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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 different abstracts that I found really exciting. I want to start with this one which is two five eight three 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 a premilast 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, pardon me, 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 we think about apremolast in this domain. The next abstract I want to highlight is this 2584, which is looking at a new agent, ZazocitinibTAC-two seventy nine, an oral selective TYK2 inhibitor entitled and Achievement of Remission and Additional Improvements in Disease Activity in Patients with Psoriatic Arthritis Enrolled in this Phase IIb Trial. This new novel agent, this TAK279, seven nine, did demonstrate higher rates of remission and low disease activity as assessed by both dabza dabza, PASDAS, and dash twenty eight CRP 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 sonolokumab, a novel IL-17A and F 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 50 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 2638 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 Riviera. 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 it's not going to give you a diagnosis of spondyloarthritis.

Last abstract for you today, 2635. 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 redo that. 2six 35 direct to patient screening 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 diagnosis, 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, 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 one thousand malignancies when they excluded non melanoma skin cancer. So this is other malignancies. Now, said it's a Bayesian network meta analysis, sort of 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 it. 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, I 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 ACR twenty twenty four.

Hello, everybody. It's Mike Putman reporting from ACR twenty twenty four for RheumNow. Today, I want to talk to you about an exciting abstract. It's number 207, which was reported this morning during one of the plenary sessions. It described the efficacy and safety of Nipocalimab, an anti FcRn monoclonal antibody for Sjogren's Syndrome.

I know, this is exciting. We don't get too many positive studies in Sjogren's Syndrome and I think that we're at the beginning of a couple of them. This is just a tough area. A lot of patients with Sjogren's syndrome come to us and they already have disease activity, they already have damage, and they've already become dry and it's just hard to recoup that. And so, I think it's been a difficult place to do good research.

But, there's been a lot of of in getting outcome measures that are functional and really getting excitement in the field. And I think that we're starting to finally see some of the fruits of that labor. So this is a novel antibody. It's an anti neonatal Fc receptor monoclonal antibody. I had to look this up.

The functional thing that it does is reduce circulating IgG, which is an obviously useful thing for people who are in the business of trying to fix antibody mediated disease. Sjogren's is obviously a disease with antibodies. It's plausible that it would work. The caveat is that the TRACTIUS trial, the TEARS trial were both with Sjogren's syndrome and they're officially failed trials, although there's enough there if you squint kind of hard to convince yourself that there might be something, in it. Now, the study today was called DALIA.

It's a beautiful name. They're getting better and better at naming these trials. It was on SSA positive patients with Sjogren's Syndrome, which makes sense. The primary outcome was this clinical SDI score at week twenty four. Also, that makes sense.

We got one hundred

and sixty three patients, so moderately sized. And what they saw was a dose dependent decrease in the clin SDI. You should check my Twitter for the graph. It's actually pretty impressive. Know, you got the higher dose, you definitely did better.

Medium dose, not quite better than placebo, but close. And then placebo did less well. Now, the thing that matters to me the most though is I think a lot of these outcome measures are kind of esoteric. And for the patient report outcome measures, they looked a little bit better. There was a numerical improvement there.

And I think with a bigger trial, longer follow-up, it's entirely plausible to me that this would actually affect and positively improve the quality of life of patients with Sjogren's Syndrome. IgG is useful, so if you're going to reduce IgG, you're going to have side effects. They did see some infectious adverse events. Most of them weren't severe. Three point eight percent of people who had a severe infection needed to get IV antibiotics compared to two percent of the placebo group.

More, but not terrible. There were no opportunistic infections or severe infections, deaths, anything like that reported. So, I think overall the safety profile you would expect with an agent for this. So, what does this all mean? Well, I think this is good news for Sjogren's syndrome.

I did think that rituximab should have worked, but it didn't and it's plausible to me that there would be a benefit from something like this. Long term, are we going be comfortable suppressing people's IgG for a disease like Sjogren's? I'm a little skeptical, so I doubt this will be used for everybody or as widely as I think people are hoping. The group that I think would benefit most is this subset of Sjogren's syndrome who has hypergammaglobulinemia. Those people often have a lot of fatigue, a lot of B symptoms, and I really think some of the hypergams, some of the antibodies are being produced are driving their symptoms and just reducing that alone, I suspect would be beneficial.

So, there's going be a lot more to learn about this drug but I just think it's exciting to talk about a Sjogren's trial that was successful. Thanks so much for tuning in to all of our coverage and have a great day everybody.

Hi, this is Bella Mehta reporting for RheumNow from the ACR twenty four convention. I'm originally from New York, and there are a few very interesting abstracts that I'm seeing at ACR this year. One very interesting one that I wanna talk about right now is the late breaking abstract number 11. It is reading ANAs under immunofluorescence in an automated approach. So as we all know, rheumatologists are almost associated with ANA.

A lot of non rheumatologists say that's all we do, but, obviously, we don't. But as we know, it's a very important laboratory parameter. And especially, it's not just the positive or the negative, but the titer and what kind of pattern or immunofluorescence does it exhibit. So what the researchers did is they took thousands of images, around 13,600 images of ANA, immunofluorescence pattern, which were already read by technician who has been doing this for thirty years. So with a lot of experience reading these.

And what they did is use machine learning as well as complex neural networks, so CNN models, to automate and see if the machines can learn by itself how or what these patterns are, and not only the pattern, but also the tighter quantification. They tried a bunch of models because, you know, not each ML model would be as good. So they tried around eight machine learning models and four convolutional neural networks. And what they found is at least one of the machine learning models did very well, and they had a 96 to 97% AUC, which is sort of the prediction probability of detecting the right pattern as well as tighter. And, you know, it pretty much correlated very well with somebody who had thirty years of experience doing this.

What it tells me is that some of these tasks which can be easily visualized might be more so outsourced to the AI models as long as they can they can work well. And again, the more data we pull in, the better these models will get. And again, these days finding technicians who are so experienced with these things is difficult, so getting some help from AI might not be a bad thing. And, again, there's a lot of coverage at ACR about AI, machine learning, convolutional neural networks, and I'll be covering a lot of those. So follow me more on Twitter at Bella underscore Mehta as well as on RheumNow live.

Thank you.

My name is doctor Philip Meese. I'm a rheumatologist from Seattle, Washington and director of rheumatology research at Providence Swedish Medical Center in that city. I'm delighted, to report on an abstract about Bimekizumab is an IL-17A and F inhibitor that has been previously approved in the treatment of psoriasis in The United States and has recently been approved for the treatment of psoriatic arthritis and axial spondyloarthritis. This abstract reported on two major patient reported outcomes that are of great importance to patients. One, of course, is pain, but the other is fatigue.

Fatigue ends up being a big deal to our patients, partly because it is a phenomenon that occurs in an increased amount in inflammatory diseases and it has central brain mechanisms, and can be improved by treatment of the underlying immune disease. And thus, we saw both in pain and fatigue very significant improvements in the both biologic naive population or B optimal and the B complete trial, which is in bio experienced patients. So for example, improvement in pain. One of the ways in which pain results are reported in the pain literature are 30% or 50% improvement in pain. 30% being something that the patients can tell and is meaningful and 50% being a really significant improvement in pain.

And what was shown was that about sixty percent of the patients achieved an MCID pain and about forty percent had this really substantial benefit. We know that this is a highly important outcome for patients and showing that the majority of patients did achieve this is great. In terms of, fatigue, there was an instrument known as the facet that was used to measure this. It has several questions. It's a composite measure.

And there too, we found that a highly important improvement in fatigue occurred in at least fifty percent of patients. And this was sustained over time, over the course of two years, as was the sustainment of pain response, suggesting that not only was there a substantial effect that occurred relatively quickly, but it was durable. It lasted over time. Plus, this gives us important information to support the use of an IL-17A and F inhibitor in achieving goals that are very important to patients, improvement of pain and fatigue.

I'm Anthony Chan reporting here for RheumNow in Washington and ACR twenty twenty four. And today, I have with me professor Andrew Cope from London who is the author of the Epipra study who presented the data last year. But here at ACR twenty twenty four, there is a follow-up, information on the Epipra study. So, Andrew, welcome.

Tony, it's good to be back.

So, tell me tell us, about the trial design for the Epipra study.

Yes. So Epipra was a randomized controlled trial of 213 at risk individuals. So positive anti CCP or ACPA or together with arthralgia and these were randomized to receive one year of abatacept or placebo and then they were followed up for a year after that. And what we found and what we discussed with you guys last year was that on drug there were very few events, few people progressing to RA compared to placebo where there were a substantial number particularly over the first six months and then when the drug was stopped we saw a subset of people receiving abadacept progressing to RA but by twenty four months there was still separation of the survival curves really suggesting to us that there may be something else going on long term and prompted the follow-up.

So you followed up these patients and what's the outcome?

Yes, so we enrolled and we invited all of the Epipra study subjects to come back in for follow-up and we managed to enroll 143 of those And because there was a gap between a PIPRA and Alto, we actually there was a delay and so some of the individuals who were recruited at the beginning of a PIPRA were followed up for almost eight years and then those who were the last enrolled in the Pepro we got at least four years of follow-up. All of the 143 were followed up for at least four years in total. That's one year treatment and three years of observation.

So some of these patients were high risk of developing rheumatoid arthritis. How did they do in the follow-up phase?

So the big surprise was that was that the the separation of the survival curves persisted to just beyond four years and we saw a statistical difference there And what was interesting is when we looked particularly at the individuals who either had developed RA or three swollen joints or had started DMARD, the survival course didn't converge for almost five years.

So looking at those with positive autoantibodies, what were their clinical features? Yes, so

the really striking thing was that those individuals with high t to anti CCP or a sort of a more complex extended autoantibody profile were at much higher risk of progressing. That was true in Epipra and also in the Alto follow-up. But the striking thing was that these individuals were also more sensitive to the abadacept treatment. So we have a high risk progressive group but who appear more responsive to drug and we saw that extending out to four to five years.

And in terms of clinical features, either clinical exam or ultrasound, did you see any differences?

Yeah we had

a good look at that so one of the things that identifies risk is we do it in the clinic the MCP joint squeeze and it turns out that if you, identify those who had tender MCP joints and had these high teto autoantibodies, their risk of progression was even higher so that was one group and then we did ultrasound at baseline and every six months during the Epipra study not during Alto And those who had a PD score of one or more at baseline were much more likely to progress together with the extended serotype whereas those who had no PD signal and there were quite a lot of those individuals in Epipra, their progression rates were were much less. It's we we've we've sort of the high risk phenotype is the joint pain, the auto antibodies, the distribution of joint pain, and the ultrasound scores.

That's very positive. So there you have have it. That's the kind of longer term follow-up from the EpiprA results which was presented last year and nice to see these patients continuing to respond long term. So, Endy, thank you very much for your time today. This is Anthony Chan reporting from Washington for RheumNow in ACR twenty '24.

Hi. I'm Quelan Connolly reporting at ACR for RheumNow. I'm joined this morning by doctor Khamani Cushanad who's an assistant professor at OHSU. Kamani presented abstract sixteen eighty nine, which looked at the impact of pulmonary function reference ranges in scleroderma and how that might be inequitable across race. So Kamani, thank you so much for joining me today.

Tell me why did you feel that this research question was necessary?

Yeah, so interstitial lung disease certainly is a very important issue for all of our patients with systemic sclerosis. We know that and we also know that black individuals with systemic sclerosis face increased morbidity and mortality from the disease. We don't actually really understand why, but it's thought to be multifactorial in nature. And so we wanted to understand how potential measurement bias in pulmonary function test reference equations may affect the care of individuals with systemic sclerosis, and particularly black individuals with systemic sclerosis. Previously, and I don't think most rheumatologists think about this, or most people think about this, I didn't prior to doing the study, previously pulmonary function test reference equations included a variable for race despite the fact that race there's no true biologic rationale for that inclusion.

And so reference equations prior to 2023 included this factor. And then after 2023, a new set of race neutral equations called the

GLI corporal equations were developed.

And so we wanted to understand how the shift from race specific versus race neutral equations may affect the care of our black and white patients.

Fantastic! So clearly a very very important research question. So what did you find?

Yeah, so what we found was that the use of race specific equations, sorry, the use of race specific versus race neutral equations fundamentally affected the classification of, restrictive lung disease severity for both our black and white patients with systemic sclerosis. I think it's important to note that there's no clear gold standard in terms of pulmonary function test reference equations, but I think it's important to note that with these race neutral patients, more black individuals were categorized into more severe restrictive lung disease categories. Conversely, increased proportion of white individuals were classified into less severe restrictive lung disease categories with these race neutral equations. And I think overall it's important to, I think just for rheumatologists to have awareness that these equations exist and these shifts are happening because if you don't know that these equations are shifting, might see big shifts in your percent predicted FVC for your patients and you might not know that this is a result of an equation change as opposed to a true clinical change.

Yeah, fantastic. Did you study or did you look at or reapply the equations to your cohort and did that impact treatment or is that a next step for you guys?

Analyzed 2,900 pulmonary function tests among white individuals, around six forty pulmonary function tests among black individuals. We looked at both the race specific and the race neutral equations and looked at how that affected both classification of lung disease severity. We created a theoretical framework to think about where we identified predicted FVC thresholds for things like initiation of immunosuppression, referral for lung transplant, clinical trial eligibility. Again, we just identified these conservative thresholds just to get a better understanding of how these equations would shift care for our patients. But we found that more black individuals met these predefined criteria with the use of race neutral versus race specific.

Excellent. Well, congratulations on your work and it's clearly very, very important and important to have this awareness among rheumatologists and that we're all applying it in our clinical care every day. So thank you so much for your time. If you want more information, you can go to RheumNow.

Hi, everyone. Peter Nash here reporting from ACR Washington for RheumNow twenty twenty four, and this is another session on more JAKs. And, again, anyone who thinks JAKs 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'd expect with baricitinib. So again, the JAKs will slowly establish them selves 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 stabilized disease, improved 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, stabilize and prevent progression, 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 JAKs 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 jacket 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, was used first line and they couldn't show a difference between MACE, they couldn't show a difference between malignancy in that patient 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 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 JAK had improved disease activity and better effect on patient reported outcomes, compared to cycling to another mechanism of action. So those of 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. Bepricitinib has been presented at recent meetings.

It's a JAK one tick two inhibitor. It's underway a study in dermatomy itis. 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 TIC two coming after ducravacitinib called Zazocitinib, and they showed the efficacy and safety of two hundred ninety patients with a TIC 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 with 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 tick two before we go to a biologic in, 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 and finally, we might wanna 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.

I'm Anthony Chan reporting here for RheumNow in ACR twenty twenty four in Washington DC. I've been going around looking at posters this morning, and I came across an interesting poster that I want to share with you. I think it's interesting, because it talks about people having psoriatic arthritis before psoriasis. This is post 2328. Now usually we would think about, patients having psoriatic arthritis after the onset of psoriasis.

I work on a seventeen-fifteen-fifteen rule and that rule is seventy percent of patients will have psoriasis and then psoriatic arthritis later. Fifteen percent will have it at the same time simultaneously and another fifteen percent will have the psoriatic arthritis first before the psoriasis. And in this study from Toronto, they worked out that it was a bit lower this time and the number of patients were eight point six percent who had developed PSA before psoriasis and I'm going to share with you five key highlights from this poster. Number one disease characteristics what were they like? These patients who had PSA before PSO had a higher disability index we call it the Steinbroker score and they had more severe structural damage compared to those who developed psoriasis or psoriatic arthritis later.

Secondly, those who had PSA first before PSO, they were more HLA B27 positive whereas in the other groups they had the HLA C6 positivity which is traditionally what we see in patients who have PSO first. Thirdly, the disease activity, they looked at both groups those who had developed PSA first and those who developed PSO first and found that the mean swollen joint count was equal, no significant difference between the two groups. Number four, they had they read looked at radiographic progression and those who had developed PSA first had a higher risk of faster radiographic progression. Forty three percent of this group had more radiographic, progression compared to those who developed PSO first and this, was related to older age and also the modified steinbroker score. And finally the treatment impact.

The use of advanced therapies was protective in this group, who are at risk of radiographic progression which is the PSA first group. While only a small minority of our patients that we see in our clinic may develop, the PSA first before the PSO, it's important to, be looking out for these patients because they may not demonstrate the skin manifestations in this small cohort compared to the traditional group which have the PSOFAS. So I'm Anthony Chan. I'm reporting here for RheumNow in Washington DC. Thank you.

Hi. This is Bella Mehta reporting for RheumNow from the ACR convention. I'm from New York, and I wanted to discuss two very interesting abstracts looking at AI and ultrasound in rheumatology hand images. So the first one is late breaking abstract number four, which is basically looking at an AI model which compared the synovitis scoring, synovial hypertrophy, Doppler signals that you get on an ultrasound. When it is done by a human compared to an AI model, which was trained to detect these things.

So for patients with hand pain, they scanned twenty two joints, MCP's, PIP's, DIP's, and DIP. And they looked at synovial hypertrophy Doppler as well

as

osteophyte severity. They graded it according to the standard EULAR, OMRAT classification criteria or the Glowie score. And they had a lot of images. Right? They had 7,300 images to do this study.

And what they found is that the AI model actually performed pretty similar to what the rheumatologists who are trained in musculoskeletal ultrasound perform. So these these sort of tools might be a valid way to course antibodies because that's the best way to get to know if the patients actually have swelling or not. The next abstract, sort of on the same lines, is the late breaking abstract number 20, which is now not only automating the read the reading of the ultrasound once we have the images, But also there's a machine that they call Arthur, which which scans the patient's hand images by itself. So it it is a fully automatic machine, which is standardized and takes images from patients' hands, ultrasound images, and then they have another fully automated system which can read these ultrasounds as if it's a radio first thing is a radiograph or a technician doing it, and then the second thing is a radiologist actually reading it. And they had an automated system who could do it.

So for and they first looked at images that the computer or the AI system took, compared it with the rheumatologist, and also had a third totally blinded rheumatologist evaluate both this AI generated as well as human generated images. And the third rheumatologist whose experience with these ultrasound images is established as ground truth. So interestingly, between the AI and the rheumatologist, which is the ground truth rheumatologist, there was around 8686% similarities in their readings, whereas between the two rheumatologists, there was just 53 50 to 60% similarities in how they are reading these ultrasounds. So, basically, what I'm seeing more and more and more interest in ACR is things that we can automate machines to do for us. Given that rheumatologists are gonna be lesser and lesser and there's more requirement, automating some tasks like this might be a great thing in the field of rheumatology.

We'll see if this is open access, how expensive it is, if this actually can be deployed to clinics. But these two abstracts show a lot of promise, and I see I I wanna say that we'll start using these in the future. So with that, follow me on RheumNow and on Twitter at Bella underscore Mehta, and thank you.

Hi, I'm Quailin Connolly reporting at ACR24 with RheumNow. I am accompanied today by Doctor. Lisa Christopher Stein who gave a phenomenal talk yesterday during the great debate on the topic of mixed connective tissue disease. So Lisa, thank you so much for joining me today. Tell us,

what is MCTD? You know, Quellin, at the end of the day, I'm not sure after the great debate, I can tell you cohesively. What I can tell you is that in preparing the Great Debate and hearing from my colleagues, I learned a lot. So we classically think of MCTD as a mixed connective tissue disease. The name suggests that it is a mix of many different disease and classically we know that lupus, systemic sclerosis, myositis and even maybe some extent rheumatoid arthritis is represented in the syndrome.

But I think the reality is that it's not the right way to think about it. It's not just a mix of other things, that it is in its own right a disease. And I think what I try to convey, and hopefully swayed some people who might not have thought that way, is that we now understand that many autoimmune diseases that we see are a mix of several other features. So we can easily say that Raynaud's phenomenon, which is found in virtually one hundred percent of mixed connective tissue disease cases, is seen in scleroderma, myositis, lupus, it doesn't mean that in fact it's not its own disease, just because it shares features with another disease. I try to use an example of a platypus.

So in a platypus, we say that it can lay eggs, but it's not a chicken. It has a bill, but it's not a duck. It can actually even secrete venom. It's not a snake. It has fur, but it's not a dog.

And it seems kind of funny when you think of this analogy, but a platypus is a platypus. And what I found is that many people do not properly identify their medical platypus. MCTD was often not identified properly in the beginning. It was either undifferentiated connective tissue disease, and so one to remember is that UCTD does not equal MCTD. Or, it was probably always lupus or systemic sclerosis and was mislabeled.

So, what happened is that many people tried to discern if you follow people who are well characterized over time, MCTD, this entity, stay the same? And the answer is that in some studies between sixty and seventy one percent of people maintain that diagnosis. So I think the key is to properly identify the patient in the beginning, and in fact this is its own disease. What I would say the take home for me at the end of the talk that I'm not sure I really truly realized as much is that we owe something more to our patients. I try to make that point, but when a patient who was attending the conference came up to the microphone, it was a really wonderful moment, something I won't forget, where she said that she herself actually had, I believe as a patient of Gordon Sharp who originally described the syndrome, and she told us that she felt like she kind of never had a home because someone tried to call her maybe lupus, but not quite.

And I think that she represents how we should do better. The answer is whether we decide that the name is not a great name, whether we say this is U1 RNP disease, because one of the main features of the disease that is required is to have the U1 ribonuclear protein antibody. If we say this is U1 associated disease, usually in very high titer, then maybe we can start naming it. We don't even have an ICD-ten code here in The United States for that disease. Against the patient, they can't be part of clinical trials, and they can't often even get the medications they deserve because we don't even have a code for them.

So for me at the end of the day, it was a wonderful spirited debate. I think my colleagues did great. We had a lot of fun there on the stage, but at the end of the day is our focus and I think that the woman at the microphone who came up to tell us not to forget her is how I will remember the debate.

Fantastic. And really helpful for all of our patients. Do you think giving people the diagnosis of NCTD does that improve treatment or overall outcomes or not so much?

I think that's exactly the problem. I think that we actually don't have the ability to do that because we're still debating on how we even name this entity. So I think that if we can come to an agreement, whatever we decide to call this overlap syndrome, then we could in fact improve treatments and improve outcomes. So I'm actually glad you asked that, Doctor. Caudilley, because that's what we should be doing.

We should be doing better so that we can actually find those answers. I don't think we have them today.

We just

haven't done a good enough job.

So maybe we're getting caught in the weeds a little bit about what we're calling this but ultimately we need to characterize the patient, characterize the disease manifestations that will drive the intensity of our immunosuppression that will improve outcomes.

A 100%. And I

think we actually have precedence for that. That's what we do beautifully as rheumatologists. I think we phenotype people well. We're visual people. We take good histories.

We're very knowledgeable and observant and I think we deserve to have this conversation to do better for

the patient. Fantastic. Well, Lisa, thank you so much for your time. Lisa is the three thirty fourth female professor at Johns Hopkins and an inspiration for us all, particularly in the world of myositis, but medicine in general. So thank you so much, Lisa.

Pleasure to speak with you as always.

Thank you.

So that's it for for me. You can find out more at RheumNow.

Hi, from day three of ACR Convergence. I'm Eric Dine from New Jersey. I'm joined with Doctor. Jonathan Kay from University of Massachusetts and we're here in Washington, D. C.

And Doctor. Kay just finished a great chat about biosimilars and the experience across the world from hearing about Canada, UK and from you about The United States. Tell me first of all, if we switch from an originator to biosimilar, what would

we expect in terms of outcome difference? So a biosimilar that's been reviewed and approved by the FDA has been shown to be equivalent in both efficacy and pharmacokinetics and comparable in analytical studies and safety and efficacy without clinically meaningful differences. So it's essentially like another batch of the reference product. Switching from a patient who's on the reference product to its FDA approved biosimilar should be no different than going from one lot of the reference product to another. Someone came up to me after my presentation and said that he was used to switching patients who were inadequately responsive to adalimumab to etanercept because he was unsure about whether a biosimilar would be effective.

But there's much more risk of lack of response if you switch from adalimumab to etanercept than if you were to switch from adalimumab reference product to an adalimumab biosimilar.

Tell me, you had discussed in this talk about this concept of interchangeability. It's something we hear a lot about in terms of can you can you shed some light on what that what that means?

Sure. Interchangeability was a term that was coined by the United States Congress as part of the Affordable Care Act, which was passed in March 2010. And this is a term to imply that if a healthcare provider writes a prescription for an interchangeable biosimilar, someone other than the healthcare provider can substitute the interchangeable biosimilar for the reference product, not for another biosimilar, but for the reference product without the informing or consent of the prescribing provider. So interchangeability is a designation. The FDA came up with guidance in 2019 with a switching study where patients were randomized to either a switching arm or a non switching arm.

They were all treated with the reference product, then they were randomized. The switching arm underwent three switches from the reference product to the biosimilar back to the reference product and back to the biosimilar ending up on the biosimilar with primary endpoints being pharmacokinetic parameters. And so far there have been 14 biosimilars that have been approved as being interchangeable. Three of the adalimumab biosimilars have that interchangeability designation. But the FDA has issued draft guidance this year in 2024 that an interchangeability study may not be necessary if the manufacturer can provide data from the analytical and clinical studies that would demonstrate no expected difference in efficacy if a patient were re switched to that biosimilar.

And do have 61 approved biosimilars in The United States, 14 with the interchangeability? Not all of the 61 are on the market currently. Certainly we know that they're cheaper medications. Think the biggest question that a lot

of us have is cheaper for whom? So they're not really cheaper because they're high quality. They're less expensive in theory, but because the reimbursement system is so opaque, pharmacy benefit managers put them on formulary and the pharmacy benefit manager gets a two to 4% administrative fee based upon the list price of the drug so that the most attractive medication to be put on a PBM formulary is the one with the highest list price, which also allows the most room for discounts and rebates, not all of which are given back to the plan sponsor. So the PBM makes its profits on the basis of retained rebates and discounts as well as the administrative fee. So there's a rather odd incentive for the PBM that's disaligned with that for the patient.

So in most cases the biosimilar is less expensive but not always. But it's important that the savings be passed on to the patient in some way or else there's no benefit to the patient switching from the reference product on which they've been doing well to a biosimilar.

I think that's the most important point is that the patients see these benefits. It's hard and confusing for the patients, but I think the other speakers who have had longer term experience in other countries really talked about the transparency that's needed. So we explain what these medicines are and why there's the benefits to them and to the system.

Absolutely. So two things. One, in The United Kingdom and in Canada, there are single payer systems. In The United Kingdom, it's the National Health Service, which is national. In Canada, each province, has separate, regulations, but the provincial government is the single payer.

In The United States, we have these vertically integrated systems where CVS has its own PBM, CVS Caremark, it has its own specialty pharmacy, CVS specialty pharmacy and its own insurance, Aetna. And Cigna, the same. Cigna has its own insurance, it has its own PBM Express Scripts and its own specialty pharmacy credo. So there are benefits to the vertically integrated business, which are not necessarily aligned with those for the provider or the patient. So that has been delaying the widespread acceptance and benefit of biosimilars in The United States.

You definitely had the unenviable task of explaining the much more complicated system than the other speakers with covering The US perspective because it's definitely opaque is the right word for that.

It's complicated, but ultimately, for example, Blue Shield of California, which covers about, 40,000 Humira prescriptions each year and spends over a $100,000,000 on Humira each year, has now contracted with Fresenius Cavi for their biosimilar enlimumab and is going to be providing that at a low cost to the Blue Cross, I'm sorry, Blue Shield of California and they're going to allow patients to receive this oftentimes with no co payment required of the patient. So that's the beginning of a system where patients, where the insurer is bypassing PBMs and is going to effectively deliver biosimilars, affected biosimilars to patients at a lower cost.

That's fantastic. Last question, we know that the placebo effect is real, that people, the opposite of the placebo, that when they're expecting something bad to happen, it often will be perceived that it does, if not actually does. How do you counter that or how do you communicate with patients to help make sure that these transitions go smoothly?

Well first of all I share with the patient my comfort that with the fact that FDA approved biosimilars have been carefully studied, reviewed and approved by regulators in a highly regulated area so there should be no concern about problems that are unanticipated. There's been extensive experience in Europe and elsewhere with these molecules, so that there's post marketing experience elsewhere. And education plays a major role in decreasing the nocebo effect. There was a study called the BioSwitch Study in Nijmegen in The Netherlands where patients were informed that they were going to switch from Enbrel to an etanercept biosimilar with a lower incidence of injection site reactions and a lower cost and so it was going to benefit society. And what they found was that when they notified patients that they were going to be switched and provided them with an educational presentation made by either a nurse or a pharmacist in the rheumatology clinic, there was an excellent survival rate of drug therapy in this patient population.

So education and the physician or healthcare provider expressing confidence that this is a very appropriate therapeutic approach helps to reduce the nocebo effect and ensure the success both economically for society and therapeutically for the patient of using a biosimilar.

Well, it's definitely coming so I think it's something we all need to be knowledgeable and prepared for. So thank you very much for your time.

My pleasure. Thanks, Eric.

Stay tuned to RheumNow for lots more coverage of ACR Convergence.

Hi, I'm Doctor. Jeehao Li reporting for RheumNow at ACR Convergence twenty twenty four in Washington DC. And this morning I have Doctor. Beth Wallace, an assistant professor from University of Michigan Ann Arbor and the Ann Arbor VA. And we're going to talk about some of her work that pertains to steroid tapering.

She has abstract number zero two zero three one seven one nine, and she was also part of a scientific session 17 s 19 with discussing on this topic. So the discovery of steroid in 1950 was a pivotal moment in medicine, and it was awarded the Nobel Prize but increasingly there's scrutiny regarding its long term use and we're

going to delve into what that means for rheumatology. So Doctor. Wallace, how risky is steroid use? Well, when steroids initially came out they were touted as a miracle cure for rheumatoid arthritis. But within a few years of that seminal paper that won the Nobel Prize, we started to realize that steroids had fairly significant toxicity.

And that toxicity has really been a problem for over seventy years. We've learned a lot about the risks of high dose steroids over that time, but really only over the past ten to twenty years have we learned that even low doses of steroids and even short durations of steroids can be very toxic. Even fourteen to thirty days of steroids can be associated with increased risks of serious infections, gastrointestinal bleeds, broken bones, blood clots, and these risks really should be discussed with patients when we're prescribing steroids for them.

That duration is shorter than what we would expect because with bridge therapy it's very common we have to use it for a couple

of months. So how low is a low dose steroid and how bad or how much long term and low dose steroid are we seeing in rheumatology patients? So definition of low dose is really variable depending on who you ask. In the guidelines, it's been cited anywhere from five to ten milligrams, but the consensus now is really anything below about seven point five milligrams is considered low dose. That being said, even doses as low as two and a half milligrams have been shown to have toxicity, so we can't assume that five below five is safe.

How

much are we seeing in terms of this low dose long term steroid use and are physicians aware of it?

Yeah, anywhere from a third to a half of RA patients use steroids long term and the definition used in the literature typically for long term is more than about ninety days or three months. About a third to a half of patients who start steroids when they're diagnosed with RA are still on steroids twelve months later. And a lot of this is because we have trouble tapering people off steroids once they start, not because people mean to remain on steroids for that long.

The tapering is an interesting question. I don't think it's definitely in our guidelines to recommend to do so, but it's not routinely taught or do we know actually how to do that.

What are some challenges with tapering? Yeah, tapering is definitely an art and not a science. Part of the reason for that is the studies that have been done around steroids, which I study, focus on their effectiveness at various doses and not really their safety or the ability to get people off of them. We're realizing that now, especially since the American College of Rheumatology guidelines are now recommending against steroid use when possible in RA, but we really need more data to help us learn how to effectively get people off steroids once they start. One major problem is when people have symptoms, when they taper, we don't always know why.

We don't know if it's because it's their disease coming back, their rheumatoid arthritis coming back. We don't know if it's because they have problems, endocrinology problems related to high dose steroid use or even low dose steroid use having to do with their adrenal glands and we don't know if it's called the steroid withdrawal syndrome which is a very common complex of symptoms that happens when people reduce their steroid dose and don't have physiologic issues. So we need more studies looking at that question. Steroid withdrawal syndrome, what kind of symptoms

that be and how do you differentiate that from chronic pain or fatigue syndromes that our

patients already commonly have? It's extremely difficult to differentiate it. Way that steroid withdrawal syndrome is defined in the literature is basically any symptoms that happen when you taper steroids that aren't because of your disease coming back and aren't because of an endocrinology problem. So it's very very difficult to distinguish those things. The symptoms are very non specific.

They're things like fatigue, muscle and joint pain, can be nausea or GI upset, can be mood disturbances, and these things very commonly happen with active rheumatoid arthritis. They also very commonly happen with adrenal insufficiency or endocrinologic issues related to steroid tapering. So again, we need more data, we need more research to learn how to differentiate these things from each other. Absolutely, and I think one

of the key themes that I'm hearing throughout this conference is that we need to aim for remission, but also that remission should be steroid free. Because as you said, there's a lot of documented steroid use, but I think I saw in one of your work is that there's also stockpiling of steroids and patients may be taking annoyingly so we need to actually make a concerted effort to ask about their active use. So until we have some approaches what should rheumatologists do? Does the amount of steroid that they're started on at the beginning have any correlation with how much steroids they are on at the end? And how do you approach taper now when

we actually don't have evidence but need to inform and engage patients now? Yeah, the factors that influence how much steroids people remain on are not clearly known yet. Some that have been suggested are if you have more chronic pain, you tend to remain on steroids for longer. If your RA is more active or more severe at the beginning and if you don't get enough what we call steroids bearing treatment, so the disease modifying drugs we have rheumatoid arthritis that do not include steroids. We should really be trying to get people on adequate treatment quickly, which we've known for many years treat to target in rheumatology especially rheumatoid arthritis.

When we do taper, we should make sure patients have their disease in remission or at least low disease activity before we start. We should start relatively quickly above a dose of about ten milligrams, so reduce by ten or twenty milligrams every one to two weeks down to ten, but below ten or really 7.5-5mg we need to go a lot slower. When people have symptoms it would be helpful, it's helpful if we can try to figure out what those symptoms are from, so try to differentiate whether someone's disease is active versus they're having symptoms from another reason, But if you can't do that and you end up going back up on the steroid dose or the patient themselves goes up on the steroid dose because about a quarter to a third of patients, as you said, have a stockpile of steroids at home, resume a slower taper. That can mean reducing the dose by one milligram with a larger interval. Maybe instead of one milligram a month, it's one milligram every six weeks.

Or it could mean alternating. Instead of going from five to four milligrams, going from five every day to five for alternating. Or even from five every day to five every day except one day before. A lot of people will tolerate a slower taper like that with less symptoms.

So what I take from you from that is that it's not a one size fits all and that if you fail tapering one time doesn't mean this person is not going be able to taper down. You just have to be more cognizant of the time duration and have patience with these patients. So as we're learning more and more about the increased risk of steroid use even at low dose, it's very important as rheumatologists for us to really embrace treat to target aiming for remission as studies have shown even that difference between low disease activity and remission give better functional outcomes. Though there are more studies to be done, we need to be as the prescribers very aware of the impact we have in terms of steroid use and make a concerted effort to try to get our patients off for better outcomes.