Don’t Buy Guitars (12.6.2024) Save

Hi, everyone. It's 12/06/2024, and this is a RheumNow podcast. We're back from a long hiatus with a very long and busy ACR twenty twenty four. I want to, extend my thanks and admiration for the RheumNow faculty and reporters who at this meeting were prolific. They, in the span of just four days, they produced over 800 tweets, 56 written articles, a 117 videos, and 28 podcasts, all for you.

Any of you who are tired of ACR, well then, that's okay. Those of you who haven't really scratched the surface of it and like to learn, my suggestion is the following. One, start with Rheumatology Roundup. Artie Cavanaugh and I do that every year for the last twenty years. We did it last week.

It so far has over a thousand views. It's a one hour banter where we discuss what we thought was important, you know, themes like steroid sparing and steroid minimization and the role of GLP-one drugs in arthritis care. And we reviewed the lupus nephritis guidelines, etc. After that, maybe your next thing should be according to your favorite topic. If you're a rheumatoid person, we've got podcasts and videos on that.

I would suggest you go straight to the topic panel discussion. It's either a video or it's a podcast. So RA or lupus or IL-seventeen or PSA or SPA. We have one for everything. But for instance, the lupus topic panel, you'll hear a twenty, thirty minute recant from the experts that covered the meeting.

We have it for all the topics. If you want to stay on topic, then look out, look up the topic podcast on your favorite podcast distributor. So a few things today. We're going to get back into the news. I don't have my usual recording spot and backdrop, so you're seeing everything behind me to distract you.

All the books, all the knickknacks. I wanna walk you through the office. See all those those CDs back there? I don't know what to do with them. You know, I haven't played a CD, I think, in, I don't know, six years, but I got, like, 300 of them.

Look at the pictures. This one up here is Bobby Yore. This one over here is Mike Madono. That big one in the back is one of them is my favorite. I got that as a either it's coming out of fellowship in 1990.

It's a hand drawn chalk illustration that I requested of an anatomic artist at one of the booths. In fact, it was the Syntex booth. And I said, draw me a hand, a rheumatoid hand taking a few pills. That's from the great Vincent Perez, a truly wonderful artist. You'll notice a bunch of guitars.

The count is nine. Not all of them real. My favorite amongst them might be the second one over here. It's a Washburn. Or maybe the lap steel over here, a very nineteen fifties guitar.

If only I could play them. But, you know, the more you buy, right, I think if I buy expensive skates, can skate better. It might happen. So let's get into what was, mentionable, memorable in the literature this week. I want to begin with two articles that I think are must look must see, must read, must download for you, because they're great references and they got great tables and illustrations in them.

One is from BMJ. It's a full read review about the advances in the management of psoriatic arthritis written by Daphne Gladman and Doctor. Kharouf. Again, BMJ, the citation is in the notes, show notes. And then JAMA just yesterday published a full read review by Doctors Deyadar and Bittar on, a review of axial spondyloarthritis.

And, you know, I just put down a few facts. The delay in diagnosis is six to eight years. And here's some numbers you may not be familiar with. What's the sensitivity and specificity of B27? Sensitivity, 50.

Specificity, 90. 50, really? Well, I'm going to believe those guys than what I remember, which was much higher than that. What about an elevated CRP in active disease? Sensitivity, thirty five percent, just like RA.

It may not be elevated even though they're active, but specificity ninety one percent. X-ray sacroiliitis is about two thirds for both sensitivity, specificity. MRI is better sensitivity 78 MRI specificity almost ninety percent. It's got great tables. Download it.

It'll be a good read. It'll be a good reference if you're teaching other people. Speaking of diagnostic delays, there was another, study at ACR Abstract fourteen fifty six, the Monitor PSA study, that, said that we still have problems in the die a diagnostic delay in psoriasis, even though we've got, you know, you're getting tons of information, drug reps, articles, papers. We got more drugs than we got patients with psoriatic arthritis, but yet there's still a delay. This is a big challenge.

And, yeah, all this focus should change those numbers over time. I put up this week, a few stats from the Osteoarthritis Action Alliance. Fifty three million people in The United States have osteoarthritis, and this is going to go up significantly in the next fifteen years. Societal costs are currently 132,000,000,000. And they claim osteoarthritis is the third most rapidly rising disability behind diabetes and dementia.

That sounds right to me. A few regulatory or agency announcements, the DEA and Department of Health and Human Services has extended the lax rules on telemedicine that were established during, the pandemic. These telemedicine flexibilities are now going to run through the end of twenty twenty five. This has to do with interstate prescribing, but more importantly, prescribing medicines via telemedicine, including narcotics, without the need of an in person face to face on-site visit. So they've looked at the data and found, that it still is, a substantial benefit to patients, especially in certain areas and in certain situations.

Think, I think more of you should be doing telemedicine or practicing telemedicine. It is a big part of your future, whether you want to join it or not. J and J has submitted, a new supplemental application for its guselkumab anti IL-twenty three drug for its future use in juvenile plaque psoriasis, and in juvenile psoriatic arthritis. One with a start age of five years, other one started to six years. I'll look it up and they had done the phase two trials and the pharmacokinetic trials.

The FDA now just has to look at the data and come up with a decision. I'm going to guess we're going to see that in 2025 sometime. Another J and J drug, ustekinumab, also called Stelara, has gone generic, meaning biosimilar, a few years back. And we have yet another biosimilar of ustekinumab. This makes the sixth one.

This one is called YESINTEK, and it has the same indications, right? Plaque psoriasis, Crohn's, ulcerative colitis, and psoriatic arthritis. So do you need that many eustekinumabs? Are you using eustekinumab? Is dermatology using eustekinumab?

It's a bit of it's been a good seller. As a 12/23, it did well. The problem is that the efficacy data in clinical psoriasis trials shows that the 23s are better, that the 17s are better, that that I mean, the hierarchy here is like, what is it 23 and the dual IL-seventeen inhibitor, vimekizumab being the best at skin outcomes, and then the IL-17A inhibitors, secukinumab and ixekizumab, potentially bredalumab. And then you go down the list, and then there's going to be ustekinumab, TNF inhibitors, blah, blah, blah. So the question is, I think that they're not getting the use that they once had in psoriasis.

And there's some use. Should you use more? It's a cheaper therapy now. It's more widely available. Will biosimilars change the way you practice?

The FDA has made a new rare disease designation to study a new investigational drug called one hundred one PCG-five, remember that. There's going to be a test later on. It's a recall test about your memory and level of wakefulness. One hundred one PCG one hundred five. It's a type one pro drug of dexamethasone that theoretically targets CD206 macrophages.

Those are usually called tumor associated macrophages, but they are seen in Still's disease. And what's unique about these macrophages is that they are promoters of CXCL nine, the chemokine, and therefore interferon gamma. We've talked about emapalumab before, the anti interferon gamma monoclonal antibody that's proved for HLH called gamma fan, and about its we talked about this in the in the Rheumatology Roundup, that, there's now a thirty nine patient cohort study showing its efficacy in macrophage activation syndrome associated with Still's disease. So this is another unique approach to a problematic disorder. You don't want to use steroids, it gets your patients in trouble, but you got to use steroids acutely.

IL-one, IL-six, there's research on IL-eighteen inhibitors, even JAK inhibitors. Now this is a new investigation. No data yet. I don't even think they started their trials. They're probably just ramping those up.

If you're following the medical news and you get stuff in your inbox, you can see a lot of ACR reports and videos and interviews. I put up one citation, a good video with Alexei Grom from University of Cincinnati, where he discusses the clinical trial results of this 39 patient Still's disease trial, both kids and adults who received the monoclonal antibody emapalumab, you might want to look at that. Since I'm on the topic of Still's disease, get off the soapbox, will you? Nature Reviews has a discussion of an opinion put forth by EULAR in the Pediatric Rheumatology European Society called PRESS, which is in alignment with the FDA and the EMA, where they now say that systemic JIA, Still's disease, and adult onset Still's disease are the same darn condition. They should all be called Still's disease in the kid or in the adult, right?

So the sort of the nasology here has changed, but it's important for these regulatory agencies and societies, to recognize that the diseases are the same, have the same, almost the same genetics, and we don't really understand genetics. They have almost the same lab tests and pre modes of presentation and response to therapy. And that's why this kind of report can be an important one. Brian Jaros did a nice video for RheumNow about and Brian Jaros is in Northwestern, Zazocitinib, yet another, or second in line as a TYK2 inhibitor being used in patients with psoriatic arthritis. He talks about the biology of it, talks about the clinical phase two clinical trial results that are encouraging, and that more trials are going on.

We certainly know that we have a currently existing TYK2 inhibitor. So TYK2, and that seems to be taking off. We're gonna see more about this in other diseases as well. A report from scientific reports talks on what happens in CAD patients when you look at their serum uric acid levels and their CRP? We certainly know that CAD patients, you know, they got there because they're probably at risk for multiple reasons.

We do that gout's a risk factor for CAD and CV events. We do know that inflammation risk factor for CV and CV events. So in this study, they showed that in patients with normal high res CRP values, less than two milligrams per liter, increasing serum uric acid levels did not predict a future risk of more MACE events, major adverse cardiovascular events. But in patients who had an elevated CRP, greater than two millimeter, and this is a high res CRP, than two milligrams per liter, rising SUA levels significantly increase MACE event levels for each one milligram rise in urate,

there

was eleven percent increase in the risk of MACE and that was highly significant. Hence, it's not just uric acid alone, it's uric acid inflammation. And these patients, you might need to treat both, or watch both. Think about it. Another report from Nature Reviews where they review the autoantibody profile of patients with idiopathic inflammatory myositis showed that the take home line that I put in there is that over half the patients with adult or pediatric inflammatory myositis have autoantibody specific to myositis.

And that may not be, it's certainly not really a new revelation, but it may be one to talk about and consider. For years, many years, I've been doing RheumNow ten years, I've often said that I don't do myositis specific autoantibody testing. I don't see how it helps me in managing or in prognosticating, or doing extended panels. I think that's even maybe a special kind of crazy. What are you going to do with a PL twelve?

What? You know? And, but, you know, more recently, the data seems to be, aligning so that there is a value in prognostication, especially with adding the three new ones to the mix, the NXP two, the MDA five, and the other one I'm forgetting right now. So, you know, with a 50% predictive value or 50% of them having myositis antibodies, I think maybe we should be doing it. When you see me, me what you do.

I'd like to know what you're doing. Again, I leave in the show notes the link for Rheumatology Roundup. You can look at that on Twitter, LinkedIn, Facebook for even, but on our website and our YouTube site or on listen to it on the podcast. It's a good listen. Speaking of good listens, I've got an Ask Cush Anything case from Doctor.

Corey Afruse. Let's listen to what he has to say.

Hey, Doctor. Cush, this is Corey Afruse, rheumatologist in Greenville, South Carolina at Piedmont arthritis clinic. I have an interesting case of a 34 year old female with seropositive rheumatoid arthritis. Her symptoms started a few months postpartum with a very stressful postpartum period with her baby. She is currently on methotrexate twenty milligrams a week.

For the most part she has really improved she was seen by another rheumatologist before she transferred to me currently although she is improved she still certainly has active rheumatoid arthritis diffuse PIP synovitis. The problem with this case is in 2012 she was struck by a pigeon while in London and a few years later she had a ripple or a blind spot in part of her visual field seen by a retinologist and was diagnosed with presumed ocular histoplasmosis syndrome. So now I have a patient that has his history currently not well controlled in methotrexate. The question is what can I safely give her? Is there any data that she would be at risk for recurrence or worsening symptoms of her background history of histoplasmosis.

Thanks.

Thanks, Corey, from the great Piedmont Arthritis Clinic. This is a straightforward case for me, very easy for me because I studied this a long long time. 34 year old RA patient, she's young, she's on methotrexate, but she still had active synovitis in multiple joints. She needs more than methotrexate, but she's got this case of retinal histoplasmosis. Rule number one: if you, the risk of getting recurrence or reactivation of either TB or histoplasmosis is greatest, and largely, and only seen with TNF inhibitors.

Those infections are walled off and secluded by TNF driven granulomas, and removing TNF will lead to their breakdown and spread. So the drugs you can't use, or any TNF inhibitors, or drugs that have a substantial anti TNF effect. Theoretically, all the other drugs are fine. In the case of TB, you can cure TB, whether it's LTBI, latent TB or active TB, the regimens that are approved will allow you to go back to a TNF inhibitor. But if you have atypical mycobacterium or non tuberculosis mycobacterial infections like M fortuitum, M.

Cansassi, MAI, you can never go back to a TNF inhibitor, because you never fully eradicate them. Same is true for deep tissue occult or active, fungal infections. You never fully eradicate them. So, Cory's question to me is an easy one. Keep her on the methotrexate and put her on the other MOA drugs that are two logs lower in their risk of a fungal reactivation.

I would not wait one second in giving her rituximab, abatacep, an IL-six inhibitor, and maybe even a JAK inhibitor. The way she's going to reactivate that histoplasmosis is by giving her a TNF inhibitor, or by getting real old, or by getting immunosuppressed from whatever cause: new cancer, new chemotherapy, high dose steroids. And then maybe combination of immunosuppressors might lower the risk, like leflunomide, mycophenolate, and methotrexate together. I don't know why anybody would do that, but that would because that would be a special kind of stupid, right? But nonetheless, you know, extreme immunosuppression, which often comes with combination, oral DMARDs and immunosuppressants.

But abatacit, rituximab, tocilizumab, sorrelimab, easy choices, the patient will do well, and there'll be almost no risk. So last mention is going to be remind you to remind you about our RheumNow Live coming up February eighth and ninth. We have a limited number of on-site seats, and we're really filling up our registration. If you intend to be in Dallas on February eighth and ninth, which I think you should, based on this program, I'm looking at some of the people, we're going to have JAK inhibitors in dermatomyositis, we're going to have, treating elderly patients with RA, we're going to talk about, multi morbidity management RA, we're going to talk about interferon role in lupus. There's a lot of great speakers.

Check out the agenda that's going to be on the website. Go to roomnow.live now to register and we'll look forward to seeing you. RU, Cavanaugh and I are in the program, put it together. We think you're going to love it. February eighth and ninth in Dallas, Texas.

Thanks for tuning in. The holidays are coming for Christmas. Please don't buy me a guitar. I I gotta work on these first. Thanks.