ACR24 - JAK TYK2 Save

Hi, everyone. Jack Cush. I'm on the floor of the ACR Exhibit Hall. It's ACR convergence twenty twenty four. We're in Washington DC.

This is day one, morning one. We're excited to be here. Looks like a lively meeting. Lots of folks, lots of buzz. The exhibit floor and our booth is really happening.

If you're here at the meeting, come by, visit us. We'd love to meet you. Say hello. Give you one of the new RheumNow pens. Hope you like that.

I want to talk to you about what I think you should be doing and what's new at this meeting. You know, the meeting is is really the same meeting. Right? It's face to face and that's what people want. Some things are new.

And we have the same old sessions, the great debate. This morning they had the the year in review. We're gonna have knowledge bowl and other highlights including a wrap up at the end. But plenary sessions are have flipped. They're in the morning at 09:00, and the posters are beginning right about now at 10:30.

So that's something that's new. I think for you watching this video, how am I gonna learn the ACR? I'm gonna give you a few pointers that I think you should pay attention to. Number one, come to the meeting. See us at the booth.

Go to your favorite sessions. Number two, if you're at home, I'd recommend that you follow us on Twitter. On Twitter, you're gonna get this constant stream of information and what's happening really right to the minute. And it's almost like watching the ticker tape of what's going on at the meeting. I think that's kind of exciting, but maybe you're not a Twitter person.

And maybe you want to get a feel for what happened at the meeting. I'm gonna give you three ways that you can do that. Number one, that is at the end of every day at 6PM eastern time. We're gonna live stream the daily recap where it's gonna be me and three or four of the faculty. We're gonna review the happenings of that day and what was notable, exciting, and something you wanna take home.

Number two, starting next week when you get home, you can view the video that's gonna be called the lupus topic panel or the RA topic panel or the PSA. We have topic panels with me and four experts in lupus, RA, etcetera. And we're gonna do RA, PSA, SPA, lupus, JAK inhibitors, tick inhibitors, and IL seventeen drugs. And so that's like six different videos that you'll be able to look at. And the third way that makes the most amount of sense is to go to the RheumNow website and you might already subscribe and get a daily email or a weekly email.

But if you're an RA person or a lupus person, we have an email list and you could sign up, check the box. I want the topic email list that'll come out once a week. And if you check the box on whatever topic you like, you're gonna get an email after ACR and all the lupus stuff that we produce. So you'll have that in your inbox to review. By the way, everything I just said that's in video form will also be in podcast form.

You can listen to the daily recap podcast. You can listen to the topic panels in a in a podcast. And you can also listen to podcast accumulated podcast reports from all our faculty who are here covering the meeting for you. Hope you enjoy this meeting. I'm going to.

We'll talk more.

This is Catherine Bakewell. I'm reporting to you today, 11/18/2024 on the best thing that I saw today in psoriatic arthritis at ACR. Today, I'm actually gonna take you on a rapid fire tour of several different abstracts that I found really exciting. I wanna start with this one, which is 2,583 and it's entitled Apremilast reduces axial inflammation in patients with psoriatic arthritis as assessed by CANDON MRI scoring results from a phase four study. So what is very exciting about this trial is that Apremilast has not been considered effective for axial disease.

It's one of the things that we say absolutely new in ankylosing spondylitis, and we're considering it now, though, as potentially effective in axial psoriatic arthritis because of the results of this phase four trial that demonstrated by the CANDON MRI scoring system, which is a very detailed anatomy based comprehensive scoring system for inflammatory lesions both at the vertebral bodies and at the posterolateral elements demonstrated significantly reduced inflammation versus placebo at both twenty four and forty eight weeks. So this may change the way that we think about a cremolast in this domain. The next abstract I want to highlight is this 2584, which is looking at a new agent, zazocitinib, TAK-two seventy nine, an oral selective TYK2 inhibitor, and it's entitled Achievement of Remission and Additional Improvements in Disease Activity in patients with psoriatic arthritis enrolled in this phase two b trial. This element or this new novel agent, this tac two seventy nine, did demonstrate higher rates of remission and low disease activity as assessed by both DABSSA, DABSSA, PASDAS, and DAS 28 at twelve weeks, and we'll move forward now to phase three. So excited to see more on that.

The next one is twenty five eighty two, which is efficacy and safety of sonolocumab, a novel a novel IL seventeen ANF nanobody. These are the little bitty tiny antibodies potentially with better tissue penetration and lower vascular areas like the enthesis. This was active psoriatic arthritis, twenty four week results from a global randomized double blind placebo controlled phase two trial. This is Ian McGinnis, and it had very nice looking results with ACR fifty scores up in the sixty percent at twenty four weeks, which again is not normally what we see. No unexpected safety signals again moving forward to phase three trials.

Fantastic. Next abstract is gonna be twenty six thirty eight, defining sonographic enthesitis in psoriatic arthritis, developing a data and expert driven diagnostic criteria for the inflammatory enthesitis at the single enthesus level. This is Andre Ribiero. What I can tell you about this trial is that they were dialing down on what increases experts said, like, confidence that what they are looking at ultrasonographically represents enthesitis and a spondyloarthritis and the results were that a two plus power Doppler, very important, or four or more elementary lesions. So that would be hypoechogenicity plus thickening plus enthesophyte plus Doppler one plus for example.

Enthesophyte is not specific seen in the healthy population, so the heel spurs, as we all know, is not going give you a diagnosis of spondyloarthritis. Last abstract for you today, twenty six-thirty five. This is Doctor. Jessica Walsh's group out of the University of Utah. Direct to patient screening for psoriatic arthritis patients with psoriasis.

Pardon me. I'm going to read you that. Twenty six-thirty five, direct to patient for psoriatic arthritis in patients with psoriasis, appropriateness of rheumatology referrals, and treatment outcomes. This is important because she mailed out surveys to patients with a psoriasis asked them to undergo the PEST screening questionnaire, and they self referred to rheumatology for a positive PEST screening questionnaire. About a third of patients got a new psoriatic arthritis diagnosis, really underscoring how exciting this is as a method of finding these psoriatic arthritis patients in the community.

So with that, that's all I have for you today. Thank you for your time and attention.

I'm Richard Conway reporting for RheumNow from ACR twenty twenty four. And today, I'm gonna talk to you about an abstract presented in Sunday's poster session. This was by Mark Gibson and colleagues from King's College London. It's abstract number nine eighty nine. So this was a Bayesian network meta analysis.

And I know a few people have already glazed over at that combination of words, but I'm going to try and keep it real simple for everyone. And we'll try not to get too bogged down in the details. But I think it's an important and provocative study that's being presented. So this was looking at malignancy. And it was looking at JAK inhibitors, TNF inhibitors, and patients on placebo, and trying to compare those different groups.

It was across inflammatory diseases. So there's patients with rheumatoid arthritis, with psoriatic arthritis, with psoriasis, and with inflammatory bowel disease, and axial spondyloarthritis. They included 196 studies. So this is a large meta analysis. They had over 120,000 patients and one hundred and thirty thousand patient years of exposure.

There were sixty eight thousand patient years of exposure to JAK inhibitors, fifty six thousand to TNF inhibitors, and ten thousand to placebo. During this, they saw just over a thousand malignancies when they excluded non melanoma skin cancer. So this is other malignancies. Now, it said it's a Bayesian network meta analysis, so the figures they report as a log ratio, which is we're not used to looking at that. It's confusing to us.

So I'm not going to get too bogged down in this. If you want to go check out the poster, please do for those finer details. But I'll just stick to the bottom line of what they found, because I think it's very interesting. So they found that TNF inhibitors at a significantly lower risk of malignancy than JAK inhibitors. So we expect this given oral surveillance.

So this kind of fits with our priors. But then it got really interesting. So TNF inhibitors compared to placebo have a significantly lower risk of malignancy. JAK inhibitors compared to placebo seem similar for any type of cancer. And JAK inhibitors seem to have a lower risk than placebo for hematological malignancies.

So this is a very provocative study, would say. It's kind of jiving with what some of us have been saying about oral surveillance, that maybe it's not that the JAKs are bad, it's that the TNFs are good at preventing malignancy. It's one meta analysis. We can't place too much weight in it, but I think it's a very, very interesting one. So I'm Richard Conway.

You can follow me on Twitter at RichardPAconway. Remember to tune into RheumNow for all the best coverage from ACOR twenty twenty four.

Hi. This is Bella Mehta reporting from from ACR twenty four for RheumNow. And I came across a very interesting abstract, abstract number seventeen eighteen. It is discussing whether to hold or not to hold JAK inhibitors or IL seventeen agents when patients get COVID nineteen injections. So I get this question a lot in my clinic.

You know, patients with RA or spondyloarthritis, they've they messaged saying, do we need the boosters? And most likely, we'd be like, hey. These guys are immunosuppressed enough. We'll give them boosters, but should we hold them? So this was a study by Jeff Curtis and colleagues using the COWA study, which is a multicenter randomized control platform trial.

And they took patients with rheumatoid arthritis as well as spondyloarthritis. And they use the energy research network, so pool of rheumatologists who are interested in research and contribute data. And there was a one to one hold versus not hold randomization where some patients were asked to hold their medications and some were not. And what they found was that when they saw the the group that held the biologics were more likely to flare than those who were not. And, also, they did measure, like, the antibodies, and they found that the antibodies antibody response groups were pretty much similar.

The JAK inhibitors probably lower, but still enough that I don't think they recommend holding either JAK inhibitors or IL seventeen agents when giving COVID nineteen boosters. So that's a big take home message, especially useful in clinical practice. And last year, the same group talked about TNFs, and they they decided, looking at the data, that even TNFs and abetacept both don't need to be held during the vaccinations, especially boosters, which is gonna be a yearly thing with our patients. I hope this helps. And with that, I'm signing off here.

Please follow us on RheumNow and follow me on Twitter at Bella underscore Mehta. Thank you.

Hello, everyone. I'm Mike Putman reporting from ACR twenty twenty four. Today, wanna tell you about five zero one which reported the results of one of the results of the jackpot study. I'm very excited to be interviewing Doctor. Kim Lauper from Geneva for that.

So Doctor. Lauper welcome and I'd just like to start by asking you so what did you do here with the Jackpot study? What was it all about?

So Jackpot is a collaboration of register that we started because we wanted to look at safety and effectiveness of Jack in The Middle East. We have up until 21 register that work together to answer research questions.

I think it's a fascinating topic and in the wake of the oral surveillance study, I think we've all been very concerned about JAK safety and then also, just interesting comparing DMARS. There's not a lot of comparative effectiveness research And one of the things I have always heard about and wondered about is whether or not JAK inhibitors work faster than TNF inhibitors. And so that kind of piqued my interest in this abstract. So why don't you tell us about what you studied here and what you found?

So yes, so the idea was really comparing most of the second line treatment we have in RA. So we wanted to compare JAK inhibitors, TNF inhibitors, IL-six inhibitors, and abatacepts and see if there was one of this treatment that was acting faster. And for this, we collected data from 12 of the registers of Jackpot that had data on three or six months after starting the treatment. So what we saw is that all the treatment really act really fast in the first two months, then they act a bit snowier, and in terms of CDI, pain and HAC. And then we compare them adjusting because of course it's an observational data, so there were some confounders, so after adjusting, what we saw is that Jackie and TNF inhibitor were still faster in terms of CDI, HAC and pain than the other treatment, which was surprising for us.

Yeah, I thought that was surprising for me as well. I would have expected Jack's to be faster based on what I knew already, but the curves on your poster really looked superimposed. There was no real difference between them. So quite an interesting finding. Were there anything else that you gleaned from your data that you thought would be clinically relevant for folks?

So thought abatacept was a bit slower than the other one, what I can say is abatacept, really have not a lot of patients that were really in early RA. So have we seen that abatacept maybe works better in early RA? We can't say anything about that in our data.

That makes sense. I always like a measured conclusion. Well, I think this is a very interesting study. It definitely will at least impact the way I see starting DMARDs. I think my preference has been trending towards TNFs as first line, especially given some of the safety data.

So final question for you, is that your practice as well or how did this change your practice?

Yeah, so I'm really more comfortable starting with TNF inhibitors because I see that I act really faster and that's then gonna be my practice.

Alright, I love it. Well thank you so much for joining me. Thanks so much for following all of our content on RheumNow. You can follow me at EBRoom and Doctor. Lauper what was your Twitter

handle? KLauper.

Alright. I follow her as well and everyone else should too. Thanks so much for having us and, hope you're all enjoying the meeting.

Hi everyone. Peter Nash here at, ACR Washington twenty twenty four reporting for RheumNow. Today we're going to discuss what we saw at this meeting on JAK inhibitors and anyone who thinks they're going away really needs to take another look because there was over 50 abstracts on JAK inhibitors and they covered all kinds of different aspects of therapy. So one of the first things that we'll talk about is JAKs and herpes zoster vaccination, which is an important issue for most of our patients now. There are a couple of abstracts on that.

Many abstracts on safety that we'll delve into. Lots of abstracts on novel indications for the use of JAKs as well as novel JAKs themselves that we can discuss. Abstracts on combination therapy, JAKs and other b DMARDs. Things about the JAKs signature, the JAKs signaling, trying to understand a little bit more how JAKs work, proteomics, and even combination therapy as we've discussed. So if we take tackle some of those and to summarize them, they showed in a Spanish study and it was followed up by, Jeff Curtis that being on a Jack particularly long term Jacks blunts your response to zoster vaccination and I'm talking about the inactive Shindrix recombinant vaccine.

So the response is blunted, you have a lower, antibody levels, you have suppressed CD four and CD eight cells, you don't get the same response. So it makes sense to vaccinate people before you put them on their JAK inhibitor if you can and it's something really to think about early on in the patient's journey because Jeffrey Curtis showed that if you stop for fourteen days it makes absolutely no difference to the blunted response so to say we're just going to interrupt therapy for a couple of weeks the response is still blunted it's probably adequate but not not as good. So there are lots of other issues that we can discuss. Safety of course was a major, area where we had many abstracts. Why?

Because oral surveillance just about devastated the JAK market. There were abstracts looking at the effect it had on prescribing and mostly initially prescriptions dropped off only to pick back up again over time but it did tend to push the Jack's into the third line of therapy rather than the first line unless there was a good individual patient reason to go first line. There were meta analyses of the trials that were undertaken where they tried to compare JAKs with TNFs and they looked at all the usual stuff but this particular trial looked at malignancy but excluding non melanoma skin cancer which we know the JAKs have a signal. So they meta analyzed a 198 studies including a 123,000 patients, a 133,000 patient years of exposure and they came up with a background malignancy rate in these populations of RA, PSO, PSA, IBD, AS of about seven point seven per thousand patient years of exposure and the TNF's bottom line showed that there was significantly less risk of malignancy with the TNFs compared to the JACs and even the TNFs compared to placebo and there wasn't much difference between the JACs and placebo. So the reasoning for that is a little hard to understand however there's two issues one that TNFs might well be protective and that might have explained the difference that popped up in oral surveillance and the JAKs like to suppress NK cells and NK cells are involved in viral, and neoplastic surveillance.

Personally I don't believe the lung cancer story from oral surveillance, if you have a good hard look at the actual numbers you'll find out of fourteen hundred in each arm the Jack side had forty more chronic smokers, the TNF side had forty less ever smokers and you only had to move seven cases from one side to the other and there was no difference between the two arms and if you look further at other malignancies in oral surveillance melanoma five to one on TNF side compared to the JAK and prostate cancer three to one on the TNF side compared to the JAK. So I think it was a quirk of the study but there's definitely a non melanoma skin cancer signal. Now there have been a number of other papers as we'll briefly mention combination studies, a very small case series, I think combinations are here to stay for the very difficult to treat PSA patient where you combine one of the safer drugs the 17s and the 23s with either a TNF or a JAK. One group combined JAK plus TNF and low and behold they got lots infection and I wouldn't recommend that as a choice.

So the combo studies are being done and then new indications like dermatomyositis is a study that's being promoted and uveitis, JAKs being used as a treatment and ILD where the JAKs have been shown to stabilize and prevent progression but complicated by chest infections in one case of TB. So lots of different aspects of JAK inhibition here at Washington, RheumNow twenty twenty four, we'll discuss the novel JAKs and the novel indications another time. Peter Nash signing off.

Hi. I'm doctor Janet Pope here at RheumNow at Washington DC ACR twenty twenty four. I wanted to talk about things that will change my practice in polymyalgia rheumatica. So I'm gonna talk about a finding that I never thought about too much, and I'm gonna talk about treatment. So the abstracts I'm gonna cover are zero eight five nine, zero eight five eight, and one six nine seven.

So the first abstract I'm going to talk about is really looking at polymyalgia rheumatica and aortic dissections compared to age and sex matched general population in a very large database and compare it with GCA. Not surprising, aortic dissections were very high in GCA, about five times the background general age match population. However, they were a little bit higher as well in PMR, and we have to always remember that probably twenty percent of our PMR patients have either clinically relevant concordant GCA or maybe smoldering vessel disease and they're not diagnosed. Will I start imaging patients more? No, but will I think about it when I'm uncertain or their PMR isn't responding to treatment properly?

I will and I'll probably move on to see if it's GCA. Now a couple things that will transform my practice, so there was a nice study looking at PMR starting with four milligrams of baricitinib going down to two milligrams and then following over time and then RCT or giving steroids alone. Steroid tapering was better on, baricitinib and it was a strongly positive study, I think it's pretty neat. Another study that kind of disappoints me but it's no surprise, it's not in guidelines or anything was the failure of methotrexate in polymyalgia rheumatica, a nicely designed randomized controlled trial and what it showed that methotrexate plus glucocorticoids was no better at steroid tapering or any outcomes than glucocorticoids alone. Barry in, methotrexate out, it seems, and we'll wait for more data over the meeting and beyond.

Follow me at Janet Burdo. Thank you.

Hi, this is Eric Dine from New Jersey here at ACR Convergence Day two. We just wrapped up a great day and I'm here to talk about some of the oral rheumatoid arthritis abstracts that were presented. So, we had a wonderful afternoon session where one of the things that we talked about, the first abstract was seventeen forty three which looked at the difference between low disease activity and remission. The goal is we love having patients in remission, but, you know, from the guidelines, we often say that that low disease activity is good enough that we got them pretty close so we don't need to up titrate their medicines to the highest degree. But is there a difference between LDA and remission?

The study looked at LDA, which is, again, that C. Diffeile less than 10, remission less than 2.8, and they also had another group of very low disease, which is between the two point eight and six, kind of the lower part of the very low disease. What they found is that, particularly when you look at that higher level of the lower disease activity between six and ten, the patients did not do as well as those patients in remission activity. They were not feeling as well. Their patient reported outcomes, their fatigue, their pain were notably higher.

It's not a surprise, of course, that they're not quite as good, but it did have significant impacts and it showed that they were utilizing health care more. They were using ambulatory devices like canes more. And so this is a suggestion that says, maybe we should have a little bit of a higher target. Maybe we should be going for a little bit better disease control. If not remission, maybe a c die of under six for a very low disease control.

So I I think that is something that that we can change our practice with and and take into account when we see someone who's kind of has that sea dive eight or nine doing kind of okay, but, you know, maybe not well enough for for what we want. The next oral abstract that came just afterwards was seventeen forty five which was taking a look at the oral surveillance study again. So, we've talked about the oral surveillance a lot over time. They did another post hoc analysis, but I think this one really adds a little bit more color to what we've heard. Of course, with the oral surveillance, we know that the main takeaway was tofacitinib was not non inferior to TNF inhibitor, that that JAK inhibitor showed that there was the higher MACE events.

One question they had though is what if we specifically look at statin usage? Does that make a difference? And what was interesting was first of all, at baseline, there was not enough statin usage in the group. Only, you know, less than a quarter of patients were using a statin. And of patients that had the known risk factor of MACE events, it was fifty percent of them.

Half of them were not on appropriate treatment for someone who has had a history of a MACE event. In the patients that were on a satin, they did as well as the patients on TNF regardless of if they were in the TNF or TOFA category. So that provides some reassurance to me that if you have a patient that has been doing well on tofacitinib and they're worried about their MACE risk, then maybe you can still do it as long as you're doing the other preventative things well or secondary prevention by having them on a statin, you know, for appropriate care. And this is something that I think is helpful, give some more information as to why patients may not do as well on the TOFA. Again, you know, they weren't on the appropriate background therapy with a statin.

And so, you know, there's always more information we can glean when we go into those numbers from the oral surveillance. So I thought those were two of the highlights from that oral session and a lot more that me and my colleagues will be having on RheumNow.

Hey, everyone. My name is Brian Jaros, and I'm reporting to you live from ACR Convergence twenty twenty four in Washington DC. I'll be telling you about abstract number thirteen sixty two. So as we all know, as rheumatologists, rheumatoid arthritis is one of our bread and butter conditions that we treat, and one of the most common diseases that we see in rheumatology. We're lucky enough now that we've developed really an arsenal of treatments that we have to offer patients with rheumatoid arthritis.

That leaves us with the question of always which medications will be the most effective. Several groups have sought out to kind of answer this question, and one group in particular is trying to see is there a particular type of JAK inhibitor that's more effective for rheumatoid arthritis compared to the others? Of course, this is really relevant to our patients. If we can pick a JAK inhibitor that we know upfront has better data, has better success for putting people into remission, it'll hopefully decrease the amount of time we spend cycling through meds and getting patients to an area where the disease is quiet. So this abstract is from Peter Taylor, et al, and they used real world data to complement trial data that's been shown in the past regarding this question.

They had a really clever design to try to increase the power of this study where they sent out surveys to rheumatology practices internationally throughout North America, Europe, Japan, many countries being involved, and they included patients who had rheumatoid arthritis and had been treated with any kind of JAK inhibitor for at least six months. Now, when they sent out these surveys, they were asking physicians to report on outcomes of these patients, specifically DAS28 scores, outcomes of pain and fatigue, and outcomes of compliance to the JAK inhibitor that the patient was prescribed. They then took all of this data back and tried to look for statistically significant differences between the different types of JAK inhibitors. Ultimately, they accrued a pretty good sized population of 1,400 patients, a majority of whom were taking upadacitinib fifteen milligrams, and some other patients taking mostly tofacitinib or baricitinib. Analyzing this data, they found that patients on upadacitinib fifteen mg compared to the other JAK inhibitors were actually more likely to achieve DAS28 remission in comparison, and this was on the order of about fifty four percent of patients on upadacitinib achieving DAS28 remission compared to an average of forty four percent on the other JAK inhibitors.

An absolute difference of ten percent between medications is significant, both statistically and clinically, for when we're treating our patients. There are other outcomes in terms of patient reporting fatigue and pain mirrored this DAS28 response. They saw that patients on upadacitinib had less fatigue, higher rates of decreased pain, and actually higher rates of compliance, which is of course multifactorial. It might suggest that the patients had less side effects or maybe just also suggests that the patients had more success with the medication, were feeling better, and were more likely to stay on it. The study is really important because we've had meta analyses of phase three trial data which have suggested that numerically upadacitinib might be more effective compared to other JAK inhibitors in RA, but this is one of the first studies to look at real world practice data, and again, internationally representing a huge body of patients, and further demonstrate this finding.

For me, I might now reach for upadacitinib a little earlier compared to other JAK inhibitors given the choice in treating patients with rheumatoid arthritis based on this data complementing the trial data, again, these post hoc analyses showing that upadacitinib might be more effective in putting our patients into remission. That's all I have for now. Thanks for listening and keep tuning into RheumNow.

Hello, everyone. I'm Richard Conway reporting for RheumNow from ACR twenty twenty four. What an opening day we've had here at ACR. As you know, I'm a big vasculitis guy, and it's been a great day for vasculitis. In the opening plenary session of ACR, we've two massive vasculitis abstracts have landed.

And I've already written an article on the TAPER study, and that should be up on RheumNow. So go check it out there. And that is a landmark study and is going to change clinical practice. But I'm here now to talk to you about the other study that was presented, which is the SELECT GCA study. It's a study of upadacitinib in giant cell arteritis.

It's abstract number seven seventy. So this study compared upadacitinib on a twenty six week steroid taper to a fifty two week steroid taper on placebo. There were two different upadacitinib doses, there was fifteen milligrams and seven point five milligrams. The 7.5 wasn't really as good, so we'll just forget about that and not talk about it anymore. So we're focusing on the fifteen milligram dose, which is the same dose that we use in rheumatoid arthritis, so the dose that we're used to using.

Now, this study is the largest study ever done in giant cell arthritis, four twenty eight patients recruited. Primary outcome here was sustained remission at week fifty two. The numbers here for the upadacitinib group, it was forty six percent were in sustained remission at week 52. And for the placebo and fifty two weeks sterile taper, it was twenty nine percent. When you first see those numbers, they might not sound terribly impressive.

But if you think back to the GIACTA study of tocilizumab, they are quite similar numbers. And in fact, I would say that these two studies are two of the most positive studies that we have in rheumatology. This is the biggest impact that we see from a drug in changing outcomes for patients. The other thing we saw here, again, very similar to what we saw in GIACTA, is that upadacitinib group got much less steroids. So they were getting twenty six weeks instead of fifty two weeks.

But of course, if they've been having relapses or whatever else, they'd be going back on steroids. But it ended up that they got about half the steroids, 1.6 versus two point nine grams. So I've mentioned it a couple of times and that this study reminds me so much of the GIACTA study of tocilizumab. The results are very similar, the design is very similar. And coming out of it, you'd be hard pressed to say which of these two drugs is better.

In fact, they look so similar that it could really be a flip of a coin between them. And that brings us to the crux of the potential problem for how this trial will get into clinical practice, in that we have the JAKTA study, which is seven years ago now, it was published, we have tocilizumab available, we're using it in giant cell arteritis. This drug seems to be as good. But we couldn't reasonably say that it's better. And then there is all the other stuff that's gone on with the JAK inhibitors, regards safety warnings, regulatory issues, and then potential reimbursement issues.

And it's quite hard to know at the moment how upadacitinib is going to fit into the giant cell arthritis disease management algorithm. I think we see with tocilizumab that it's extremely effective in giant cell arthritis. It is unusual that somebody would truly fail tocilizumab or tocilizumab would truly fail them. There are a small number of people that does happen to. There are a small number of patients who do have side effects and can't stay on the drug.

There are a small number of patients who do not want to do an injection treatment. And for these, upadacitinib might be an option. Of course, the other thing is we have other agents coming as well. There's other medications coming relatively soon to the giant cell arthritis treatment space. So it'll be an interesting time ahead.

So I'm Richard Conway. You can follow me on Twitter at RichardPAConway and tune into RheumNow for all the updates from ACR twenty twenty four.

Hi everyone, I'm Mike Putman. I'm at ACR twenty twenty four in Washington, DC. And today I want to tell you about Abstract seven seventy, which is one of the plenary sessions on the first Saturday of the morning. Now, this was a long awaited study, and full disclosure, one that I participated in but did not manage to enroll any patients. It investigated the Janus kinase inhibitor upadacitinib against placebo among patients with relapsing and new onset giant cell arteritis.

Most of the patients in the study were actually new onset, about seventy percent, and all of them were randomized to either receive either fifteen milligrams of upadacitinib, seven point five milligrams of upadacitinib, or placebo. Now, this a is really important question. We have currently one approved medication for giant cell arteritis and I think we all have been awaiting some of these trials coming down the pipeline to tell us about new mechanisms. So the interesting thing about this study is the people in the placebo group got a fifty two week steroid taper, quite a lot of steroids, similar to the prior GIACTIA study. The people who got upadacitinib all received a twenty six week steroid taper.

So for me, even if they had held serve, that probably would have been considered a success. What did they find? Even better than that actually. So at week 52, the rates of sustained remission were forty six percent in the upadacitinib fifteen milligram group versus twenty nine percent in the placebo group. So we gave less steroid and we had a substantially significantly higher rate of sustained remission at week 52.

Now those results held across many many other things that they evaluated. Facet fatigue scores, patient reported outcome measures, various other ways to assess remission response in giant cell arteritis. So I would say kind of across the board it was a successful study and one that I would expect to go on to get approval. Now a couple other things to know. The first is obviously the concern about safety for Janus kinase inhibitors.

We have not necessarily seen that with upadacitinib, but we have also not run a study comparable to the oral surveillance study where we saw that risk with Topacitinib. So something that's sort of out there in the ether that makes it a little more challenging. I will tell you when I have approached patients regarding this medication and said, I think this might work, but there's a potential risk of cardiovascular events and malignancy. Folks who are by definition over the age of 50 are all quite worried about those things and it has been a tougher sell than I think you would expect. And then the other problem, and this is a problem that's sort of endemic to the way that we run trials, is that we compared upadacitinib to placebo, which is reasonable.

The clinical question here was, does this work at all? The question that I also would like to know as a practicing clinician is, is this better than the alternatives, namely tocilizumab, perhaps some other conventional synthetic DMARDs? And at this point, we don't know that. I could see a creative network meta analysis ferreting that out, but I think in the interim it'll probably be up to clinician judgment and the particular mix of your patient's comorbidities and preferences. So this is me, Mike Putman, reporting from ACR twenty twenty four.

Be sure to follow along with all of RheumNow's coverage, and thanks so much for having me.

Hey, everyone. My name is Brian Jaros. I'm coming at you from ACR twenty twenty four here in Washington DC with RheumNow, and I'll be telling you about abstract number sixteen ninety five. So as you probably heard yesterday, a big topic in this convergence is Select GCA. And you may have heard from Doctor.

Mike Putman's session yesterday with RheumNow, but Select GCA is a trial from Doctor. Merkel et al, showing that upadacitinib at fifteen milligrams daily was more effective than a placebo fifty two week glucocorticoid taper in inducing remission for patients with GCA. Now, the abstract I'll be telling you about today is going to be presented by the same group and was a subgroup analysis of the different types of patients within select GCA who received upadacitinib versus the placebo arm and whether there were differences between the two treatment groups when the patients were stratified by different characteristics. As you can imagine, this is really important for our clinical practice. It would be really useful for us to know if certain patients, certain GCA patients would benefit more from upadacitinib initiation compared to other patients where there may not be as favorable or as different of a profile.

So many subgroups were used and in general upadacitinib at fifteen milligrams was more favorable than the glucocorticoid profile. But I'll break down a few of the particular subgroups that I found most interesting and helpful to our clinical practice. So one of the subgroups, they separated the GCA patients by new disease and relapsing disease. And when they looked between both of those subgroups, upadacitinib was more favorable than the placebo arm. And this is really helpful information because oftentimes we think about new disease and relapsing disease as different phenotypes or different severity, but this tells us that upadacitinib looks like it's effective in both of these, patient groups.

They also looked at, subgroup analysis by whether the patient had prior use of an IL-six inhibitor. And again, regardless of prior use of IL-six inhibitor or not, numerically patients with upadacitinib had a more favorable response rate compared to the placebo arm. Though there was a very limited sample size of patients who had received prior IL-six therapy due to strict inclusion criteria, so a wide confidence interval, sort of, marred the ability to draw conclusions from that subgroup analysis. Another interesting point is that patients with PMR actually did better with upadacitinib or had a more favorable response compared to those without PMR. And this brings up an interesting question in terms of future directions with upadacitinib and JAK inhibitors.

Could they be effective in isolated PMR? And I think that's an area of a lot of interest at this conference and question a lot of groups will be asking after this trial. Other subgroups that they included, included, racial groups, so white versus non white racial groups both favor upadacitinib. Smoking status, it looked like former smokers or non smokers seemed to benefit a little bit more than active smokers. And whether baseline glucocorticoid dose of less than or greater than thirty milligrams influenced response, it seemed like numerically both favored the upadacitinib group, though again with a wider confidence interval in the greater than thirty milligram group not meeting statistical significance.

The last subgroup I'll talk about is an important one which is patients who, experienced ischemia related vision loss. And actually patients who did not have an occurrence of vision loss seemed to have the most favorable response with upadacitinib compared to those who did experience vision loss. The caveat here is that the overall event rate of vision loss was very low in the group, and so again, we're looking at very wide confidence intervals, a lot of variability, which makes it difficult to draw conclusions, but may suggest that those with, ischemic vision loss have a more severe phenotype, which is not surprising and might require more intensive treatment and monitoring. The authors also used the subgroup analyses to look at their secondary endpoint, which was clinical remission similar to the primary endpoint, but adding on inflammatory markers. And again, upadacitinib fifteen milligrams seemed to really be favored in most of those subgroup analyses, actually with more narrow confidence intervals in a lot of the cases compared to the primary endpoint.

So in conclusion, this adds to our information we got from the original Select GCA data yesterday that most patients, a very heterogeneous group of GCA patients, seem to benefit from upadacitinib fifteen mg daily, which is very reassuring for our use, again, as we see a wide variety of patients in clinical practice. That's all I have for today. Check out RheumNow for more information.

Hi. I'm doctor Janet Pope here at ACR twenty twenty four in Washington, and I'm an at RheumNow reporter. So I wanna talk about as the meeting is soon drawing to a close. So, really, are JAK inhibitors safe? So first of all, there was a big absence of anything much about oral surveillance at this meeting.

So not that the safety issues of tofacitinib that we know about have gone away. I think it's kind of died down, I believe in a good way. So what did we learn from oral surveillance? There were slightly more cardiovascular events numerically than TNF inhibitors. Maybe they both reduced MIs.

That's what I would wonder about. We also learned there's more of a legacy and more studies are probably needed to know why. However, I think JAK safety is helpful because there's a lot of populations. Atopic dermatitis has approval for some JAKs in very high doses. IBD has approval for two JAKs, one in U two in UC and one in Crohn's often at higher doses than we use.

JIA has approval for JAK inhibitors. Lupus has the ongoing trials of both a TYK2 and a JAK inhibitor. The JAK inhibitor trial is upadacitinib thirty milligrams a day, so higher doses than we use in RA and GCA had the upadacitinib fifteen milligrams a day looked safe in the population of older people on glucocorticoids. So the bulk of the data of what I've seen over this last meeting is that I think the safety will continue to be monitored. I think it looks acceptable, at least in my eyes, and I think there will be an expansion of new indications for the JAK inhibitors.

So are JAKs really safe? Yeah. And I think they're here to stay. Thanks, and keep following us at RheumNow.

Hi, everyone. Peter Nash here reporting from ACR Washington for RheumNow twenty twenty four, and this is another session on more Jacks. And, again, anyone who thinks Jacks are going away, reconsider because there was over 50 abstracts on JAKs. And when I at this meeting, when I look on clinicaltrials.gov, 270 clinical trials around the world ongoing. So I've selected a couple of aspects of JAKs that were presented at this meeting.

Everyone saw the select GCA study at EULA represented here upadacitinib in giant cell arteritis, separated early, efficacy out over time. Interesting, we looked at the safety signals. There was a zoster signal and a CPK signal as you would expect and four VTEs in the treatment arm versus zero in the controls and nine malignancies if you include non melanoma skin cancer versus four on the placebo side. But good efficacy in GCA and likely to be something we will use when we're allowed to by the regulators in the future. Presented here to marry the GCA study was the polymyalgia rheumatica study called the bachelor study from France.

Small number of patients thirty four followed for about six months and they used baricitinib four milligrams for twelve weeks then two milligrams for twelve weeks compared it to placebo and you're allowed to have a glucocorticoid injection baseline at a month and that really quite nice results, very significant, efficacy compared to placebo in controlling symptoms, reducing the number of flares, reducing pain, and really, over the six months, there was no major safety issues that were different to what you would expect with baricitinib. So again, the JAKs will slowly establish themselves in the GCA PMR market, and we have to learn how to use them wisely and well. There was a number of abstracts on a difficult area to treat, which is interstitial lung disease, and they showed smallish studies, forty two patients, seventy two patients of all the Jack's in in interstitial lung disease. Bottom line, they stabilize disease, improve symptoms like dyspnea, improve infiltrates on imaging, improve joint symptoms, but you don't get dramatic improvements in DLCO. You get some improvements in FVC, but stabilize and prevent progression, which also means that this will be added to the treatment armamentarium.

There's a very nice little study from Korea where they followed where they looked retrospectively at twenty thousand patients who had had cervical cancer in early stage CIN disease. Because Jack's are have this issue of do they encourage viral replication reactivation because of the interferon pathway? So they asked the question, people cured of their CIN surgically on a JAK compared to TNF, do they get reactivation of the HPV virus? And the bottom line was there was no reactivation in this particular retrospective study, and any that they saw the rates were very low and comparable between the JAK and the TNF. So no major signal there, but I still think we should be cognizant of HPV vaccination in female patients of a young age in particular when we're thinking about this particular therapeutic option.

The Spanish did a very interesting retrospective study of three thousand rheumatoid patients followed between 2017 and 2022. And they asked the question of safety when you compare the JAK which was used third line to the TNFs which was used first line and they couldn't show a difference between MACE, they couldn't show a difference between malignancy in that population. Followed over that period of time, there was some non specific increase in what they call vascular events, cardiac events. We need to see more details about that in the paper when it finally gets published. Next study is a very common practical problem.

That is, do you cycle Jack to Jack if you're failing therapy or do you switch mechanism of action? Well, the CORE A VITAS study in The US of Rheumatoid Arthritis looked at a hundred and ninety seven patients, twenty eight percent of them cycled from Jack to Jack. And just to be aware, that first Jack was the fourth line therapy in sixty percent of the patients. So they'd already had a long journey before they got there. And they compared that with the seventy two percent of the hundred ninety seven patients who went from JAK to another mechanism of action, usually a TNF.

And they showed cycling JAK to jack had improved disease activity and better effect on patient reported outcomes compared to cycling to another mechanism of action. So though the those of us who are using an alternate Jack after one Jack's been inadequate or intolerant, there's evidence for the efficacy going in that direction. Indeed, one in four of those patients that cycle Jack to Jack went into low disease activity. If you had fibromyalgia central sensitization, if you'd failed a couple of biologics, you're more likely to be the patient who cycles between JAKs. Uveitis can be a difficult problem.

There was a very small study of nine patients that suggested the JAKs might be a treatment choice in refractory uveitis that's failed a biologic like adalimumab. We need more details when that paper is finally published, but that might be another treatment option. And finally, we'll mention the new JAKs that will be coming soon. Watch this space. Bepracitinib has been presented at recent meetings.

It's a JAK1Tik2 inhibitor. It's underway a study in dermatomyositis. It's already been studied in psoriatic arthritis and psoriasis. They had not they had a animal model, a a skin model, and they showed good efficacy on gene expression and the skin element of dermatomyositis. We await the results of the VALOR study.

There's another tick two coming after ducravacitinib called zazocitinib and they showed efficacy and safety of two hundred ninety patients with a tick two that's a million times more selective for tick two than the prior agent. It's gonna leave JAK one and JAK three alone. The supposition is you'll get less interference of interferon, etcetera, with this new agent. But the real question is where do we put the tick twos in our treatment armamentarium? In our country we have to file two conventional synthetic DMARDs before we can get reimbursed biologic therapy.

And we're forced to use methotrexate and sulfasalazine with very weak evidence in PSA and leflunomide also with not particularly strong evidence in PSA. So it'd be very nice to use methotrexate and a TIC-two before we go to a biologic if we can get good efficacy, good skin efficacy, good efficacy across all the domains with a much improved safety profile. We might want to use a TYK2 in the elderly, the frail person who has lots of co morbidities, again because of good efficacy and good safety. We might want to use it in someone who's recovering from some biologic adverse event. So there are roles and finally we might want to use it in combination.

Someone who's doing well, has a flare, needs a bit of additional help. I think the safety will allow combination studies, tick two and a TNF. I'm not sure I'll tick two and a JAK, but that stuff needs to be looked at in registries. And last of all, very interesting oral molecule that blocks the STAT pathway, leaves the JAK pathway alone. It'll target IL six and IL 17.

It's reversible, and it should then have no effect on interferon, and you lose the zoster signal, which is particularly important in the Asia Pacific, the Koreans, the Taiwanese, the Japanese, etcetera. Peter Nash at RheumNow, ACR Washington signing off. Thank you.

Hi, Dave Lou here again. Talking to you a little bit today about PMR and JAK inhibitors. I hear a lot said about, well, there's potential for JAK inhibitors to help in PMR, but what about the data from oral surveillance, the concerns there, and really let's wipe that off the table? And it's been a really interesting conversation because I think there's an increasing realisation, especially now that we've got a registered medicine for polymyalgia rheumatica in the form of cirilimab. There's been a really interesting conversation about glucocorticoid side effects in polymyalgia rheumatica, the burden of persistent disease in polymyalgia rheumatica, the fact that we have over half of patients having over a year of disease, over a third of patients having over two years of disease, we've got this massive burden of polymyalodramatica that's really been unaddressed.

And it is one of the diseases, especially as far as common disease is concerned, it really stands out as something which we've left unsolved. So, what we saw at this meeting was some data on polymyoidramatica and JAK inhibitors. I just want give you a bit of a schema first in terms of where polymyoedema therapy sits. Because we often think about refractory disease and I guess that's what we think about in rheumatoid arthritis, we think about moderate to severe disease. That's similar to refractory PMR.

We've also got newly diagnosed PMR as well. So, thinking about starting a steroid sparing agent or DMARD at the very beginning of therapy when we're first starting steroids. So, they're two different paradigms and there's different challenges with both. I guess if we think a lot about the refractory paradigm, which is where cirulimab is registered in And and JAK inhibitors make a bit of sense there because they're hitting all the relevant cytokines and in particular they're hitting the cytokines relevant to interferon, well, to the Th1 pathway in GCA and that potentially we might be stopping the risk of future GCA there in those refractory patients. And we know that JAK inhibitors have had success in GCA in the SELECT's GCA study which was presented at this meeting as well.

So, that is certainly something to think about, but that also probably does involve more persistent use of JAK inhibitors. Whereas actually in newly diagnosed PMR, there are some certain advantages to JAK inhibitors which might be of real relevance. And that's where the Bachelor study came in. So the Bachelor study was presented at this meeting, Abstract eight fifty eight, from French colleagues, from Valerie de Chevelle Pensek and her colleagues in breast, looking at baricitinib in newly diagnosed PMR. So starting at the same time as glucocorticoids, starting baricitinib then, first at a slightly higher dose and then gradually tapering down.

And what they found in fact was that in that first twelve weeks versus placebo, they found that actually baricitinib was able to deliver a seventy seven percent response rate versus a thirteen percent response rate for placebo. In fact, it's surprising that placebo was even that high. And, really, I think there's a lot of encouragement there, because this is a new therapy in an area where we don't actually have any proven therapies newly diagnosed polymyojaumatica. This is obviously not phase three level data, gives but us a lot of encouragement. I think there's a lot of reasons why we could get excited about JAK inhibitors in newly diagnosed PMR.

Firstly, they've got a relatively rapid onset. They're able to be titrated as well. The daily dosing or twice daily dosing in case of tirfosidenib means that we can titrate up and down. And so, in fact, in the Bachelor study, they looked at titrating down from four milligrammes up to twelve weeks down to two milligrammes after that. And that's certainly a very valid strategy that you could imagine rolling out with upadacitinib or tofacitinib.

And really the key as well is that we're talking about an early short, sharp burst at the beginning of PMR to try and prevent future damage. So really the safety risk is limited because we know that with JAK inhibitors, cardiovascular and cancer risk does appear to be related to, exposure when we're looking at TNF versus TNF inhibitors in rheumatoid arthritis. So, when we're talking about this context, we're talking about maybe twelve weeks, maybe twenty four weeks of JAK inhibitor at the beginning of a polymyo dramatic patient's therapeutic course. That's really quite limited risk. And of course, then the final kicker is that tofacitinib is coming off patent or has come off patent in most of the world.

And that really means that generic tofacitinib, it would be cheap to produce, could really open this up and get down to a cost which may be, while not competitive with prednisolone, is certainly in the rough ballpark. That's a key factor here for a common disease that affects a lot of people. So for plenty more on JAK inhibitors and actually putting more on polymyalgia rheumatica, you know where to go, roomnow.com. Hi, David Lou from Melbourne, Australia, reporting on ACI twenty twenty four. And really just to talk to you about JAK inhibitors and where the future lies.

And my premise to you today is that actually, while JAK inhibitors were first developed in rheumatoid arthritis, and that's where the majority of the use is, and the majority of the use apart from rheumatoid arthritis is inflammatory arthritis, the real value is going to be in other diseases. In diseases where there's great need at the moment. Because we've got lots of options in rheumatoid arthritis, we've got lots of options in PSA, we've got lots of options in AXPA, it's a crowded market. And as much as the JAK inhibitors have advantages there, and they're drugs there, a lot of the benefits are going to come in places where we're really struggling for options. And so, I'm picking out a case series today to talk about.

And I think it just really gives an example of the kind of benefit and what we might need to do to get to the point where we see true benefit in the clinic. So, this is a case series from Beijing in China of eight patients who have had upadacitinib for Behcet's disease. And the long and the short of it is they get had Behcet's as open label for twelve weeks, it works really well, the Behcet's disease activity score dropped down, steroids able to be weaned. It's all open label. So, there's all the caveats around that.

But it was really well tolerated. And it worked really well. And there are good reasons why it might work in infectious disease. A lot of the same pathways are pathways that are relevant to JAK1. Now, you might say this is a case series, since when do we talk about case series on RheumNow?

I think gives us a bit of an illustration as to where things might go. Behcet's disease is a classic example of a disease which we've really underserved in terms of therapies before and in terms of clinical trials. We haven't had good options. We've tried to co op therapies from other diseases like rheumatoid arthritis, taking methotrexate, say, from rheumatoid arthritis, and trying to fit a square peg in a round hole when it comes to Behcet's disease. And it works, it works okay.

TNF inhibitors, you know, there's clearly some role for benefit there. But we're really lacking a lot of good options in Behcet's disease and patients do suffer as a consequence. Something like Behcet's disease is a classic candidate for JAK inhibitors. And, we've seen that. We've seen previously there have been some reports about once again K series, but tofacitinib in Behcet's disease, baricitinib in Behcet's disease.

We need to do a bit better to be able to get structured investigation of JAK inhibitors in diseases where JAK inhibitors are needed, less common diseases perhaps, or perhaps just generally historically underserved diseases, so that we've got good options there. And that's going to become easier once we look at things like tofacitinib coming off patent. Because when we're able to churn out generic tofacitinib at low cost and the cost starts to plummet, then we can start doing investigator initiated studies, or thinking about clever ways in which we can look at the impact of these therapies and these diseases, trying to document that better, and then really giving these patients options. And the fact is as well, is that all the questions that come about because of oral surveillance, comparing TNF inhibitors versus JAK inhibitors and rheumatoid arthritis, all become much more distant questions when you're making a different comparison, like higher dose steroids versus upadacitinib in Behcet's disease, which is a very different story. So, hope that we can do better from that.

I hope that in iterations of ACI to come that we all look at JAK inhibitors for diseases that need it. So for plenty more on JAK inhibitors and everything else, ACR, you know where to go, roomnow.com.

Hi, I'm Doctor. Janet Pope. I'm here at RheumNow, ACR twenty twenty four in lovely Washington DC with pretty good weather. Okay. I wanna talk about when, what to use, and for how long to treat GCA and PMR.

And I'll be covering a lot and a lot of my personal opinions in this, but there was a whole bunch of abstracts of RCTs, 1695, sixteen ninety eight, sixteen ninety seven, and 1,700. So here's the take homes. Number one, cirulimumab is approved in The US and is a prednisone sparing drug. And doctor Jeff Curtis actually looked beyond that and found that cirulimumab was superior to methotrexate, looking at effectiveness from a very large database. And another group looked at a trial of methotrexate versus placebo and PMR.

And guess what? Methotrexate didn't do any sparing. So cirilimumab is in for PMR and does steroid spare. And it's for PMR that has failed steroids, or it's recurred or you can't get the dose down. Okay, what do we do in GCA?

Number one, in GCA, the standard of care in many places now is starting at the beginning of a person with proven or highly suspected GCA glucocorticoids and an IL-six inhibitor, tocilizumab, which has approval in many countries. What if tocilizumab doesn't work? What if it's stopped and the patient rebounds? What if they're partial responders? Because there's never a 100% response.

We do know in PMR, if you withdraw tocilizumab at six months, even in PMR, the disease wakes up. So we know you have to go longer in PMR. We know that a lot of the, initial trial, the approval, was based on the initial trial of tocilizumab in GCA. So here's what we know. We know that upadacitinib fifteen milligrams a day is as superior to, placebo and a more rapid taper of glucocorticoids better benefit.

We don't know how long to use upadacitinib. We know there's an IL-seventeen trial underway, and we also know that there was an attempt using, IL-one inhibition with anakinra for four months that was not successful. It was underpowered, didn't show any benefit. So I think the take home is number one, GCA, use a steroid sparing drug from the beginning. Number two, PMR.

If it's difficult to treat, you can't get the steroids down or it relapses, consider a steroid sparing drug. We already have a menu with a couple options on it for each of those diseases, and more will come. Follow us at RheumNow. Thank you.

David Lu here from Melbourne Australia reporting on ACR conversions 2024. I wanted to talk a little bit about cardiovascular risk and JAK inhibitors, just in case we haven't heard enough about it. Actually, there was surprisingly little overt mention of oral surveillance at this meeting. There's a lot of data about JAK inhibitors and cardiovascular risk, and actually other therapies in cardiovascular risk, and that's what I want to talk about today. So one poster that I saw from the Monday session of posters was looking at self reported international data from the Fares database.

So that's spontaneous pharmacovigilance reports looking at side effects and therapies. And so you can look at how reports come in from Verusly and how they relate to the proportions of other reports they have for any given medicine and then see whether there's a disproportionate amount for a certain adverse event for a certain medicine. So that's commonly done with FAERS data. So what we can do is look at our rheumatic disease drugs and then look and see what the risk, whether there's a disproportionate reporting of myocardial infarction, stroke, angina, cardiac failure. And so investigators from Louisiana did just that, looked at FERS data and looked at our medicines.

And yes, for tofacitinib we saw some increased reporting odds ratios for myocardial infarction of about one point five straight from one point six, not so much for angina or cardiac failure. But do you know what else was up there? And in fact, as far as myocardial infarction was concerned, certainly exceeded that? Prednisolone. And I think that's always a missing part of the discussion.

So as much as we talk about oral surveillance as controlled trial environment versus TNF inhibitors where both therapies had good effect, similar effect, and so therefore really had similar steroid exposure in that controlled trial environment, The reality is that the reason why we have DMARDs is to try and reduce down steroids, and steroids are actually a big part of what conveys cardiovascular risk. We actually saw another abstract from the last day oral sessions, abstract 2,673, which came from colleagues in British Columbia, looking at reported data there about steroid exposure, what happens when you stop steroid exposure, and then cardiovascular risk after that. So they looked at twenty eight thousand steroid exposures in rheumatoid arthritis patients. And what they saw was that actually there's a substantial increased risk still in patients after they'd stopped steroids. So if you'd only been on steroids for six months and then stopped after that, you still had one and a half years of cardiovascular risk after that, for cardiovascular death.

If you were on steroids for twelve months, three and a half years of risk. Twenty four months, ten years of risk. Now, you know, are some caveats on these data and there's a risk of residual confounding there, and it may not all be entirely the steroids. But certainly it's a good reminder that as much as we're worried about the relative cardiovascular risks in different DMARDs versus other DMARDs, the real cardiovascular risk we should be concerned about is prednisolone. For plenty more on JAK inhibitors, you know where to go, roomnow.com.