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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 JAK signature, the JAK 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. I'm talking about the inactive Shindrix recombinant vaccine. So the response is blunted, you have a lower antibody levels, you have suppressed CD4 and CD8 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 JAKs 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 analysed 198 studies including one hundred and twenty three thousand patients, one hundred and thirty three thousand 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 JAKs and even the TNFs compared to placebo and there wasn't much difference between the JAKs 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 1,400 in each arm the Jack side had 40 more chronic smokers, the TNF side had 40 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 seventeen's and the 20 three's with either a TNF or a JAK. One group combined JAK plus TNF and low and behold they got lots of 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 Room Now twenty twenty four. We'll discuss the novel JAKs and the novel indications another time. Peter Nash signing off.

Hi, my name is Doctor. Jihao Li, a rheumatologist from Michigan. I'm here with Doctor. Sherlyn Hurden from Duke University and I am very excited to have her on the platform because just before ACR, The Lancet Rheumatology released a series on aging and one of the commentary discussed the role of palliative care in rheumatology which is not a concept that we often talk about. So, I was thrilled to find that Doctor.

Hurdon had not one, but two posters focusing on palliative care. Her abstract numbers are two zero four and ten sixty four, and I have her here to talk a little bit more about it. So Doctor. Harden, tell me, we don't think about palliative care in rheumatology, what is palliative care?

Yeah, this is a really great question. I'm so happy to be able to answer it for you today. So palliative care is really a specialty that's dedicated to improving quality of life for people with serious illness. So that can be anything from lung disease on oxygen to heart failure, to things like cancer that we more commonly associate with palliative care. And really the emphasis is on improving symptoms, reducing caregiver burden, and then developing serious illness communication, so helping the patient prepare for the outcomes that

we hope don't

happen. So this is really unique from hospice, which is for patients at the end of their life. But palliative care is much broader and encompasses more stages of a patient's health.

I appreciate that you point out the difference between hospice and palliative care because I think that's the reaction a lot of us have. When we hear about palliative care, does it mean we're the we are withdrawing care? But it sounds like from what you're saying, it means that not only are we treating the rheumatic disease but also the multimorbid conditions and treating the patient as a whole. So are we actually utilizing palliative care and actually doing it appropriately?

So that's again another great question. You know, there's very limited data out there on utilization of palliative care and rheumatology. And actually, one of my two abstracts focuses on this question. And so, we looked retrospectively at data from our institution, inpatients and outpatients, and found exceedingly low rates of palliative care utilization. And this is mirrored by some other studies in the literature looking, for example, at patients hospitalized with lupus or patients with rheumatic disease in their last year of life.

I see. And when is the right time then to consider palliative care referral? So this is an evolving question with an evolving answer. One of my other studies kind of looked into this question at least from the perspective of rheumatologists and palliative care. And rheumatologists voiced the concern that really their top barrier to referral to palliative care is that they're uncertain about when and how to refer.

And again, kind of looking to the literature, there's not much to guide us. What we do know is that patients who have what we call a serious illness, so I mentioned this a little bit earlier, but again, thinking about patients with ILD, pulmonary hypertension, who need oxygen, or patients with scleroderma who have GI dysmotility and trouble eating. These are patients that could benefit from palliative care because they have a serious illness, high symptom burden, and at times poor prognosis with many years of life lost due to their disease.

When you talked to the rheumatologists in the palliative care, what did they recognize or identify as the barriers to being able to have this interdisciplinary care model?

So aside from the barrier from rheumatologists about uncertainty about how to or when to refer patients, the other top barrier on the rheumatology side was fear that if they referred their patient, the patient would feel that they're giving up on them. So again, I think for me that really gets back to the question you asked at the beginning, what is palliative care? As you mentioned, astutely, palliative care can be delivered alongside our other treatments or DMARDs, our biologics. It's really just a focus on quality of life. So those were the main barriers by rheumatology.

And I do think there's ways to address them. On the palliative care side, we found that overwhelmingly palliative care providers voiced concern that they had inadequate rheumatology knowledge, so specifically related to prognosis, disease complications and treatment side effects. And so again, kind of pointing to education, having a key role for addressing some of these these barriers and hopefully improving our current utilization rates of palliative care.

Thank you. So relationship and education seems really key. And the other player in this dynamic are the patients. How do the patients feel about this and do they

actually have better outcomes with palliative care involvement? So in terms of outcomes, there is no data looking specifically in rheumatology, but what we know from other disease specialties, for example in cancer, there has been evidence that palliative care, especially early integration of palliative care, actually prolong a patient's life, kind of in contrast to what I think a lot of us may think. And then in other diseases such as COPD, ILD, heart failure, you know, and some of our patients even suffer from these disease, that incorporating palliative care into their treatment team really improves their quality of life, reduces caregiver burden, and helps improve rates of anxiety and depression. In terms of what patients think about this, that's an excellent question and I'm actually really excited because I recently received an RF grant to look into this further. And so we will be serving patients across the country with lupus and scleroderma, specifically looking at what their attitudes towards palliative care is and then also looking at how do those attitudes relate to their outcomes by patient reported outcome measures.

Well, that's really exciting and we look forward to hearing from your results in the future. As we heard, palliative care is something that can enhance how we approach care of rheumatic patients. Throughout this conference, we've heard a lot about the importance of treating the patient as a whole, having a team approach, and engaging in shared decision making. Palliative care definitely seems to encompass all of that, and it's an area of interest that we should all consider so that we can improve the care of our patients. With that, thank you.

Hi everyone, Jack Cush here on the Convention floor at ACR twenty twenty four. Great meeting, even better when I run into great friend, great colleague, great mentor, Doctor. Ted Pincus. Ted, how long have we known each other?

Oh, close to forty years,

I think. Yeah.

Yeah. And he's still trying to teach me. Yeah. So we met on the on

And you're teaching me, sir.

Well, that's the great thing about education, right? It's it's always the give and take. Yep. So we met on the poster floor yesterday. Were talking about a poster that Ted did today that was about estimating using a scale that you can use at practical use for patients that'll address a lot of things that we often don't address.

Tell me kind of what you did.

Okay. So the impetus for all of this is that as you know, even before Jack was a fellow, we were taught that we should do a formal joint count on all patients with rheumatoid arthritis. Most doctors don't do that. And there's a simple reason for that, I think, which is that a joint exam can be performed in fifteen seconds that tells us whether we have two, twelve, or 22 swollen joints, and we can make a clinical decision. But in order to recognize whether we have one or two or 11 or 12 or 21 or 22, we have to spend an extra sixty to ninety seconds to write down 54 clicks or notations of a joint count.

So we developed a zero to 10 scale for inflammation, which we have found actually explains variation in the swollen joint count at our poster with a correlation of point seven versus a physician global of point three seven, so it's twice as likely to be found there. In addition though, we've added a zero to 10 global scale for the physician for damage and for patient distress. And it turns out today, and this has been found now in New York, Chicago, Nashville, and Sydney, Australia, that the scores for damage and patient distress are actually higher than inflammation. So and, unfortunately, the original 28 joint count included a score for deformity or limited motion, which has been dropped from the 28 joint count that's done in clinical care because in clinical trials, you don't include that. And so we only measure tenderness and swelling, but we should be aware of damage because we have now data of several, RA cohorts where the median swollen joint count is zero, meaning that half the patients have no swollen joints, but the median pain score remains four to five, and that's because of damaged joints and patient distress.

And that shows up on this scale

on these scales. Right?

Yes. Absolutely. That's wonderful.

That's where the data come from, Jack.

Okay. So when you are taking these scales and putting them into practice, give me a practical application as to how it works. The good one was that one right there. You see, SJC swallow a zero. Right.

And then, but these are abnormal. How does that going to affect what you do next?

Well, for example, I have seen a number of patients who've been tried on five or six biologicals who have a damage score of five and a patient distress score of five. And these patients I have to think about because all I'm really doing by giving them another medication is exposing them to side effects that isn't gonna necessarily help them.

Right.

So I think we should recognize that because that's true in all rheumatic diseases as you know. Damage once it occurs and we published only around 1979 that seventy percent of patients with rheumatoid arthritis have erosions within the first two years of disease, and it's still the case that from first symptom to biological is one point four years in our clinic. Right. All the patients have damage, which proceeds on a biomechanical basis. So it's the real issue now is early treatment if we're going to meet the best capacities of our biological agents.

So I wanna tell the audience that this man is responsible for the hack, the modified hack, the MD hack. Rapid three, and at his center, when he was in Vanderbilt, his center developed the 28 joint count. So when Ted Pincus comes with scales that you should be using to estimate what's going on, where can people start to use this? Or where is this gonna be?

I I use it in all patient. I've been doing that for twenty years. And there's a very important point that I'd like to make to anybody who is listening to, or watching this, video, which is that it actually saves you time to have an MD hack. It saved me three minutes. I used to see 30 patients a day when I was very active, and most of the doctors could see 20 or 25 because I saved three minutes on average per patient.

And the Rheumatrix takes, which is the scales with the 10 clicks, takes about twenty seconds, whereas a 28 joint count takes ninety to a hundred and twenty seconds, which we've published in the past. So you're actually saving time by using these tools and having quantitative data about damage and patient distress really helps you a lot.

Do you know the poster number?

Poster number, I have it in my pocket if

Okay. I I'll I'll I'll you look it up and I'll I'll I'll close. So make sure you tune in for more, videos and more content. Again, we everything on video is gonna show up in daily podcasts and in podcasts and whatnot. So hopefully, you'll follow this poster and this report.

Here we are.

Poster 1077. Check it out. Thanks very much.

I'm Jonathan Kaye reporting from ACR Convergence twenty twenty four in Washington DC for RheumNow. Here on the second day of ACR convergence twenty twenty four, with Rebecca Blank, doctor Rebecca Blank of NYU Langone Medical Center, who presented poster number thirteen ninety five about the effect of the microbiome on methotrexate administration to patients with new onset rheumatoid arthritis. So you conducted a prospective clinical trial where you randomized patients to initiate therapy with methotrexate either with or without butyrate. And you looked at the response to therapy?

Yeah, and so yes. So our group has been really interested in the gut microbiome, how it plays a role in pathogenesis of disease, and also how it may play a role in predicting responsiveness to methotrexate. Methotrexate, as we all know, first line drug but is only effective enough to fifty percent as a monotherapy. So we were wondering how can we increase the efficacy of methotrexate and can we do that by manipulating the gut microbiome in some way? And so we had looked at studies, basic science studies looking at mice models and short chain fatty acids which are gut microbial metabolites.

They have been found to ameliorate inflammatory arthritis in mouse models. In particular, butyrate has been shown to ameliorate inflammatory arthritis and also inhibit bone erosion, increase T regulatory cells, increase tight epithelial junctions in the epithelium. So we said why not try to add butyrate as a supplement to patients starting methotrexate monotherapy and see if we can somehow help change the gut microbiome composition possibly with the short chain fatty acid which can then enhance methotrexate response. And so that was the interest, in why we did this

So clinical do you think that the change in the gut microbiome alters the metabolism of methotrexate?

So, some of our collaborators, Rinuka Nayak at UCSF, she has found that gut microbes do metabolize methotrexate into inactive metabolites, and that those microbes coming from non responders, methotrexate non responders actually metabolize methotrexate into inactive metabolites more so than the responders do. And so what we were thinking was that butyrate could change the gut diversity into having higher abundance of microbes that did not metabolize methotrexate into those inactive metabolites.

So your findings were that there was greater response in those patients taking methotrexate and butyrate compared to those without?

I wouldn't say that. So this is a pilot study. There were only seventeen patients in the methotrexate butyrate group and nineteen in the methotrexate alone. We saw a slight trend in more methotrexate responders in the methotrexate plus butyrate group but I think what we can strongly say is that we found an increase in gut microbial diversity in the butyrate group that we did not see in the methotrexate alone group that changed over time with butyrate supplementation. And that in fact we found that there were certain taxa that were abundant in the methotrexate plus butyrate group that we did not find in the methotrexate alone that were correlating with disease response such as Fascobacterium, Clostridium, and Bacteroides.

And so we want to look further into those particular taxa to see if they are methotrexate metabolizers or not to determine whether or not they, you know, play a role in increased efficacy.

And butyrate is a small organic compound, so it should be relatively inert in terms of therapeutic toxicity?

Inert in terms of therapeutic toxicity, whether it passes through the small intestine and gets to the colon is a big question and depends on I think how the formulation of the metabolite in the capsule that it's in. There are a number of things to consider when actually administering it. But in terms of, you know, side effects, really none. Maybe some like gassiness.

So are you planning a larger prospective clinical trial to confirm these findings and perhaps be able to look at the microbiota for metabolism or metabolites of methotrexate?

Yeah, that's exactly what we want to do. So with funding, we would like to expand our trial to a larger cohort.

Well this is very exciting. Methotrexate is the anchor of therapy for rheumatoid arthritis and as Doctor. Blank said, there are a number of patients who don't respond adequately to methotrexate. And is this because methotrexate is metabolized more rapidly by certain microbiota and might we be able to alter the microbiota to prevent this from occurring? This is a very exciting area and I look forward to seeing results of your subsequent studies.

Okay. Thank you so much.

Great. So this is Jonathan Kaye reporting for RheumNow from ACR Convergence 2024. For more information about this and other studies, go to rheumnow.com.

Hi. I'm doctor Janet Pope here at RoomNow 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 matched 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 Verdope. Thank you.

Hello. I'm Jonathan Kaye reporting from ACR Convergence twenty twenty four in Washington DC. Here on the second day of the meeting, I'm with Professor John Isaacs of Newcastle in The United Kingdom, who presented poster number 1349 about withdrawal of therapy from patients with rheumatoid arthritis taking conventional synthetic DMARDs. And you developed a molecular signature that predicts flare among patients in whom therapy is withdrawn.

Yeah, that's the case. Well, a circulating biomarker signature. And we increasingly achieve remission in patients with early RA on simple drugs like methotrexate, maybe with some hydroxychloroquine. And patients are starting to ask us whether they need to take these drugs for the rest of their lives. Traditionally, we've always said yes, but because we're being asked more and more, we've started to set up studies to find out what happens when we stop drugs.

And actually, that population, if we do stop, then fifty percent of patients flare and fifty percent of patients stay in remission. The ones who flare, we can readily re achieve remission with a shot of steroid and putting them back on the original drug in most cases. But what would be really cool is if we could develop a signature which tells us when it's safe in inverted commas to to stop that treatment.

And the biomarker signature that you derived was what?

Yeah. It's it's three circulating mediators. One of them is an acute phase reactant s 100. I'm gonna say three a. I forget I forget the exact name.

There's an IL six receptor. And the third one I'm struggling to

MMP nine.

MMP nine. That was what it was. That was right. So so so that yeah. So an interesting three biomarkers.

You wouldn't necessarily associate them with with prolonged remission, but they seem to predict.

And this was a prospective trial, and it's difficult to enroll patients in trials. But if you're telling patients that you're gonna find out whether you can predict flare if they stop their drug, they must be excited about enrolling in a trial like that.

I've never found it so easy to recruit to a trial. In my in my entire career. Patients were knocking on our door to to to take part because they don't wanna take their drugs, and and so we we were way ahead of our recruitment target. So it was a a nice study to run.

So with this molecular biomarker signature of MMP nine, S 103 a, and the IL six receptor, if you find this signature, you could predict which patients might flare upon withdrawal of therapy, and you might not withdraw therapy from them. But if they don't have this signature, a negative predictive value of lack of FLAIR would be very helpful.

Yeah. That's right. And we validated it actually on a separate cohort. So we've done we've done this twice now, and it and it validates area under rock curves about 70%. So it's, you know, it's it's good enough, think.

And you're right. So so if if we then would prospectively apply that signature, we would avoid flares in about fifty percent of patients.

And this is the type of biomarker panel that is useful in patients with rheumatoid arthritis. A panel that predicts which patients do not need to continue therapy, whether patients might not respond to a TNF inhibitor with a genetic signature, or in this case with a biomarker signature, patients who might flare if they were withdrawn from their therapy. So this is very exciting, and for more information about this and other presentations at ACR Convergence twenty twenty four, go to rheumnow.com. I'm Jonathan Kaye.

Hello. My name is Rinalini Day. I'm a fellow in The UK, and I'm here at ACR twenty twenty four in Washington DC reporting for RheumNow. And I would like to highlight abstract one six seven six, which is being presented today on Sunday of the press, which is on changing the mindset of people taking methotrexate with with regards to the side effects. Now, this really caught my eye because as a clinician, we prescribe methotrexate quite a lot.

I see a lot of patients with rheumatoid arthritis in my practice, and it's often quite a significant part of the conversation about what the side effects would be. Also, many patients do come back after a while and do say they're reporting side effects such as nausea and various other side effects as well. So, this abstract really looked at whether we can use an intervention in order to just reframe those side effects to positive signals and see if that actually changes patients perceptions off whether to continue with their drug and how they see those side effects. So this was an abstract that came out of work done in Switzerland and it involved forty seven patients with inflammatory arthritis and twenty six of these patients did experience a side effect. But with the intervention, most of them were able to reframe the side effect of positive signals.

So what was this intervention? The intervention was approximately a seven minute video, which was sort of basically reframing the non severe symptoms of methexate as positive signs that the medication is actually working. And so, in the end, the group found that the mindset intervention in the form of this video reframes the role of these non severe side effects. And this looks to be a good approach to improve the symptom experience and also crucially just keeping the patients on this drug

which we

know works for conditions such as rheumatoid arthritis. This is something really to think about because actually creating a video, while it does take a little bit of work, it clearly is a good investment in ensuring that our patients are able to understand the side effects of their medications more. Provided it's framed in the correct way, it can actually improve aspects of just medication adherence, for example. So if you'd like to know more about that particular abstract, it was one six seven six. And if you'd like to know more about everything going on here at ACL twenty twenty four, do head over to the RheumNow website or you can follow me on x at doctor.

Vk. Thank you.

Hello. I'm Adela Castro at ACR twenty twenty four in Washington, DC, and I wanna talk to you about monotherapy versus combination with conventional DMARDs in psoriatic arthritis patients. I want to start with an abstract number five eighty four that evaluated the effectiveness of tofacitinib versus monotherapy versus combination therapy with other conventional DMARDs in patients with psoriatic arthritis. For this study, they included the data of patients from the core Avedas registry for psoriatic arthritis. In the total of the study population here was one hundred and forty one patients with psoriatic arthritis, out of which forty six percent of these patients were on tofacitinib monotherapy.

There was no statistical significance between the effectivity of this medication monotherapy versus combination with conventional DMARC in psoriatic arthritis. It was very interesting that it seemed that patients that were on monotherapy, they stayed longer on this medication compared with the ones that were on combination with DMARDs. On that same note, abstract five ninety five evaluated the drug survival of combination with conventional DMARDs, predominantly methotrexate, in patients with psoriatic arthritis. In this study, this was actually a large systematic review and meta analysis of 19 studies that involved over twenty eight thousand patients with psoriatic arthritis. Interestingly, which I think is also a limitation of this study, all of the studies were observational and only two of them, included non TNF, biologics.

In this study, it did show that methotrexate, particularly in combination with TNF inhibitors, seemed to improve the drug survival in patients with management with psoriatic arthritis. For more information, stay tuned at RheumNow.

Hi everyone, it's Mike Putman reporting to you from ACR24 in Washington DC. Today I want to tell you about Abstract six seventy,

which is

a very interesting randomized controlled trial of mycophenolate versus cyclophosphamide and tacrolimus. Now this is a very interesting study to me because we all have a rough sense that for patients with lupus nephritis, mycophenolate and cyclophosphamide are roughly equivalent. That was what was shown by the ALMS trial. Because of the safety profile, most of us favor mycophenolate, although in some cases I'm still using cyclophosphamide. Now these investigators performed an open label, everyone knew which group they were getting into, randomized trial of Mycophenolate Cytoxin or Tacrolimus, which I think is really exciting because I would be curious to know if there were another option in this disease.

Ultimately it was a relatively small trial. Each group had about 30 patients. What they found was surprising. Patients in the tacrolimus group, mid sixty percent response. The primary endpoint was assessed at week twenty four, complete or partial renal response.

So the tacrolimus group, sixty some percent. Same as mycophenolate group, didn't look any different. The cyclophosphamide group did a little bit worse, but I think that's probably because this was a smaller trial. I suspect if they scaled up, you wouldn't see that. But the nice thing here is that we do see that tacrolimus might be an option for induction therapy of lupus nephritis.

I would have not expected that. I have to say that I don't think this is going to change my practice immediately. The truth is that this is a very serious disease and I think I'm going to want to lead with the standard of care therapies. But if there situation where I was trying to find something else, this was quite encouraging and something I would at least think of as maybe an add on. So interesting study, would not necessarily start doing this right away, but it merits further investigation.

And given the known utility of calcineurin inhibitors in lupus nephritis, think there's certainly some biological plausibility that this could be an option. Thanks so much for tuning in to all the coverage from RheumNow, and have a great day.

I want to tell you about a study that will actually change my practice. So I found a poster six twenty seven and it was a really important clinically question. We get patients all the time referred and they have a high positive ANA, we don't find an autoimmune disease or rheumatic disease and we go I don't know what it means. So this, study was trying to address it. So they had about eight thousand five hundred patients with an ANA, didn't know what to do with it because there was no autoimmune disease associated.

So they decided to look at high titer and low titer and about two thirds of three quarters were low titer, no surprise, but what did the high titer patients have? Very interestingly they had far more liver disease, not autoimmune, cirrhosis, fatty liver, other things like that. So what does that mean in my practice? Well I think we always thought that in, autoimmune liver disease we'd see an ANA and sometimes we'd see a false positive rheumatoid factor and say cirrhosis but they were probably in those days from hepatitis C because we couldn't measure it. What I think it means is if I get a patient with a high positive ANA and I don't know why and it could be variable patterns, there were all sorts of patterns with it, I'm going to consider looking at the liver, maybe liver function, maybe transaminases, maybe even an ultrasound or FibroScan.

So we'll change what I do in clinic next week. Please follow me at JanetBirdope. Thanks.

Hey everyone, my name is Brian Jaros. I'm coming at you from ACR 24 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 52 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 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. And as you can imagine, this is really important for our clinical practice. It'd 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 potentially 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 patients 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 statistically significant 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 a 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 favoring upadacitinib. Smoking status, it looked like former smokers or non smokers seem 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 milligrams 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.

Hello. My name is Rinalini Day. I'm a clinical fellow from London in The UK and I'm here with RheumNow reporting from ACR twenty twenty four in Washington DC. Thank you for joining us for this video. I'm delighted to be joined by Doctor Chris Wincup who is a consultant rheumatologist and academic clinician working at King's College Hospital in London in The UK.

And today we are going to be talking about neuropsychiatric lupus. So for those of you who may have reviewed the program here at ACR, this is actually a relatively less spoken about set of symptoms. And so I'm really interested to hear Chris's thoughts on neuropsychiatric lupus in general, but also what we can do to raise awareness of, this particular manifestation of, lupus, which is of course a very complex condition. So thank you for joining me, Chris. So first of all, can you just tell the audience briefly about what is neuropsychiatric lupus?

Sure. So neuropsychiatric lupus, we can define easily because the ACR has already done that and it basically reports a number of symptoms the patients with lupus may suffer from involving the central nervous system and the peripheral nervous system and it's a fairly exhausted list of symptoms but sometimes we consider that there may be symptoms beyond this that are not included within that criteria. So we know that we've got good definitions they're very broad but we know that patients can present a number of different ways and it's often difficult as clinician to delineate between what is neuropsychiatric lupus due to active lupus within the nervous system versus the side effects of medicine versus damage versus something else entirely and I think that really does pay some of the challenge that we see when treating patients with these symptoms, but perhaps more importantly identifying those symptoms.

Okay. So just picking up on that last point. So identification of symptoms. A lot of our audience are going to be practicing clinicians. How can we better identify these symptoms?

And I know there's been a large body of work done in The UK recently about this.

So if you want a one word answer is how do we better identify these symptoms? That is ask. And I think asking about these symptoms is important. And I look at my own practice over recent years and, I've noticed the importance of asking about these symptoms. So I think sometimes as clinicians, particularly rheumatologists looking after people with lupus, that you think that you would identify the rate of symptoms that the patients are experiencing because we expect them to be fairly profound.

So if a patient has a seizure you would imagine that you would at least if they if you don't see that patient have a fit you would see it on their medical records the patient may tell you they've had a hospital attendance with this but from the research we've done we note that patients are often under identified even with fairly profound and obvious symptoms such as that. Now imagine you're looking at other symptoms for example hallucinations, mood disturbance, cognitive dysfunction which are a lot more subtle then you really do need to inquire about these. And some of the work that we've done in the past has shown that many rheumatologists under appreciate how many of their patients with lupus experience these symptoms and when I first saw the data I I thought well this can't be true that many patients are reporting these symptoms so I did a test myself and in clinic I started asking patients questions I hadn't asked before for example have you suffered a hallucination, have you had, auditory hallucinations or visual or tactile hallucinations, how is your mood and I think as rheumatologists we often think that we we encompass many of those in the questions that we do ask.

I'm surprised by the number of patients who do have these subtle symptoms that do very well at masking them because we're not asking about them and I think some of that is a degree of it is challenging for patients to talk about these very distress ing symptoms and so we must make an environment for patients to feel comfortable and that they'll be heard to talk about this but I think as rheumatologists we also have to take a look at ourselves and say I find it very difficult to talk about these symptoms with patients because if they do say I have got one of these symptoms we're often under trained and under prepared to know what to do with this and so close working relationships with psychiatry can also help so to identify the symptoms I'd say inquire but you will inquire more easily and more confidently if you had good relationships with psychiatry and neurology to I to understand what to do when you identify these symptoms.

Yes. Yeah. I know from my own clinical practice, is very difficult. As you say, we don't get trained. So particularly so I'm a fellow at the moment, and we don't get trained about these symptoms.

But I think actually reading about the work that's been done recently, I have tried harder to ask about these symptoms. And actually, I think patients really appreciate it. So what can we do from a research standpoint to try and increase awareness in the research world? Because clearly, there there's it's an unmet need, both in terms of how we treat these patients, identify these patients. Yeah.

What can we do from from the the the research side of things?

So I think clinically, let's imagine you've got someone with severe neuropsychiatric lupus that is fitting or psychotic or has a lymphocytic meningitis. Sometimes it's relatively easy clinically to say that's active neuropsychiatric lupus but it can be challenging because some patients will have possible other comorbidities could there be an infection in particular in the setting of meningitis so I think I answer your question about research first and foremost saying clinically it's often very very difficult even with the most marked symptoms to quantify them and we can see depending on which study you look at and which has been done, the prevalence of these symptoms are vast when you compare different papers. So we know that we have these very good definitions from the ACR of what neuropsychiatric lupus is classified as, but we should be very, very accurate in terms of our research, but we're not. And I think that even if we're looking at these severe symptoms, it's difficult to quantify. You go to the slightly more subtle ones such as cognitive dysfunction, mood disturbance, even hallucinations.

I think that what we need to do is find a way of better quantifying this. So number one comes back to what I said before, you need to ask and do the studies where you try and accurately quantify but number two I think is a rheumatologist we need something that we know that we can treat and make better. So for example if you have someone who's got proteinuria, you say they've got lupus nephritis and I will initiate treatment and if the proteinuria improves I know I'm treating that patient effectively. With neuropsychiatric lupus many patients have very normal labs, normal investigations, even their CSF and MRI scans can be normal on very simple terms. So I think we need to have better biomarkers and imaging to fully quantify that this is due to an inflammatory component and therefore you quantify it better and importantly you empower clinicians to treat that better because you see something that's abnormal that you can make better.

So I think research needs to focus on biomarkers when we have actually quantified these symptoms properly and I think new imaging techniques that can pick up some subtle neuro inflammation and there's a lot of very interesting work in MRI PET with different ligands going on at the moment that may make clinicians feel more confident in asking about these symptoms and when identifying them get the patient treated. So I think those are the areas we really need to focus on.

Great. We could talk about this all day and we have spent time talking about this before. But I think just to wrap up, can you maybe direct our audience to resources or particular landmark papers in this area that you feel that they should read if they wanna know more?

Sure. So I I I mean, I don't like to self promote, but I think one of one of the papers that I was fortunate to work on was it was a piece of work published in rheumatology a couple of years ago with Melanie Sloan as the first author in which we asked patients how frequently symptoms are and then we also asked rheumatologists neurologists and psychiatrists how frequently do you think your patients with lupus have these symptoms and just look at the figures I would just say look at those figures to start up to see how often we are wrong in terms of where our prediction of the prevalence of these symptoms are compared with prevalence actually reported by patients. So I think that's very helpful. I think resources is really important and I think resources can take a number of forms but particularly patient support organizations. So Lupus UK back home in England and the rest of The United Kingdom, but also Lupus Europe are doing a lot of work, to try and help patients when they experience these symptoms.

And I think as clinicians, we just need to talk about this more and make this more of an agenda of what we're doing, particularly in the treatment of patients with lupus.

Perfect. Yeah. No. I am I definitely also as as the reader, I wasn't involved in the work, but when I read that particular paper that Chris has referred to, I was very struck by those graphs. So I would I would recommend, listeners to go and, take a look at that particular paper.

Well, thank you for chatting with me today, Chris. If you'd like to know more about RheumNow's coverage at ACR twenty twenty four, do go over to the RheumNow website or you can follow me at doctor mini day on x. Thank you for listening.