Quiz Talk (5.22.2026) Save

It's 05/22/2026. Happy birthday to my stepdad Harry Lyons. This is the RheumNow podcast. I'm Jack Cush, today's host for today's podcast. I want to start by talking to you about Room IQ.

I don't know if you've been following or been using Room IQ. It's a quiz. Comes into your inbox every Saturday morning. It's a quiz based on this past week's news, And, you know, we worked on this for a while. I really like this game.

It's really quick. It's like less than five minutes. Six, seven, eight questions. Half of them truefalse. And, but you know this last week, what happened?

You know, a few 100 of you took this, quiz, and the pass rate was only 66%. I mean, you're falling down. You're not following the news. What's the deal? I think maybe you, who didn't take the quiz as a podcast listener, maybe you're better than those who did take that five minute quiz.

I mean, for example, a question that only half got right was: An RA patient has a current or new cancer. For which cancer would you stop or avoid a TNF inhibitor? You know, I gave you a few choices: lung cancer, colon cancer, melanoma, and then D was none of the above, and the answer was D none of the above. Oh, what happened there? Anyway, you can check out next week's quiz.

It's in your inbox on Saturday morning. Let's get to the podcast. Medical Economics reported, I think an astounding statistic that I was surprised by. How many physicians in The United States are working for corporate entities, institutions, hospitals, and how many are employed by MD owned practices, either as solo practitioners or, as a member of a group. And the number is down to 18% are working for MD owned practices.

Holy moly. In January 2026, hospitals or corporate employment of physicians rose to 550,000, whereas independent employment by physician owned groups, a 121,000. This is the way it's going. Is that a good thing? I do know there are benefits.

I mean, I ran a private practice for, well, really about twenty years. At the end of my practice I got bought out and I didn't stay there very long. You know, when you work for a hospital group, an institution, private equity, God forbid, they'll pay you better, they'll give you better benefits, they'll kind of take care of your employees better, but they're gonna hammer on you for output. It's gonna be the mill. It's they want you to become, you know, a six to eight minute visit just like dermatology, and churn out the numbers because it's hard to make money off a rheumatologist in practice.

I think this is a sort of a I don't know. It's a scary, scary statistic to me. Not so scary and not so uncommon is fatigue in lupus. An NIH cohort study looked at fatigue and lupus, and I've always thought it's probably unrelated to activity. They did not show that.

It was related to organ damage and obesity. And I don't think they looked at the other things that fatigue is a big driver of, and that includes fatigue and fibromyalgia. But organ damage and obesity were significant contributors to fatigue and lupus. Okay. The Clinical Rheumatology Journal addressed an unmet need, although it did so in a very uncontrolled, experiential observational study from Japan where they asked the What happens when you treat neuropsychiatric lupus, CNS lupus, lupus cerebritis, all its names, with rituximab?

And I don't think I would know that answer, so that's why I reported it. They reported on seventeen patients with refractory neuropsychiatric lupus, meaning they didn't respond to steroids and maybe another medicine. And I guess this is over a long period of time, a few years certainly. And sixteen out of seventeen had significant improvement. What's the metric?

They don't say. One had partial improvement, and none of these patients had a relapse of their neuropsychiatric lupus. Two patients died during COVID. There were two other strange viral infections viral reactivations. Encouraging enough that, you know, maybe it's the way to go.

Steroids are the acute answer to managing neuropsychiatric lupus, not in all situations, but in many. But what's the long term out on therapy? Especially when they occur, because you know you can get CNS lupus whether you're controlled or uncontrolled. Whether you're on biologics and DMARDs or not. It's kind of funky that way.

Anyway, I think this provides a reasonable treatment option that should be investigated further. Right now, all I'm showing you is an observational 17 patient trial. A press release this week looked at a new drug that's in clinical trials, looks like it's probably a phase two trial: IMVT1402. This is a human on a human monoclonal antibody targeting FcRn, the neonatal Fc receptor, of which there are a bunch of drugs out there and in development. This is a JIA trial design.

That design means you put people with active disease in the study, open label, and then you get to an endpoint, and those that are responding are then they then go into phase two where there's a blinded withdrawal to placebo in half the patients. So they did an open label study of one hundred and seventy patients with active, really kind of refractory, D2TRA patients, and at the end of week 16 again this is open label study open label studies you have inflated numbers. So an ACR twenty was seventy three percent holy cow! But it's open label everybody knew they're getting drug. ACR fifty was fifty four percent, and ACR seventy was thirty six percent.

Those are good numbers. Really good. But now the fun begins. Now the responders are gonna be blinded and go forward either continuing on the IMVT fourteen o two or a matched placebo. We'll see what the blinded results will show in the months to come, hopefully.

I like this review that sort of connects the dots in rheumatoid arthritis between what's going on with the innate immune system and how do we transition to an adaptive immune derangement. This report from Nature Rheumatology, I think it was, sort of explained the role of the NLRP3 inflammasome, that it gets activated by a number of different signals. There are many pathways to activate PAMPs and DAMPs, as a simple way of looking at it, pathogens or damage associated molecular patterns, and that triggers the release of PAD2 and PAD4 from human neutrophils, which lead to citrullinization of a lot of intracellular proteins giving you CCPs. That further drives the pathogenesis of the disorder. To substantiate the role of the innate trigger was that PAD concentrations and PAD activity correlated with IL-one beta release, which is the prime product coming out of an activated, an LRP3 activation.

So I like that report, think it kind of clarifies some of the origins of what's happened. Now, what is the trigger? What's the pathogen molecular pattern, damage molecular pattern that leads to that? Well, are a lot of theories, right? That's another report.

An Israeli study looked at the risk of major congenital malformations with non steroidal exposure. These were non selective non steroidals, and they looked at 240 two hundred and sixty four thousand pregnancies. Eight percent of those pregnancies were exposed to NSAIDs compared to the other, you know, eight ninety two percent that were unexposed, and the overall major congenital malformation rate was eight point two percent versus seven percent, and adjusted an adjusted relative risk ratio zero point nine nine, not significant. NSAIDs don't. And this is first trimester exposure, I should say.

As you know, it is verboten, not allowed, bad news, to treat patients in the third trimester with nonsteroidals of any kind. It causes premature closure of the ductus arteriosus and putting the fetus at risk. So but this is a first trimester exposure, and again, no malformations, especially when you look at musculoskeletal, cardiovascular, neurological, cleft palate, GI, GU, those are the big, major malformations that are often seen and reported and worried about. Not seen here. So that's sort of good news, and yes you can use nonsteroidals early on in pregnant pregnancy or when they're trying to conceive.

There's again the ACRE reproductive guidelines said that same thing. They said don't use selective COX-two inhibitors because there's some negative signals there and we don't know enough about that. So use, you know, the ones that you might have used before: ibuprofen, meloxicam, naproxen, or sorry, naproxen. Diclofenac is my least favorite of all of those, but that's okay too. A report about biomarkers and ANCA associated vasculitis also in a review article this week said: You know what?

Vasculitis and its management is great. We got lots of options. They did an analysis and they really find no biomarkers to predict either the renal outcomes or the risk of relapse. And that included, you know, IL-six and a few others. They talked about the future that CD163, which is a good biomarker for renal lupus, that that could be studied in ANCA ASV, and maybe we'll know more about that in the future.

The other biomarker study was in RA, but it was only forty patients with treatment naive RA who were starting methotrexate. And they did serum cytokines looking at IL-six, IL-seventeen, TNF alpha, GM CSF, and they basically showed none of these qualify as a biomarker for methotrexate responses. So, high baseline IL-six and IL-seventeen levels were associated with non response significantly so, but not good enough to qualify as a predictive biomarker. And then with all the other ones they measured, we're still a long ways away from having a biomarker on RA or other disease responses. We need more research on this and I know you think it might tell me there are some biomarkers out there.

No, there isn't. They predict the past, meaning all their data proving their value was based on retrospective data. None of those companies have done a prospective biomarker study, sizably powered, to prove the point. Their biomarker, you know, serum applesauce levels versus what? Usual care or twenty eight CRP, or choose another potential biomarker sed rate calprotectin levels CCP if you like.

And then show that that your newly proposed high priced, biomarker from some new company that's knocking on your door, show it's not inferior to something you already do. Then you just have to grapple with the cost analysis. It's an interesting way to look at it. There's a Japanese company called Kissei, k I s s e I. They had a press release this week.

They are the marketing company for Avacopan in Japan. And they put out a press release talking about twenty deaths related to the use of avacopan in Japan. Since it was approved in June 2022, the drug has been given to eight thousand five hundred patients and there are these twenty deaths. This is not good since avacopan is under the microscope with the FDA, and the FDA is supposedly calling for them to voluntarily withdraw the drug, the FDA may shut down the drug. Again, the incidence here is really really low.

The problem as I see it is that FDA decisions, even though there's an incredibly low incidence of these events, can be driven by a serious deadly event that's never been described before. And that's the vanishing bile duct syndrome, which is a part of these bad outcomes with avacopan. Look it up. It doesn't exist with anything else. And now it's been linked or almost nothing else.

Now it's been linked with avacopan. I think this is bothersome, and I think the outcome is not gonna be good for avacopan. AxSpA studied, three zero five patients with newly diagnosed axSpA to see how they were diagnosed in the role of imaging. The profile was good: thirty eight years, fifty five percent male. Axial SpA, fifty five percent male.

Well, yeah, we are making more female diagnosis, right? But this is not non radiographic axospA, this is axSpA. The delay in diagnosis: six years, that's a little bit better than seven or eight, that's been reported. Seventy five percent B27 positive. Okay, so this is the right population.

The interesting thing about this study was that twelve percent the diagnosis was made without imaging, without proof of sacroiliitis. Congratulations to you twelve percent rheumatologists who don't need an x-ray or an MR. I think there's a value in doing x rays. I'm not convinced there's a value in doing MR if you're not doing clinical trials research. The other interesting thing about this cohort study was that five percent developed secretly it is during eight year follow-up.

And again, there was something about the males with high CRPs maybe being better study subjects here. I don't think that's as important as the twelve percent diagnosis made without it. Another five percent diagnosis was made later on over time, meaning they did not have baseline sacroiliitis when they were first seen. Two more reports: the B. BOLD study we had previously reported on as a press release from UCB it's the first head to head trial of their dual IL-seventeen inhibitor bimekizumab against the IL-twenty three inhibitor rizenkizumab from AbbVie.

This was a prospective randomized controlled trial, and this week, because now the results are published on the EULAR site, and this data is going to be presented at EULAR on Wednesday June 3, I think is the date it's going to be presented. This is a study of five fifty three active PSA patients who were either biologic naive or had received one prior TNF inhibitor. I don't know the breakdown in percentages there. And the primary endpoint that's reported here is the week sixteen outcome. The primary endpoint was ACR fifty.

And it was significantly in favor of bimekizumab forty nine percent versus rizenkizumab thirty eight percent. That was significant. There were a lot of other secondary measures secondary outcomes numerically favored the IL-seventeen inhibitor, but there was not significant. And that includes MDA, minimal disease activity, forty three versus forty percent, and PASI 100 total skin clearance 53 versus forty seven percent. Anyway, this is going to be presented at EULAR and hopefully we'll get more complete data, put it under the microscope, see what's going to happen after week sixteen.

I assume this is going to be a one year trial where we find out what happens. But I want to know what happens to non responders after the primary endpoint. Are they going to continue them, or what? Let's see what happens. We'll report on that coming from EULAR twenty twenty six.

Lastly, we had reported previously about abataciferous hydroxychloroquine and palindromic rheumatism. I contend palindromic rheumatism is a subset of clinically suspect arthralgia, at risk RA, preclinical RA. This study was a study of seventy seropositive pyelondromic rheumatism patients from 14 centers in Spain. The outcomes clearly favored abatacept, only twenty one percent developed RA or inflammatory arthritis that was chronic versus fifty percent with hydroxychloroquine. We know hydroxychloroquine does not fare well in this arena.

We know abatacept does fare well in this arena of CSA preclinical RA and applies to palindromic rheumatism. This is a twenty four month outcome study. Those that were on abatacept had a longer time to progression and they had reduced intensity of flares, but not the frequency of flares were the same between both drugs. So, I think that's valuable data. Want you to be on the lookout for the Advanced Practice Rheumatology Tutorials, a series of videos that are up now.

These are about fifteen minutes each. Topics include: Evaluation of rheumatic patient, lab testing, ANAs, sed rate CRPs, rheumatoid factors, CCPs, methotrexate use, difficult to treat RA, fibromyalgia, lupus. There's all going be a whole bunch of them. These are designed for trainees, residents, new hires, APPs. Any of you that want to see them, you're welcome to.

I stand by what I say, because I'm looking to educate the larger audience that doesn't that wants to know more about these topics and rheumatology. I know that you're a a world class expert. Maybe you won't get as much out of it, but feel free to look at that or tell your trainees and APPs to check it out. I wanna remind you, we're covering EULAR. Begins Wednesday, June 3.

We got a team that's gonna be there. We're looking forward to it. And I got one last, ask Cush anything case from London's doctor Ali Jawad. Ali's a loyal listener, and thank you doctor Jawad for your kind, comments. He sends in a case.

A 59 year old RA patient who's double positive has been treated for I think he said fifteen months with methotrexate twenty milligrams per week and adalimumab, and the patient's done well for almost a year. The question arises when the patient wants to lower their methotrexate, and also when he found out at a visit the patient had dropped it from 20 to 17.5. Is this a good idea? How should he monitor this? What's the response here?

And, you know, there are studies about methotrexate and JAK inhibitors, and then you withdraw the methotrexate and still do well. I think it's pretty clear that you can more likely withdraw methotrexate from Jack if the patient is in remission, alright? In RA, on methotrexate and a TNF inhibitor, it's less clear. There are some studies that support that, but there are equally as many studies showing that the patient will flare if you wean off the methotrexate. Can you lower the dose?

Yes, you can. With a usually a small increase in activity, but if you stop the drug there's going be an increase in activity in too many, and maybe a worsening of outcomes where that has been looked upon. I'll let my patients lower the dose, especially if they're having toxicity at doses above, you know, fifteen. I'll go down You know, the data on infliximab development, this is a CA2 trial done by Jim Woody and, others in Tiny Mani and others in Lancet, going back to 1998, showed that if you gave RA patients on CA2, also called infliximab, you could reduce the amount of anti drug antibodies with ten milligrams of methotrexate, with sulfasalazine. So the idea is you can go down to ten milligrams, but I would say the patient who's having side effects from methotrexate, you can lower the dose, and go down to fifteen, go down to twelve point five, go down to ten, I still think you're getting benefit as far as avoiding anti drug antibodies, as far as avoiding flares and maybe x-ray worsening.

What do the guidelines say? The guidelines from EULAR, the most recent guidelines on RA care, are very clear in saying after someone fails or has an incomplete response to methotrexate, you should be one and done and move on. Move on to a biologic or targeted synthetic. And then if you fail on that one, change your MOAs. One and done.

You keep moving. But you stay on the background of methotrexate. There are a number of studies that have been done that if you stop the background of methotrexate, and two of them from Japan in fact, show that patients can get worse. A recent Japanese study just a few months ago, small cohort, about 90 patients, showed that there was no difference when you stop the methotrexate. But they weren't measuring, I think, anti drug antibodies in that study, and they did not have a long term outcome.

The idea is I think it's an okay idea. You monitor the patient as you would monitor the patient, which means you should be doing a metric. If you don't do a 28 that you can monitor, do a composite measure like the rapid three, where it's pain, hack, and disease patient's assessment of disease activity. I prefer that you do a CDI, which is a tender joint count swollen joint count, with patient measures. But that requires you to do a detailed twenty eight joint count.

My measure that I use in practice that's, I think, as good as anything, actually better than anything, is the GAS score, the global arthritis score. That's patient pain, zero to 10. The HAC score, zero to 24. And the 28. Add them up, zero to 62.

You've something that performs equally well to any of the measures that are out there. But it does require the joint exam. Measure something, and that's the best way. The clinical exam is the best way to monitor, and outperforms any laboratory study by far. That's it for this week.

Check out the quiz. Watch our coverage of EULAR coming up. Take care of yourself.