Rheumatology Pitfalls (3.20.2026) Save
Transcription
March 20, 2026. Welcome to the RheumNow podcast. Hi, I'm Jack Cush, executive editor with RheumNow.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-23 inhibitor. Well, not such a big idea. Whatever. But wait a second. It's actually an oral IL-23 inhibitor from J&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 oral IL-23 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 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 40 kg who are candidates for systemic therapy or phototherapy. Approval is based on the ICONIC trials. There were four phase three trials involving 2,500 patients and sort of unique aspects of 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 this past week secukinumab, Cosentyx, for use in pediatric patients over age 12 for moderate to severe hidradenitis suppurativa. The drug Cosentyx is already approved for plaque psoriasis in adults and ankylosing spondylitis, non-radiographic axial spondyloarthritis, as well as now 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 there are new studies. The FDA has accepted a supplemental BLA for another IL-23 inhibitor, tildrakizumab, 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 anifrolumab — two interesting reports this week. One is sort of a subset lupus nephritis study. As you know, all the anifrolumab studies were all called TULIP. This was the lupus nephritis study and research done by Andrea Fava, Michelle Petri, 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 what they've shown before — that urinary CD163 and MCP-1 are significantly improved as early as week 12, and I think it was a 24 or 48-week study where it's still significant at that point. So the idea is that anifrolumab, 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 response. Hm. So will that make it useful clinically?
Other studies done by the same group at Hopkins show that CD163 and IL-16 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, the sort of disappointment of anifrolumab is its biomarker should be its target, which is the interferon signature, and that 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 — I would be my guess. So anyway, I think it's interesting and it may be more data that will 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 5-year real-world study of 236 patients with lupus who are initiating treatment with anifrolumab. They had a baseline SLEDAI-2K of 7, kind of like mild to moderate disease, and mainly they were getting the anifrolumab for either mucocutaneous disease in two-thirds of patients and musculoskeletal complaints in half the patients. At 6 months, a quarter achieved remission, and ultimately 66% 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, I think it's not as rapid as a JAK inhibitor. The half-life of anifrolumab is 12 hours. So, you know, it works and it works
reasonably well and sort of 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-23 inhibition. Guselkumab — it's the SOLSTICE study. This is a phase three randomized controlled trial of guselkumab versus placebo in 451 patients with active psoriatic arthritis. They either received placebo or two different regimens of guselkumab, either given Q4 weeks or Q8 weeks. Didn't seem to matter. The results were the same at week 24. Obviously guselkumab beat placebo. ACR20 responses were 59 to 62% for guselkumab versus 35%. That's pretty good. That's almost a 25% delta in treatment effect. And I think anything over 20 is highly respectable. The ACR50 was 31 and 32 versus 12. That's a 20% delta treatment effect. And ACR70 was 17% versus 2%. PASI was also improved. You know, this is an arthritis trial. PASI results are always a little bit dicey, you know, because how good are you as a rheumatologist in doing a PASI score or managing people with significant skin disease. Anyway, in this study the PASI 90 scores were achieved by 49, 45% on guselkumab versus 12%. And then MDA was 19 and 24% versus five. 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. I put this up because it's just a 13-patient open-label study of people getting pioglitazone, which is a drug that's used for diabetes. It's a PPAR-gamma agonist — wish I knew what that meant other than that's its mechanism of action, but it's also how you can measure its biologic effect. After 32 weeks of therapy, the patients weren't clinically better. How do you measure clinical improvement in inclusion body myositis? Would it work by 32 weeks? I think it would. But they did show significant changes in muscle metabolomics, especially looking at those PPAR-gamma C13 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 likes to put up patient education handouts and I 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 got a patient who has it, you've got nothing to give them. I mean, other than a few good words and what 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 d'orange, stippled effect on the skin. And oh yeah, it doesn't involve the hands or the toes — eosinophilic fasciitis, that is — and Raynaud's 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, and I guess that's why they put it up as a patient 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 1980s, 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 retrospective 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. Don't put it on your list. Hydralazine does cause drug-induced lupus.
A single-center study of 137 patients with Takayasu's arteritis looked at the incidence of coronary arteritis using strict criteria and it was found in 9%. So those people who actually had evidence of coronary arteritis were not really distinguished by their demographics or 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 complications in Takayasu's 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-6 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 a cross-sectional analysis of 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 get all that just from the CBC. The PMR-AS is a much more multimodal definition of
disease activity. So, in this cohort of 180 patients, half of them had moderate to high PMR AS 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 .47. I'd like to see .7 or above — that would be like a really good correlation — but for these numbers a .47, roughly .5, is sort of a reasonable assay. And 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've got to 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 you don't get the SII or the NLR or the PLR, because 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 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 Medsger and Wally Chatty — uh, 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 described the outcomes of 19 patients with systemic JIA or Still's disease from the University of Pittsburgh. These were all adults. And among the many things that we wrote in there, I wrote that the patients that we had — there were 21, two were excluded because they didn't have Still's in the end — they actually distinguished themselves by what kind of course they were going to 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 82 patients, mean age of diagnosis was 6.4 years. So these are kids, right, and they followed them for 3 years. When they looked at the course, 34% 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. And 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 20% had persistent disease activity. 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 — and 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 going to last? How long do I have to treat them with an IL-1 or IL-6 inhibitor, or maybe more? No one knows. I say 8 months. If Still's disease and systemic disease lasts 3 weeks and it's done, I don't think that's Still's disease. That's not what Eric Bywaters and Joseph Bujac described 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 8 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. That's not the purpose of this paper — 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 734 patients treated with checkpoint inhibitors. About a third of them — 32% — developed any kind of irAE, and you know musculoskeletal isn't the most common; puffiness and GI and other things are much more common. But 7.35%, or 54 of the 227 with irAEs, were rheumatic in nature, and this basically accounted for about 24–25% of all irAEs. Patients included in this cohort were mostly lung cancers 44% and melanomas 33%. Again, most of these irAEs occurred within 6 months of initiating checkpoint inhibitor therapy, with the vast majority of people getting anti-PD-1 therapy — 89% — and fewer taking PD-L1 or CTLA-4 therapies. The most frequent rheumatic irAE manifestations were first arthritis or arthralgia in 26 out of the 57 — right, 57 is
the number yes 54 — 26 out of 54 — so half. Polymyalgia rheumatica in 12, and fewer had myositis and Sjögren'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, most of which was steroids, sometimes DMARDs, um myositis is the worst one. Myositis usually is really hard to manage, often severe, um 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, i.e.
Uh, I like this report in Lancet about worldwide trends in hyperuricemia. It's basically looking at many many countries, extensive review between 2000 and 2023, and they showed that in that time span of 23 years the prevalence of hyperuricemia went up from 6.7 in women to 11.2 — 11.2% of women in 2023. It's higher in men. In 2000 it was 12.3% and it went up to 18.6% in men. What does that mean in real numbers? In women it went from 26 million to 305 million by 2023. In men, it went from 226 million to 500 million by 2023.
Number one, these increases were seen in nearly all countries. Some were higher than others. 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 lb gorilla on your desk, and that is the obesity epidemic, which may not be as prevalent um in non-western countries, but um 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, uh, those who don't do a lot of ordering of serologic tests and hence they use them as screening procedures. Big no. Really a big no-no. Um, 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 for autoimmune or connective tissue diseases is fraught with difficulty and problems. It's cost ineffective, etc. Um, 10 to 20% of healthy individuals are going to be ANA positive with a variety of titers, obviously skewed more towards lower titers, and that's assuming a cutoff at 1 to 80, which you know some labs it's even lower than that because it's based on local criteria. Again, even of that 10 to 20% that do have a positive ANA and you say sorry Charlie, sorry Charlene, you don't have lupus, um we don't know what percentage of them will develop lupus because it's estimated that as much as 5% 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. Um, if an ENA is present like the ANA, it does not represent autoimmune disease. Moreover, ENAs are done usually — the commercial ENAs are done by ELISA and have horrible um specificities. They have good sensitivities but horrible um specificities. Double-stranded DNA is best done with um indirect immunofluorescent assays. Doing them by ELISA also has a very high sensitivity but poor specificity. Um, and ELISA monitoring is most useful in monitoring DNA titer changes over time. If you want to confirm the validity of a double-stranded DNA, order a Crithidia or Farr 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 and your ANA is due to that." I don't do the testing, but if you feel compelled, knock yourself out.
Um, speaking of knockouts, um, at EULAR last year — and EULAR's coming up in June, going to be in London. We'll be there. You'll be there if you're following RheumNow. Um, they published an update uh in ARD this week. It's the EULAR um updated 2025 recommendations for the management of rheumatoid arthritis. It's an interesting document. Um, a few things that are worth noting. Um, 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 removing a few. Um, the bottom line 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. EULAR, 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 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 and 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 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, methotrexate is ideally used in combination with short-term glucocorticoids. If they have an insufficient response, they say don't change to another DMARD or add on combo DMARDs — add on a biologic DMARD, and it could be a JAK inhibitor if you considered the risks: MACE, malignancy, thromboembolic events, according to the host and their particular characteristics.
And then again, with sustained remission — sustained remission means at least 6 months of remission numbers, real numbers, not like you think they're in remission and you don't measure anything, you don't do a joint exam. Come on, do the joint exam, do a CRP, do a RAPID3, do a MDHAQ score, do something. But 6 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 RheumNow Live 2025, fabulous meeting. It's now available on demand. Go to RheumNow.live to sign up. Register. You'll get full access to 2 days of the best lectures, best panels, lots of discussion. It is the most interactive meeting of all meetings. You get full access to everything — the downloads, the slides, the podcasts, the pre-learn modules. Watch it anytime in your fuzzy slippers at home. Hope you enjoy it. We'll talk next week.
Let's begin with FDA regulatory announcements. A few of them this week. The FDA approved an IL-23 inhibitor. Well, not such a big idea. Whatever. But wait a second. It's actually an oral IL-23 inhibitor from J&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 oral IL-23 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 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 40 kg who are candidates for systemic therapy or phototherapy. Approval is based on the ICONIC trials. There were four phase three trials involving 2,500 patients and sort of unique aspects of 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 this past week secukinumab, Cosentyx, for use in pediatric patients over age 12 for moderate to severe hidradenitis suppurativa. The drug Cosentyx is already approved for plaque psoriasis in adults and ankylosing spondylitis, non-radiographic axial spondyloarthritis, as well as now 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 there are new studies. The FDA has accepted a supplemental BLA for another IL-23 inhibitor, tildrakizumab, 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 anifrolumab — two interesting reports this week. One is sort of a subset lupus nephritis study. As you know, all the anifrolumab studies were all called TULIP. This was the lupus nephritis study and research done by Andrea Fava, Michelle Petri, 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 what they've shown before — that urinary CD163 and MCP-1 are significantly improved as early as week 12, and I think it was a 24 or 48-week study where it's still significant at that point. So the idea is that anifrolumab, 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 response. Hm. So will that make it useful clinically?
Other studies done by the same group at Hopkins show that CD163 and IL-16 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, the sort of disappointment of anifrolumab is its biomarker should be its target, which is the interferon signature, and that 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 — I would be my guess. So anyway, I think it's interesting and it may be more data that will 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 5-year real-world study of 236 patients with lupus who are initiating treatment with anifrolumab. They had a baseline SLEDAI-2K of 7, kind of like mild to moderate disease, and mainly they were getting the anifrolumab for either mucocutaneous disease in two-thirds of patients and musculoskeletal complaints in half the patients. At 6 months, a quarter achieved remission, and ultimately 66% 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, I think it's not as rapid as a JAK inhibitor. The half-life of anifrolumab is 12 hours. So, you know, it works and it works
reasonably well and sort of 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-23 inhibition. Guselkumab — it's the SOLSTICE study. This is a phase three randomized controlled trial of guselkumab versus placebo in 451 patients with active psoriatic arthritis. They either received placebo or two different regimens of guselkumab, either given Q4 weeks or Q8 weeks. Didn't seem to matter. The results were the same at week 24. Obviously guselkumab beat placebo. ACR20 responses were 59 to 62% for guselkumab versus 35%. That's pretty good. That's almost a 25% delta in treatment effect. And I think anything over 20 is highly respectable. The ACR50 was 31 and 32 versus 12. That's a 20% delta treatment effect. And ACR70 was 17% versus 2%. PASI was also improved. You know, this is an arthritis trial. PASI results are always a little bit dicey, you know, because how good are you as a rheumatologist in doing a PASI score or managing people with significant skin disease. Anyway, in this study the PASI 90 scores were achieved by 49, 45% on guselkumab versus 12%. And then MDA was 19 and 24% versus five. 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. I put this up because it's just a 13-patient open-label study of people getting pioglitazone, which is a drug that's used for diabetes. It's a PPAR-gamma agonist — wish I knew what that meant other than that's its mechanism of action, but it's also how you can measure its biologic effect. After 32 weeks of therapy, the patients weren't clinically better. How do you measure clinical improvement in inclusion body myositis? Would it work by 32 weeks? I think it would. But they did show significant changes in muscle metabolomics, especially looking at those PPAR-gamma C13 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 likes to put up patient education handouts and I 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 got a patient who has it, you've got nothing to give them. I mean, other than a few good words and what 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 d'orange, stippled effect on the skin. And oh yeah, it doesn't involve the hands or the toes — eosinophilic fasciitis, that is — and Raynaud's 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, and I guess that's why they put it up as a patient 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 1980s, 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 retrospective 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. Don't put it on your list. Hydralazine does cause drug-induced lupus.
A single-center study of 137 patients with Takayasu's arteritis looked at the incidence of coronary arteritis using strict criteria and it was found in 9%. So those people who actually had evidence of coronary arteritis were not really distinguished by their demographics or 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 complications in Takayasu's 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-6 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 a cross-sectional analysis of 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 get all that just from the CBC. The PMR-AS is a much more multimodal definition of
disease activity. So, in this cohort of 180 patients, half of them had moderate to high PMR AS 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 .47. I'd like to see .7 or above — that would be like a really good correlation — but for these numbers a .47, roughly .5, is sort of a reasonable assay. And 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've got to 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 you don't get the SII or the NLR or the PLR, because 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 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 Medsger and Wally Chatty — uh, 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 described the outcomes of 19 patients with systemic JIA or Still's disease from the University of Pittsburgh. These were all adults. And among the many things that we wrote in there, I wrote that the patients that we had — there were 21, two were excluded because they didn't have Still's in the end — they actually distinguished themselves by what kind of course they were going to 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 82 patients, mean age of diagnosis was 6.4 years. So these are kids, right, and they followed them for 3 years. When they looked at the course, 34% 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. And 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 20% had persistent disease activity. 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 — and 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 going to last? How long do I have to treat them with an IL-1 or IL-6 inhibitor, or maybe more? No one knows. I say 8 months. If Still's disease and systemic disease lasts 3 weeks and it's done, I don't think that's Still's disease. That's not what Eric Bywaters and Joseph Bujac described 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 8 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. That's not the purpose of this paper — 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 734 patients treated with checkpoint inhibitors. About a third of them — 32% — developed any kind of irAE, and you know musculoskeletal isn't the most common; puffiness and GI and other things are much more common. But 7.35%, or 54 of the 227 with irAEs, were rheumatic in nature, and this basically accounted for about 24–25% of all irAEs. Patients included in this cohort were mostly lung cancers 44% and melanomas 33%. Again, most of these irAEs occurred within 6 months of initiating checkpoint inhibitor therapy, with the vast majority of people getting anti-PD-1 therapy — 89% — and fewer taking PD-L1 or CTLA-4 therapies. The most frequent rheumatic irAE manifestations were first arthritis or arthralgia in 26 out of the 57 — right, 57 is
the number yes 54 — 26 out of 54 — so half. Polymyalgia rheumatica in 12, and fewer had myositis and Sjögren'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, most of which was steroids, sometimes DMARDs, um myositis is the worst one. Myositis usually is really hard to manage, often severe, um 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, i.e.
Uh, I like this report in Lancet about worldwide trends in hyperuricemia. It's basically looking at many many countries, extensive review between 2000 and 2023, and they showed that in that time span of 23 years the prevalence of hyperuricemia went up from 6.7 in women to 11.2 — 11.2% of women in 2023. It's higher in men. In 2000 it was 12.3% and it went up to 18.6% in men. What does that mean in real numbers? In women it went from 26 million to 305 million by 2023. In men, it went from 226 million to 500 million by 2023.
Number one, these increases were seen in nearly all countries. Some were higher than others. 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 lb gorilla on your desk, and that is the obesity epidemic, which may not be as prevalent um in non-western countries, but um 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, uh, those who don't do a lot of ordering of serologic tests and hence they use them as screening procedures. Big no. Really a big no-no. Um, 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 for autoimmune or connective tissue diseases is fraught with difficulty and problems. It's cost ineffective, etc. Um, 10 to 20% of healthy individuals are going to be ANA positive with a variety of titers, obviously skewed more towards lower titers, and that's assuming a cutoff at 1 to 80, which you know some labs it's even lower than that because it's based on local criteria. Again, even of that 10 to 20% that do have a positive ANA and you say sorry Charlie, sorry Charlene, you don't have lupus, um we don't know what percentage of them will develop lupus because it's estimated that as much as 5% 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. Um, if an ENA is present like the ANA, it does not represent autoimmune disease. Moreover, ENAs are done usually — the commercial ENAs are done by ELISA and have horrible um specificities. They have good sensitivities but horrible um specificities. Double-stranded DNA is best done with um indirect immunofluorescent assays. Doing them by ELISA also has a very high sensitivity but poor specificity. Um, and ELISA monitoring is most useful in monitoring DNA titer changes over time. If you want to confirm the validity of a double-stranded DNA, order a Crithidia or Farr 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 and your ANA is due to that." I don't do the testing, but if you feel compelled, knock yourself out.
Um, speaking of knockouts, um, at EULAR last year — and EULAR's coming up in June, going to be in London. We'll be there. You'll be there if you're following RheumNow. Um, they published an update uh in ARD this week. It's the EULAR um updated 2025 recommendations for the management of rheumatoid arthritis. It's an interesting document. Um, a few things that are worth noting. Um, 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 removing a few. Um, the bottom line 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. EULAR, 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 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 and 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 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, methotrexate is ideally used in combination with short-term glucocorticoids. If they have an insufficient response, they say don't change to another DMARD or add on combo DMARDs — add on a biologic DMARD, and it could be a JAK inhibitor if you considered the risks: MACE, malignancy, thromboembolic events, according to the host and their particular characteristics.
And then again, with sustained remission — sustained remission means at least 6 months of remission numbers, real numbers, not like you think they're in remission and you don't measure anything, you don't do a joint exam. Come on, do the joint exam, do a CRP, do a RAPID3, do a MDHAQ score, do something. But 6 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 RheumNow Live 2025, fabulous meeting. It's now available on demand. Go to RheumNow.live to sign up. Register. You'll get full access to 2 days of the best lectures, best panels, lots of discussion. It is the most interactive meeting of all meetings. You get full access to everything — the downloads, the slides, the podcasts, the pre-learn modules. Watch it anytime in your fuzzy slippers at home. Hope you enjoy it. We'll talk next week.
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