Follow the Money (4.23.2026) Save

It's 04/23/2026. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, the podcast is all about follow the money.

Maybe that'll be apparent by the end of the podcast. Last ACR, I I got excited about an abstract that showed rheumatoid factor had predictive value in EGPA, But it was surprising. I wouldn't have expected it. It was interesting. I hope you remember it.

That's why my lead story today is on citrullinated histone three in patients with ANCA associated vasculitis. So the story here, it's a small study, it's 65 patients with either MPA or GPA, and they looked at biomarkers and reported on citrullinated histone three, and that comes about in the formation of neutrophil extracellular traps, which we know is a bad player in autoimmune disease. It's driven by alpha interferon and a number of other signals. It's a main amplifier, and they looked at this as a possible marker of neutrophil activation. So they studied it in sixty five patients with MPA and GPA, and showed that citronated histone three had a significant correlation with both the BVAS and the risk of end stage renal disease.

BVAS, the Birmingham Vasculitis Activity Score, had a correlation coefficient of 0.39, almost 0.4, you know, not fabulous, but significant and good enough, saying that there's probably something there. And the risk of end stage kidney disease was about eighteen percent higher in the presence of this specific histone. And again, I like it because it's a citrullinated product that it has got a relationship then to CCP, and that rheumatoid factor EGPA thing makes me think we should be doing rheumatoid factor and CCP and ANA testing in patients with GPA and MPA. I think it tells us that there's a lot going on, that there's heightened immunologic activity, and it could be a potentially useful marker. Right now, have to order, you know, a CCP or a rheumatoid factor to get maybe the same value.

I don't believe that this is commercially available as a lab test for your patients. A study of perioperative risk when you're using biologics and DMARDs was undertaken through a TriNetX study. As you know, TriNetX is a network of many, many, many electronic health records where you can do studies that you wouldn't normally be able to do. They link up all the clinical data. They then try to normalize it by doing propensity matching.

Some of these trinetic studies are very, very good. Some of them are, you know, I think a stretch. This one, reiterates a point that was made by Doctor. Susan Goodman of HSS at RheumNow Live, where she talked about, should you continue therapy biologics DMARDs in patients undergoing surgery, the ACR guidelines? And she say yes.

This TriNetX study looked at, almost eight thousand patients on DMARDs. And two thousand six hundred of those people were on biologic DMARTs. And they looked at these RA patients who are undergoing elective hand surgery and what the influence of being on the drug, meaning continuing it or not continuing it, one third of the patients under study were continuing their biologic DMARDs after and during, or during, hand surgery, and they showed no significant difference as far as key outcomes that the surgeons worry about, that being wound healing and soft tissue infections. Wound healing was the same in both groups, one point four percent. Soft tissue infections was either two percent or one point five percent, not significantly different.

You should continue patients on DMARTs and biologics who are undergoing surgery. And to stop it is a bit goofy, especially since these drugs have long half lives, right? And then to really be off the drug would really put the patient at risk for FLAIR inflammation, which is far worse for surgical risk than being on these drugs. Inflammation drives infection risk, not biologics, not DMARTs. The FDA accepted Genentech's application to extend its indication on obentuzumab, which as you know is an anti CD twenty monoclonal antibody recently, what, eight, nine months now, back in September, I believe, approved for lupus nephritis.

Now because they've done the phase three allegory study showing that Gazya or obinutuzumab, significantly reduces disease activity as measured by general lupus measures or disease activity, and that is going to be now their extended indication. They've submitted it. It's not yet approved, but it looks good based on this, this data, and, we should look forward to that in the future. DeSEARE, as you may know, is an inception ankylosing spondylitis or axial spondyloarthritis cohort study. In this specific study that we reported, six hundred and thirty one patients who, who had ankylosing spondylitis sorry, axial spondyloarthritis did not have hypertension, were started on nonsteroidals, and compared to axSpA patients, no hypertension, who did not take nonsteroidal.

They followed them over ten years and found no significant increase in the risk of incident hypertension. So in early axSpA, nonsteroidals with ten year follow-up don't seem to cause hypertension. They had a total of eighty eight cases out of six thirty one, and again, it was not significant. I bring it up because I don't think many of our fellows or younger rheumatologists are using nonsteroidals. I think you've been taught that they're dangerous or they really don't work or whatever, but honestly, what do you have to treat pain, especially early on, especially before you start them on, you know, other more aggressive therapies for axSpA?

I still use nonsteroidals except for when I can't use them and shouldn't use them. And there are contraindications. Right? Age is a relative contraindication, but, obviously, no hematologic, cardiac, and GI reasons would be to avoid reasons to avoid nonteroidals as adjunctive therapy in all your patients, not just axial spondyloarthritis. So one of the issues I think that we worry about in axSpA is X-ray progression.

We really don't have great studies on that because unlike our AMPSA where you could see X-ray progression in as little as sixteen weeks, and certainly within one or two years, X-ray progression and the methodology used to prove that in ACT SPA is slow, slow, slow. You need really two, five, ten year studies. So I like this study that looked at x-ray progression over time in a large cohort of three thousand four hundred AS patients, seventy five percent male, eighty four percent b 20 seven positive, and they looked at the influence of comorbidity. And we know comorbidity and other disorders is a bad player for disease severity, and such was shown here. AS patients who had, greater than two comorbidities, had a much higher rate of x-ray progression.

Also, the comorbidities specifically of psoriasis and uveitis were associated with more X-ray progression, in AS patients. Again, the question is, you know this data, most other people, including primary care, does not. Who's managing the comorbidity? You should be managing the comorbidity, at least starting the management and ensuring proper management if you're not going to take it on whole handedly going forward. It is a big, big issue throughout all the disorders that we treat with inflammatory arthritis.

ILD, a big concern, and I learned from, Christina Charles Schulman at RheumNow Live, two years ago when she lectured on, I l actually, dermatomyositis. You know, ILD is a bad player throughout the, connective tissue disease, autoimmune disease spectrum, PSA not p s well, it's rare in PSA. Right? In RA, in, lupus, and especially in systemic sclerosis. I mean, it's the outcomes are really bad.

And that's why we devoted a whole month to interstitial lung disease back in September on RheumNow. But Christine has showed me that dermatomyositis patients with ILD do really, really well. And you they just have to treat them, and you can turn around their ILD. It can respond. So I like this study coming out of China, which is a target emulation trial of MDA five positive dermatomyositis with ILD.

Dermatomyositis ILD, bad. MDA five positive, even worse. As you know, MDA five has bad skin disease and bad progressive lung disease as part of the autoantibody association. So what they did was they studied one hundred and six patients who were taking upadacitinib and three twenty eight who were taking tofacitinib and looked at their outcomes, especially the devastating outcome, one being six month risk of being transplant free. And it's a fairly short follow-up, but the numbers and the outcomes were good.

Seventy two percent and sixty seven percent for upa and tofa respectively. And that shows you, one, that dermatomyositis ILD can respond. Two, it likes to respond to, JAK inhibition. And there's a lot of evidence of that, not just this study, but this study sort of supports the preexisting evidence. And all this is encouraging because we now, are on the verge FDA of approving, a JAK inhibitor.

I think it's brepicitinib that we talked about last week, the New England Journal paper. Brepicitinib in dermatomyositis looks very good. And we can expect, I think, I hope that it'll get approved by the FDA, within the next six months. So in this study, OPA was non inferior TOFA, meaning they're about the same in MDA five positive dermatomyositis with ILD. Other poor outcomes that we worry about, antiphospholipid patients, a lot of things can go wrong there, but thrombocytopenia, we always talk about that.

You know, I say the triad is recurrent fetal loss, you know, and then also, thrombotic events, and then, thrombocytopenia. I gotta say, I haven't seen a lot of that in association with APS. So this was a retrospective study of four thirty two patients with APS, and looked at the influence of thrombocytopenia. Any thrombocytopenia was seen one hundred and forty two or thirty three percent, a third. That seems maybe I'm not looking hard enough or maybe I'm not looking longitudinally at those patients.

But thirteen percent had severe thrombocytopenia, meaning a platelet count of less than 50,000. Who did that happen in? It happened in the APS patients who were classified as having ITP or CAP, the catastrophic antiphospholipid syndrome. And when it was present, it was associated with significantly higher mortality rates. When this happens, I think it's time to call in the cavalry, the hematologist, and to get aggressive on the management of these patients.

And there are good new guidelines on that, are there not, that you could look up and help to guide you as well. I know rheumatologists and physicians in general over time have been often bothered by direct to consumer advertising on television. You know, it is a thing in The United States. It's not in Canada, although American TV goes over the border, and that is infuriating, I guess, to some. And the thing is a recent report shows that, yes, again, DTC is up this year compared to last year.

If you look at the top 10 pharma companies on ad spending, that DTC was up to almost $3,000,000,000 up from 2,100,000,000 last year, 3,000,000,000 in 2025, 2.1 in 2024. The total amount spent on DTC from the pharmaceutical industry, I think I saw that it was 35 or 39,000,000,000 in 2025. It's a lot, right? But here's the kicker, that the top three spenders in DTC are your drugs. Number one, SKYRIZI, 440,000,000.

Number two, Tremfya, 431,000,000. And number four number three, RINVOCA, 376,000,000. You know this because you watch TV. Why do they let this happen? Is it a good thing or a bad thing?

I've actually followed this, information. I've got a good lecture on this topic. And the you know, it infuriates people because, physicians because patients come in and ask inappropriately about should I be on Tremfya when I have osteoarthritis. Right? Obviously, that makes no sense.

And that means you have to now devote time to this. But the FDA who has studied this in many ways, including back to when they approved this over twenty years ago, has shown that because of DTC, patients will now discuss with their physicians either drugs or diseases that they would not have normally discussed, and there's very strong evidence for that. And that's why DTC is a part of your medical life. What may not be a part of your medical life is rare diseases, autoinflammatory diseases, like hyper hyper IgD syndrome, which is due to a genetic defect in mevalonate kinase. It's an MVK deficiency or defect.

It's rare. It's autosomal. It's autosomal recessive. It's an autoinflammatory disorder where because of this gene defect, there's exaggerated innate immunity activation of the inflammasome. It leads to lots and lots of IL-one beta and probably IL-eighteen and IL-six and other things, but mainly IL-one beta.

And they present with, in its milder forms, actually. You know, there are severe forms of mevalonate kinase deficiency that give a lot of developmental problems and whatnot. But the hyper IgD syndrome, the periodic febrile syndrome, usually presents in kids, as a febrile disorder. It can present in adults. And there are actually a number of reports, and this particular report that we put up was a discussion of an adult and the syndrome.

Again, how do these people present? It's usually periodic fever, but it's not like Still's disease or Schnitzler syndrome, which is daily fever and daily quotidian fevers. Right? Especially in in Still's. Here, they get fever.

They call it a periodic febrile syndrome because they get three to seven days of fever that recur every several weeks, sometimes, two times a month. But there's no predictability, no true periodicity. But what is important diagnostically is two things. One, that the fever, are bouts and they're recurrent, and they last three to seven days. And that's in contrast to stills, which is every day, contrast to traps, which is two weeks of fever, ten days to fourteen days.

Right? So three to three to seven days. And the other big red flag is that they don't meet criteria for Still's. And how do you know? Well, you get someone who you think has Still's, You go to still'snow.com.

You look at the Still's disease diagnosis calculator. You check the boxes on the symptoms, and it'll tell you whether you meet Yamaguchi, Cush, or ILAR criteria for Still's disease, and that's for kids or adults. And if you don't, you're now stuck mislabeling this patient, and that's your invitation to do genetic testing for, an autoinflammatory monogenic disorder, which would include MVK deficiencies, right? Again, they present with fever, although not as high as the others, like 101, 102, just for a few days and up to a week. They have GI symptoms, oral ulcers, myalgia, arthralgia, they can get serositis.

Again, it looks a lot like the other auto inflammatory patients that you've seen. Consider doing the genetic testing. Consider using monotherapy or combination therapy in RA. You want to get me riled up, tell me how important monotherapy is in RA, and I'm going to tell you, really? The disease I spent my whole life studying and battling and trying to treat you think is gonna be treated by one drug with one mechanism of action?

What do add to your mind? And I truly, believe that to be true. Nonetheless, here's a network meta analysis report of 31 studies, looking at 13 different conventional synthetic DMARDs, traditional oral DMARDs, asking the question, does monotherapy work? Using as an outcome, does it benefit or retard x-ray progression scores when done annually? And the answer is yes.

Laflinamide, sulfasalazine, and gold were better than placebo and equal to methotrexate. Congratulations. Methotrexate, sulfasalazine, leflunomide, and gold that nobody uses anymore does work as monotherapy. The big fault in this study is why are they looking at monotherapy alone and not comparing it to combination? I did, after looking at this and reporting this.

And, you know, combination therapy, methotrexate with any combination, Jim O'Dell and the RAIN network proved that. Methotrexate plus any biologic, tons of studies have proven that. Combination is the way to go. Hence and I do this, and I'm just thinking about this now. I see a brand new RA.

I usually start them on methotrexate, and then I order labs, and I bring them back. Maybe that's good for the very first visit just to make sure everything's good. And then at your second visit, four weeks later, why are you not putting them on combination therapy? I've written about the fact that everybody with RA should also be on hydroxychloroquine. I don't care what you're on.

It has the same benefits in RA as it has has in lupus. Or instead of adding hydroxychloroquine to methotrexate, use a triple DMR therapy of the RAIN network or put them on methotrexate and a biologic. You can always withdraw therapy later on, but why not be aggressive right from the outset? Again, combination works better than mono. Congratulations.

Mono does work, but that's 1980s thinking in RA management, is it not? There was a report this last week, from JAMA Network Open about, a large cohort of giant cell arteritis patients who were treated with aspirin. So this is a retrospective French study of fourteen thousand five hundred patients over age 50 diagnosed with newly diagnosed with, GCA, and, a a portion of the group got aspirin in low dose and the others did not. And they looked at cardiovascular outcomes, MACE, major adverse cardiovascular events. At one year and at three years, the patients treated with low dose aspirin had better outcomes.

Fourteen percent or twenty two percent less better cardiovascular and all cause mortality outcomes. That's impressive. Why would then would you not put everyone on aspirin? Well, that's the flip side to this study that showed there was a significant increase in bleeding, from the GI tract. And that was only seen in the first year, not in the three years.

In subanalyses, they showed that the biggest protective effect was, for the low dose aspirin group, was for MACE in women, where there was a twenty two percent benefit, and also in GCA patients who also had diabetes. So do you use aspirin or not? I would, unless there was a contraindication to it, And you know the contraindications. And and age could be one. Age plus GI plus renal plus heme heme, obviously, you're not gonna be putting them on aspirin.

Right? But aspirin does have some protective effect. And, you know, twelve to twenty percent is nothing to, you know, discard 14, excuse me, to 22% is nothing to discard as being an insignificant benefit. I'd walk a mile for that. So the big downer of the week was rheumatology salaries.

Medscape came up with its annual report on physician salaries, congratulating us physicians, I'm patting myself on the back because I'm one of those, with a roughly 3% increase in salaries overall with eight specialties earning more than $500,000 per year. Who are these people? And we know they're not rheumatologists who haven't invested in Bitcoin. So, yeah, the bad news is survey of almost 6,000 physicians, only 1% of whom, by the way, were rheumatologists, showed that rheumatology ranked in the bottom four of overall annual salaries. In The United States, that was 284,000 according to this, Medscape survey.

Doximity did a similar survey showing that, it was about the same, maybe about, $2,030,000 dollars less. But the other bad news from Doximity and other reports is that their lowest paid are pediatric rheumatologists. I'm sorry. They're the second lowest paid. I think it was I can't remember who it was.

I think it might have been physiatry. Might have been the second lowest paid. And that's sad. Their average salary was, 231,000 per year. So, you know, should we cry?

Should we invest in Bitcoin? No. Again, you've got the best job ever. Rheumatologists are happy for a lot of reasons. One is the quality of the interaction.

Two is the intellectual stimulation. Three is that you're well paid. Four is that you love your job. If you want more money, there's a lot of ways to make more money. Get your own website, start your own blog, and your own podcast.

Good luck. You maybe you'll make some more money. But there's a lot of other things. And a lot of rheumatologists do have side gigs that to augment their income. And by the way, that's a nationwide salary.

If you look at that Medscape article, salaries different or differ significantly throughout the country. They're highest actually in the West Coast. And there are other things in there that tell you about how, you can do better. One of the biggest problems is first off, the other thing they said is, rheumatologists expect their salary to be the same this year as it was last year. I mean, we're not there were several specialties.

I think there was eight of them that had significant more than 5% increase in salary expectations for next year. Rheumatology is not one. We're expecting the same next year as we got this year, as we got last year. And last year, it was again $284,000 But they made some points in there, including that most physicians are not very good at negotiating salary. You should think about that if you wanna increase your salary.

Anyhoo, hope you enjoyed this podcast. I did. We'll talk next week. Take care.