Early RA Referral Clinics Work (9.18.2026)

It's September 18th, 2026. This is the RheumNow podcast. Hi, I'm Dr. Jack Cush, executive editor of RheumNow.com. This week we begin with a report on fibromyalgia, very common, very underdiagnosed and proven by this paper. This is from the UK Biobank which is a large data collection coming out of the UK mostly from primary care from this very large many thousands of patients they identified 4,200 patients with fibromyalgia who meet criteria for fibromyalgia but in their chart reviews only a minority have a diagnosis of fibromyalgia — 72.6% were not diagnosed with fibromyalgia. What's that about? Well, it's primary care. Maybe they need more support. Maybe it's hard to get those patients in to see you. People not likely to be diagnosed were more likely to be males, older, have milder symptoms or have symptoms ascribed to another rheumatic condition like OA, CRPS, chronic fatigue syndrome. They also are likely to have less fatigue. So it's almost like they have to have full-blown fibromyalgia before they get diagnosed. Gee, that shouldn't happen. We need to spread the word. We need to teach more on this.

An open label study of calcinosis cutis in juvenile dermatomyositis patients. You know we see calcinosis in our scleroderma patients. We see it occasionally in dermatomyositis. It's a bigger problem in JDM in the pediatric population. In this open label study of 20 JDM patients, 11 boys aged 10, they had calcinosis cutis for 31 months. They were all treated with tofacitinib in standard doses. And the interesting thing about this open label report was tofacitinib was associated with a decrease in calcium mass as measured by the Agatston scores. That's the same as you get with your calcium coronary artery scores on CT scan. It measures total calcium. Prior to treatment the mean result was 3,449 and post treatment it went down to 4,000. That's a significant decrease. They measured other things including the clinical dermatomyositis activity score of Victoria Werth's group, but they didn't report on that. So I'd like to know what did the tofacitinib do to the disorder — as you know we had a recent brepocitinib approved for dermatomyositis, and that's a JAK1/TYK2 drug, so I would assume it would have helped the other features of disease including the cutaneous features. But this is impressive that it would lower calcinosis burden.

A retrospective evaluation of many thousands of electronic health records showed that VTE is not increased in RA patients who are taking JAK inhibitors. In this study they looked at patients undergoing either hip replacement or knee replacement and if they were on a JAK or if they were on a TNF inhibitor — 284 versus 288 — the VTE events were 17 with the JAK inhibitor, 6%, and 11 with the TNF inhibitor, 3.8%. Although that's a numeric increase, it was not significant with a relative risk of 1.57. But again, this data does not negate the results of the ORAL Surveillance study. This is a retrospective view trying to refute ORAL Surveillance, which was a prospective double-blind randomized controlled trial that was appropriately powered. It's going to take a lot to undo that data.

The FDA this week had a few interesting actions. They did grant a priority review for zasocitinib for plaque psoriasis. This is a drug that's been through phase 3 trials with about 3,000 patients — that's their LATITUDE PSO 3001 and 30002 clinical trials. It's expected that they're going to have a regulatory decision first quarter of 2027. Zasocitinib is another TYK2 inhibitor that will compete with deucravacitinib.

Also received a notice from the FDA this week of a fast track designation for a drug for VEXAS syndrome. This is called pacritinib. Pacritinib, or the trade name is Vonjo. I'm not familiar with this drug because it's approved for intermediate or high risk myelofibrosis, so not surprising that I wouldn't know about it. But anyway, this is a JAK2/FLT3 inhibitor that they are putting on the fast track to study in VEXAS syndrome. There's a little bit of debate about what the best drug for VEXAS syndrome is these days. A lot of drugs have been tried including cytokine inhibitors, but the JAKs have looked good in anecdotal reports, so you got to like this because it's going to lead to a well-designed trial which will hopefully answer the question even in a rare disorder like VEXAS.

A meta-analysis of 87 studies gives us some insight into who is not going to respond to methotrexate well. We all think that most of our patients respond to methotrexate. The data from last week's JAMA review by Smolen et al. said that out of the gate 40% of patients respond to methotrexate, which means 60% don't. In this meta-analysis it says people who are likely to respond to methotrexate have early
disease have low disease activity who receive methotrexate early and do not have erosive disease. Things that can sort of undermine the efficacy of methotrexate would include smoking and a higher BMI. So it makes sense — mild disease, early disease is going to respond better almost no matter what you give them, but why not give them methotrexate? It is your first line therapy.

A study coming out of India looks at how frequent RA patients flare. There are 85 patients who were either in remission or low disease activity state with a DAS-28 sed rate less than 3.2. They were followed for 6 months. 46% had one or more flares with the DAS jumping higher than 3.2. The time to flare was 12 weeks, ranging from 8 to 18 weeks. And that was unrelated to activity, right? It's not like they had — you know, again, these people were doing pretty well, and therefore it's somewhat unpredictable. If there was a predictable variable for who was going to flare, it seems like seropositivity either for rheumatoid factor or CCP gave you greater than a two-fold higher risk of flares. Interesting.

Falls in RA can be a bad thing. This is a study of 124 ambulatory females over the age of 50. In fact, their average age was 68. Their DAS was doing good, 2.6. 16% had sarcopenia, 25% had a prior fall. In their follow-up study, 27% had falls, and predicted by — if you had a fall before, you're going to get a fall again. And the odds ratio of that is 2.76. Being on a hypnotic or an anxiolytic gave you almost a four-fold higher risk. Although there was a trend suggesting that steroids or sarcopenia may be a risk factor, it was not significant. Other studies have suggested steroids or sarcopenia — steroids because they cause weakness, sarcopenia because it is weakness. That makes some sense.

Meta-analysis of gout patients shows that erectile dysfunction is about 40% higher, relative risk of 1.37. This is 11 studies, 104,000 patients with gout and hyperuricemia. Hyperuricemia also has an increased risk of erectile dysfunction. The question is why? The one thing that they showed clearly on this was that it did have a relatedness to lower testosterone and lower estradiol levels. Other factors were obesity, age, diabetes, and cardiovascular disease. But it's really thought to be an endothelial issue — that there's endothelial dysfunction in patients with gout and with hyperuricemia.

A Chinese study of a novel drug, another humanized anti-IL-17A and AF inhibitor — this is called XKH0004, being studied in China — was studied with 323 ankylosing spondylitis patients. They looked at their outcomes at week 16. The dual IL-17 inhibitor was superior with regard to the ASAS40: 45% versus 19%. And by 52 weeks, 66% of these people were improved. I think we'll see more of these dual inhibitors. There's another one in development beyond the one that's currently available, in 2022.

A study of Swiss psoriatic arthritis patients showed that overweight and obesity accounted for 66% of the population. That compares to the risk of obesity and overweight at 43% in the United States. The most recent numbers are — sorry — 72% of our population is either overweight or obese, but in psoriatic arthritis it's 82%. So both studies, both areas show higher risk of obesity and being overweight. In their study, they showed things that you should know: that obesity is associated with a higher CRP, 56% versus 37%, meaning obese versus non-obese; higher patient global assessments; worse MD global assessments; and lower functional scores with the EQ-5D-3L. Don't ask me what that is, but it's another standard metric that is used for functional outcomes.

As you know, this month is our obesity campaign — the obesity imperative. We have a lot of great things going on. Last week we had a number of really interesting videos. We had a great Tuesday Rheumatology on inflammation and obesity. Next Tuesday, we've got a great session on treatments for obesity that are out there, things that you probably want to know about. Tune in Tuesday night, 7 p.m.

At the 2025 ASMBS — that's the American Society of Metabolic and Bariatric Surgery — they showed that between 2020 and 2024, weight loss surgeries, bariatric surgeries, dropped 23%, going down from 230,000 to 177,000. They point out that less than 1% of eligible patients are going this route, suggesting that there's a higher amount of medical management with the new GLP-1 drugs. Another article from JAMA Surgery showed that between 2022 and 2024, bariatric surgery fell 34%. At the same time, GLP-1 directed drugs rose 140%. So again, these shifts are on — they are real. But we had an article this week that says that bariatric surgery works, it should be considered, it's very effective. And there's nothing to say you can't get bariatric surgery
surgery and be on a GLP-1, but I would recommend that being done with the guidance of a weight loss specialist. You may have seen my video on the therapeutic update videos that we have. I think we have six or seven of them up right now. All around the four pillars of weight loss, things that you really need to know if you're going to be talking about weight loss with your patients. We're going to go into nutrition. We're going to go into exercise. We're going to go into coping and the psychology of weight loss. My video, fairly short, was called "Introducing Weight Loss" and it's about the three-minute script. What can you do in 3 minutes as a rheumatologist with your patients to bring up this issue of weight loss?

And I'll just quickly go over for you. You know, I start by saying one other thing that can really affect your arthritis or your disease is your weight. Is it okay if we talk about this for a few minutes? You know, it's not just about the weight. You know, being overweight reduces your activity. That makes you weaker. That makes you hurt more when you do things. Have you thought about losing weight? How much would you like to lose? What are your goals? Find out whether they have buy-in or not. And then you've got to hit them with, you know, the extra weight increases not just mechanical stress but the inflammation load, and that makes your disease worse. That makes responding to drugs harder.

So, you know, you have to point out, you know, everyone has a plan, but it's not a good plan. And everyone's tried something, but it never worked. I mean, and most of that is going it alone. Going it alone is unsuccessful. Why don't you do something different? Why not go to a specialist? Why not start on a new medicine? Why not pair up and join Weight Watchers with your best friend? Why not pair up and get into an exercise program with your best friend? Again, a new plan is needed. What do you want to talk about here? How can we do this?

And then when you get into talking about diet and exercise, you can't say eat less, move more. That ain't helping people who are overweight and in pain. You've got to give them really tangible goals. You know, how much weight can I lose, how much calorie restriction should I try? And if you are unfit or unable to do that, send them to a nutritionist. You'd be shocked at how good that is. I went to a nutritionist and she took me shopping, told me what not to buy, what I should buy, and that really has helped. They have to be motivated. They have to gradually increase their exercise. They've got to go from doing 2 to 3 minutes on a treadmill to working themselves up to 15 and then 30 and then 60 minutes. And who is their multidisciplinary team?

Lastly, you've got to write it down. I have a Post-it pad on my desk and everybody leaves with a Post-it note, a sticky, and I tell them stick it on the refrigerator. You know, you've got to look at this. You've got to look at this repeatedly. Your family's got to look at this. And then the last thing you need to do is arrange for a follow-up, because follow-up is where all the great things happen.

You know, there was a 52-week follow-up to the TOGETHER PsA trial. We talked about that in our first week of Tuesday Rheumatology. We did journal club. We talked about the TOGETHER PsA trial that showed that the combined endpoint at 36 weeks for 10% weight loss and ACR50 was 31% versus 0.7%. Now at week 52 it's 39% versus 1.7%. So it goes up. The same was held for the TOGETHER PsO trial, where the combined endpoint of a PASI 100 plus 10% or more weight loss was now up to 30%. Previously it was, I don't know, 26% I think, versus 4.4% with tirzepatide alone. So again, encouraging data on combination therapy.

An NHANES study looked at the utility of measuring waist size. You know, I think this is a problem. I'm going to ask this on my Tuesday night rheumatology to my diabetes and rheumatology experts. Are you actually measuring the waist size of your patients? I have found that to be — most patients don't even want to get on the scale, right? How many of them want to have their waist size measured? You know, they've been saying, "No, I, Jerry Seinfeld, no, I have 36, you know, jeans, 36 waist jeans, and they're not, you know." So anyway, in this study of 5,500 CKD patients, waist index was associated with a higher risk of all-cause mortality and cardiovascular death, 17 to 24% higher. And these were mediated by inflammation as measured by the neutrophil-to-lymphocyte ratio, a good measure of inflammation. So again, waist size probably should be something we're doing, but I don't know that we're doing it enough.

Are you doing weights on every — there are some rheumatologists that don't do vital signs. I don't understand that. You've got to do vital signs on everyone. Lastly, two more reports. The early arthritis clinic from Leiden — they have an EAC clinic that's
been going on a long time with the idea of reducing uh of improving referrals from primary care. So from 2010 to 2020, they evaluated over 2,000 patients. 800 had arthritis. Not saying what kind. 132 of the 2,000 had RA. These were people referred to the early arthritis clinic. That was compared to 690 patients who were referred in usual ways. 342, a higher percentage of those had RA. All right. The question is which gave you a better outcome. It's shocking. The EAC referrals had lower disease activity like P equals 0.00003 over 5 years. They had less functional disability also highly significant, higher rates of sustained DMARD remission twofold higher P.001, and a lower uh time from GP delay to referral, a median of 5 weeks versus 9 weeks. So early arthritis clinics do work. I haven't — I mean I lectured on this a long time with US rheumatologists and couldn't convince anybody to carve out an early arthritis clinic because it would leave open spots and most people are more interested in filling their spots than being proactive about early RA. And again there's a business to run here. I understand that. But there is a benefit to having an early arthritis clinic.

Uh, another study this week looked at IVIG. As you know, that was approved a few years ago. Uh, Octagam 10% was approved for uh use in myositis. This is a double blind randomized placebo controlled trial of 44 patients. It's not a big study, right? And the other thing that's interesting about this study is that they were not your run-of-the-mill IIMs. There were 16 patients with immune mediated necrotizing myositis. There were 11 with HMGCR — that's the statin associated HMG-CoA reductase marker. There were three with signal recognition particle disease. Two seronegative. Three with dermatomyositis. One with TIF1-gamma. One with NXP2. But the good news is that the scores with IVIG versus placebo were significantly better. The TIS, total improvement score, which is a measure of functional CPK and functional outcomes — it's not measuring skin outcomes, it's just measuring myositis outcomes — 60 versus 42. And the other point that was important here, the median time to a moderate response was 4 weeks with IVIG and 12 weeks with placebo.

So uh I want to encourage you to look at RheumNow IQ, comes out every Saturday. Last week you didn't do very well as a group. A lot of people missed this question uh about hidradenitis — showed that a study of hidradenitis showed that IL-17 inhibitors significantly increase IBD risk. That was false. More of you answered true than false. The other question — I was surprised a lot of people got this wrong. Only about — I think it was 37% got this right. What is the minimum amount of weight loss that you need to improve psoriatic arthritis? And the number is 5%. Most of you answered 10%, which is right, but the minimum threshold is 5%.

Lastly, I want to remind you RheumNow Live is coming January 30 and 31, a little bit earlier this year, in Dallas. Registration begins October 1st. We hope to see you there. Our faculty — we're going to put up the agenda really soon. It looks really, really good. I think you'll find that you're going to enjoy the meeting whether you're on site or online. That's it for this week. Take care of yourselves. We'll talk next week.