Pitfalls in Rheumatology (3.20.2026) Save

03/20/2026. Six. Welcome to the RheumNow podcast. Hi. I'm Jack Cush, executive editor with roomnow.com.

This week on the podcast, regulatory action in psoriatic arthritis, anifrolumab, a few interesting reports, and finally the EULAR 2025 guidelines and update, on the treatment and management of rheumatoid arthritis. We'll discuss that as well. Let's begin with FDA regulatory announcements, a few of them this week. The FDA approved an IL-twenty three inhibitor. Well, not such a big idea, whatever.

But wait a second, it's actually an oral IL-twenty three inhibitor from J and J for plaque psoriasis. It's called icotrokinra icotrokinra. The trade name on this is icotide, I c o t y d e. It is an IL-twenty three oral inhibitor, taken, once a day, I believe, and it's been approved not for psoriatic arthritis, sorry, but for psoriasis. There are trials in progress that, that will affect us at some point, but it's approved for use in moderate to severe, psoriasis in adults and children over age 12, or at least forty kilograms, who are candidates for systemic therapy or phototherapy.

Approval is based on the iconic trials. There were four phase three trials involving two thousand five hundred patients, and sort of unique aspects of a difficult psoriasis, including genital or nail or scalp psoriasis, I think. But nonetheless, a very successful drug development campaign, now approved for use in psoriasis. It is not yet approved for psoriatic arthritis. It is being studied in PSA, inflammatory bowel disease, including Crohn's disease and ulcerative colitis.

That's good news. The FDA also approved past secukinumab Cosentyx for use in pediatric patients over age 12 for moderate to severe hydradenitis suppurativa. The drug Cosentyx is already approved for plaque psoriasis in adults, enclosing spondylitis, non radiographic axial spondyloarthritis, as well as pediatric patients with psoriasis, enthesitis related arthritis, and juvenile psoriatic arthritis. So, juvenile, hidradenitis suppurativa. And then lastly, the FDA also accepted a supplemental biologic license application, that's what you submit when you already have a drug approved and you want to get the indications modified to include a new indication, because they're new studies, the FDA has improved a supplemental BLA for another IL-twenty three inhibitor, Tildrekizumab, called ILUMYA from Sun Pharma, and it's being studied and their application is for use in psoriatic arthritis, something that will affect you down the road.

So, let's get into anifrolimab. Anifrolimab, two interesting reports this week. One is sort of a sub study of the Tulip Lupus Nephritis study. As you know, the anifrolimab studies were always called Tulip. This was the lupus nephritis study and research done by Andrea Fava, Michele Petrie and their co workers looking at urinary biomarkers and their utility in this study.

They studied 112 patients, they looked at almost 200 urinary proteins. In the end they showed that, what they've shown before, that urinary CD163 and MCP1 are significantly improved as early as week 12. And I think it was a twenty four or forty eight week study, where it's still significant at that point. So the idea is that anifrolimab, the alpha interferon inhibitor, reduces these pro inflammatory biomarkers and does so regardless of responder status. It's a biologic effect, not entirely linked to a response.

So, will that make it useful clinically? Other studies done by the same group at Hopkins shows that CD163 IL16, they correlate much better than proteinuria, much better than UPCR as far as outcomes and responder status, and they correlate really well with renal histology changes. We need to have these urinary biomarkers in practice. This is good for anifrolumab, but you know, sort of the disappointment of anifrolumab is its biomarker should be its target, which is the interferon signature, and doesn't has not proven to be so. The interferon signature does seem to improve best in patients with, I think skin and joint disease, but not so much with all global measures of lupus, or lupus nephritis, would be my guess.

So, anyway, I think it's interesting, and it may be, more data that help us get urinary biomarkers approved and being used. Another study published this week in Lancet is an Italian study called the REVEAL study. It's a five year real world study of two thirty six patients with lupus who are initiating treatment with anifrolumab. They had a baseline SLETEI2K07, kind of like mild to moderate disease, and mainly they were getting anifrolumab for either mucocutaneous disease in two thirds of patients, and musculoskeletal complaints in half the patients. At six months, a quarter achieved remission, and ultimately sixty six percent achieved LLDAS and sort of again showed its efficacy, over time.

Again, the authors claim a rapid onset of action, but I don't think so. I mean, it's not many I think it's not as rapid as a JAK inhibitor. The half life of anifrolimab is twelve hours, so, you know, it works, and it works reasonably well and in line with what you say when you're giving a biologic to a patient with lupus. Another important study this week is again on IL-twenty three inhibition, guselkumab. It's the Solstice study, it's a phase three randomized controlled trial of guselkumab versus placebo in April patients with active psoriatic arthritis.

They either received placebo or two different regimens of guselkumab, either given Q4 week or Q8 week. Didn't seem to matter, the results were the same at week twenty four. Obviously guselkumab beat placebo, ACR twenty responses were fifty nine and sixty two percent for guselkumab versus thirty five percent. That's pretty good, that's almost a 25% delta in treatment effect, and I think anything over 20 is highly respectable. The ACR fifty was thirty one and thirty two versus 12, that's a 20% delta treatment effect, And ACR seventy was 17 versus 2%.

Posse was also improved, you know, this is an arthritis trial. Posse results are always a little bit dicey, you know, because how good are you as a rheumatologist in doing a Posse score? Or managing people with significant skin disease. Anyway, in this study the PASI 90 scores were achieved by forty nine-forty five percent on guselkumab versus twelve percent. And then MDA was nineteen-twenty four percent versus five percent.

Again, really good results, guselkumab obviously looking good in psoriatic arthritis. A phase one pilot trial for something that we don't treat well, and we don't know really how to treat, And that's inclusion body myositis. And I put this up because it's just a 13 patient open label study of people getting Actos, pioglitazone, which is a drug that's used for diabetes. It's a PPAR gamma agonist, which I knew what that meant, other than that's its mechanism of action, but it's also how you can measure its biological effect. After thirty two weeks of therapy, the patients weren't clinically better.

How do you measure clinical improvement in inclusion body myositis? Would it work by thirty two weeks? I think it would. But they did show significant, changes in muscle metabolomics, especially looking at those PPAR gamma C1-three expression, which is a reasonable biologic effect. So, it's not got great promise, but at least it has a great biologic effect.

Maybe it needs a disciplined, randomized trial to know what to do. I always scan the major journals for what's new, what's happening. JAMA JAMA likes to put up patient education handouts. And they put up one this week of concern to you that you should print out. It's on eosinophilic fasciitis.

It's rare, right? But, you know, if you've a patient who has it, you've nothing to give them. I mean, other than a few good words and what you know. You know, yeah, it begins with swelling and redness in the arms or legs, and then it becomes thickened, and the skin changes to get that peau de orange stippled effect on the skin, and oh yeah, it doesn't involve the skin or the toes, eosinophilic fasciitis that is, and Raynaud is not a feature. And that's how you make the diagnosis, then maybe you go on to a full thickness skin biopsy, and whatnot.

But it's a difficult condition to, manage, especially if it's not in the hands of a rheumatologist. I guess that's why they put it up as a education piece that you can download on RheumNow, or on JAMA. A few reports on vasculitis. One's like a negative report. Hydralazine and vasculitis.

You know, since the nineteen eighty's Hydralazine has been a notable cause of drug induced lupus, often inferred to cause other musculoskeletal manifestations, including vasculitis, small vessel vasculitis, medium vessel vasculitis, who knows? Anyway, this cohort study from Canada showed that it was increased in causing vasculitis compared to controls, but the rates were incredibly low. I mean, reaffirming that this is rare rare rare, so rare that it's inconsequential, inconsequential, don't put it on your list. Hydrolysine does cause drug induced lupus. A single center study of one hundred and thirty seven patients with Takayasu's arteritis looked at the incidence of coronary arteritis using strict criteria, and it was found in nine percent.

So those people who had who actually had evidence of coronary arteritis were not really distinguished by their demographics angiographic pattern, but the bad news is that they had a high complication rate when it came to those people getting vascular grafts and stents. Meaning that complication in Tachyasius could be problematic, and those people probably need systemic therapy. And we don't have anything approved for Takayasu's. I myself would use an IL-six inhibitor to start with, but there are other regimens that have been talked about. How do you follow your patients with polymyalgia rheumatica?

There is a PMR activity score, the PMR AS, and this particular report was sectional analysis of one 180 PMR patients looking at their PMR AS to see how it would compare to something called the Systemic Immune Inflammation Index, the SII, which is the product of platelets times neutrophils divided by lymphocytes, and you all get all that just from the CBC. The PMRAS is a much more multimodal definition of disease activity. So, in this cohort of one hundred and eighty patients, half of them had moderate to high PMRAS scores of seven or higher. And when you looked at the performance of the SII, it had a moderate correlation with the PMR activity score with an R value of point four seven. I'd like to see point seven or above, that would be like a really good correlation.

But for these numbers, a 0.47, roughly 0.5, is sort of a reasonable assay to do. You know, we've talked about these assays before, right? The lymphocyte to neutrophil to lymphocyte ratio, the platelet to neutrophil ratio, these are measures of inflammation that you can get from the CBC. They're cheap, they're easy, except you got to get out your take off your shoes and your socks and start counting with your fingers and toes to do the math. It's too difficult.

I don't know why, when you get a CBC report, why you don't get this SII or the NLR or the PLR. If you got it on a regular basis, you'd be using it just like you use a SED rate and CRP. They're really that useful, and I think we should if you could push for that in your center, I suggest you go ahead and do so. Still's disease is on is in the news, and I like this because they basically were ripping off one of my research papers that I wrote in 1984 with Tom Metzger and Wally Christie, at the University of Pittsburgh, my first paper on Still's my second publication ever, my first paper my second paper on Still's disease, where we describe the outcomes of nineteen patients with systemic, JIA or Still's disease from University of Pittsburgh. These were all in adults.

And the many things of the many things that we wrote in there, I wrote that the patients that we had, there were twenty one, two were excluded because they didn't have Still's in the end, they actually distinguished themselves by what kind of course they were gonna have. They either had a monophasic, what I call monocyclic single spike of systemic disease that then dies down after some unknown number of months, or a polycyclic course that's multiple spikes with disease free intervals, or a polycyclic course with chronic arthritis, right? And so in this particular report of eighty two patients, mean age mean age at diagnosis was 6.4 years. So these are kids, right? And they followed them for three years.

When they looked at the course, thirty four percent were monophasic monocyclic. About half of them were polyphasic, and this was higher than expected, meaning they had multiple spikes of systemic activity with no major dominance of arthritis in between, but with disease free intervals in between. The first patient I ever saw when I was in my residency was 23 years old with her second or third wave of inflammatory systemic activity, and the last time she had it was when she was age 12. But she had a polycyclic course. And she also went on to have chronic arthritis.

And then they also said that twenty percent had persistent disease activity, and I have to assume that those are the ones with the chronic arthritis. So that's kind of what you can expect. Now, what we don't know with Still's disease, that Still is the head scratcher for everyone, once they get sick with systemic disease, that's when you can diagnose them best. How long is that gonna last? How long do I have to treat them with an IL-one or IL-six inhibitor, or maybe more?

No one knows. I say eight months. If Still's disease and systemic disease last three weeks and it's done, I don't think that's Still's disease. That's not what Eric Bywaters and Joseph Bujak described it in their first two papers in 1971 and 1973. It's got to be a sustained six month course of inflammatory activity.

So, I say on average about eight months before they die down, but we don't really have a biomarker for that. My biomarker is checking their aldolase. When the aldolase goes down, I think their systemic activity is done and you can withdraw therapy, but that's not the purpose of this paper, or we've talked about it in the past, and don't get me started on Still's disease, you know how I am. There was a nice review paper on, rheumatic, immune related adverse events, IRAEs, with checkpoint inhibitor therapy for cancer. This was a retrospective study of seven thirty four patients treated with checkpoint inhibitors, and about half of them, maybe about, I'm sorry, about a third of them, thirty two percent, developed any kind of IRAE.

And you know, musculoskeletal isn't the most common. You know, palphicitis and GI and other things are much more common. But seven point three five percent, or fifty four of the two twenty seven with IRAEs were rheumatic in nature. And this basically accounted for about twenty four percent, twenty five percent of all IRAEs. Patients that were in this cohort included were mostly lung cancers, forty four percent, and melanomas, thirty three percent.

Again, most of these IRAEs occurred within six months of initiating checkpoint inhibitor therapy, with the vast majority of people getting anti PD-one therapy eighty nine percent, and fewer taking PD L1 or CTLA-four therapies. And the most frequent rheumatic IRAE manifestations were first arthritis or arthralgia in twenty six out of the fifty seven. Right? Fifty seven is the number? Yes, fifty four.

Twenty six out of fifty four, so half. Polymyalgia rheumatica in twelve, and fewer had myositis and Sjogren's, five each, and three with psoriatic arthritis. I think that approximates the kind of patients I've seen over time. While all the patients seem to respond very, very well to whatever therapy was being used, mostly butcher steroids, sometimes DMARDs. Myositis is the worst one.

Myositis usually is really hard to manage, often severe, often presents during the first or second cycle of treatment, and does carry a high morbidity and mortality rate. We need better options for the myositis IRAEs. I like this report in Lancet about worldwide trends in hyperuricemia. It's basically looking at many, many countries, an extensive review between 2000 and 2023, and they showed that in that time span of twenty three years the prevalence of hypocemia went up from six point seven in women to eleven point two. Eleven point two percent of women in 2023.

It's higher in men In 2020 in the 2000, it was twelve point three percent, and it went up to eighteen point six percent in men. What does that mean in real numbers? In women, it went from a hundred and twenty six million to 305,000,000 by 2023. In men, it went from 226,000,000 to 500,000,000 by 2023. That number one, these increases were seen in nearly all countries.

Some were higher than others. They asked, they projected that this increase was related to population growth and aging. They didn't seem to mention the big elephant in the room, 800 pound gorilla on your desk, and that is the obesity epidemic, which may not be as prevalent in non western countries, but nonetheless the prevalence still is higher in high income individuals living in urban settings, and does affect men and women equally. I put up a report this week on pitfalls of autoimmune serologic testing. You know, I did that because it's a good resource.

You know, this is one of the biggest problems with our primary care colleagues, those who don't do a lot of ordering of serologic tests, hence they use them as screening procedures. Big no no. Really a big no no. And anyway, I put that up there as a resource, download it, hand it out, send it to your colleagues. The highlights of this was that one, laboratory testing should be done to support a diagnosis that you already have in mind, not to find one that you're really not sure about.

Mass screening, therefore, of autoimmune or connective tissue diseases is fraught with difficulty problems, it's cost ineffective, etcetera. Ten to twenty percent of healthy individuals are gonna be ANA positive, with a variety of titers, obviously skewed more towards lower titers. That's assuming a cut off at one to eighty, which you know, some labs it's even lower than that because it's based on local criteria. Again, even of that ten and twenty percent that do have a positive ANA, and you say, sorry Charlie, Charlene, you don't have lupus, we don't know what percentage of them will develop lupus because it's clear that as much as five percent of them may develop lupus over time. The ENA is equally problematic.

Don't do ENAs if the ANA is negative. That's a special kind of stupid. If an ENA is present like the ANA, it does not represent autoimmune disease. Moreover, ENAs are done by usually, the commercial ENAs are done by ELISA and have horrible, specificities. They have good sensitivities, but horrible specificities.

Double stranded DNA is best done with indirect immunofluorescent assays. Doing them by ELISA is very good. Has also a very high sensitivity, but poor specificity. And ELISA monitoring is most useful in monitoring DNA changes over time. If you want to confirm the validity of a double stranded DNA, order a Crithidia or FAR assay, an immunofluorescence assay, and that way you'll know for sure.

And lastly, most ANAs and autoimmune serologies are due to thyroid disease, or nothing. Hence, it wouldn't be unwise to check for anti thyroid peroxidase or anti thyroid thyroglobulin antibodies. I don't ever do that. I just say, oh, you got thyroid disease, your ANA is due to that. I don't do the testing.

But if you feel compelled, knock yourself out. Speaking of knockouts, UR last year, and UR is coming up in June. Gonna be in London. We'll be there. You'll be there if you're following RheumNow.

They did a they published an update in ARD this week. It's the ULAR updated twenty twenty five recommendations for the management of rheumatoid arthritis. It's an interesting document. A few things that are worth noting. It is largely a reproduction of the 2022 guidelines, although they did drop from 11 guideline recommendations down to nine by merging a few and and removing a few.

The bottom line is, on these guidelines, is everybody should get prednisone and everybody should get methotrexate. And that's different than ACR. ACR says everybody should get methotrexate, and they're, like, iffy about prednisone. You are, they strongly believe, everybody should get prednisone. It leads to better initial outcomes, and very few people stay on prednisone long term.

If that's your plan, that seems like a good I a good one. The other idea is once you start a DMARD or biologic, they're pretty much one and done. Meaning, use that drug, messing around within the same class is a bad waste of time putting off the inevitable, which is getting to the drug that's going to work. And lastly, they say it's okay if patients are doing great, you can reduce this their their dose, you can reduce their interval, but don't stop. I've been saying that for years, have I not?

So, again, for RA, methotrex is ideally, used in combination with short term glucocorticoids. If they have an insufficient response, they say don't change to another DMARDs, or add on combo DMARDs, add on a biologic DMARD. And it could be a JAK inhibitor if you considered the risks: MACE, malignancies, thromboembolic events, according to the host and their particular characteristics. And then, again, with sustained remission. Sustained remission means at least six months of remission numbers.

Real numbers, not like you think, I think they're in remission, and you don't measure anything, don't do a joint exam, come on. Do the joint exam, do a CDAI, do a rapid three, do my gas score, do something, But six months of a sustained remission number, DMARDs can be tapered or doses lowered, but if you stop, they're going to get a flare. That's it for this week on the podcast. Hope you enjoyed it. If you missed RoomNow twenty twenty five, fabulous meeting.

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