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This is an ACR twenty twenty five podcast coming to you from Chicago. Hope you enjoy it.

I'm Jonathan Kaye reporting from ACR Convergence twenty twenty five in Chicago. Today, there were two presentations in different sessions. One in a session, an oral abstract session about lung disease and rheumatoid arthritis, and the other poster about rheumatoid arthritis and depressive symptoms. But both of these were tied together, interestingly, by GDF 15. GDF 15 is called growth differentiation factor 15.

It's a member of the TGF beta superfamily. It's induced both by tissue injury and inflammation, and it's widely expressed, in lung, heart, liver, pancreas, and has diverse roles. It can increase cardiovascular risk. It can be tumorigenic. It is renal protective, and it suppresses appetite, especially in cancer.

There's even been a therapeutic trial, published which suppressed, GDF 15 levels to improve cancer cachexia. So in the Veterans Administration early rheumatoid arthritis cohort, Bryant England and colleagues identified GDF fifteen as being associated both with incident and prevalent rheumatoid arthritis interstitial lung disease. Now this is an interesting finding. It was statistically significant, and is a correlate of interstitial lung disease and rheumatoid arthritis. Now in another presentation, a poster, a group looked at about forty patients with rheumatoid arthritis and scored depressive symptoms using the PHQ nine score, and they found that GDF 15 levels were higher among those who were less depressed and lower in those who were depressed.

So there was an inverse correlation of GDF 15 levels with depressive symptoms. So it's interesting that this member of the TGF beta superfamily, which is induced both by tissue injury and inflammation, is both inversely correlated with depressive symptoms and associated with the development of interstitial lung disease in rheumatoid arthritis. This brings GDF 15 to the fore in rheumatoid arthritis and should be the subject of future studies looking at other aspects of rheumatoid arthritis. For this and other aspects of rheumatoid arthritis and other diseases at ACR Convergence twenty twenty five. Go to roomnow.com.

I'm Jonathan Kaye.

Most rheumatologists don't consider themselves as pain experts, but all of us who treat patients, of course, are going to have to manage both articular and non articular pain, but what I really want to cover is to speak to inflammatory and non inflammatory pain. Regardless of what disease or diagnosis or what the patient has that you're treating, we all have to contend with this on a day to day basis. In late breaking abstract three, doctor Leslie Crawford from Vanderbilt studied TENS, transcutaneous electrical nerve stimulation, to help patients who have fibromyalgia and the novelty about this study is a TENS device sometimes is used in physical therapy settings but in fact is often not being used by patients in an outpatient setting. She randomized almost 400 individuals to get two hours a day of tens with PT versus just PT alone. What she found is is that there were significant benefits.

Seventy two percent of patients found improvement in their pain compared to only fifty two percent of individuals getting PT alone. The other thing that I find quite intriguing about this study is not only was movement related pain improved, that's one of the features of her study, fatigue was better. And you and I have very little that we can do with good evidence about helping fatigue. So I think that the relevance here is is that TENS is an old treatment, quite safe. She's shown it to be effective in patients with fibro, even coupled with PT, to benefit not only pain but fatigue.

The second abstract I wanna cover is an observational analysis out of Mass General, where patients who are taking tirzepatide, this is one of the newer GLP one drugs, in a very large cohort of 27,000 people were shown to have a ten to fifteen percent lower likelihood of needing health care utilization for joint related problems, as you might expect, mostly hip and knee pain and arthritis, as well as a twelve to fourteen percent lower likelihood of needing opioids or NSAIDs. As GLP one drugs are becoming increasingly ubiquitous in our field, Whether GLP ones are gonna be prescribed by rheumatologists, I think, remains yet to be seen. But some of the important benefits, I think, that both of these studies are demonstrating is whether it's a TENS unit or or whether it's weight loss drugs that are now taking the world by storm, we've got some options to help manage, non inflammatory pain to benefit patients with fibromyalgia, like in the 10 study, or probably most other conditions that have non inflammatory related pain.

Hi, everyone. Professor Peter Nash reporting for RheumNow from ACR Convergence in Chicago. This is gonna be an overview of the PSA axSpA abstracts that I found interesting. There's not a lot of fantastically new stuff, so I'll just give you the bottom line from my point of view. There's a couple of papers on the difficult problem of patients with ongoing fibromyalgia type pain once you've got their inflammation under control and they, showed in one paper from the Desirea cohort that if this is the case, it interferes with the, assessments of disease activity, and the scores, and the people most likely to get this kind of issue turn out to be females with enthesitis and there's a, fibromyalgia rapid screening tool that they use.

Another abstract looked at were the upadacitinib and the JAKs seem to have a separate pain control element whether upadacitinib could improve some of this fibromyalgia ness seen in this patient population and the answer was yes it can and this may be because of a peripheral effect on GM CSF and IL-six in the peripheral tissues to assist with pain control. I've always been concerned that what we call fibromyalgia when you can't find any inflammation, no joint swelling, normally SR, CRP, these patients are prone to have a lot of enthesitis and we should examine some of these enthesial points and not write them off as having fibromyalgia and give them Pregabalin, amitriptyline, physiotherapy, and when some of them might respond to, adequate medication for their underlying inflammatory disease, upadacitinib was mentioned as an option. The other thing of interest was the oral twenty three inhibitor, Icotrokinra worked very nicely in psoriasis. The psoriatic arthritis trials are underway. It worked very nicely compared to placebo.

The IGA was the primary endpoint and something like 57 response to six percent with placebo. And these were a couple of the studies looked at different aspects. One of them looked at those difficult to treat areas like scalp, genitals, hands and feet. It worked very nicely for that and another abstract looked at biomarkers and showed that it very nicely turns off IL 17, IL 17, A and F, as well as nineteen and twenty two. There was a paper, following up the foremost and premolar study which really showed that early disease is less than four joints in over two thirds of the patients that you and I are going to see and that it stopped the progression from porcie to polyarthritis and the people who had the most risk of progressing were females, those who had no background standard of care when the trial started and those with a lot of emphasitis.

We've already mentioned a number of papers looking at the GLP-one agonists in reducing MACE in psoriatic arthritis, in reducing a lot of inflammatory rheumatic disease, lupus nephritis, etcetera. That's in a separate video. One of the questions very quickly asked from the gastro's is should you use NSAIDs in patients with inflammatory bowel disease. A paper looked at hospitalization rates and showed that if you use an NSAID, you're much more likely to be hospitalized, so it's not recommended. Another very nice paper from, Chris Richland looked further into the mouse model that he has and he injected it with sera from patients with PSA and lo and behold he could transfer the development of axial PSA and the development of classical changes in this mouse model from transferring blood and PBMCs from patients with disease to the mouse model.

What's in the serum and the PBMCs that can cause disease is the question that needs to be asked. These are bio naive patients who had their sera and PBMCs transferred. Very interesting, watch this space. There's a head to head, we need head to head. This one was against secukinumab versus ustukinumab in active PSA and lo and behold the secukinumab was superior for PASI, HAC, MDA and ACR responses when you compare the two head to head.

There was a very intriguing paper and the meta analysis recently published by Matthew Brown that again is pushing the line that inhibiting IL A and F with bimekizumab reduced the rates of uveitis. They're not going to do a separate uveitis study at this stage, but it's intriguing that blocking F can reduce the incidence of uveitis in these patient populations and they claim it's not selection bias being the third 17 to market, people not putting patients in who had a history of uveitis. They claim the background rates were normal but the rates on treatment compared to placebo were reduced with a seventeen inhibition if you block F. Is F important in the uveal tract? That I'm not so sure about but there needs to be some more work done in this area.

There's another paper from the Accura group who have a IL-seventeen inhibitor that only needs to be given every six months and showed very good efficacy. The question is if you do run into candidiasis issues, say, rather than just nuisance mouth, or you run into the rare incidents of inflammatory bowel disease, new onset, if the drug hangs around for six months, is that going to be a problem? They also have an IL twenty three inhibitor that lasts six months. That needs to be given once a year sorry, twice a year. There are even talk of extending it to once a year by changing some of the amino acids.

And the twenty threes have such a nice safety profile. I think twice yearly or yearly injections really looks very exciting with, twenty three inhibition. Finally, there's an intriguing paper looking at axial PSA and the IL-twenty three inhibitor, Ruzankezumab. Because up till now the only flaw in the twenty three landscape is that it hasn't been able to show improvement in axial disease either axSpA or the axial element of PSA has never been studied. In this study again it was a retrospective study but they looked at patients sorry it wasn't retrospective it was a study done in The US and Europe and a couple of 100 people, two thirds of them had one third derm, two thirds rheumatologists, and the patients on risankizumab had less spinal pain, less morning stiffness, less night pain, less persistent low back pain, less sleep disturbance, but they had no validated ASAT ASAS outcome measures.

However, these patients were aged about 45 as a mean, and they had very marked reduction in spinal type symptoms acknowledging that only ten to twenty percent, sorry twenty to thirty percent of them had radiographically proven sacroiliitis but they got significant improvement numerically at least in their symptoms related to axial involvement. Very intriguing because up till now the 20 three's haven't been able to show efficacy in the axial domain. The large guselkumab axial study is underway given they had a post hoc analysis of radiologically proved sacroiliitis and they showed benefit in that particular post hoc analysis. So another watch this space. Will the 20 threes work for axial?

We're gonna wait and see. So signing off. Thank you very much.

Hello, everyone. Today is day three of ACR twenty twenty five, A lot of data being presented about patients, with axial spondyloarthritis. I found these few abstracts, are very clinically relevant for our patients, is those patients with axial spondylo arthritis that have inadequate response to first TNF, what to do in them next. There was a prospective study that was presented from 31 centers. The study looked at whether those patients with axial SpA have inadequate response to TNF inhibitors should switch to a different TNF inhibitor or completely switch the class like to an IL-17A inhibitor.

The study showed that the primary endpoint at twenty four weeks was response, and the study showed there was no significant difference between the two groups. That ASAS forty response at twenty four weeks was similar between the IL 17 a switch or a switch to a second TNF. The take home message from this abstract was that this switching is an individualized decision, shared decision making between the physician and the patient to decide where to switch to the next medication. Another abstract on the same line was from a Spanish registry which also looked at switching for patients to a different TNF inhibitor or to IL-17A inhibitor, and that registry also showed that the retention and survival was much longer on patients that switched from one TNF inhibitor to another TNF inhibitor, suggesting that switching maybe within the same family may be better than switching to a different class. We did a real world study using TriNetX database where we looked at initial start, what should be their first start of biologic in these patients, and whether it should be a TNF inhibitor or an IL-17A inhibitor or a JAK inhibitor.

We found that the odds of survival were much higher in TNF inhibitors than in patients with IL-17A JAK inhibitors. These data need to be looked into further, but maybe giving us some idea about what to start first in these patients with axial spondyloarthritis. Thank you.