Rheumatology Pay Up (9.25.2026)

It's September 25, 2026. This is the RheumNow podcast. Hi, I'm Jack Cush with RheumNow. This week on the podcast, you know, the most dangerous drug of the GLP-1s is being advertised on television. Good news, the money is up in rheumatology. Bad news is two famous drugs that we often use don't work in osteoarthritis. This and more on the podcast.

Let's begin with an announcement from the European Medicines Agency, the EMA. Their regulatory group that makes recommendations on drugs that should be approved is called the CHMP, and they announced this past week the recommendation that the EMA authorize the marketing and clinical availability of secukinumab Cosentyx for the treatment of polymyalgia rheumatica. This is based on the REPLENISH trials and other data. It's not yet approved in the European Union, but this is likely going to happen and it's certainly not yet approved for use in the United States, although the same data has been submitted. And the PDUFA date, the date upon which the FDA makes a decision, is probably due in October or November. So right now we only have one FDA approved steroid sparing agent for refractory PMR and that would be of course sarilumab, and this would be the second addition to the market. Will it change your use? Should it change your use? I think so.

A new report — I saw it in Medical Economics — comes from an agency that looks at reimbursement for the many specialties, and they showed across the board in 2026 it looks like in seven major specialty areas reimbursements were up for adult medicine by an average of 7.2%. That's got to make everybody a little bit happy, but especially the rheumatologist, because when you look at the total cash payments, rheumatology led the list at 10.4% increase over the year before. Pretty good. Whoever's working on that for us, the ACR, CSRO, congratulations on all your lobbying efforts.

The MMWR came out with a report this week that's germane to our population. It's a report about unintentional falls and death rates. You know, certainly not something we deal with, but honestly, the data clearly shows that it's an elderly-related phenomenon. The rates go up substantially after age 65, where the rate is about 75 per 100,000 in men and 67 per 100,000 in women. But when you get up to 85 and over, it's like 350 deaths per 100,000. I mean, that's like almost a five-fold increase. It's a big jump. You need to be wary about this. And I always tell — I think that the one thing that we should be doing in rheumatology, and I've said this before, is maybe our biggest message that we never deliver is: let's get stronger. The stronger you get, the less problems you're going to have. I don't care what your problem is. In rheumatology, strength is a part of protection and prevention. We need to work on this. That's clearly underscored by this MMWR report from this past week.

Speaking of the elderly, two important studies about osteoarthritis. The CLOAK study, a three-month double-blind randomized placebo-controlled trial of colchicine versus placebo in 120 symptomatic knee OA patients who were not on non-steroidals. By the way, their symptomatic knee OA was on the mild to moderate spectrum with a Kellgren-Lawrence grade of 2 to 3, not 4 bone on bone. It basically showed no benefit on the primary endpoint, which was visual analog scale pain after 3 months. Interestingly, in this study however, those treated with colchicine showed some significant changes in biomarkers, especially high-sensitivity CRP and NGF, and maybe some other ones — PGE2, IL-1Ra, etc. But even though there's a biologic benefit, it did not translate to a clinical benefit. Again, not much to do as far as effective therapies in knee OA.

Another study: single-center double-blind randomized placebo-controlled trial of tofacitinib 11 milligrams a day versus placebo in 100 knee OA patients. This was Kellgren-Lawrence grade 1 and 2, somewhat milder. At week 12 they hadn't had a lot of pain going in, but they had enough pain to get into the study. At week 12, no significant difference in VAS pain. Other secondary outcomes — WOMAC, Oxford Knee Score, a functional measure called EQ-5D, analgesic use — again a failure. In a way, for the knee we need more effective therapies in knee OA and OA in general.

Somewhat related but quite different is CPPD. A nice analysis — I think it was in Arthritis and Rheumatology — a phenotypic cluster analysis of 134 CPPD patients. This is taking patients from the CaReCPPD study and another cohort called Chronic CPPD. It's a European cohort analysis. They basically showed that phenotypically these patients sort of subsetted themselves into four groups. Cluster 1: monoarticular recurrent flares, older, mostly women, high CRP. This looks like pseudogout to me. Second cluster: monoarticular with persistent arthritis. That's that chronic RA-like arthritis, chronic OA/CPPD-like disease. Cluster
three, polyarthritis with lower CRP levels. And cluster four, polyarticular joints including shoulder and spine with recurrent flares. That's a group we don't see much of. But I think understanding these phenotypic clusters can help to design better trials because right now what are you doing for CPPD disease if it's not pseudogout-looking disease where you're using colchicine and steroids — what are you doing for the other ones? We need better focused analyses on homogeneous subsets and this kind of exercise helps in study design.

Another study, not in CPPD but in gout, was published by Orin Troum and colleagues. This is the FORWARD study. It's a follow-up to the MIRROR study, which is a study of pegloticase in patients who received concomitant methotrexate to reduce the immunogenicity of anti-pegloticase or anti-PEG antibodies and make the drug more tolerable and more successful. FORWARD is a phase 4 open-label trial of 51 patients with refractory uncontrolled gout. All of these people were given pegloticase and methotrexate. But what was unusual about this study is they wanted to see if you could give the drug at higher doses and less frequent intervals, and it showed that you could. So they used doses of 16 or 30 milligrams for the IV infusion. And at week 24, responses — which were largely hitting target SUA levels — were similar between both those high-dose groups.

They did show that over time, 31% — not quite a third — of patients had a future elevation of their SUA, suggesting that there was a loss of control and a subsequent failure. But really, about 70% of patients had good long-term sustained benefit of methotrexate plus pegloticase. The dose of methotrexate used in these trials was 15 milligrams per week. MIRROR showed very little immunogenicity — I think 40% immunogenicity in their studies. In this study it's really confusing because they show a high degree of immunogenicity even though everybody's on background methotrexate. A high number — like 70% of people before they started the study — had anti-PEG antibodies and very few anti-uricase antibodies, and then as time went on the numbers went up a little higher. I think this was because they were using maybe too sensitive an anti-drug antibody screen.

But if you really want to be confused, I like the results — I don't like the anti-drug antibody results — but I still think it underscores that this is the new standard of care, and it will help you to use pegloticase, and more of you should be using pegloticase, because there's a significant number of people who desperately deserve it and have not received it. My humble opinion.

A study out of southern Israel between 2009 and 2024 looked at the prevalence and incidence of fibromyalgia using a healthcare commercial claims dataset for a southern Israel region. They showed that the prevalence rate of fibromyalgia increased from 1% to 3.9% — almost a four-fold increase. Now why is that? Is it more awareness, better diagnosis, marketing of newer drugs leading to more awareness? This is especially true with growth in the age 30 to 59 group. They saw more males than had previously been seen, and in this group they had more psychiatric comorbidities and fewer hospitalizations. Even though there were fewer specialist visits, there was more imaging being done. During the same era there was significant growth of drugs that we commonly use — pregabalin, duloxetine, gabapentin — so again, awareness of fibromyalgia has increased, resulting in maybe better therapy, maybe some people being treated better, more males being diagnosed, better recognition of the psychological and psychiatric comorbidities, and less need for hospitalization. Kudos to you in what you're doing in fibromyalgia.

A few reports on spondyloarthritis. A Swiss study looked at whether patients are diagnosed or referred early versus late and what the outcome is. The research in the preamble of the report said that when you looked at people who were diagnosed early and treated early versus treated after 2 years, there wasn't any difference really in outcomes. In this study the readout wasn't in the clinical outcomes — ASAS 20, ASAS 40 — but instead was X-ray progression. They looked at 138 patients who were enrolled and referred with less than 2 years of disease activity compared to 238 who had established disease, with a follow-up of over 11 years. There were significant differences in X-ray progression, with less X-ray progression in those that were referred earlier — presumably they were getting treated earlier. More importantly, the differences in X-ray progression were not noticed early on. It wasn't until 10 to 15 years after diagnosis that there was a divergence in X-ray progression in this cohort that was analyzed. I think it's a strong message that earlier referral is needed, and that there
are radiographic benefits to that. A study in almost 300 patients with psoriasis and pregnancy talked about 290 pregnancies in these women. There were 211 live births — that's 73% — and all the outcomes that were seen, whether it was spontaneous abortions, miscarriages, stillbirths, congenital malformations, they were all on par with population norms. Even though these psoriasis pregnancies were — 73% of them were biologic exposed — the vast majority of those 73% were exposed and then their pregnancy was diagnosed and, guess what, they stopped the biologic. The most common biologic used in this cohort was secukinumab in 241, and only 42 with TNF inhibitors.

This diverges — this psoriasis study diverges from what we see in rheumatoid and spondylitis and probably psoriatic arthritis, where the rheumatologists are electing to continue the biologic, especially TNF inhibitors. It's a no-brainer. So here they chose that only 24 of the 290 exposed continued their biologic during the pregnancy, and most of that was either certolizumab or adalimumab. Again, the outcomes of these women with psoriasis who were pregnant were as expected with regard to live births, miscarriages, low birth weight, congenital anomalies, etc. Good news.

An Indian study — I find this study sort of surprising because I wouldn't believe that they'd be doing a whole lot of FDG PET scanning in India — but this is a retrospective single-center study of 28 children under the age of 18 who were tested with FDG PET scans and MRI scans for pyrexia of unknown origin. And what they found was, I think, telltale. 25% of these were found to have a pre-existing diagnosis of Takayasu's, with a mean age of almost 14 years. Of the remaining 21 patients, 20 went on to have an alternative diagnosis. All of these kids and adolescents were symptomatic with fever and constitutional features. They all had very, very high ESR rates and CRP. They all ended up being treated with either glucocorticoids and mycophenolate, and three went on to receive biologics. The point of this being that this is a valuable tool if you're dealing with an adolescent or child with undiagnosed FUO — or, if you're in India, PUO, pyrexia of unknown origin.

I put up another report this week about lung ultrasound having good sensitivity and good specificity in the early detection of RA-ILD. What's that all about? I don't know. We covered this during our campaign month in September. But, you know, I don't know if this is going to be real. Well, let me tell you the data. So it's a systematic review, 14 studies, and they found overall that the use of lung ultrasound, when compared to the gold standard of high-res CT scanning, was very useful in diagnosing RA or detecting RA-ILD. They used as their measure a threshold of five or more B-lines — that you see as sort of these sharp white lines on ultrasound that are sort of ultrasound artifacts but nonetheless found in RA-ILD patients. The sensitivity was 87%. Hello. The specificity ranged from 75 to, I think, as high as 90%. The AUC is 89. This looks like it's a good tool, but I think the truth here is it's a screening tool.

So if you are an ultrasound rheumatologist and you have an RA patient who is newly diagnosed and they're seropositive, you should be sticking that transducer on their chest and looking for these B-lines — having five or more. And they can be horizontally oriented, they can be vertically oriented, they can look like lightning strikes and whatnot. This is a good reason for you to then make the next step, which is the appropriate screening tool according to EULAR guidelines of doing high-res CT. Should all RA patients be screened with high-res CT? I don't think so, but this would be a really great screening procedure to know who should go on to high-res CT.

Two more reports. Anisha Dua published the results of a survey this week about steroid and drug use in giant cell arteritis. This is a survey of 196 rheumatologists from five European countries and the United States, all of whom volunteered 846 cases. A quarter of the patients that were included volunteered their own self-reported data about how they were being treated in this very large cohort. Everyone's on steroids. They said greater than or equal to 99.9% — isn't that everybody? — received steroids within the last 12 months. So within the last 12 months, they had received a cumulative glucocorticoid exposure of 4,300 milligrams. From those who had GCA from 12 months to 24 months, they received a little bit more — 5,200. For those who had a GCA diagnosis that was greater than 2 years, it went down to 2,200, suggesting that after 2 years, some of you are starting to cut back. Oh, that's great. Congratulations. That's what you should be doing. And that's the message we give our patients. You know what? I think you'll be on, you know, steroids for two
years and then we'll get you off. But here's the story. Um, uh, 80% were taking 8.4 milligrams of prednisone between months 24 and 36. Uh-oh. 75% are on 5 milligrams or more at 48 months or beyond. What happened to getting off at 2 years? Again, the title of this, my snarky title was steroid delusions in giant cell arteritis. So, in their survey, greater than 90% of rheumatologists said that they should be using um advanced therapies, I would assume that means steroid-sparing therapies uh early on in the disease. Yet by their survey, only 48% reported using any kind of advanced therapy at all after diagnosis. The point is, say what you mean, mean what you say. Get everybody off steroids. They're old. They don't need to be on doses of steroids greater than five or greater than 10 milligrams. And you have tools. You have other drugs that are FDA approved. Why not use them? I know it increases the cost of care and maybe that's cavalier of me to say that but you know this is an advance in therapy that I think is sorely needed and why wouldn't you use it. By the way, talk to all the mavens in GCA and they're using it. Don't you want to be like Rob Spiera and you know Carol Langford and all the other vasculitis and GCA/PMR mavens out there?

I ain't — I want to um — actually a few more reports on obesity. You know, this is our whole month devoted to uh obesity. We're calling it the obesity imperative. Um there's an urgency here. We have a number of different reports this week that I think are worth reviewing. Uh I saw this one report about neuropsychiatric patients treated with semaglutide. 63,000 showed that semaglutide significantly lowered neuropsychiatric events compared to metformin, compared to SGLT2 inhibitors, compared to DPP inhibitors, and this is not related to weight loss. So this means these people on the GLP-1 agonist had less substance abuse, less mood disorders, less anxiety, less CNS atrophic disorders, less neuromuscular and less eating and sleep disorders, less personality and impulse control. I mean talk to people that use these drugs. These drugs are good at addiction. These drugs work at the level of the brain and that's in fact how they work in obesity.

A study of 119 rheum patients taking GLP — a lot of different things. 65% took it for diabetes, one-third took it for obesity. Uh at 12 months, um they had lost almost 8 kg and saw 60% improved at least one BMI category. Associated with improvement were significant decreases in A1C, fasting blood sugar, lipids, LDL, triglycerides, sed rate, CRP. These drugs have significant cardiometabolic effects. I'm going to talk about that next in the SELECT study.

Um, the SELECT study um was featured in an endocrine society sort of state-of-the-art on the science and the research of obesity management. Major advances that they point out here I think worth discussing is um the experts consider obesity as a fat mass regulation model — the idea is that there's a defended fat mass, the body takes care of it, when it does it well you're not fat, when it doesn't do it very well it's a hypothalamic hindbrain problem which is addressed by GLP-1 and GIP-associated drugs. Hence those drugs produce a physiologic recalibration of that defended fat mass set point. This is unlike what happens when people do diet and exercise. There isn't a reset in that set point and unfortunately that may trigger compensatory overeating and compensatory metabolic changes that work against weight loss. Again, I think that if we understand that, we're likely to get involved in its management.

They're bothered in endocrine and obesity management by the substantial and unexplained heterogeneity in weight loss depending on what's being used, and that needs better understanding. Um, what is the best efficacy endpoint? Based on the FDA studies, they still are saying percent body weight change is the primary endpoint. But the authors of this paper say, you know, whether you're using BMI, body weight change, anthropometric like waist circumference thresholds, um that's probably not important — having metabolic thresholds, um maybe you should consider what they did in um diabetes where an A1C threshold of less than 6.5%. But it varies depending on what you're going to do. We've talked about this month that you only need 5% loss of body weight to benefit the outcomes in psoriatic arthritis. But it turns out in sleep apnea, NASH, and MASH, you need 10 to 15%. So endpoints need to be individualized.

Um and then lastly I talked about this SELECT trial. It's a semaglutide trial where they showed that those that were treated with semaglutide for diabetes um that it resulted in a 20% reduction in MACE and mortality and that half of that was explained by weight loss or waist circumference reduction, suggesting there are many other um mechanisms that are in play here that we need to be mindful of. The last
report is this warning about compounded online GLP-1 drugs. It's estimated that 7 million Americans are taking GLP-1 drugs, or about a third of the adults — sometimes at least one in eight adults — are on GLP-1 drugs. A high number of them are getting their drug online from a compounding source. These are not FDA approved, but they are FDA allowed because of something called the 503B loophole, which allows compounding pharmacies to take approved drugs and make their own versions of them. That's what's being sold on television by Charles Barkley and tennis players and other people. Most of those are unregulated. They are not FDA approved products. A tremendous problem with these copycat drugs as far as impurity. A tremendous problem. The FDA is currently considering outlawing this by changing that 503B loophole, which was allowed in the last two years because there was a shortage of GLP-1 drugs. There's no longer a shortage. So again, recognize that it's up to you to counsel your patients on receiving the real thing, the drugs that we know are going to work.

I want to remind you to take a look at the RheumNow IQ quiz. You're doing very well on that. This question — from this question here — a Trinetics retrospective study found that JAK inhibitors significantly increase VTE risk in RA patients. True or false? Half of you got it right, half of you got it wrong. Turns out JAK inhibitors had no change in VTE risk in these RA patients getting hip and knee replacement on JAK versus TNF inhibitors. The answer was false, but half of you said yes. So anyway, check out the quiz. I think you'll find it challenging and interesting and you can learn from it.

I want to invite you to join our Tuesday night rheumatology this upcoming Tuesday on the 29th. We have a really great session — it's going to be about how we do weight loss in the clinic and the benefits to patients. I think you're going to find that really interesting.

And lastly, registration for RheumNow Live opens seven days from now, October 1st. Register early, you'll save money and feel good about yourself. Take care.