Remission – Believe it or Not (10.2.2026) Save

It's 10/02/2026, and this is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week on the podcast, some top line study results of yet to be presented big trials, giving you a heads up on what probably will be presented in the next few months, maybe even at ACR. We get some regulatory announcements.

We have growing interest in Sjogren's and a sort of rheumatology, believe it or not, called remission, believe it or not. Let's begin with an announcement from the EMA and the European Union where upadacitinib is now approved for use in treating polyarticular JIA. The indication is for kids over age two not responding to one or more DMARDs. We know that this drug is approved, OOPA, for both polyarticular JIA and juvenile PSA in The United States, so this is a good good news for kids on the other side of The Atlantic. The FDA has also approved in The United States baricitinib, also known as Olumiant, for the treatment of pediatric severe alopecia areata.

And it's pediatrics. I'm not really pleased when I see that the age is for 12 years and older, and that does qualify as pediatric. But what about those other kids? And the reason why that is, why was the other one two years and this one's 12 years? That's what was recruited in the trial.

And the trial design may have been designed because getting kids under 12 with either alopecia areata, alopecia universalis might be really, really hard. But anyway, think it's a good thing, and we certainly have seen dominance of the class of JAK inhibitors in this unfortunate area. I've treated a few patients over the years with great success and not with just improved drugs, I've used other unapproved drugs, now we have a number of them that are approved now, baricitinib approved in adults and now also in pediatrics. Jay and Jay announced top line, results of their STARR study. STARR is a phase four study using guselkumab in patients with axial PSA.

I don't know if you remember the story, but it goes like this: IL-twenty three inhibitors, we know, work in PSA. The early data was they didn't work in axial ankylosing spondylitis. And then Philip Meiss and a few others started doing sub analyses of PSA trials and finding axial PSA subsets where they did respond to IL-twenty three inhibition. Hence the phase four STARS study, which is a twenty four week endpoint looking at BasDi as the endpoint measure. They enrolled four eleven biologic naive PSA, axial PSA patients, and they showed significant improvement in axial symptoms, but also importantly in MRI outcomes.

So this is a big win and a big reversal on our thinking about where IL-twenty three belongs. Obviously, is not yet an indication, but this probably would be... It's a large enough trial that it could be used to support a new indication for guselkumab. Amgen also announced the phase three results of their OASIS, o a s I z, three zero one study showing that dasodapolep dasodapolep was... And that's a c d forty ligand antagonist, was studied in patients with active Sjogren's disease.

And again, these are just top line results. I'm not giving you the actual numbers of the SDAI, ESSAI, it's the Sjogren's Syndrome Disease Activity Index, improvements at week forty eight. But again, this is encouraging data I expect for both the STAR study and for this OASIS three zero one study. We'll see that maybe at ACR and be able to dissect that a little further. Sjogren's is a popular area right now.

It's a hot market. I put up some data that says worldwide the market size of Sjogren's treatment in seven of the major continents is a billion dollars in 2025. In the next eleven years that's expected to grow to $10,000,000,000 with an annual rate of growth of 26% going up to 2036. So we have a number of drugs. You know, this dasodileppe is still in development.

Know, right around the corner are enalumab or enalumab, I should say, and the FcRn receptor drugs that are really maturing and expected to go in front of the FDA very soon. I think we're gonna hear about a Sjogren's indication before the end of the year. So just get ready. It's gonna be a lot of talk, lot of buzz, a lot of promotion, and you got to decide who are these drugs for. You know, I've been really hard on Sjogren's syndrome in the past.

It's dry myalgia, you know, exocrine gland that's been burnt out by inflammatory disease, not suppressed by autoimmune disease. Because when we've used every DMAR known to man, and most biologics known to man, dry eyes, dry mouth don't get better. But for severe cases, they may get better, and for patients with a certain degree of disease activity, they may get better, and that's what these newer agents and these newer outcomes seem to be proving. BMJ had a report this week as a part of our obesity campaign month about an EHR Trinetic study looking at GLP-one use in knee OA patients and the need for future total knee replacement, they showed with, you know, again a really large cohort that GLP-one receptor agonist used was associated with significantly lower P. One future risk of TKA.

One year of any GLP-one drug lowered the risk by ten percent significantly. Three years of a GLP-one drug exposure lowered the risk by twenty eight percent. And these were looking out eight years later, you know, upon being followed for the future need for joint replacement. So again, these are adjunctive therapies. Are they immunomodulatory?

Are they anti inflammatory? Studies like this, although this is a TriNetX propensity match study with VALTs, do suggest that there's something going on there more than just weight loss. I like this report. I think it was remarkable looking at lupus patients and the risk of metabolic syndrome. You would imagine, you know, a fair number of our patients are 40, a fair number of them have obesity and comorbidities.

So this meta analysis of 65 studies, 11,000 patients showed that the overall prevalence of the metabolic syndrome was twenty seven percent, and that was significant. Higher in males at thirty six percent than in females. But here's the interesting thing about this data. When lupus patients were treated with hydroxychloroquine, they had significantly less metabolic syndrome, a significant thirty three percent lowering. But when they were treated with more aggressive medicines for lupus, cyclophosphamide, azathioprine, mycophenolate, that a significantly higher risk of metabolic syndrome.

So that kind of goes makes sense, does it not? That really aggressive disease gets a lot of aggressive therapies, and maybe that with steroids might spawn more comorbidity, including the metabolic syndrome. Again, the significant risk was thirty nine percent for cyclophosphamide, twenty five percent higher azathioprine, thirteen percent with mycophenolate, but they did not show an increased risk with steroids or methotrexate use. Not surprisingly, those with metabolic syndrome had higher age, obesity, higher cholesterol, more LDL elevations. A Spanish study did a cluster analysis of their SLE cohort.

This looks like it was almost a thousand patients or 900 patients. It's called the RELES study, R E L E S, from Spain, And in their analysis, they did a cohort analysis and they found three groups. The first group, one hundred and sixty eight patients were younger patients with lupus nephritis, low compliments, the need for intensive immunosuppression, and high risk of infection and organ damage. These are the ones we worry about. It goes along with younger disease having more aggressive disease.

Now they're all from Spain, they didn't go into racial differences here. The second cohort, one hundred and seventy five patients, were the serositis cytopenia patients with more double stranded DNA, antiphospholipid antibodies, low C3. No, no, no. Compliment levels were not elevated there. So that seems like an intermediate group, probably easier to treat.

The biggest cluster here, the C3 cluster was four fifty two patients. These were mild skin and joint patients, less serologic activity and less complications. The question is, I like cohort studies because, you know, if you're in a cohort, can see things happening together, can you might predict what could happen. I mean, I remember a report back from my fellowship that said thrombocytopenia went along with CNS lupus and GI lupus. I haven't seen that report ever since, by the way, but it does make me think, right, when I see problematic thrombocytopenia.

But again, these studies are easy to do, but you gotta be clear. You gotta ask where are the clusters? If you do a cluster study, you're gonna get clusters, But then you need to show them graphically and by a kappa statistic, whether they really are separate and distinct. And are they truly independent of the other cohorts? Are they confounded by treatments and disease duration or severity?

And do they predict an independent outcome? Or do they predict a treatment response? They did not show this in a study, but if you're gonna be all gaga about cluster studies like I am, you gotta have a little bit of a jaded eye on some of these analyses. Let's talk about PSA. An observational study looked at 200 and this is from Daphne Gladman's group in Toronto.

Two twenty eight patients with psoriatic arthritis were treated with biologics, and the question they asked, what happened if they got their biologics early, less than two years, or later, after two years. Well, the early group got their biologics on average at six months. Yeah, six months or zero point six, maybe that's seven, six or seven months. And the later group got their biologics at three point six years. So it's not really that late, right?

But here's, and the bottom line was, it didn't make any difference if they got early aggressive biologic or later aggressive biologic. But I would fault the study by saying the early and the later weren't chronologically that different. It's not like two months of early disease versus ten years of late established disease. They were kind of close. More importantly, when you looked at the clinical parameters, age, DMARDs use, how bad they were, both cohorts had a mean of two swollen joints and one tender joint.

So it's not that big a deal that they had a different out... Didn't have a different outcome. They did show that the biologics worked regardless of whenever they were started. But, you you gotta look at the... You know, it's a grand statement, then you got to look at the details to see if you agree with that.

Another important issue that keeps coming up is does aggressive treatment of psoriasis prevent the development of psoriatic arthritis? Is psoriasis a preclinical PSA state? Would more aggressive therapy prevent progression? This is a meta analysis of 15 studies and one hundred and twenty four thousand psoriasis patients followed for seven and seventy eight thousand patient years of follow-up. That's a lot of data.

But it's observational data, right? They did show that biologic use lowered the risk of future PSA by forty six percent, and that was significant. It was very significant for IL-seventeen inhibitors where it dropped at thirty five percent, and the IL-twenty three or the IL-twelvetwenty three where it dropped it by fifty four percent. They, in this study, compared IL-twenty three inhibition to IL-seventeen and showed that IL-twenty three was superior to IL-seventeen inhibition by as much as thirty three percent in preventing future PSA. Get together with your derm colleagues, let them know, have at it, be aggressive, work together on this.

A long term study of RA patients looked at whether early aggressive treatment works. This is a long term follow-up of the ARCTIC trial, which was a treat to target trial. Two thirty DMARR naive patients, eighty five percent ACMA positive, who were treated with treat to target. They had ten year follow-up on eighty two percent of the patients. And guess what?

Ten years later, these patients, eighty two percent had a DAS less than 1.6, DAS remission ten years later. What? That's insane. I think that they could only do this in Scandinavia. It's a good paper, it's well done.

Most treat to target studies fail because patients bail out, doctors bail out, and don't interfere to treat to target. They don't give a statistic on how vigilant the treat to target was, but not only did they show that they were in remission ten years later, and I mean they had low, low activity. And by the way, they weren't using a lot of biologics here. This is mostly CS DMARDs in more than fifty percent of patients. I think the number was around fifty percent on CS DMARDs, thirty percent on biologic DMARDs.

Early aggressive treatment works. I'd like to see more studies like this before I can believe it fully, because we all think we're doing remission most of the time, but the observational data says that we get there somewhere between thirty and forty percent of the time. In this study, oh my goodness, it's a lot. It's eighty two percent. A study from Anisha Dua and her vasculitis maven friends did a survey about GCA management.

A 155 specialists worldwide really tapping into a number of different GCA networks and vasculitis networks worldwide. And they provided answers on cases, they provided patients. So, of the 150 respondents, fifty one percent were rheumatologists, thirty three percent ophthalmologists. They all had a GCA diagnosis. Controversial point number one, aspirin was only used in fifteen percent.

With the onset of a GCA diagnosis, only fifteen percent were recommending the use of aspirin. Yet, seventy percent said they were uncertain on this issue. And you know what? That's reflected in the guidelines. There's like four guidelines out there: ACR, Ular, Panlar, and, know, I don't know, Cush, and they all do not recommend aspirin with a new diagnosis with GCA.

They do recommend it if there's vascular complications, and you do know that with the onset of GCA you're obligated to do large vessel vascular imaging. And maybe if you find something in vessels outside the brain, maybe you would do that. But I guess the concern is that there would be more bleeding. There's not a lot of studies showing bleeding when aspirin was used, or bleeding being a big time complication of GCA. But still it is a concern.

There are some anecdotal, not well designed trials that say that there might be a benefit to aspirin. This needs to be examined. They also looked at whether you should get IV glucocorticoids or oral. Ninety three percent of rheumatologists, eighty five percent of ophthalmologists preferred IV steroids, and that was followed by oral. But uncertainty around IV versus high dose oral, again, sixty eight percent.

So as much as the guidelines have been good, maybe we need more work or better guidelines. A study out of India looked at the association of calcinosis with dermatomyositis. I like this study because they had one hundred and fifty seven JDM patients, juvenile dermatomyositis. And in that cohort, twenty eight percent of forty four kids had calcinosis. These patients were unified by having a long delay in diagnosis of their JDM.

Or was it a long delay in diagnosis of calcinosis? You know, I don't know, you'll have to look it up. But forty one percent were NXP-two positive. We do know that that has a strong association with calcinosis. I did not know, but these kids with calcinosis are also at higher risk of lipodystrophy, thirty nine percent versus five percent, if they had calcinosis.

So the good news is the calcinosis improved in thirty nine percent. The bad news is it was static or progressive in sixty one percent. This is really difficult stuff. I like these descriptive studies. I wish I had more on treatment and treatment success.

Speaking of treatment and treatment success, Vexis, how are treating them? A few weeks ago we talked about the FDA giving a fast track, I think, approval for a new JAK inhibitor to be studied in Vexis patients because of anecdotal reports. This is a collection of fifty two patients with Vexis who were treated with a number of advanced therapies, And using pretty coarse kind of outcomes, they said that the patients either had a complete response, partial response or treatment failure. When they looked after six months of treatment, those who were treated with an IL-six inhibitor, three out of nineteen had a complete response. I don't know, it's fifteen percent.

Four out of nineteen had a partial response, that's twenty percent. That's thirty five percent had a complete or partial. Most had a treatment failure. What about JAK inhibitors? Two out of seventeen had a complete response.

Three out of seventeen partial response. That's again no more than a third, with six out of seventeen having treatment failure. Nobody treated with an IL-one inhibitor or a TNF inhibitor had a complete response, thus it really only looks like IL-six and JAK inhibitors gave you some, but limited efficacy. This is where we need some clinical trials. And I'm surprised that the literature has so many reports on Vexis.

There's enough out there to do the trial. A Spanish cohort retrospective analysis looked at cancer patients with RA, seven twenty eight patients with a prior history or current history of cancer who were treated with biologics. They were followed for eleven thousand patient years of follow-up and found that new or recurrent cancers was not increased. The rate was seven point three per one thousand, and that was equal to patients who were treated with just conventional DMARs. The hazard ratio was zero point nine four, that overlap one, zero point seven three to 1.21.

It was not increased with TNF inhibitors, IL-six inhibitors, rituximab, or JAK inhibitors, or Avatasa. Yes, I agree with that data. I like this study because it was sort of a novel title about lifestyle interventions in RA patients, but it was really a study about difficult to treat RA. So this comes out of China. It was systematic review of 21 papers, twenty three thousand RA patients.

And overall, they say the number I've always said, it's about ten, fifteen percent of RA patients will have difficult to treat RA according to EULAR definitions. And they said that the... Basically what they were saying is that the lifestyle issues were the dominant associations. So risk factors for D2TRA were smoking, obesity, fibromyalgia, and depression. Odds ratios of smoking 1.16, obesity 1.38, fibromyalgia 2.20, depression one point seven four, all those being significant.

There was no association with current smoking or anxiety, but again, that fits the profile of difficult to treat RA that you wouldn't necessarily give a biologic to. Those are the peers, not the peers, those are the nearest, the non inflammatory refractory RA patients. The peers are the ones with high -twenty eight swollen joints, high CRP, persistent inflammatory. Those are the ones you give aggressive therapies to. A new study looked from Portugal, looked at not Portugal, Spain.

The SUN project showed that long term adherence to a Mediterranean diet was associated with substantially lower risk of RA, but not PSA. What? Now we do know that PSA does respond to Mediterranean diets. That's the DIPSA study, I believe, that we talked about before. But in this study from Spain, almost sixteen thousand patients, no prior arthritis.

They get a Mediterranean diet. They're assessed at baseline serially with big outcomes at ten years and twenty years, and they scored them by their adherence to the Mediterranean diet by turtles. Again, they were young going in, most of these were college students. The mean age was 36 years. Who goes to college at age 36?

I don't know. But the risk of incident RA was one hundred and nineteen cases of long term follow-up, zero point five two per 1,000 patient years. One hundred and sixty five cases psoriasis, point seven three per one thousand patient years, a decreased risk of RA comparing Tertile three to one, there was a fifty one percent significant lowering. Interesting. But for psoriasis, the hazard ratio was 0.86, but it overlapped one, zero point five seven to 1.32, not significant.

And they found that the greatest association was a low with a low meat intake, where the risk was lowered by as much as fifty nine percent. Fruits and nuts did not necessarily, predict, a lower risk of either of these diseases. So one of the limitations of the study was that the diagnoses were self reported, and that may be why this data might differ with some other data that's out there. So, I want to thank you for watching the Obesity Imperative campaign this past month. What I learned this month is that it's a beginning for us as rheumatologists.

If you're not familiar with this issue, this gigantic issue that affects almost all your patients, eighty two percent of your PSA patients, you need to have an understanding, you need to have an approach. I think it's an important beginning to help us learn about the interventions and what they could do for our patients, to help us know how to discuss these issues with our patients. If you want to get into how to discuss the issues with the patients, look at the therapeutic update we did. Seven or eight videos on what's called the four pillars of obesity management. It's all about the psychology, the diet, the exercise, the conversations, less about the drugs.

The drug, the information you're going to know about, you already know about Together PSA and other trials. I talked about one here tonight. And I think the other thing is, should you be doing this in your clinic? I'd recommend you look at this past week's Tuesday night rheumatology, where we had a nurse practitioner from an obesity clinic and three rheumatologists who are very involved in obesity, two of whom have an obesity clinic in their practice. Listen to the podcast, watch the video, I think you'll find it really instructive.

And lastly, the registration for RheumNow Live is opened as of this podcast. We hope to see you there. Take care.