ACR20 - Day 4.2 Save

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

Hi. This is Bella Mehta from New York reporting for ACR twenty twenty. The abstract number that I want to talk about is 1633 and it's titled a randomized double blind placebo controlled trial for anakinra in pediatric and adult patients with Still's disease. The trial is named Anna Stills. ANNA for anakinra and STILS for Still's disease.

As we all know, anakinra is an IL-one receptor antagonist. And IL-one is a predominant cytokine that they think about as a pathology in Still's disease. This was a twelve week study in patients with active and newly diagnosed Still's disease. 12 patients were enrolled in this randomized study where six patients were assigned to the placebo arm, six patients were assigned to the treatment arm. In the treatment arm, two patients were given the two milligram per kg per day subacute dose of anakinra, whereas four patients were given the four milligram per kg per day subacute dose of anakinra.

All patients met either the ILAH criteria if they were less than 16 or the Yamaguchi criteria if they were greater than 16 years of age. The primary objective was to reach ACR 30 and the absence of fever at the two weeks time point. So five patients received the placebo. One patient dropped out because the patient was actually diagnosed with lymphoma and did not have the original diagnosis of Still's disease. Six patients continued on the drug over the twelve week time point.

Of the six patients, all six of them achieved the ACR30 criteria at week two. Not only that, all of the six patients achieved the ACR50 as well as 70 criteria at week two. Five of the six patients also reached the ACR 90 criteria at week two. And all of these effects were sustained over the twelve week period. At the twelve week time point, five patients were at the ACR 90 mark and one patient was at the ACR 70 mark.

Of note, all patients in the placebo arm did not have any response. And there was a high rate of dropout towards the end of the study in the placebo arm. Again, it's very difficult to enroll patients with Still's disease in a trial like this. And it's possible that most patients do not want to get into a randomized study with a placebo arm as you can see. Still, this is a big study with 12 patients.

As the authors also note that it was difficult to recruit and they had to stop the study early. But overall, an important study showing the utility of IL-one blockade in Still's disease. A lot of exciting posters and presentations in this area. For more, tune in to RheumNow or follow me on Twitter bellaMeta. And thank you for listening.

Hi, Jack. I'm back. I'm out of my party clothes. The election party ended. I shaved.

I got a little bit of a haircut. It's a new day. I'm feeling good. I spent the day today, Sunday in the bright sunlight here in Portland, Oregon, beautiful fall colors. Everyone's happy here finally, and I was happy to sit down and troll around RheumNow in ACR.

There's a lot of cool stuff going on. So, I wish I was there like everyone else, but I'll tell you what I found today that was interesting and make a few comments. First about steroids. Doctor. Hanley from Halifax presented some nice data, poster abstract ten fourteen looking at corticosteroid use in Canada among elderly individuals, patients over age 65 with RA.

Surprising, well maybe not surprising, corticosteroid use is quite common. I was surprised though to see that the bulk of the prescription use there, at least in Canada, was prescribed by primary care doctors and not the rheumatologists. Only about a third of it was by the rheumatologists. Suffice it to say, which was interesting that even though there's been this great uptake of biologics, small molecular therapies there over the years, which we all know are steroid sparing, almost every molecule has a study showing that when patients start them, they're able to wean their dose or get off prednisone. So we know there's good steroid sparing data with most of those agents or really all of them.

But, looking in the real world population wise in Canada at least, we see the uptick of those therapies yet the use of corticosteroids has been, largely flat. About thirty of RA patients over, this time period have stayed on, or have used corticosteroids. Now the good news in the data showed a decrease, in the total dosage patients were using and the decrease in the duration of each prescription. So I think there's some good signs there. It sounds like people are trying to wean corticosteroids, but maybe the message also needs to get to the primary care doctors and that's what I took home from that.

And obviously this is going to vary upon region and where you are in the world and how you practice, but it's looked like from that data that rheumatologists are getting that message and acting on it and trying to reduce steroids. And so maybe we need to talk to other groups as well that care for these patients. So I transitioned a really nice study that was just published in the annals of internal medicine. And, the nice thing about that is I think a lot of internists do read it, and family practice docs, primary care doctors do read it. And this is Mike George's work, who's an outstanding young researcher from UPenn and I was, privileged to work with him on this project as well as several others.

But, we looked at, Medicare and Optum data in The US and looked at the harms of even low dose steroid use and we this is well known stuff. However, most of our observational studies when we look at steroids, are often confounded by the fact that patients on steroids have higher disease activity. And so the best we can do, we control for it in all these studies the best we can, but unless we have good discrete information on disease activity, we can't really control for it. So, the beauty of that study is Mike did it and he used tax scores and inflammatory markers and a subset of these patients was able to show that even, when you control for those things low dose steroids on their own, are a risk factor for serious infection and the rates of infection at one year time is something like five to twelve percent of these patients, depending on the database, would be in the hospital with a serious infection, even at lower doses of steroids. So, I think the message is clear to me that we need to keep working on this.

We probably need to reach out to other types of physicians. I guess the point of that was I got emails and calls from friends and colleagues that were primary care doctors who said, hey, this is great. You know, I don't normally read about this stuff. Thanks for putting this out there because a lot of the sync low dose steroids probably aren't that big a deal or a lot of us see our patients on them or we use them. So anyway, I think, I think we're moving in the right direction.

That being said, I want to just point a few other things out because I think we're moving in the right direction with vaccination. I know there was a lot of talk today and I think tomorrow about COVID vaccine development, which I'm not going to comment on, but I'll comment on the fact that I'm using the idea that we are likely to have vaccination for COVID next year. I'm using that as a reason to make right now my vaccine moment, meaning, you know, it's time to get vaccinated for everything else because getting a COVID vaccine on its own is going to have all sorts of questions surrounding it. How to do it, when to do it. So why not get your vaccines that you need done now?

Shingles vaccine, pneumococcal vaccine, influenza vaccine, obviously prioritizing respiratory infections right now, influenza is influenza season, this is something we need to do. Just highlighting a couple things presented yesterday, abstract six thirty two and six thirty four on Saturday had to do with vaccine hesitancy and barriers. One of the biggest, reasons patients don't get vaccinated, this was a peds practice, rheumatology was efficacy or perception of lack of efficacy. The other study, six thirty two, this was Doctor. Cole Magna's study in McGill, a large adult room population.

And they found that, again, questions of efficacy were some of the lack of efficacy were associated with a strong, chance that the patient would refuse the, vaccine. Today, Doctor. Horomanski from Stanford, they surveyed refusers and acceptors of vaccines and this is, number eleven thirty five today, Sunday. And a lot of people, as you know, they go off the flu vaccine, they say they get sick from it or they had a bad experience from it before. So, those are the things we try to overcome by saying, hey, the vaccine's a lot different than it used to be or it's, it's better tolerated or we give it differently sometimes in some cases.

So there's various ways to deal with these problems that come up and, one way is showing effectiveness and efficacy and I'm just going to park it right there because tomorrow that's what we're going to do. We're going to focus on vaccines and some of the data presented at ACR talking about effectiveness and efficacy. I think that's important as clearly the data presented today highlighted the lack of efficacy or perceived lack of efficacy of many of our vaccines that drives, some vaccine hesitancy. So I think those types of studies that show effectiveness are important and I'm happy to see some of that work here at ACR. And, what else am I going to talk about?

Oh, yeah, we'll get back into JAKs, we'll get back into herpes zoster and zoster prevention. There's a lot of cool stuff on Monday and Tuesday this week. So, I'll sign off now. Have a great night, and enjoy ACR. Cheers.

Hi, good evening. This is Leanne Gensler from UCSF in San Francisco reporting for the ACR twenty twenty conference. I'm reporting on spondyloarthritis. Today is the third day of the meeting, and today I'm going to be talking about a study that was presented in the plenaries. This was abstract number fourteen forty four presented by Anna Malto from France.

She presented the tycospora study, which is the tight control study in axial spondyloarthritis, and this was a cluster randomized pragmatic trial where they randomized patients, they randomized centers actually with patients to either tight control or usual care and followed them up over one year. This included 18 centers, including centers in Belgium, France, and The Netherlands, and patients were really selected by the centers based on the diagnosis of axial spondyloarthritis. They needed to meet the ASUS classification criteria. They needed to have enough disease activity greater than 2.1, which would be high disease activity, and they needed to be biologic naive. They also could not have had two full courses of NSAIDs and that was because part of the strategy in treating patients with axial spondyloarthritis would include using a full dose of a nonsteroidal as first line therapy, and so the patients, if their cluster, their site was randomized to tight control, those patients were seen every four weeks versus usual care sites, those patients were seen every three months, and their target that they used was trying to get those patients into at least low disease activity or less, which would be an SDAS less than 2.1.

Now the primary outcome that they used was the proportion of patients meeting the ASUS health index of at least 30% improvement, and so this is a newer disease specific outcome that really is about health and about functioning. And so it's not a disease activity outcome measure, which is nice in that it's separate from thinking about this being active disease. However, we know that it does improve with treating disease activity and it's been used in several randomized control trials already as a secondary endpoint. And so they randomized about 80 patients to each arm of the study and 72 patients met the end of the year follow-up, and really they looked quite similar, the patients with access spondyloarthritis at baseline. The only difference was that more of the patients in the tight control group were in university study level centers, and more of those patients had had a history of uveitis, but they were able to adjust for these baseline characteristics and the clusters and really sort of the imbalance that was there at baseline.

Now, they did not meet their primary objective. The primary outcome was not met, so forty seven percent of patients in the tight control group met the thirty percent improvement in the ASSIS health index versus thirty six percent in the usual care group, and that was an 11% difference and that was not significant, statistically significant, and so unfortunately they didn't meet their primary endpoint. Now usually in studies, if you don't meet your primary endpoint, you don't go on to do analyses or report on the secondary endpoints. They did report on these endpoints which included several disease activity domains and other usual domains of efficacy that you might see in clinical trials, but really it's hard to interpret those knowing that the primary outcome was not met. They also looked at health economics, and so this is important, particularly in Europe, where they did show a significant difference in the qualities and actually noted that those patients in the treat to target group, in the tight control group, really actually have less sick days, which is a good thing, and there was no difference in safety, in particular no difference in infections, but keeping in mind that these patients in a tight control group or even a usual care group, what is it that we treat axial spondyloarthritis patients with?

If you follow the algorithm, it's NSAID, then TNF inhibitor, then perhaps another TNF inhibitor, an IL-seventeen inhibitor, but we're not really adding DMARDs or glucocorticoids to these patients' care, and so it's not that unexpected that patients did not have a higher number of infections in the tight control group. The other notable point is that the patients in the tight control group did have a higher prescription prevalence for biologics. That's not a surprise, but there was no difference in NSAID prescriptions. So what accounts for this negative trial? I do think it's a really important trial.

I think we need more trials like this. We know that these trials in rheumatoid arthritis and psoriatic arthritis were significantly positive and that treating to target is a good thing in those disease states. So one possibility is that the target was too difficult to reach and that ulcer's health index, at least at a 30% improvement, may have been too stringent. It is possible also that they weren't powered particularly at that endpoint. Now, under the assumption that they did a power calculation to drive their sample size, it is expected that probably the difference was going to be bigger and that difference was not as big as it actually was expected to be.

The other possibility is that the usual care patients did better than they were expected to do. And now if you think about the fact that these usual care patients were at expert centers, they were being seen every three months, and then the next stage for the next intervention was performed if they weren't at that target of less than 2.1, it's possible that those patients are doing better than we might expect them to do in daily practice. I certainly do not see patients every three months in usual care, so that is also a possibility. Needless to say, a really important study despite its negative result. I think we're now at a point where we have some data, and I don't think, at least in The US, it changes the recommendation that we don't have enough evidence to treat to target yet in axial spondyloarthritis, but hopefully this will generate more research and studies to really optimize the outcomes in these patients.

This is Leanne Gensler reporting on spondyloarthritis for the ACR twenty twenty conference. For more information, please go to RheumNow.

Welcome to this RheumNow roundtable on gout at the twenty twenty ACR convergence meeting. I'm Michael Pellinger from NYU Grossman School of Medicine and I'm pleased to be this year's gout editor for RheumNow. I'm joined today by two really wonderful goutologists and colleagues and I'm very pleased to introduce them to you. These are Doctor. Naomi Schlesinger, who is Chief of Rheumatology at the Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

Hi, Naomi, welcome.

Hi, good afternoon.

And Doctor. Robert Keenan from the Florence Rheumatology Center of Articularis Healthcare, who is also adjunct associate professor at Duke University School of Medicine. Hi, Rob.

Hey, thanks for having me, glad to be here.

So I wish we were together in the same room, there's lots of interesting things going on at this year's meeting regarding gout and other crystal diseases. So let's chat about a few of those things. Rob, let me talk or ask you to talk about imaging a little bit. When we first started hearing about dual energy CT deck a couple of years ago, it seemed really exotic and almost impossible to get done anywhere anyway. But I'm seeing a lot of abstracts this year that it might be moving into, if not routine use, at least maybe routine research.

Is there anything worth noting for our audience about Yeah,

there's been, there were several abstracts this year and a few talks as well about doing GCT specifically and just imaging and gout in general. Like you said, I think it's not quite standard of care at this point or in routine use, but the more research that comes out then hopefully kind of will lead the way to a little bit more routine clinical use. Also just better diagnostics in general, which you know, of the abstracts that, well there's a couple of abstracts I wanted to mention or at least talk about or touch on was, and as far as the quality of imaging, there's still not quite, I guess a consensus on what joints you want to, might want to actually image. And everybody assumes, okay, the feet, that's a good one. That's a relatively easy one to do.

And maybe the knees. And there was a study actually by Sarah Christensen out of Denmark that was probably one of the best talks, best explanations of the 160 I've actually ever heard. And what they found was interestingly enough that it seems that the patella tendon specifically as well as the first MT in their mind and their cohort that they were looking at was probably the most sensitive and specific areas to look at imaging and to pick up those monosodium urate crystals and distinguish them from other crystals such as CPPD, for example. So that was one interesting. And then there was another study I thought was pretty interesting as well that kind of contradicted a lot of the studies that are already out there.

And that was by Doctor. Schafer out of Germany. And what they showed, it was a little bit of a smaller study, but what they showed was the sensitivity and specificity of the 100 and CT compared to ultrasound was not that much better. The sensitivity actually was a lot lower than that of ultrasound while the specificity was much higher than other reports or at least was 100% in their study which was about 10 to 15 or maybe 20% higher than in other published literature over the last several years versus ultrasound being around seventy, seventy five percent. Now the, I know I was supposed to mention the abstract numbers on that.

So that abstract number was 15.42 and then the Christensen abstract number was, what was that? That was I wanna say 4.45. That was in the big, that was in some of the talks.

I guess you can remember these things.

So, but I thought they were both interesting studies and there were a few other studies out there looking at ultrasound versus Deloitte CT and out of the, there was a group out of Paris and Spain specifically, and I believe it's the Crystal Ile or Crystal Ile cohort that they're looking at. And I think Doctor. Singh, Jazz Singh was involved in this one abstract specifically that looked at doing your CT versus ultrasound and alone in combination or in which is better basically, which is a better diagnostic tool. Are they both better together or is one better than the other specifically? And what they found was that the donor CT was actually better and what joints they found that probably had the most sensitivity as well as specificity were the knees and the feet, which is similar to what Doctor.

Christianson found just not quite as detailed as saying the patella insertions versus and the first MTP. So, I mean, all that's exciting stuff and hopefully we can at least in routine clinical care, this becomes a little bit more easy to get or easy to find. But I know that it's still somewhat cost prohibitive especially compared to ultrasound. And I think too as technology improves and not only with ultrasound, maybe eventually the doing your CTs will get cheaper as well. Which if I can say one more thing that kind of as a segue, there was another interesting study I wanted to bring up and this goes along with comorbidities as well.

I know all of you, both of you are in the camp, the same camp of mine I'm in about cardiovascular disease and gout going hand in hand and being an independent risk factor for cardiovascular disease. And there was a study here again of that same group out of Spain and France, the Cristalile cohort, Cristalile cohort, I'm not sure how they say it of course, but they and this was abstract nine fifty four. And what they found was they looked at one hundred and twenty eight patients. And what interested me was, it's not the fact that sick only sixty two percent of them, sixty two percent of these patients were not on rate lowering therapy, but only forty eight percent or thirty eight percent were. But they found that the higher volume, the crystal deposition was associated as well as serum urate levels were associated with all cause mortality over history of MI, over BMI, over hypertension, over smoking, over stroke history.

All those things did not show overall all cause mortality as the serum rate levels and the crystal deposition on dual energy CT did. And what was another interesting point with that study was the even though they couldn't figure out or it wasn't clear what volume had to be there to distinguish those folks from the rest of the group of lower risks was the duality CT deposition, crystal deposition was the only predictor of new onset cardiovascular disease or heart attack and diabetes. Here again, weight wasn't associated with it. Other cardiovascular risks weren't associated with it. PAD wasn't associated with it, etcetera.

It was interesting findings and it's just, it was a decent sized cohort, but I think further studies would obviously be needed to kind of validate those findings, but it's still definitely something to think about.

So I guess, and maybe I'll ask you this, Naomi, quickly. It sounds, Rob, a little bit like what we're learning is how to maybe use this modality. If we're trying to make a diagnosis, there are probably places to look where the sensitivity and specificity is good and others that aren't. On the other hand, if we're trying to examine a cause of pain that might be gout, it might be a different situation where you might go to a normally less sensitive area and it might be either from that last study, a really good, a better severity marker or it might be telling us biologically something completely I don't know, Naomi, do things

I wanna add a few things actually. We haven't revised this for publication as of yet, we looked at our cohort of dual and I was actually pretty shocked how few were actually this is not in a study, this is a real life cohort How few of my patients that I asked them to have a DoloCH CT had it because the insurance did not approve it. And then, looking at patients, so within the first three years, many of them don't have any changes. It doesn't mean that they don't have gout, it just means that they didn't have changes suggestive of gout. I want to add that I saw today a Pearl's lecture by Doctor Stone and he talked about temporary neuritis and how it used to be the golden standard was to do biopsy, but maybe now imaging.

And I wonder if in our field as well, doing fluid analysis for the monosodermuri crystals is done by only about ten percent of rheumatologists, so few of us. So could this actually the dual energy CT or maybe ultrasound actually replace this in the future? That could well be. And I want to also add to what Rob said very eloquently that it could be that we are going to be doing dolodular CTs of the joints and then maybe carotids and then maybe heart and then maybe is an area that's just starting to have research and study. So that is very exciting.

I mean, GAP is a disease state, not just joints and so on. Treatment goes along with that. It's not just the joints.

I have to add a case, it was supposed to be a study but it became a case report for us, Rob. I was thinking about what you were saying about ultrasound and we treated one patient with TOFI, with pegloticase, knowing from Nikola Dalbe's studies that TOFI have a rind of fibrosis around them. And what we found was that when this patient's TOFI were not clinically resolved and were not fully resolved on ultrasound, all the urate was gone out of them. It was like we deflated a balloon and the deck was the thing that you could use to say the problem is no longer the urate that's there, it's you have this fibrotic capsule and who knows what will happen with that.

And there's an abstract presented, the number I don't know, but in this meeting, looking at this appearance of what we called the icing and the other group called double contour assignment, but we described disappearance of the monosodium merry crystals within seven months of treatment. There's a delinquent study, a larger study, showing what we showed ten years ago. It's interesting how people are doing similar studies.

Yeah, that speaks to

that's getting a little better.

No, I was saying that what you're, you both were saying is what speaks about the Christianson's lecture in her talk and her slides. She just, she distinguishes in the reasons why we're seeing what we're seeing. And some of the things are kind of merged or blurred on doing your ZT. And there's not as specific and sensitive as we want them to be is because of this something called a competent effect and something called a photoelectric effect. And the difference between how the CT works and how the dual energy CT works.

And those are the kind of, I guess the duals of the competent effect and the photoelectric effect. While the latter kind of is important for picking up those crystals and the former is important to pick up the soft tissue and distinguishing the two from one another and not kind of confusing, you know, other calcifications or mineralization from the and I think from the uric acid crystals specifically. And I think here again as technology hopefully improves not only with CT but maybe even ultrasound that I think we will hopefully do a better job of figuring out, okay, the difference in distinguishing those two.

Let me, I think that's a good segue having talked about that and having talked about mentioned peglodecase too. Let me just turn to another question I wanted to ask both of you and maybe I'll throw this one out to you, Naomi. There are a lot of abstracts at this meeting using basically using DMARDs with peglodecase and it is definitely for a problem that I've experienced and I was wondering if you could tell us about that and we could have a conversation about that.

Sure. So basically pegilodecase is pegylated recombinant mammalian uricase to treat refractory gout. This approach was used to increase the half life of the enzyme. But what happened was that there was development of anti pyglovicase antibodies. And then the question starting in 2018 was use of immunomodulators initially Pivo decays with methotrexate.

Then Doctor. Pillinger described in the patient getting azotipurine, miran and so on. And I'll just discuss a few of the abstracts I saw treatment with immunomodulation. So actually, will start with the study that was a multi center open label study looking at peglodecase

in

patients that have undergone kidney transplantation. And I thought this was very interesting because these patients post kidney transplant had very bad gout and were given peglodecase. And these patients were on two or more immunosuppressive drugs due to their transplant. Hence, they were on immunomodulation. And in this study, although a small study, they just started enrolling the PROTECT trial.

They saw the HAC pain score had gone down and really they didn't see any infusion reactions, which is what we worry with these pegyloticase antibody formation. So that was one study that I thought was interesting. And this was something that was discussed yesterday in the gout lecture. And what do we do with our kidney transplant patients? So that is an interesting option.

And that was the abstract six forty nine. Then moving on to abstract six seventy seven. This is the MIRROR trial was an open label study. Batson who led this and initially published the data in 2018 using methotrexate. He uses fifteen milligrams four weeks prior to starting pyglodecase.

And this was very successful. Initially, primary outcome was serum urate proportion of responders during month six, half a year with a serum uric of less than 680% of the time. And eighty percent met the primary outcome in this study. And this is double what it was. Was double what it was in the original trials, which was forty two percent.

It's fourteen patients. So this was the MIRROR trial. So that was presented and interesting. And I think we feel very comfortable using methotrexate. Interesting that's four weeks before, interesting that's fifteen milligrams.

Some of you would use other doses and so on. But I think that's a good place to start. And then there's the triple trial using Imuran or azotiraprine in chronic refractory gout. This was after June and presented by Herb Barrev and patients are screened for the AZA metabolizing enzyme to pre mantyltransferase and they have a dose escalation after two weeks, a twenty four week study and they all received the infusion prophylaxis and hydrocortisone just like in the initial trials. And 12 patients who are enrolled to date, they all had bad gout and had to face your scalp.

They also did well. These patients with Imuran, one patient had an infusion reaction, but really other than that, it looks good. Safe and efficacious. With, it was discussed in one of the meetings, but that people worry about Imuran and GAP. It's really Imuran and allopurin.

Allopurin interferes with the metabolism of imuran increasing the plasma levels of mycryptopurin but belylodecate is a totally different treatment and mechanism

And we're not supposed to use allopurinol with peglodecase so.

That is correct. That is correct. But I'm talking about the Imuran and allopurinol. People are worried using Imuran in gout patients because of allopurinol. But they're not an allopurinol, they're an Imuran Right.

And peglodecase. So it's nothing to worry about. Mean, it's a different drug. And then there was the recipe trial after September where patients are now giving mycophenolate, which was the phase two double blind randomized controlled trial. The first offer is Doctor.

Pujakana. And they compare mycophenolate, which they again increase the dosing and they compare it to placebo, thirty two patients receive at least one dose of piclodecase. And the problem I found here is that the mycophenolate arm had higher adverse events, more musculoskeletal problems, respiratory problems and infections. And however, the placebo arm had more infusion reactions, which is expected. And the percentage of subjects maintaining the What serum did you say?

I'm sorry.

Yeah, I'm sorry.

Yeah, I'm almost done with this.

No, I was just gonna say that sounds like you might generally.

Yeah, so yeah, it sounds, it definitely does what mycophenolate does and that's a kind of an unusual side effects or adverse reactions. The issue with using mycophenolate is basically in my opinion really clinically is not super practical in the sense sometimes insurance companies will deny it. It's not always the easiest medication to get even though it is generic. It's not as cheap as azathioprine of course. Seems to maybe work better than azathioprine at least in the data we have so far.

But so far it seems the most practical reason even though it's sometimes still not as easy to get as should be is methotrexate.

And I

haven't, I have not started anybody on pegilodecase in the last probably twelve to eighteen months, maybe more than that now on pegilodecase without starting them on a DMARD of some sort, whether whether it's methotrexate or whether it's stronger immunosuppression like azathioprine or mycophenolate.

Well, agree with you that methotrexate probably should be the go to drug. It's the one in some ways, even though it's not the oldest of the three, it's probably the one we're most comfortable with. But of course some of our gout patients may drink alcohol and it's good if we have options.

And then this leads me to the last abstract that I'm gonna be discussing is six sixty five. Although I could discuss a few more, but it's the trends in immunomodulation with peglodecase. So basically they took a large medical claims database and reviewed the use of peglodecase with an immunomodulator. There were 1,300,000,000 claims. And they looked at patients that were prescribed methotrexate or Imuran within sixty days before after receiving the first piclodecase infusion.

And what they found is really that since 2018, exactly what you described, Rob, we're using more immunomodulation. And if the four percent were using immunomodulation, now it's up in twenty nineteen to fifteen percent of patients on pegilodecase receiving the immunomodulator mostly within thirty days of starting pegilodecase and mostly methotrexate. So, goes with what we just discussed that methotrexate most commonly used in this database. I think with the new trials that are going be coming out in publication, not just abstract form, we're going to be seeing more immunomodulation being used with pegilodecase. So

Yeah, it just raises questions about, okay, when to start, what dose to start, what to start. All those questions kind of arise. There's data out there that shows, okay, in some case reports, they've started at the same time as pegilota case. Some are starting two weeks prior. Some are starting four weeks prior.

I think I believe in

the What do you do Rob? What do you do?

I usually, if I can, I usually do four weeks? A couple of times it's been shortened because the patient ended up getting infused sooner than I anticipated for whatever reason. And, but usually I try to do four weeks prior just to be on the prudent side, just to making sure, okay, if it's methotrexate, it's gonna start doing something, it's got time to do it. You know, the recipe trial I believe was what two weeks prior starting MMF. And so I mean it's, it's and I think the, well the MIRROR trial was, I think MIRROR trial was four weeks prior I think too.

So I guess it depends. And I think, you know, it's still the questions are still out there.

And also the fifteen milligrams, I use ten milligrams, but mine is anecdotal. It's not based on any trial, but I feel very comfortable using ten milligrams.

I've and depending used on the situation I guess and how.

Yeah, it's anecdotal not supported by trial data. I wanna add something important that I know that you know but

Our time is almost up, Naomi, so we'll give you the last word here.

I'm sorry. No, I don't need the last word, but let's get all actually published data about antibodies and say that over sixty percent of patients that are over 70 develop our responders do not develop the antibodies. Whereas the younger guys less than 60, most of them develop antibodies. The younger patients getting pegvodecase, those are the ones that we have to worry about infusion reaction, while the older patients, not so much. And maybe the younger, heavier patients, those are the ones that we have to worry about, my infusion reactions.

So there is so much more that we might talk about. I actually wanted to talk about what diet does now. That seems to be a

So please do, More please confusing

question but our time is up. So on behalf of Doctor. Keenan and Doctor. Schlesinger and myself, those of you who are watching this, thank you for joining us and keep looking at RheumNow for more gout reports and have a wonderful meeting.

Thank you so much.

Thank you all.

Have a good night. You so much. You.

Hello. I'm Jeff Curtis, a rheumatologist at the University of Alabama at Birmingham. Full disclosure, I'm not a disc jockey. But if I was a DJ, I would probably, at least at times, reach for music that's familiar and comfortable that everybody likes. So if this were research, though, what kind of a study would that be?

Well, probably a treat to target study in arthritis. You're familiar with Tycora, kind of dated now, but the concept, of course, is very familiar and you can that tune. Then we had Tycopa, tight control in psoriatic arthritis. And to complete the triad, we've got the third verse, same song, but not quite the same as the first. So this is TycoSpa.

So this is the spondyloarthritis version of the tight control trial that may seem quite familiar to you. But let's look a little bit past the melody line and think about how it's different. It's coming out of Europe, and one unique aspect to it is it's primarily done in centers that are experts in the management of spondyloarthritis. This is not a large pragmatic trial. This is not routine care.

Not really. Because the centers that are participating in Europe, and there are only 18 of them, are not your average run of the mill community practice centers. It's 160 patients, now ninety percent completed, and so that's a total of one hundred and forty four. And the interesting feature of this trial, tycospora, is that the sites themselves were randomized. You might ask, why would you do that?

You would do that, and you randomize sites when there's the threat that you basically have contamination at the site. Contamination meaning that docs overall are going to get used to doing things in a certain way. So if you have a protocol that's in place that's supposed to be on your mind at any given moment about escalating and measuring things, it's going to be hard for you not to do that, even if this is a usual care arm. So that's the contamination part. It's that your practice behaviors will be contaminated because for some, but not all patients, they're supposed to be getting this aggressive treatment that is metric driven based on disease activity.

That's why you randomize sites or clusters. You do pay a statistical penalty when you do that. You have to control for that clustering, and those observations are not independent. So you typically need a somewhat bigger sample size to take care of this so called design effect where patients clustered or nested within sites are more alike and aren't truly independent, and there's statistical ways to account for that, But you are going to need a somewhat bigger trial. So what's the intervention?

Well, intervention is what its name might seem for it to be. It's tight control. In this case, tight control meant we're going to take biologic naive people who need ACEST criteria for spondyloarthritis and they're going to have a tight control protocol applied at that center. They're going see the rheumatologist once a month, every month for a year, and there's going to be a treatment escalation protocol according to a disease activity measure, the ASDAS, that frankly most U. S.

Rheumatologists don't measure in spondyloarthritis patients. The interesting thing about this trial, they didn't use the same measure to escalate care as for their outcome. That's actually a strength because otherwise if you're using the same measure, if this was the DAS 28, for example, in RA, you know, it becomes a little bit self fulfilling if you're escalating according to a number. Of course that number should be better at the end of the study in the intervention arm. So these investigators I think took the high road, they're measuring something at the end that isn't quite the same thing as they're escalating treatment to look at the outcomes.

They also looked at a variety of other outcomes, and it's a bit of alphabet soup. Bottom line, what did it show? It showed that overall for the primary outcome, there wasn't a significant difference. There wasn't a significant benefit in the tight control arm. The difference in their main outcome, which was the ASAS Health Index, which is kind of a global measure of disease activity as it affects overall patient function, there was a delta of roughly ten to fifteen percent in that outcome and multiple other outcomes.

So not trivial, but it's not an amazing difference. The primary outcome wasn't statistically significant. The p value was point zero nine. Some of the other things like the ASAS 40, again, the delta 10 to fifteen percent range. So modest, probably clinically relevant between groups, but not extraordinary and overwhelming.

One has to think implication wise though, you know, do patients even want to come back once a month? The other thing that you need to consider is, you know, what proportion of people needed biologic therapies? These are biologic naive individuals. They could have been on NSAIDs. You know, maybe the alternative approach, just put everybody on a biologic that has spondyloarthritis.

If you had spondyloarthritis, that's maybe what you would want. You know, give me my best shot of doing great. So in the intervention arm, fifty seven percent of people went on a biologic, so clearly not everybody, not even most people. There's, you know, just over half. In the usual care arm, it's about twenty seven percent.

So the fact that not everybody got put on a biologic and not even most people in the intervention arm to me makes good sense to rebut the notion we should just put everybody on a biologic and not worry about measuring stuff and having them come back a lot. So I do think that that was another strength. They did a health economic analysis. Not surprisingly, the healthcare perspective, you spend more money in the intervention arm if you're going to use a lot more biologics, but because it wasn't everyone, there was a fair amount of thought applied. So bottom line, I think this is a helpful trial.

It rounds out the triad of type control and RA, psoriatic arthritis, and now spondyloarthritis. In terms of the practicality of it, you know, are U. S. Rheumatologists going to do this? Probably not exactly, and I doubt most are even measuring, you know, the ASDAS or the ASAS or anything else in a formal way.

On the other hand, having a discussion with your patient, you know, here's what remission or something close to it or minimal disease activity looks like. Let's talk about that, and let's keep changing treatments until we get there. You know, we want you doing well, not just doing better. That's the notion here. I think that that concept is generalizable and should resonate with patients.

It'll take a little bit of extra time to explain, but I think that the results from this trial suggest that patients are actually going to feel better, their function's going to get better if you're adhering to the principle and the main concepts, even if the implementation in your own practice might look a little bit different. Thanks for your interest.

Hi. David Liu reporting for RheumNow for ACI twenty twenty, here from Melbourne, Australia. Zoster's the issue I wanna talk about today, and in particular, what to do about vaccination and whether Shingrix might have adverse events on our our patients or not. Now we know that zoster is a real issue for our patients, especially for those who we immunosuppress. Those are the patients who are at greatest risk, and I think we've all had patients who have suffered through zoster, suffered through postherpetic neuralgia, and really regret it.

At the same time, the first vaccine that we had, zoster vaccine, the Lyme vaccine, was an issue for these patients, at least on paper. And so we've been looking to the recombinant vaccine to Shingrix as a solution to that even when there have been global shortages. But we want to know what to do when we are able to get it. And the question always has always come about about because of the adjuvant. Now the adjuvant is there to boost up the response.

It's very immunogenic, but that gives you that burden of reactogenicity. And we've been concerned for some time now for the last few years as to what would happen to our rheumatic disease patients and their disease when we give them the vaccine. It's always been a big question mark. So Cleveland Clinic and, Tiffany Levant in particular, have looked and captured the experience of rheumatic disease patients in their six twenty two patients who got vaccinated, three fifty nine of whom had inflammatory disease. A variety of different diseases rheumatoid arthritis, vasculitis, lupus, PMR and comparing those to the non inflammatory disease patients.

The long and the short of it was that flares certainly did occur in that twelve week period after the dose and after the two doses. In fact, about one in six of those patients did have a flare at some point, but those flares were quite mild, really. Quite mild and quite manageable. There were certainly risk factors. Well, were certainly associations that the patients were more likely to get it.

Steroids at the time of the vaccine conferred a higher risk of FLAIR. But really, all these were fairly manageable, and I think that really speaks to the idea that even though maybe there's a hazard ratio of two point four for FLAIR, But this isn't something that we should necessarily be scared of and payoff is certainly there as well for our patients in terms of zoster prevention. So I think that's more reassuring data once we get access to the vaccine again, or for those of us who do have access, I think this is going to be the kind of thing which we can really bring to the clinic. For more about vaccinations, infection related rheumatic disease and the whole of ACR twenty twenty, head along to roomnow.com.