at two xanthine oxidase inhibitors, it just makes it very difficult to disentangle whether we're actually seeing a safety signal or we're just seeing a difference possibly due to chance or possibly due to one drug being a little more protective than the other.

Yeah, I agree, but I also think actually we can take some things out of it and actually there's

been this huge fear about allopurinol dosing and if

you look at the protocol in the Cares trial, people with CKD had allopurinol dose escalation up

to 400. Those who had normal kidney function, allopurinol

up to 600, and at least as good outcomes as with leboxistat. So I think this is actually reassuring at least that dose escalation of allopurinol is safe and effective. And that's really what

we should And that's really been a great contribution of you and Lisa to the field of showing us that we the old handy criteria really are not very evidence based and that we probably if we go start low and go slow we can get away with a better dose of our xanthine oxidase inhibitors even with CKD.

One of the points in the study that there's no placebo arm could be that actually allopurin is protective and is not so bad. Had you had the placebo? The placebo arm, we

may And I think that's for the free

to in Igs, actually. So so I think the word is not is not out yet. I think this is not the final end for febuxostat. I think we still need to see further studies comparing

Well, it's still around in fila flare. I wanna thank the panel for an interesting discussion.

Well, thanks for your

interest in gout. We're glad

we got

some Yes. Party here in ACR this year. Eight point three million to it.

And many more over the world. Yes.

Alright. It's growing, unfortunately. Yeah.

As we are growing. Yes.

Alright. Thank you. Hi, I'm Jack Cush with RheumNow. We're here at the RheumNow booth in ACR twenty eighteen in Chicago. Great meeting so far.

We're going to have a panel discussion, a group discussion about what's new and exciting in psoriatic arthritis here at the meeting. I'm very fortunate to have with me my friends Eric Ritteman from Chicago, Doctor. Philip Meese from Seattle. Gentlemen, what's been the highlight for you? Philip, why don't you start with one highlight from this meeting you'd like to talk about?

Well, one was obviously the data on filgotinib and psoriatic arthritis that was a plenary lecture. The data showed that this very selective JAK1 inhibitor had good efficacy across all domains of psoriatic arthritis. Modest in skin, but very good in the musculoskeletal elements. And then in terms of the selectivity the molecule, what it's aiming for is not to have a JAK-two effect on hematologic parameters. And indeed, the hemoglobin went up.

There were no grade two, three, or four changes. So that suggests that there was something about the biology that was true to form. So this drug is now going on into phase three, and it will be hopefully another JAK and oral agent taken once a day that can be effective for psoriatic arthritis.

So what did you think of again, is an early trial.

It's a

100 and thirty patients. It's their first phase two. The results were great. Eighty versus 33 in ACR twenties. That really is the safety profile was either understated or just really it is that safe.

So they had very few SAEs, very few, you know, events.

I I think it's too early to say. Just too few patients, short period of time. My guess is that on many of the Jack side effects, it's going to show up further exhaust or cholesterol, just some LFTs. But on that team stuff, think that was very interesting and very cool.

Eric, what was the highlight for you at this meeting?

You know, I think what honestly upfront on the big highlights is the number of control trials that we're seeing in the psoriatic early space. And And one of them was a trial of a molecule called bemikizumab. We know we've had IL-seventeen inhibitors, but IL-seventeen inhibitors is a broad category. The two drugs that we've had to date, secukinumab and acecizumab, inhibit IL-17A, a specific monomer of IL-17A. Then mekizumab is an interesting molecule that inhibits both IL-17A and IL-17F, which may potentially bring added benefit.

In preclinical data, particularly for skin, there's suggestion if you block both, you actually get a greater response than just blocking IL-17A. And we previously had it, we saw a trial actually in psoriasis. It was an early trial that maybe showed that, it wasn't clear. So here we had a phase two trial in psoriatic arthritis and the key question was, do you get more mileage out of blocking both IL-17A and IL-17F? And the answer was not really yes.

It looked kind of like the other IL-seventeen inhibitors. It was a phase two study. Was from a limited number of patients, but broadly there was not a sense that there was this huge uptake in response relative to what we're used to seeing in IL-17A inhibitors in psoriatic arthritis. Safety didn't seem different. Again, it's phase two and like Phil said in the Filgotinib study, you don't want to make too many safety calls at a phase two level with smaller patients.

But it didn't look like blocking both molecules added a safety concern. I'm just not sure it added a efficacy benefit. We'll see as they go into later stage products.

So do you think this says anything about the importance of blocking IL-17F? I mean, most go after a. Isn't that correct? Yes. And the question is, is f important in this equation?

So based on I'll I'll echo what Eric said. Based on some translational studies looking at heat maps of inhibition and expression of inflammatory molecules, it looked like there is some benefit to f addition to a. The proof is gonna be in the pudding in

the phase three proof.

So I I I think it I I would completely echo Eric's comment. So you you asked me to comment on the the thing that I one item, but I have to say that there was another trial that really was a fundamentally important trial, you know, for all of us as rheumatologists to take care of psoriatic arthritis patients, and that was the SEEN trial.

SEEN. Absolutely.

So this was a trial in which we took patients very early in disease, median duration of disease, six months. And they were virgin to methotrexate, and we put them on either methotrexate alone, etanercept alone, or on the combination of the two.

Modeled after the TEMPO study in rheumatoid arthritis. Exactly.

So what did we learn from TEMPO? We learned that methotrexate was similar to monotherapy etanercept and that the combination of the two was clearly superior in all of the arthritis domains and X rays and so forth. And so what did we learn from the SEEM trial? As it turns out, methotrexate did very well. There was a good a set of ACR responses.

It worked in penthesitis and bactulitis, which we had not previously known. It had decent skin scores. The one area that had sort of fell down was that there were some progressors in the X-ray arena. So there was some structural damage progression that

Only only on methotrexate?

Only on methotrexate.

There wasn't a lot of people,

though. No. It wasn't a of Very very small number of people, but at least there was a trace of a signal. Etanercept did better than methotrexate, but not by a whole lot. But it was clearly superior.

And when you wove in the issue of side effects, which were nausea, etcetera, with methotrexate, I think patients, if they had a choice, would prefer being on a Tanner cell monitor. But the real difference from the TEMPO trial was by taking a Tannercept and methotrexate together, it really didn't have benefit over what we

saw with either high broad monitor.

So in relatively early RA, adding methotrexate to a standard of at standard of didn't mean much. But because it was relatively early, you probably maxed out your methotrexate response. You probably had really good methotrexate responses, which is, again why you don't have big separation between all these arms that itanercept was better and the combination was better than methotrexate. But, Eric, what's your impression of the trial?

No, think we very much saw all of that. I mean, I think, you know, the intriguing part was that it was different than what we've seen in RM, the second, adding the methotrexate to the biologic. The challenge is how do you then translate this into clinical practice, right? So the two questions that come up is, so does this trial say we shouldn't be using methotrexate or because methotrexate worked really well? Maybe that's absent the tolerability issues, this trial actually more than anything we've seen to date said methotrexate is a really effective drug, so then it's a glass half full, half empty.

Should we be using more methotrexate based on this? Yes, TannerCept was better, but it's way more expensive. The other issue was it was clear that adding methotrexate to etanerCept didn't make any difference. Is that just an etanercept thing or is that a TNF issue? And we can't tell if that's the next question of this because in RA across all the TNF molecules, adding methotrexate gives you better response and psoriatic arthritis doesn't with the tantacet, I don't know unfortunately about the other molecules.

So let's wrap up with a little commentary from two of you about this tick inhibitor. I mean, that's sort of novel and not seen by our community yet. Who wants to take a stab at that? I'll I'll

start by just commenting that so this is a drug that has an interesting mechanism of action. It very selectively binds to a portion of the TIC molecule that is, quote, not conserved. So it is not promiscuous across JAK domains. It's very specific for TYK2. And and so what they're going for, is specific inhibition of interleukin 23, which signals, through TYK2, and it showed very they they showed data from a psoriasis trial in which there were PASI seventy five responses in the high sixty percent range.

So not dissimilar from what we've seen with the monoclonal TNF inhibitors. Correct. I think pretty good. Not necessarily as high as the IL seventeen or IL twenty three inhibitors Right. But still very good.

And the safety profile was pretty darn good. Interestingly, at higher doses a little bit of acne was noticed. But they did a novel thing. They asked patients at the beginning of the trial, do you have musculoskeletal pain symptoms? And then they measured pain versus response in those patients.

There were about thirty percent of patients that had pain at baseline, so that could have been at least largely a psoriatic arthritis population. They didn't specifically ask about PSA, and they found a very significant drop in pain. So it gave them a little bit of a signal about, the possibility of of testing it in PSA. And and as I understand it, they are going forward with the trial on its way out of

the place.

Exciting. Eric, what did do there? It

is interesting.

I think

it was more interesting in concept than what we actually showed. I actually was a little disappointed. So we spent a lot of time talking about over the last few years the various JAK isoforms JAK1, JAK2, JAK3, and TIC2 is sort of the fourth in that group. And we've seen pretty clearly all the data we've had that inhibiting the different JAKs gives you fairly similar clinical response. We've talked a lot about it.

It doesn't seem much different. This is the first data we've seen with inhibiting the fourth member of that family.

So I

thought that was really as Phil pointed out, the hook for this ideally would be IL-twenty three, which we know is an incredibly important molecule in skin psoriasis particularly, signals through TYK2 and not through any of the other members of the family so that maybe you can isolate the IL-twenty But the

trial didn't really show that and

I think that's a really key point is that when you looked at the skin, this is a skin trial, it's a psoriasis trial,

when you

look at the skin results, it didn't look like an IL-twenty three inhibitor.

Looked more like a TNF inhibitor,

as Philips said, maybe in IL-seventeen. So, you know, the promise of this would be an oral drug that works like an IL-twenty three inhibitor, which we've seen is really sort of pinnacle of what we've got in treating psoriasis. We don't know yet psoriatic arthritis where they're gonna go. I don't think it answered that promise.

But it's still a new molecule and it's exciting It's to too expensive. Right

to And it's very cool and I

want to see more with

it. Absolutely. Gentlemen, thank you very much for your very instructive comments. I think it's really educational.

Thank you.

Yes. Bye.

Hi, I'm Salome Anbana. I'm a practicing clinical rheumatologist from New York and we're here at ACR eighteen in Chicago. I just finished giving my talk on technology tools for rheumatologists. This was version four of the talk. So what I thought we could do is discuss some of those tools which we have here, and I have some of my colleagues with me to help in that discussion.

So part of the inception of this talk was a need for us to involve personal technology that advances very quickly into our rheumatology practice where technology is a little bit slower to adapt. And how can we take things which traditionally are very expensive to take into a rheumatology practice in ways that are much more cost effective, but still give us the results that we need. So a lot of these things are add ons to smartphones or tablets, electronics that you can use within a rheumatology practice. So, one of the things that, we have been using, are devices that we clip on. So one example is, this particular device, is called a thermal imaging camera.

This is from a company called FLIR, which makes thermal imaging, and it allows us to look at heat maps of patients' skin and joints for purposes of inflammatory arthritis or vasculopathy. And in terms of using it, it's pretty simple. You just have to activate the little attached device here and it gives you a thermal imaging scan of that area though. Know John, we were speaking about thermal imaging. Do you think you could have a use for use

of this in your office?

So, definitely. I mean, I'm interested in two of the applications that you mentioned. The first one is to see whether joints are inflamed. As you know sometimes one of the challenges that we have in clinical practice is that sometimes for patients either because of their body habitus or other issues it's sometimes challenging to tell whether a joint is actually swollen or not or if there is synovitis or not. I know that musculoskeletal ultrasound can play a role in trying to distinguish those two cases, but this seems like a much more simple way of sort of seeing whether joints are inflamed or not.

Yeah, there's a low barrier of entry for use of a thermal imaging camera as opposed to an ultrasound where it's high cost, there's a lot of training involved in it too. I think the downside is that, at least right now for these consumer grade devices, thermal imaging is probably not great for very small joints just because of the resolution you need. But I think for a medium to large joint, it's something you can be fairly confident that you can look for inflammatory joint and have pretty good reliability compared to an ultrasound.

Great. I think the other application that you mentioned is for patients that have vasculopathy such as Raynaud's phenomenon. Do you think that you would use it to diagnose patients or to monitor treatment?

You can probably use it for both. Raynaud's is more of a clinical diagnosis if you're having biotriphasic color changes. But in terms of the severity of it and then monitoring progress, think that's where thermal imaging comes in. So ideally capturing images prior to interventions, whether it's pharmaceutical or non pharmaceutical, the patient comes back now on an intervention and can you reliably track them over time by using a image capture equipment that you could then import the image into a chart. Yeah.

And now we can always go back and look. It's like, well, let's look at their thermal scan from three months ago when it was winter versus now it's spring. Is it any different, though? So it it may have applications for that too.

Yeah. I'm I mean, I'd love is it how much does it cost? Is it something that, you know, many of us can purchase and on our own?

Yeah. You probably could. It's not extremely cheap, but the device has two different models. There's a standard model, which is $2.99, $2.99 US dollars. And there's a more advanced model, a better resolution for $399.

But if you look at an industrial grade thermal imaging camera, it could be anywhere from $2,000 up to $10,000 So you have look at it in relative means.

I imagine at least using it clinically, just trying it on a few patients, maybe patients that you're going to send for that ultrasound anyways because you're unsure what's going on, maybe sort of seeing whether the images that you get in your clinic would match whatever they find in ultrasound. I think that would be an interesting, at least a test case, where I think I would definitely use cameras such as this.

That's what I've been trying to do now that I have incorporated ultrasound into our practice, is try to see if there's some ability to correlate thermal imaging with ultrasound. In some cases there is, some cases there isn't. Paul, you've seen some vasculitis patients also, large vessel vasculitis. Do you think you could use thermal imaging for prognostic monitoring of large vessel vasculitis?

Right. You had described a case of Takayasu's disease affecting someone's hand in your presentation, showing, you know, improvement in the temperature of their their extremity with with treatment, that would be a great thing to monitor some of these patients. Patients can have damage, mononeuritis multiplex or similar problems that might be neuropathic type pain. And if they come back to you having problems with pain and your exam is a little bit equivocal, something like this could totally make the difference in defining their therapy.

Yeah. So I think it's a matter of using it, trying it. The the challenges are right now, it's not reimbursed by insurances. Mhmm. So that this is really something you would use on your own ability.

But, you know, if it takes more time to do a thermal imaging and then assessment, you can bill on time if you need to. But hopefully with alternative payment models, these extra technologies can get wrapped up into that as well. Moving along, have some other devices that we use. This device here is called an Aloclip. Aloclip company that makes lenses that you attach onto a smartphone or in this case an iPod Touch.

And what it allows you to do is enhance the camera to allow better digital photography. This particular camera lens is called a macro lens where it gives you 21 times magnification and it can have applications within rheumatology, particularly for nail fold capillaroscopy. So if you're evaluating for somebody with Raynaud's disease and they have symptoms of systemic conditions, you may be able to use this. So Paul, you were playing with this for a little bit. Do think this is something you'd probably use or what kind of aspects would you use this for?

Right. So this is extremely useful, put right up to someone's neofold capillaries. I can snap a picture, take a

look at it, show it

to the patient, and if they have nail fold dilations or drop out of their capillaries, that really suggests to me that there is a secondary process such as scleroderma, myositis,

so I

have to worry a lot more about that patient. Whereas if it's relatively normal, I can probably be more reassured that this person just has a primary type of Raynaud's, they're not going to be at risk for other organ dysfunction, and we can treat them and ease their worries. Is a great device, and I think you said it's How much does this cost?

I think it retails for about $60 to $70 If you compare that to derm light imaging system, that's over a thousand dollars. You can get as good resolution, probably more because you're using your digital zoom as well too.

I think one of the things that I think this two things that this does not have so I have one of the the cheap dermatoscopes. I think that my dermatoscope has a polarizing lens that sort of allows for to prevent some of the bounce of the of the light that goes in there, so it the images look a little bit better. And then the the other thing is the light. So, you know, you mentioned that this device blocks the your flash.

Yes.

And it blocks the light. And the only way that you get light in is through the sides.

Through the cone.

So the derm light is nice because the light is directly from around the lens. Have you had any issues with lighting?

Far not, granted within my examination rooms it's pretty bright fluorescent lighting that's in there and the walls are all painted white in our exam rooms. There's been enough ambient light to do that, but I can imagine if you're maybe on an inpatient setting where it's like kind of a darker room and you don't have necessarily an external light source, you know, this may be an issue. You can't really look at what you need to. And the separate issue is immersion oil. I haven't really tried using this with immersion oil to see if you get the same resolution, which you can do by using a germline.

But granted, the price difference is in order of magnitude different.

That's great.

I mean, if you have unlimited funds, can get whatever you want. But, know, like I said, we're rheumatologists. We have to be mindful about cost and quality.

Right. And and the newer iPhones, such as the iPhone XS, has such really, really good, you know, pickup For low light. Yeah. For light low light aperture. So

That's a good point.

Might not even be an issue. Yeah.

Yeah. Because their their image sensor is much more robust than it used to be. That that's a good point, though. Just got moving on to imaging as well. This is hard to appreciate, but this is what's called the Gosky universal microscope lens attachment.

So this is meant for using on a microscope to capture still images or video. The way it works is this part of the device you put on the microscope objective, and this is where your smartphone kind of fits into. So for example, if this is your smartphone, it would basically clip in this way, and you would point your camera right over the microscope objective, and it all locks into place pretty solidly. You can use that to capture synovial microscopy or if you are doing some dermatology biopsies, want to look at the light microscopy, you can do that and you don't need a very cumbersome setup. Typically image capture equipment can be over thousand dollars or more, and you can get it all from about a $30 device.

Yeah. So not too bad.

I think this is great. I mean, two weeks ago, I was with my fellows. We were trying to look for crystals, under the microscope, and one of the fellows had issues in, using the microscope to focus. And even though, one of the other fellows was able to see the images, she was not able to see them. So having some a device like this that all three of us could sort of appreciate at the same time would have been very, very valuable in that setting.

Sure. I think we're all old enough to remember the teaching microscopes that had multiple objectives though. So that's the way we used to do it, to share images. I think we

still do that.

We still do it, right? Yeah. Do you do any microscopy often on your own?

We do a little bit in our clinic, but for those of us that might not do it as much, you said we can get on FaceTime or text someone an image and get a second or third opinion with this.

That's true. Easier to collaborate.

That's a great point. So let's say John, you have a microscopy you're looking at, you're not 100% sure, you can take a still image, you can launch Skype or FaceTime, you can call a call if you want, be like, hey, could you take a look at this for me? It's all being done through the power of your phone with this very simple device. So it's pretty neat and not too expensive, easily obtainable. Also, while we're on kind of smartphone and tablet devices, we were looking at kind of a range of applications from a company called three d for Medical, which is based in Ireland.

And three d for Medical is featured in one of Apple's keynotes, I think a couple of years ago for one of their new iPads, and since then has been using universities and teaching sessions and they have a different suite of apps and they have literally 20 or 30 different applications. I just picked out a few of them that rheumatologists can use. So we were looking at one of the hand applications here. So you can manipulate a three d model of a hand here, you can do cross sections and look at it all in real time rendering, you can look at pre canned videos of different pathologies that are going on, procedures also too. And this is great for education, for trainees also.

Think Paul, you work with trainees as well, right? Yeah. Do you think this is something they would probably like or help them through their training?

What I'm actually seeing is a lot of them will purchase this to correlate the anatomy that they're seeing on ultrasound and being able to peel away layers of a joint or some atypical position and just get a better understanding of it. I don't know if any of us are strongly ultrasound trained, you're kind of learning it.

Getting there, yeah.

Are you using this to help?

I am using it to augment ultrasound, trying to extrapolate a two dimensional image to three-dimensional. So this does help for that though. John, you treat pediatric and adult patients also too. Do you find that when you're explaining things to the parents about how an illness or anatomy works that these visual apps can help with

that capacity?

I think, yeah. I mean, parents, especially parents of children with chronic diseases, are always very concerned about the illness and really want to get to the bottom of trying to understand what's going on. So this would be very helpful to sort of explain to them exactly, like, you know, about speaking with a parent of a child with JIA, know, sort of having them understand what JIA is all about and how we use medicines to affect the inflammatory pathways. I think this would be very helpful.

I was thinking also when we do arthrocentesis for adult patients, it's a very quick consent, it's done point of care in the exam room, you have more challenges from a pediatric point of view. You have to book studies, there's sedation involved, there's more involved consent. So when you're consenting for a knee arthrocentesis with sedation, how much AV material are you using with parents?

Currently, none at all, but I can imagine this can be helpful.

They have applications here for the knee where you can render the knee in real time and you can kind of strip down layers of the knee and get down to different parts of the anatomy and see the places that you may need to give an arthrocentesis or an injection. Yeah,

and I wonder, Sulaiman, if you have any tools here today that may help patients during procedures.

Yeah, so that's a great point. So we've been having a few talks in the past couple of years, last year and this year, on use of virtual reality in management of pain, anxiety relief, pre procedural management. There's different ways to incorporate virtual reality in there. Some of the devices can be very expensive because they're medical grade, thousands of dollar per year, and they can be very helpful. There's some ways to be able to do it a little bit cheaper.

So what we found here was a very generic kind of virtual reality headset, literally just bought off Amazon, And it's about maybe $30 $35 and it's essentially a shell, where within that shell you have a smartphone that clips in here that has an attachment for the headphone jack or for a data port to get audio. And it has a stereoscopic lens, and so the smartphone basically fits right within here, and the application you're using has a split screen stereoscopic view that then the user would look inside the goggles and have audio that comes in through the headset. And there's dozens of applications that can be used for VR. Some of them are used for what's called mindfulness based stress reduction. So basically taking a user to a virtual environment, either that's three d rendered or maybe captured from a real environment so that they're away from their stressful situation.

So whether it's in an operating room, a procedure, or maybe they have chronic anxiety, chronic pain, there's a neurobiologic effect that can happen with that. Know Paul, we've talked about chronic pain that come in. Do you see a lot of patients on chronic opioids or narcotics from other providers? What do do with those patients typically in terms of how to manage them? You're obviously not the person prescribing their opioids, but how do you get them off their opioids?

Right, I'm fortunately working in a system where we have an amazing pain clinic and management group, but a lot of patients have trouble with anxieties or just issues with how all that works. This would be a great adjunctive piece of equipment and therapy that they can use.

Yeah, absolutely though. I think for your pediatric patients, I'm sure if you're about to do a procedure or something, there's a lot of anxiety and stress involved. How would a child respond to a VR headset?

I know that in my hospital, they're using VR in the emergency department for procedures like IV placements or blood draws, lumbar punctures and things like that, so it's been already well used. We currently don't have a setup in the rheumatology clinic, but I can imagine that something like this that is not too expensive I think would be very welcome for our patients.

Sure, absolutely though. So anyway, these are all tools that are readily available, easily obtainable, not too expensive. It's just a matter of if you're practicing and want to incorporate these, will it fit into your workflow? But it only takes a little bit to try it. So I would encourage anyone if they think about it, can contact any of us and we'd be happy to help with lot more information.

So thanks for joining us for a look at some of these products and hope you have a good conference. Thanks.

Hi. I'm Jack Cush with RheumNow, and we're gonna have a mini panel discussion myself and my best friend Janet Pope.

Hi there.

Yeah. We're having a good meeting.

It's been a really good meeting.

One to ten. What do you think of this meeting?

I think it's an eight point two five repeating.

That's pretty good.

It is pretty good.

That's nice. I must say it's the same thing. Sometimes we come and it's to hard be impressed. I think I've been impressed by a bunch of new things. I wanna talk about rheumatoid arthritis and the high points for you at this meeting.

What comes to mind when you think of rheumatoid arthritis and high points? What do tell your fellows when you get back?

Right. So there's a couple practice changes and then surprisingly not surprisingly, but reassuringly, of the same, which is always a good thing. So some of the practice changes are the flu shot data that there's certain flu shot. One might be actually more effective in people with immune related diseases. However, whether that pans out to being different for preventing influenza, who knows?

But still to get the flu shot because we saw the decreased mortality, decreased infections all cause, is decreased and people get the flu shot and that in Canada is suggested for everybody.

So the the the high dose flu versus the standard dose flu, you're obviously, it's available. How often do you use high dose flu vaccine in your practice?

Right. In general, I don't. I wouldn't know in whom to use it. I would think that in general, it'd be severely immune suppressed chemo therapy kind of patients, but something's better than nothing and we don't even know if it pans out to less influenza, but there are more antibodies. But I think it's still the flu shot is the message.

Absolutely, but this data, I've always been, I kind of always practice like you, something is better than nothing. So I always give them, they're in my office. Let's get this done while you're here as opposed to go searching for the flu vaccine, the high dose flu vaccine, which is indicated in the elderly, but this data from McGill, you know, two seventy patients, very convincing, two to three fold higher seroconverters really makes me think I really should be doing this in my RA patients. These RA patients on either DMARDs or biologics worked for everybody except for rituximab, not so good.

I think it's tough to say though is more serial conversion translating to less influenza makes sense, but we don't really know that. And I agree something is better than nothing. So we have, yes, get the flu shot in every room in big capitals. Yes. Get the flu shot as though they've asked.

And we facilitate by having it in the fridge. Because if you can facilitate, they can get it right then and there.

And there isn't good data on if you got the vaccine, how much protection you got because it's only they have good data on on on the the serologic proof, but not necessarily, but they do have good proof about not getting vaccine and dying. And that's the problem. So it's like seventeen thousand deaths last year, eighteen thousand deaths in people didn't get in The United States who didn't get vaccines.

And it encourages our patients to say, actually it's super safe to get the flu shot. This is not a live vaccination at all. So it's safe to get it, and it can prolong your life.

Excellent.

I think there's one other take home that I might have, and that would be the reassurance that looking at the JAKs, they had two presentations of these long term extensions, plus there was data from databases, market scan and other ones. And the bottom line is they're not seeing an increased risk of infection over time. What we found or not me. What others have found at the beginning still persist, persist, but the rates aren't going exponentially higher or anything like that. And that VTE is still something we're gonna talk about.

It's I think the data are real. Whether the risk is, going to even lower over time or not is tough to say. It was higher in the RCT than long term extension on the baricitinib data and whether it's a class effect or some drugs and not others. But the bottom line is not to maximize a rare event, but to really get the patients better and to know that if they're on treatment, the safety seems to be very consistent over time.

You know, one of the messages that I find myself teaching a lot lately, we know because we live it, often most people aren't reminded of it and by patients don't know is that the longer you're on a drug, the safer it is. Absolutely. I mean, all that long term safety data, which I don't generally don't like really does help me a great deal in dealing patients who continue to worry. The more I take methotrexate, the more I'm rotting out my liver. Well, that's actually not true.

You know, the data is very clear that if you're going to get problems with methotrexate, it's going be in the first year. The same can be said for almost most drugs. I wouldn't say all drugs, but most drugs and the ones we, our patients worry about, the longer they're on them, the better they're going to do. Including, I say in case of VTE, the long term data on VTE is not impressive and not related to the drug. So, again, I think that the, it is incumbent upon us to remind the patients, you know, this is a good thing you're doing.

You're not harming yourself by long term therapy.

And I'm gonna agree partially. So it's a bit circular. If you're on it and you're still on it, you've probably done well, the drug works. Right. And you've tolerated it and you haven't had major serious adverse events.

So you kind of get people channeled into that. But in general, you always think there's adaptation, so the initial risks are things like cytopenias with our DMARDs, some transaminitis early, rash intolerant, but there is a long term risk of liver toxicity with methotrexate, it's very low and that has been borne out. Have either different patients or different problems compared to in the 70s and 80s psoriasis when it was given daily and had a real problem. We just don't see that, which is really great. So I think what you're telling me is totally true.

Plus life happens. If you live long enough, you'll actually die.

And let's hope you do live long enough to die. What about again, always at these meetings, always hard to know where it's going. In The United States especially, we've got, I think five biosimilars approved in the rheumatoid space. We're largely not using much of them. We're using some of the infliximab biosimilar, although it's not very well discounted.

You have biosimilars in Canada. What's been your experience so far?

Right. So we actually just got a second infliximab. So we have two infliximab, two etanerceptin. As we all know, will come. The market penetration is very close to The US at about seven percent of all biosimilars across the board, and I think there's two issues.

One issue is we don't want to rock the boat when a patient's been on in general three DMARDs or four DMARDs with RA before they get on something. So the path of least resistance is to really say you're doing well, let's do your follow-up and maybe let's talk about the safety of Right. You know, you're getting your drugs monitored, you should stop smoking. You only have so many minutes in there. But also I think there's a fear that so there's complacency on both parts, but there's a fear of the no cebo effect because I believe most people think that a biosimilar when it when Health Canada or FDA says there's etanercept, etanercept, etanercept.

I think people believe that etanercept, etanercept, etanercept exists but if patients are switched and they break through, people feel badly because what do you do next? You went backwards to the other product, backwards meaning recycling backwards,

it

doesn't make sense if you've actually broken through and the drug doesn't work, but yet some people will have nuisance side effects and say put me back on the other one. So I do believe in Canada until it's mandated, we won't have the uptake. And why should it be mandated? To actually save money. If you should do equally well, and it's mandated, we would help people go through it.

And if you have positive advice, they've shown that at several meetings, if you have positive talk to the patients, Health Canada, FDA has approved other etanercepts, I'm only talking about it because it saves the system money. If you have that kind of positive thing, you should do the same, not worse, not better, but the same. Right. I think that helps people transition and most of my patients don't say no. But if they do, they have every right to say no at this point in time because I don't have a medical reason to switch them.

So if their reason is they get co pay help, if it's an infusion and they're closer to them, if I switch, they have to drive further, then their reason will always trump mine.

Alright. You know, we go to, Arti and I go to Sweden every year for the last four or five years to lecture in January. And when they started introducing infliximab biosimilar there, there was a great deal of reluctance. There's a lot of concern, a lot of combustible rheumatologists talking about this. Over the years, it's now a non issue and now they're at at the point that they're switching from the biosimilar to another biosimilar back to the originator

Depending on the cost.

Depending on

the cost. Right. And they Yes. And the government's determining it. And it's being well received by the rheumatologist because they know it's a big savings.

They don't see much in the way of trouble. Patients are accepting it and I think one of the things I'm seeing is that the issue of patients and patients acceptance is largely dictated by the physician attitude. If your attitude is the physician, as a prescriber is, darn it, I don't, I wish I'd have to do this. They're making us do this. And if you have no confidence in this or don't believe it's the exact same, then the patients worry and then they get, you know, all kinds of effects that they shouldn't have.

And then, and then, then you're faced with, can you go back? Do I have to go to another therapy? Am I going to actually cost the patient more? Am I now risking more? So, I mean, need to be comfortable.

They need to buy in and understand this.

So we need practice talks. So I tend to run basically little workshops on communication

Mhmm.

Looking at risk benefit of anything, but including practice talk there. Mhmm. Because it's not just what you say, it's your body language. And people that say, I think you'll do just fine. The body language says no, so that's one thing.

The other thing is we do debate where are the savings. So if it went back for innovator drugs to be funded for my patients, or if it went back to a more cohesive model of care for my patients, of course, possibly I, meaning the rheumatologists in Canada, I'll speak on behalf of them, would embrace it probably more fully, but, our Canadian patients, they're very used to generics. I realize a biosimilar is not a generic, but they get the idea that if we prescribe drug X, they'll get ApoX, Novax, Zivax, They realize that their drugs change and that in general, for most of them, there's not a problem. A rare person would say no substitution only on this because one seems to be absorbed better for me than another. But that's the uncommon.

I think if patients got on board to know that we're in this together, that these are costly items and that the market is growing, and the market's growing meaning the next four patients, possibly even one in their family with another autoimmune disease, will have to be treated. We actually have to have resources to do what is needed for all our patients, but the patient in front of me, while I'm talking to them, is obviously the most important at the time.

I really believe that the biosimilar story is going to be playing out sooner and faster in Canada than The United States, which means I'm going be looking to you to gain confidence on how it's going to

play out.

And I can tell you I've tried to switch many people, and as I say, little resistance. And the only reason I'm switching it is for cost savings.

Alright. Janet, thank you very much. It's very interesting. Thank you. Come to ACR.

This is where you learn.