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It's October the 2nd, 2026, and this is the RheumNow podcast.
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Hi, I'm Dr. Jack Cush, executive editor of RheumNow.com.
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This week on the podcast, some topline 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.
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We got some regulatory announcements. We have growing interest in Sjögren's and a sort of rheumatology believe it or not called remission — believe it or not. Let's begin.
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With an announcement from the EMA and the European Union where upadacitinib is now approved for use in treating polyarticular JIA.
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The indication is for kids over age two not responding to one or more DMARDs.
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We know that this drug is approved — upadacitinib — for both polyarticular JIA and juvenile PsA in the United States.
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So this is good news for kids on the other side of the Atlantic.
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The FDA has also approved in the United States baricitinib, also known as Olumiant, for the treatment of pediatric severe alopecia areata.
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And it's pediatrics — I'm not really pleased when I see that the age is for 12 years and older.
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That does qualify as pediatric, but what about those other kids?
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And the reason why — why was the other one two years and this one's 12 years?
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That's what was recruited in the trial, and the trial design may have been designed that way because getting kids under 12 with either alopecia areata or alopecia universalis might be really, really hard.
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But anyway, it's a — I think it's a good thing, and we certainly have seen dominance of the class of JAK inhibitors in this unfortunate area.
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I've treated a few patients over the years with great success, and not just with improved drugs — I've used other unapproved drugs, but now we have a number of them that are approved.
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Baricitinib approved in adults and now also in pediatrics.
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J&J announced topline results of their STAR study.
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STAR is a phase four study using guselkumab in patients with axial PsA.
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I don't know if you remember the story, but it goes like this.
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IL-23 inhibitors we know work in PsA. The early data was they didn't work in axial ankylosing spondylitis, and then Philip Mease and a few others started doing subanalyses of PsA trials and finding axial PsA subsets where they did respond to IL-23 inhibition.
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Hence the phase four STAR study, which is a 24-week endpoint looking at BASDAI as the endpoint measure.
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They enrolled 411 biologic-naive axial PsA patients and showed significant improvement in axial symptoms but also importantly in MRI outcomes.
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So this is a big win and a big reversal in our thinking about where IL-23 belongs.
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Obviously this 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.
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Amgen also announced the phase three results of their OASIS 301 study showing that dazukitug — and that's a CD40 ligand antagonist — was studied in patients with active Sjögren's disease.
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Again, these are just topline results; I'm not giving you the actual numbers of the SSDI — you know, the Sjögren's Syndrome Disease Activity Index — improvements at week 48.
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But again, this is encouraging data. I expect that for both the STAR study and for the OASIS 301 study, we'll see that maybe at ACR and be able to dissect it a little further.
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Sjögren's is a popular area right now. It's a hot market.
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I put up some data that says worldwide the market size of Sjögren's treatment in seven of the major markets is a billion dollars in 2025.
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In the next 11 years that's expected to grow to 10 billion dollars with an annual rate of growth of 26%, going up to 2036.
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We have a number of drugs — dazukitug is still in development, but right around the corner are iscalimab and the FcRn receptor drugs that are really maturing and expected to go in front of the FDA very soon.
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I think we're going to hear about a Sjögren's indication before the end of the year.
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So just get ready. It's going to be a lot of talk, a lot of buzz, a lot of promotion, and you've got to decide who are these drugs for.
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I've been really hard on Sjögren's syndrome in the past.
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It's "dryalgia" — exocrine glands that have been burnt out by inflammatory disease, not suppressed by autoimmune disease — because when we've used every DMARD known to man and most biologics known to man, dry eyes and dry mouth don't get better.
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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.
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BMJ had a report this week, as part of our obesity campaign month, about an EHR-based study looking at GLP-1 use in knee OA patients and the need for future total knee replacement.
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They showed, with a really large cohort, that GLP-1 receptor agonist use was associated with significantly lower — P less than 0.001 — future risk of TKA.
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One year of any GLP-1 drug lowered the risk by 10% significantly.
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Three years of GLP-1 drug exposure lowered the risk by 28%.
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And these were looking out eight years later upon being followed for the future need for joint replacement.
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So again, these are adjunctive therapies.
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Are they immunomodulatory? Are they anti-inflammatory?
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Studies like this — although this is an EHR-based propensity-matched study with faults — do suggest that there's something going on there more than just weight loss.
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I like this report. It was remarkable — looking at lupus patients and the risk of metabolic syndrome.
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You would imagine a fair number of our patients are over 40, a fair number of them have obesity and comorbidities.
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So this meta-analysis of 65 studies and 11,000 patients showed that the overall prevalence of metabolic syndrome was 27%.
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And that was significantly higher in males at 36% than in females.
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But here's the interesting thing about this data: when lupus patients were treated with hydroxychloroquine they had significantly less metabolic syndrome — a significant 33% lowering.
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But when they were treated with more aggressive medicines for lupus — cyclophosphamide, azathioprine, mycophenolate — they had a significantly higher risk of metabolic syndrome.
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That kind of 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 metabolic syndrome.
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The significant risk was 39% for cyclophosphamide, 25% higher with azathioprine, 13% with mycophenolate, but they did not show an increased risk with steroids or methotrexate use.
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Not surprisingly, those with metabolic syndrome had higher age, obesity, higher cholesterol, more LDL elevations.
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A Spanish study did a cluster analysis of their SLE cohort.
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This looks like it was almost a thousand — or 900 — patients.
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It's called the RELES study, from Spain.
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In their analysis they found three groups.
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The first group, 168 patients, were younger patients with lupus nephritis, low complements, the need for intensive immunosuppression, and high risk of infection and organ damage.
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These are the ones we worry about — goes along with younger disease having more aggressive disease.
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The second cohort, 175 patients, were the cytopenias patients with more double-stranded DNA, anti-phospholipid antibodies, low C3 — complement levels were not elevated there — so that seems like an intermediate group, probably easier to treat.
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The biggest cluster was 452 patients — these were mild skin and joint patients with less serologic activity and fewer complications.
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I like cohort studies because you can see things happening together and might predict what could happen.
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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 when I see problematic thrombocytopenia.
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But again, these studies are easy to do, and you've got to be clear.
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If you do a cluster study you're going to get clusters, but then you need to show them graphically and by a kappa statistic whether they really are separate and distinct.
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Are they truly independent of the other cohorts?
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Are they confounded by treatments and disease duration or severity?
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And do they predict an independent outcome or a treatment response?
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They did not show this in the study. But if you're going to be all gaga about cluster studies like I am, you've got to have a little bit of a jaded eye on some of these analyses.
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Let's talk about PsA. An observational study — this is from Dafna Gladman's group in Toronto — looked at 228 patients with psoriatic arthritis who were treated with biologics.
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The question they asked: what happened if they got their biologics early, less than two years, or later, after two years?
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The early group got their biologics on average at six or seven months, and the later group got their biologics at 3.6 years.
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So it's not really that late. But the bottom line was it didn't make any difference if they got early aggressive biologic or later aggressive biologic.
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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 10 years of late established disease; they were kind of close.
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More importantly, when you looked at the clinical parameters — age, DMARD use, how bad they were — both cohorts had a mean of two swollen joints and one tender joint.
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So it's not that big a deal that they had a different — didn't have a different — outcome.
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They did show that the biologics worked regardless of whenever they were started.
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But you've got to look at the details to see if you agree with that.
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Another important issue that keeps coming up: does aggressive treatment of psoriasis prevent the development of psoriatic arthritis?
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Is psoriasis a preclinical PsA state? Would more aggressive therapy prevent progression?
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This is a meta-analysis of 15 studies and 124,000 psoriasis patients followed for 778,000 patient-years of follow-up.
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That's a lot of data — but it's observational data.
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They did show that biologic use lowered the risk of future PsA by 46%, and that was significant.
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It was very significant for IL-17 inhibitors, where it dropped the risk by 35%, and for IL-23 inhibitors where it dropped the risk by 54%.
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They compared IL-23 inhibition to IL-17 and showed that IL-23 was superior to IL-17 inhibition by as much as 33% in preventing future PsA.
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Get together with your derm colleagues, let them know, have at it.
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Be aggressive. You'll work together on this.
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A long-term study of RA patients looked at whether early aggressive treatment works.
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This is a long-term follow-up of the ARCTIC trial, which was a treat-to-target trial.
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230 DMARD-naive patients, 85% RF-positive, were treated with treat-to-target.
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They had 10-year follow-up on 82% of the patients.
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And guess what? 10 years later, 82% of these patients had a DAS less than 1.6 — DAS remission — 10 years later.
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What? That's insane. I think they could only do this in Scandinavia.
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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 adhere to treat-to-target.
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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 10 years later — and they had low, low activity — by the way, they weren't using a lot of biologics here.
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This is mostly csDMARDs in more than 50% of patients — around 50% on csDMARDs, 30% on biologic DMARDs.
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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 achieving remission most of the time, but the observational data says that we get there somewhere between 30 and 40% of the time.
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In this study — oh my goodness — it's 82%.
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A study from Anisha Dua and her vasculitis maven friends did a survey about GCA management — 155 specialists worldwide, really tapping into a number of different GCA networks and vasculitis networks worldwide.
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Of the 155 respondents, 51% were rheumatologists and 33% were ophthalmologists.
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They all had a GCA diagnosis. Controversial point number one: aspirin was only used in 15%.
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With the onset of a GCA diagnosis, only 15% were recommending the use of aspirin — yet 70% said they were uncertain on this issue.
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And you know what? That's reflected in the guidelines.
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There are like four guidelines out there — ACR, EULAR, PANLAR — and they all do not recommend aspirin with a new diagnosis of GCA.
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They do recommend it if there are vascular complications.
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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 you would do that.
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But the concern is that there would be more bleeding.
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There's not a lot of studies showing bleeding when aspirin was used as a big-time complication of GCA, but still it is a concern.
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There are some anecdotal, not well-designed trials that say there might be a benefit to aspirin. This needs to be examined.
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They also looked at whether you should get IV glucocorticoids or oral.
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93% of rheumatologists and 85% of ophthalmologists preferred IV steroids, followed by oral, but uncertainty around IV versus high-dose oral was again 68%.
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So as much as the guidelines have been good, maybe we need more work or better guidelines.
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A study out of India looked at the association of calcinosis with dermatomyositis.
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I like this study because they had 157 JDM patients — juvenile dermatomyositis.
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In that cohort 28%, or 44 kids, had calcinosis.
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These patients were unified by having a long delay in diagnosis of their JDM — or was it a long delay in diagnosis of calcinosis?
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I don't know; you'll have to look it up.
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But 41% were NXP2-positive — we do know that has a strong association with calcinosis.
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I did not know, but these kids with calcinosis are also at higher risk of lipodystrophy — 39% versus 5% if they had calcinosis.
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The good news is the calcinosis improved in 39%.
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The bad news is it was static or progressive in 61%.
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This is really difficult stuff. I like these descriptive studies; I wish I had more on treatment and treatment success.
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Speaking of treatment and treatment success, VEXAS — how you're treating them.
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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 VEXAS patients because of anecdotal reports.
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This is a collection of 52 patients with VEXAS who were treated with a number of advanced therapies using pretty coarse outcomes — patients either had a complete response, partial response, or treatment failure.
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When they looked after six months of treatment, those treated with an IL-6 inhibitor: three out of 19 had a complete response — that's 15% — four out of 19 had a partial response, that's 20%, so 35% had a complete or partial response, and most had a treatment failure.
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What about JAK inhibitors? Two out of 17 had a complete response, three out of 17 a partial response — again no more than a third — with six out of 17 having treatment failure.
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Nobody treated with an IL-1 inhibitor or a TNF inhibitor had a complete response.
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It really only looks like IL-6 and JAK inhibitors gave you some, but limited, efficacy.
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This is where we need clinical trials. And I'm surprised that the literature has so many reports on VEXAS — there's enough out there to do the trial.
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A Spanish cohort retrospective analysis looked at cancer patients with RA — 728 patients with a prior or current history of cancer who were treated with biologics.
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They were followed for 11,000 patient-years of follow-up and found that new or recurrent cancers were not increased.
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The rate was 7.3 per 1,000, and that was equal to patients who were treated with just conventional DMARDs.
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The hazard ratio was 0.94, overlapping 1 — 0.73 to 1.21.
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It was not increased with TNF inhibitors, IL-6 inhibitors, rituximab, JAK inhibitors, or abatacept. Yes, I agree with that data.
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I like this study because it had a sort of novel title about lifestyle interventions in RA patients, but it was really a study about difficult-to-treat RA.
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This comes out of China — a systematic review of 21 papers, 23,000 RA patients.
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Overall they say — and the number I've always said — it's about 10 to 15% of RA patients who will have difficult-to-treat RA according to EULAR definitions.
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And basically what they were saying is that the lifestyle issues were the dominant associations.
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Risk factors for D2T RA were smoking, obesity, fibromyalgia, and depression — odds ratios: smoking 1.16, obesity 1.38, fibromyalgia 2.20, depression 1.74, all significant.
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There was no association with current smoking — wait — or anxiety.
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But again, that fits the profile of difficult-to-treat RA that you wouldn't necessarily give a biologic to.
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Those are not the purists — the ones with high DAS-28, swollen joints, high CRP, persistent inflammation.
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Those are the ones you give aggressive therapies to.
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A new study from Spain — the SUN Project — showed that long-term adherence to a Mediterranean diet was associated with substantially lower risk of RA, but not PsA.
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What now? We do know that PsA does respond to Mediterranean diets — that's the DIPS study, I believe, that we talked about before.
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But in this study from Spain, almost 16,000 patients with no prior arthritis were given a Mediterranean diet, assessed at baseline serially with big outcomes at 10 and 20 years, scored by adherence to the Mediterranean diet by tertiles.
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They were young going in — most were college students, mean age 36 years.
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The risk of incident RA was 119 cases with long-term follow-up — 52 per 10,000 patient-years — and 165 cases of psoriasis, 73 per 10,000 patient-years.
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A decreased risk of RA comparing tertile 3 to 1 showed a 51% significant lowering.
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Interesting. But for psoriasis the hazard ratio was 0.86, but it overlaps 1 — 0.57 to 1.32 — not significant.
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They found that the greatest association was with low meat intake, where the risk was lowered by as much as 59%.
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Fruits and nuts did not necessarily predict a lower risk of either of these diseases.
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One of the limitations of the study was that diagnoses were self-reported, and that may be why this data might differ with some other data out there.
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I want to thank you for watching the obesity imperative campaign this past month.
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What I learned this month is that it's a beginning for us as rheumatologists.
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If you're not familiar with this issue — this gigantic issue that affects almost all your patients, 82% of your PsA patients — you need to have an understanding, you need to have an approach.
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I think it's an important beginning to help us learn about the interventions and what they could do for our patients, and to help us know how to discuss these issues with our patients.
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If you want to get into how to discuss these issues with patients, look at the therapeutic update — we did seven or eight videos on what's called the four pillars of obesity management.
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It's all about the psychology, the diet, the exercise, the conversations — less about the drugs.
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The drug information you're going to know about you already know about from PsA and other trials — I talked about one here tonight.
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And I think the other thing is: should you be doing this in your clinic?
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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.
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Listen to the podcast, watch the video — I think you'll find it really instructive.
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And lastly, registration for RheumNow Live has opened as of this podcast. We hope to see you there. Take care.
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