Teaching You How to Think… (8.15.2025) Save

It's 08/15/2025. This is the RheumNow podcast. Hi. I'm Jack Cush with RheumNow. Glad that you're here this week on the podcast.

Good news in Sjogren's disease. Really good news. To PT or not to PT, and we'll end with words to live by.

What will the rheumatoid arthritis experts say about biologics and DMARDs and their evolution over the last twenty years? Join us for a deep dive live webinar on Tuesday, August 26 at 7PM Eastern. Doctor. Jack Cush will moderate a Tuesday night rheumatology session where the experts unpack the results of a nationwide three part survey, covering treatment milestones, changing practices, and what the future holds for RA therapy. Don't miss this opportunity to hear what your peers are saying, and where the field is headed.

Register for this TNR on roomnow.com, or catch it on the YouTube, Twitter, or LinkedIn live streams. We'll see you there! This program was sponsored by Bristol Myers Squibb.

But let's start with news from Novartis. Novartis has been working on a B cell depleter. Originally, it was called v a y v a seven thirty six. Its generic name is inalumab. We talked about this at ACR last year where they had really good results in a phase two b trial of Sjogren's syndrome, and they just came out with a press release on top line results of inalumab in primary Sjogren's disease, two trials going on at the same time, the NEPTUNIS one, NEPTUNIS two trials.

They met their primary endpoints on efficacy with significant improvements, the exact numbers of which are not known, but probably will be presented, I'm gonna guess, at ACR. This is good news because we've said it here before, a lot of drugs look good in phase two, but crash and burn in phase three. This is a big phase three trial, and we don't have any really great effective therapies in Sjogren's, do we? I'm looking forward to those results. Anifrolumab has been out on the market.

As you know, this is the type one interferon inhibitor. This is a small pilot trial that brings up a point that has been alluded to, But it's an open label trial of anifrolumab in refractory cutaneous lupus. Fifteen patients, single center study, all these people were on hydroxychloroquine had failed, topical steroids and had failed multiple immunosuppressives prior to being treated with anifrolumab. They were all treated in standard dose three hundred milligrams every IV every four weeks. All of them improved.

And they did their measurements using the classy outcomes. Classy a decreased from 16, very active, to one. That's a highly significant response, and class e d also increased or or sorry, decreased. Clearly, we need a double blind randomized controlled trial. And clearly, I think drugs, especially lupus drugs, should be going after a cutaneous lupus erythematosus, endpoint and an indication.

I mean, I know it's good to get nephritis, but we need help with drugs that work in lupus skin disease. This looks like a good one. A lot was said at EULAR about difficult to manage PSA and difficult to manage SPA. This week, we had a report, a single center study of a hundred and twenty nine axial spondyloarthritis patients. And from that cohort of one twenty nine, eight point five percent had what was classified as difficult to manage axial spondyloarthritis, defined as not responding to at least two or more biologic or targeted synthetics of different classes.

The more active definition or more active subset would be those who have treatment refractory disease, TR. So again, eight point five percent, that's a little similar to the numbers we were seeing in RA with d two TRA, about ten percent. And three percent were treatment refractory, and again, that definition is the same except it requires more markers of inflammation. Not surprisingly, the d two the d two m, difficult to manage, SPA patients had higher VASVs, higher VASDAs, higher ASDAS scores, predictors of being a difficult to manage patient with spondyloarthritis of being a smoker, having psoriasis, sacroiliitis, and evidence of X-ray damage. We're going to see more studies on difficult to manage PSA and SPA in the future.

A, interesting country based study on enthesitis related arthritis or ERA, forty five from Tunisia and forty nine from Turkey. They had very similar demographics going in. The Turkish, ERA patients had significantly more heel pain, sixty one percent versus nine percent. Significantly more enthesitis, same thing, sixty nine versus forty percent. And greater use of biologics, fifty versus nine percent.

But the Tunisian ERA patients had more sacroiliitis, ninety one versus fifty five, and more axial disease. You gotta wonder, is it the availability of the biologics that are making the difference? Is it how they are being managed in different areas? Actually, there was a difference in B27 between the two countries, so that's another factor that goes into what's seen in ERA. A study of severe psoriasis patients who were either treated with UVB light therapy, what they call, I think, Geckermann therapy, or a TNF inhibitor.

Nine hundred and forty five consecutive severe psoriasis patients over a five year period followed for a median of nine years. After they did the propensity matching, the incidence of future development of psoriatic arthritis was less than half if you got a TNF inhibitor as opposed to UVB. One point two cases per hundred with TNF inhibitors, two point five cases per hundred with UVB therapy. That's highly significant. Overall, the TNF inhibitor lowered the risk of developing PSA by sixty eight percent.

And so I think, again, there's been a number of these studies that say we we do know that that severe psoriasis is a is a very good risk factor for developing psoriatic arthritis. But we also have seen said many times before, and you may not like the statistics on these or how the data is, analyzed, but it looks like aggressive therapies can change the and lower the rate of developing future psoriatic arthritis. Maybe this is a big call for more dermatologists to be aggressively managing, psoriasis and doing basically medical psoriasis, which is not that popular these days. A study of systemic sclerosis patients and the utility of nail fold video capillaroscopy, a study of two hundred and fifty eight cases with nail fold video capillaroscopy basically says that the telltale signs of a scleroderma pattern with a high predictive value is number one, giant capillaries, has a specificity of ninety eight percent, and a capillary density of less than eight capillaries per millimeter, meaning capillary dropout. When you have both of them, it was seen in that whole big cohort in almost forty percent of patients.

But when you find those two together, it has an accuracy of predicting the diagnosis of systemic sclerosis of ninety one percent. So do you do nail fold capillaroscopy? I gotta say that I've never been able to use the ophthalmoscope. I don't know why. It's just never worked for me, and the people who own the ophthalmoscope don't like the fact that I may get goo on it or gel or or oil on it.

I did work at the university where I bought a very expensive, video capillaroscopy unit. I think it was more than $5, and boy, you could see beautifully the capillaries in any hand. But you know in my practice, my private practice that I ran for many years, we had a $6 kid microscope. It was, I think, a 10 x or a 20 x. You can see it.

Find it on RheumNow, and you can buy them on Amazon. Again, think on Amazon, I think they probably cost, like, 12 or $15 now. But I had one of these in every room. That and some KY jelly and, man, I could just dive right in and see what's going on. You really should be doing this, with suspected scleroderma, myositis, lupus, patients who have periungal erythema and those ratty, ragged changes indicating inflammation.

You wanna see what's going on in those vessels. A recent French study looked at the issue of how long you should be holding the methotrexate when you're doing pneumococcal vaccination. So in this trial of two forty eight early DMARD naive patients were starting methotrexate, They either started methotrexate the same time they got the PCV thirteen vaccine or they waited a month. Now why they waited a month when the current rule that I've been teaching is wait one week because there was first the rule two weeks and then the rule by Choi et al, I guess, said again that you can only delay one week. Patients wouldn't be hurt clinically by holding their methotrexate one or two weeks.

In this trial, they held it for a month, and these are people who are starting out their therapy. Well, number one, the month delay didn't seem to affect overall RA activity in the short run or long run, But, clearly, they had much better vaccine responses in those who had a delay in taking methotrexate. Methotrexate will screw up vaccine responses for for for sure. And the benefits of vaccination with a methotrexate delay we're seeing even out to one year. So this is sort of supports the data that you should hold the methotrexate one week, two weeks.

You could even hold it a month according to this study, and I think that we're all doing that. Do you do it with all vaccinations? Do you do it with all drugs? We talked about that last week. I'm starting to hold, JAK inhibitors for a week or two and do my vaccinations.

Again, the two drugs we definitely know will screw up your vaccine responses, rituximab and methotrexate. Everything else not so much. JAKs, I worry about a little bit. More on RA. A meta analysis looked at the issue of physical therapy, physiotherapy, and 17 RCTs, 1,300 patients, they looked at the interventions of either aerobic or resistance exercise, hydrotherapy, manual PT, electrotherapy, bimodal multimodal treatments, and they basically showed that there were a number of randomized trials that showed a significant reduction in pain with an SMD, standardized mean difference of minus 0.3.

If you look at SMDs, you know, point two to 0.5 is low, 0.5 is medium. This is a small to medium effect that favors PT. Most rheumatologists don't use enough PT. You know you should, you know you don't. This kind of data says, you know, I can do better with drugs than I can with PT, but this kind of, intervention is adjunctive and on top of.

So I'm still gonna advocate for PT, and you do get a small to moderate effect here, but this can't be the only thing alone. Right? Another Mayo study looked at, multimorbidity and its effects. This is six hundred and thirty nine new incident RA patients at the Mayo Clinic. And if patients had multimorbidity, they had a twenty nine percent higher risk of RA flare, a thirty four percent lower risk of achieving remission.

RA flares were associated being female smokers, younger age, shorter disease duration, but wasn't associated with seropositivity. I'm big on this issue of flares. We treat flares like they're important. We treat all flares the same by giving steroids, often not without even seeing the patient. This is a I think flare management's a problem, and it's indicated really by the next paper I'm going to talk about.

This is a paper that looked at a hundred and ninety five patients with RA, and showed that with multiple, like I think they had four or five definitions of FLAIR, forty nine to eighty nine percent experienced at least one RA flare and they had a median of two to four flares per month. Well, this is not good, right? But these flares last a median of two days, no more than four. And then when you look at what characterizes these flares, they were preceded by worsening of mood, anxiety, sleeplessness, and but no change in accelerometers. So what the heck kind of flares are these where there's no signs of inflammation?

No change in activity as measured by the accelerometer. Yeah. They were given one of those wristwatches that that will measure all kinds of things, including sleep, but is associated with mood, anxiety. Again, these are all pain flares, probably all fibromyalgia flares, but and they're all short lived flares. Are you really gonna be treating those with steroids over the phone?

We need a better strategy for flares. I'm gonna end with what I thought were two really smart, papers this week. It was a great ACR released some guidelines on vexus that you should look out, copy, have on your desk. I think it's a good learning lesson. It's a new syndrome.

They're out there. They may look like relapsing polychondritis, but, you know, they're usually older men, upon which you should do some gene testing. But I like these two papers, that I'm gonna end with. One, the patient journey. This is for people who have rheumatic diseases, and Loretta Carmona and her colleagues in Spain looked at this in a very detailed way.

They did a meta analysis, systematic review, 27 papers, and they basically summarized their results by saying the patient journey for patients with rheumatic diseases has a certain blueprint that's kind of ugly, and that is there are eight phases. Here are the phases. One, awareness. So this is what the patient goes through. One, awareness.

Two, help seeking. Three, first encounter. Four, clinical suspicion by primary care. Five, primary care does diagnostic tests. Six, management by someone, not rheumatology.

Seven and eight, rheumatology gets referred to and manages the case. This is bad because we're talking about they've quoted that, one study, a mean delay in RA diagnosis of twelve months. I don't think that that's the case at all. I think it's much longer than that. They said fibromyalgia, three years, spinal arthritis, six years, but there are significant diagnostic delays for the multitudes of people who have rheumatic disease.

And this is what everybody goes through. And until we address these, it's not gonna get any better. People who have rheumatic disease have fragmented care. They have encountered multiple barriers, mainly limited awareness of disease by both patients, families, and those that are going they're gonna go see for help. Symptoms get minimized by patients and families and providers.

There's poorly coordinated care, no coordinated care. There's disjointed referral patterns, significant diagnostic delays, and let's not even get into education of non rheumatologists about rheumatology. The stats are overwhelming. One point six three billion RMDs worldwide. It's the second leading cause of disability, and it's increasing.

Three hundred and twenty two million new cases in 2019, that includes a hundred and seventeen thousand deaths. These conditions have an overall peak of fifty to fifty four years when they present more so in women than men. So despite this very strong prevalence, most of the world, patients, HCPs, PCPs, and the public have limited awareness of RMDs. So what should happen here? Awareness and help seeking and first encounter, that's public education.

That's disease state information that needs to be out there. I think if you're going to get a drug approved for rheumatic disease, especially if you're gonna put it on TV, especially if you're hoping to make a billion dollars from it, you should have an FDA mandated obligation to do public education on that condition for which you wanna play in that marketplace. Why not? It serves everyone. Then the middle three, suspicion of disease, testing and management by primary care and non rheumatologists, yeah, there needs to be programs for them, but I wanna caution everyone that wants to educate primary care.

I'm all for it, but here's some real numbers. I don't know the real number of primary care doctors. I'm gonna guess like 260,000 to 300,000 in The United States. The number of primary care doctors in The United States that actually write for biologics, for RA, PSA, SPA, etcetera, you know, one time, ten years ago, it was only like 1,500. That's true.

And now add to this the fact that while we rheumatologists think that those primary care doctors need great education on how to diagnose lupus and rheumatoid, how to do diagnostic testing and serologic testing, you know, there's 19 other specialties who are also saying the same thing about primary care. We need to teach them about autoimmune hepatitis. We need to teach them about type one diabetes. We need to teach them about proper management of bronchiectasis. We need to teach them about earlier diagnosis of melanoma.

You know, primary carers are probably saying, leave me the hell alone. So, again, there's a need there. The uptake is gonna be small and it's gonna be inefficient, but you gotta do what you gotta do. I think it's mainly accomplished by those last two issues, rheumatology referral and you managing it. And you know what?

You should be managing as many people as you possibly can, but you're not going to if you're waiting for those people who don't know what they're doing to send you the patient who you wanna see. Why don't you advertise? I don't mean like a billboard or radio ad. I mean, get a list of all the primary care docs, surgeons, GIs, whoever you wanna get people referred to and say, Dear doctor so and so, I want you to know, I wanna see new patients, especially these patients. RA, you know, symmetric polyarthritis and morning stiffness with an abnormal lab, send it to me.

I'll see them tomorrow. If you don't advertise what you wanna see tomorrow, you're just waiting for any old thing to come in the door, and then you're letting chance and roll of the dice and maybe too many complainers define your practice. Again, this patient journey is an important lesson that everyone should learn from. I'm gonna end with a review article that I got from the American Journal of Medicine this week. It was written by Joseph Alpert, who's a professor at the University of Arizona Medical School.

It's a two part article where he talks about medical aphorisms and the wisdom therein. Aphorisms are concise statements of truth or principle that are often handed down by tradition from generation to generation. And you have your aphorisms, I think that you've probably heard from your mentors, and hopefully you'll pass more on. Here's a few to live by. Eugene Steed from Duke, famous for actually starting the physician assistance program at Duke, first one in The United States after the war, second world war.

He's got two quotes, most patients recover in spite of what we do, not because of what we do. Second, when in doubt, do less. Francis Peabody, who's famous for writing an article called The Care of the Patient in 1927, I think it was published in JAMA. Look it up, download it. It's a long article, but if you like and you're proud of what you do in caring for patients, this is the standard.

This is the great essay. This is the great speech. And he said the secret of the care of the patient is in caring for the patient. And I have said that before. The best doctor in the world is the one who cares a cares a lot.

Tinsley Harrison of Harrison's textbook fame, and he's from UAB, I believe. I'm not here to teach you the facts. If I want you to know the facts, I tell you to read my book. I'm here to teach you how to think. Brilliant.

The author, famous author, Lewis Thomas said, science is founded on uncertainty. Science is founded on uncertainty. Each time we learn something new and surprising, the astonishment comes from the realization that we were wrong before. So much of medicine, so much of learning is rooted in finding out you were wrong or is rooted in making mistakes and learning from them. The famous cardiologist Eugene Brunwald says, we are privileged to work in a field where what we do today can be better than what we did yesterday, but still not as good as what we will do tomorrow.

Change is necessary. Embrace it. And the author of this article, Joseph Alpert, has one of his aphorisms, being a doctor is about stories, about listening to them, understanding them, and sometimes helping to change their ending. That's it for the podcast this week. Tune in next week.

Oh, wait. Are you doing Room IQ? I am. Many of you are beating me on a regular basis. And I reported the news and I wrote the questions.

What's up with that? It's fun. Take a look at it. It's in your inbox this week, I think on Monday. Take care.