Rheumatology Pay Up (9.25.2026) Save

It's 09/25/2026. 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 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 REPREENISH 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 ceruleumap, 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 coming was 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 seven point two percent. That's got to make everybody a little bit happy, but especially the rheumatologists, 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. 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 a elderly related phenomenon. The rates are go up substantially after age 65, where the rate is about, seventy five per 100,000, in men, and sixty seven per 100,000 in women. But when you get up to 85 and over, it's like three hundred and fifty 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, you know, I think that the one thing that we should be doing in rheumatology, and I said this before, is maybe our biggest message that we never delivery is: let's get stronger. 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 one hundred and twenty symptomatic neo A patients who were not on nonsteroidals. By the way, their symptomatic neo A was on the mild to moderate spectrum with a Kellgren Lawrence grade of two to three, not four bone on bone, right? Basically showed no benefit on the primary endpoint, which was visual analog scale pain after three months. Interestingly in this study, however, that those treated with colchicine showed some significant changes in especially high sensitivity CRP and NGF, and maybe some other ones: PGE2, IL-one RA, 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 eleven milligrams a day versus placebo in one hundred neoA patients. This was Kellgren Lawrence grade one and two, somewhat milder, at week twelve, and it didn't have a lot of pain going in, but they had enough pain to get into the study, but at week twelve no significant difference in VAS pain at week twelve. Other secondary outcomes: Womack, Oxford Knee score, a functional called EQ5D analgesic use again, a failure in OA the knee.

We need more effective therapies in knee OA and OA in general. Somewhat related but quite different is CPPD. A nice analysis was seen, I think it was in arthritis and rheumatology, a phenotypic cluster analysis of one hundred and thirty four CPPD patients. This is taking patients from the culture cord 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: C1: monarticular recurrent flares older, mostly women, high CRPs.

This looks like pseudogout to me. Second cluster: monarticular with persistent arthritis. That's that chronic RA like arthritis, chronic OACPB 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, I think, better focused analyses on homogeneous subsets, and this kind of exercise helps in study design. Another study in, in not CPPD, but in gout was published by Orrin Traum and colleagues.

This is the FORWARD study. It's a follow-up to the MIRROR study, which you know is a study of peglodecase in patients who received concomitant methotrexate to reduce the immunogenicity of anti peglodicase or anti PEG antibodies and make the drug more tolerable and more successful. FORWARD is a phase four open label trial of fifty one patients with refractory uncontrolled gout. And all of these people were given peglodecase 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 sixteen or thirty milligrams for the IV infusion. And at week twenty four, responses, which were largely hitting target SUA levels, were similar between both those high dose use groups. They did show that over time thirty one percent, 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 that's about seventy percent of patients had good long term sustained benefit of methotrexate plus peglodecase.

The dose of methotrexate used in these trials was fifteen milligrams per week. MIRROR showed very little immunogenicity, or 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. So a high number, like seventy percent 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 pegilodecase, and more of you should be using pegilodecase, 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 two thousand and nine and twenty twenty four looked at the prevalence and incidence of fibromyalgia using a healthcare commercial claims data, and this is for a Southern Israel region.

They showed that the prevalence rate of fibromyalgia increased from one percent to three point nine percent, almost a four fold increase. Now, why is that? Is it more awareness, better diagnosis, marketing of newer drugs leads to more awareness? This is especially true with growth in the age thirty to fifty nine group: they saw more males than had previously seen, and in this group they had more psychiatric comorbidities, fewer hospitalizations, and even though there were fewer specialist visits, there was more imaging being done. During the same era there was a significant growth of drugs that we commonly use: pregabalin, duloxetine, gabapentin.

So, again awareness of fibromyalgia has increased, that's resulting in maybe better therapy, Maybe some people that are being treated better: more males being diagnosed, better recognition of the psychologic psychiatric comorbidities in a third, 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 on that in the preamble of the report said that when you looked at people who were diagnosed early and treated early versus treated after two years, that there wasn't any difference really in outcomes. In this study, the readout wasn't in the clinical outcomes (ASAS20, ASAS40), but instead was x-ray progression.

So here, they looked at one hundred and thirty eight patients who were enrolled with and were referred basically with less than two years disease activity, compared to two thirty eight who had established disease. With a follow-up of over eleven 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 ten to fifteen years after the diagnosis was this 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 three hundred patients with psoriasis and pregnancy talked about two hundred ninety pregnancies in these women. There were two hundred eleven live births. That's seventy three percent. And all the outcomes that we're seeing, whether it was spontaneous abortions, miscarriages, stillbirths, congenital malformations, they were all on par with population norms, even though these psoriasis pregnancies were, seventy three percent of them were biologic exposed.

The vast majority of those seventy three percent were exposed, and then their pregnancy was diagnosed, and guess what? They stopped the biologic. The most common biologic used in this cohort was ustekinumab in '2 forty one, and only forty two with TNF inhibitors. This diverges the psoriasis study diverges from what we see on rheumatoid, where now and spondylitis, and probably psoriatic arthritis where the rheumatologists are electing to continue the biologic. Especially TNF inhibitors.

It's a no brainer! So, they chose that only twenty four of the two ninety exposed continued their biologic during the pregnancy, and most of that was either cerdulizumab or adalimumab. Again, the outcomes of these women with psoriasis who were pregnant were normally as expected with regard to live births, miscarriages, low body 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 twenty eight children under the 18 who were tested with, FDG PET scans, and MR scans for pyrexia of unknown origin.

And what they found was, I think, telltale. Twenty five percent of these were found to have a pre stenotic diagnosis of Takayasus, with a mean age of almost 14 years. Of the remaining twenty one patients, twenty 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 sed rates and CRPs.

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, you know, an adolescent or child with undiagnosed FUO, or if you're in India, it's PUO, Pyrexia, of unknown origin. I put up another report this week about lung ultrasound having good sensitivity, good specificity in the early detection of RAILD. What's that all about? I don't know.

We covered this during our ILD campaign month in September, But you know, I don't know if this is gonna be real Well, me show you let me tell you the data. So it's just 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 RAILD. 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 RAILD patients, the sensitivity was 87%. Hello! The specificity ranged from seventy five percent to, I think, as high as ninety percent.

The AUC is 0.89. 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 RA, and it's newly diagnosed, and they're seropositive, you should be sticking that transducer on their chest and looking for these beelines, and 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 eight forty six 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 ninety nine point nine percent. Isn't that everybody? Received steroids within the last twelve months. So within the last twelve months they had received a cumulative glucocorticoid exposure of four thousand three hundred milligrams.

From those who had GCA from twelve months to twenty four months, they received a little bit more: five thousand two hundred. For those who had a GCA diagnosis that was greater than two years, it went down. It went down to two thousand two hundred, suggesting that after two years, some of you were 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 steroids for two years, and then we'll get you off. But here's the story: eighty percent were taking eight point four milligrams of prednisone between months twenty four and thirty six. Uh-oh. Seventy five percent are on five milligrams or more at forty eight months or beyond.

What happened to getting off at two years? Again, the title of this my snarky title was Steroid Delusions in Giant Cell Arteritis. So, in their survey, greater than ninety percent of rheumatologists said that they should be using advanced therapies I would assume that means steroid sparing therapies early on in the disease. Yet, by their survey, only forty eight percent 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 ten milligrams. And you have tools. You have other drugs that are FDA approved.

Why not use them? I know increases the cost of care. 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 Spira, and, you know, Carol Langford and all the other vasculitis and GCA PMR mavens out there? I wanna be. Actually, a few more reports on obesity. You know, this is our whole month is devoted to, obesity. We're calling it the obesity imperative.

There's an urgency here. We have a number of different reports this week that I think are worth reviewing. I saw this one report about neuropsychiatric patients treated with semaglutide. Sixty three thousand showed that semaglutide significantly lowered neuropsychiatric events compared to metformin, compared to SGL-two inhibitors, compared to DPPI inhibitors, and this is not related to weight loss. So this means these people on the GLP-one 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 one hundred and nineteen room patients taking GLP, a lot of different things sixty five percent took it for diabetes, one third took it for obesity.

At twelve months, they had lost almost eight kilograms, sixty percent 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. SELECT study, 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 the experts consider obesity as a fat mass regulation model. That the idea is that there's a defended fat mass the body takes care of. 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-one and GIP-one associated drugs. Hence, those drugs produce a physiologic recalibration of that defended fat mass setpoint.

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. 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 anthropomorphometric thresholds, that's probably not having metabolic thresholds. Maybe you should consider what they did in, 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 of psoriatic arthritis. But it turns out in sleep apnea, knee OA and mesh you need ten to fifteen percent.

So endpoints need to be individualized. And then lastly, I talked about this SELECT trial it's a semiglutide trial where they showed that those who were treated with semiglutide four diabetes, it resulted in a twenty percent reduction in MACE and mortality, and that half of that was explained by weight loss or waist circumference reduction, suggesting there are many other, mechanisms that are in play here that we need to be mindful of. The last report is this warning about compounded online GLP one drugs. It's estimated that seven million Americans are taking GLP one drugs, or about a third of the adults sometimes, at least one in eight adults are on GLP-one 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 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-one drugs. There's no longer a shortage. So, again, recognize that it's up to you to counsel your patients on receiving, you know, the real thing the drugs that we know are going to work. I want to remind you to take a look at the Room IQ quiz you're doing very well on that.

This question about, from this question here: TriNetX retrospective study found that JAK inhibitors significantly increased 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 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 twenty ninth. We have a really great session where it's going to be about how we do weight loss in the clinic, and the benefits to patients. I think you're gonna find that really interesting. And lastly, registration for RheumNow Live opens, seven days from now, October 1.

Register early. You'll save money and feel good about yourself. Take care. Bye.