A Day of Infamy (9.11.2026) Save

It's the 09/11/2026. This is the RheumNow podcast. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. Let me say it again, nineeleventwenty six.

That date will live in infamy. This week on the podcast, we were pretty much into it, full throttle on obesity, and obesity management is disease modifying therapy, as said in the title of last week's podcast. A lot of content on obesity that we'll cover, but interestingly, some of it's tempered as the durability of GLP-one agents may not be as great as we like. For that matter, the accuracy and, hoopla over AI and its diagnostic capabilities, we covered that this week showing that AI is fast but not entirely accurate, not compared to experts, so humans do win. And then there's some sobering signals about cardiovascular risk and ANCA associated vasculitis that really should inform how we screen for, comorbidities, especially in AAV.

Let's begin with, a number again, it's obesity month. The campaign is called The Obesity Imperative, and we have a lot of content. I think we did a really great journal club this past week discussing the step nine of, let's see, semaglutide in knee OA showing fabulous results, and then we showed the we also discussed the Together PSA study. That was Tirzepatide and ixekizumab together looking great. Really great discussions, by Tom Appleton from, McMaster Western, University and, Philip Meese from Seattle.

You might want to look at that podcast, or listen to it. Today, on the website, I put up a review article because as we got into this obesity campaign, we knew we were going to be discussing a lot of things around obesity non pharmacologic management. But there's this tendency right now to go to, you know, incretin therapy, GLP-one, GIP inhibitors, that this is all the rage. But today's article about weight loss improving psoriatic disease was all on data generated before incretins were commonplace. So, that review article is a nice quick read to let you know that it's not just about bariatric surgery and, you know, Ozempic and Mounjaro and Zepbound and all those drugs.

Before they were available, we had a number of studies giving us some really important insights that weight loss would improve an inflammatory disease, both the skin inflammation of psoriasis and the arthritis of PSA. What we found out from many of these studies is that five percent is the minimum threshold that can lead to substantial reductions in disease activity, especially in PSA. Secondly, it's dose dependent. If you lose five to 10% weight and compare that to greater than 10%, and compare that to less than 5%, oh my god, there's a gigantic difference in the number of people achieving really fabulous outcomes, including minimal disease activity. So that's something really worth paying attention to.

There's data about very low caloric diets of 600 calories a day that produce rapid, substantial weight loss to almost twenty percent, and very high, MDA responses comparable to TNF inhibitors and biologic responses. Like, isn't that something we should all get involved in? And lastly, you know, what diet specifically in psoriasis, the Mediterranean diet was shown to, improve PASI scores, the psoriatic, area severity index, independent of weight loss. So, this is important even for people that may have disease who have normal weight or diet resistant, you know, changing their diet can lead to disease improvement. So, you know, these trends that we're seeing here are really interesting, but are they affecting kids?

Well, there's an epic COSMO study looking at the number of GLP-one receptor agonist drugs prescribed in '20 what was the number amongst three point five million kids ages eight to 11. Very few were given these GLP-one drugs, it was about twenty thousand kids, but the interesting thing was in 2019, it was only zero point three percent. By, 2026, it had rose into nine point six percent of kids between eight and 11. That's a three ten fold increased risk. Woah.

More likely in older kids, females and males, and kids with obesity. And the other thing was most of the GLP-one treated kids did have severe obesity. It was almost ninety four percent. So this is something that's happening in kids as well. Another report looked at what's the influence of BMI on achieving minimal disease activity response, an MDA response in PSA?

It was clearly shown that, high BMI decreases MDA responses with TNF inhibitors except for infliximab, and is that because maybe it's infliximab is dosed according to weight? They did not see BMI impairing responses to IL-seventeen inhibitors, IL-twelvetwenty three inhibitors, ustekinumab, and the IL-twenty three inhibitors or JAK inhibitors, although I think we had a report last week saying it does affect JAK inhibitors. So, it depends on, you know, who we're looking at. Again, this is a longitudinal cohort of almost thirteen hundred patients with a BMI of almost three thousand and twenty nine. So, again, the odds of lowering the chance of getting, MDA were significant, but only three percent lower.

So, again, there's a real benefit to weight loss, a real hazard to being overweight, especially when it comes to drug responses. A Danish study looked at how long adults go who are treated with GLP-one drugs, for obesity, how long they stay on it. So, this was looking at semaglutide, and when it's given to one hundred and fifty seven thousand first time drug initiators this is in the Danish population followed for twelve months. Over twelve months, nearly half of them discontinued the therapy within the twelve months of follow-up. Thirteen percent at three months, twenty seven percent at six months, thirty nine percent at nine months, and then again at twelve months it was seventy seven thousand out of one hundred and fifty seven thousand, a little less than fifty percent.

Discontinuation of these drugs, the incretin therapies, and more likely in younger people, men more so than women, low income patients, patients on GI drugs, they already got GI problems or on psych meds, and patients who have multiple comorbidities. So, this is a problem. While these drugs are great in what they can achieve, not great if you don't stay on them. But then you wonder, of these 150,000 prescriptions written by doctors, I assume, for obesity, how many of them were familiar with these drugs and how they should be dosed? You've got to start low and go slow.

You've got to coach the patient up. The fact is that if you stay on these drugs, your body gets used to them and a lot of the early GI manifestations, whether it's constipation, feeling full, nausea or vomiting, dyspepsia, those things wane the longer someone stays on the drug, even if they're increasing the dose. So, things to consider if you're going down this path. Going down this path involves not just prescribing drugs and counseling patients, and that's what we're going to cover, this month, during our obesity campaign, but lifestyle management is a big issue. Lars Klariska's group in Sweden looked at eleven hundred RA patients and quantified how many of them were involved in unhealthy lifestyles or healthy lifestyles looking at alcohol, smoking and physical activity.

In their survey, at baseline fifty six percent of that ten ninety seven had three problems with healthy lifestyles, and that when they were followed for three years, it was largely unchanged, it went from fifty six to fifty eight percent, but that's not the whole story, because if you look at individual lifestyle, outcomes, there was some dynamics, some went up, some went down, so it looked like not much change. So non smoking, meaning teaching patients not to smoke, went up from seventy seven to eighty three percent. Small, but sizable. Counseling patients on healthier alcohol consumption went up from eighty five to ninety seven percent, but, changing the patient's habits on physical activity, was eighty four percent at the start and went down to seventy one percent. Lifestyle modification is a major challenge in rheumatology, and not just as regards weight, regards pretty much all the comorbidities that we manage.

So, we sometimes cover Hydradinitis suppurativa. In this week, we covered it, as an example of what happens when you use an IL-seventeen inhibitor. IL-seventeen inhibitors are effective in hydradenitis and in a meta analysis of 24 studies, three thousand patients with HS, they found that of the patients taking all the patients on this study were taking IL-seventeen inhibitors, it turns out that, colitis, either new colitis or worsening colitis, was actually quite rare, and really no difference between those treated with IL-seventeen inhibitors or placebo. On IL-seventeen inhibitors, the risk of IBD was zero point two three, or that is twenty three per one thousand, versus, and that was out of two thousand five hundred patients. There were no, IBD events in ten sixty six patients who were taking placebo, but it's really no difference in the first sixteen weeks of management.

So, and this has come up before, while this is often labeled as a risk, the real world evidence of this is not that overwhelming, but yet it does color how you use these drugs and whether there's IBD in the background, maybe you don't use IL-seventeen. I think this is open for debate. I like this report this week about difficult to manage D2M psoriatic arthritis or treatment refractory, psoriatic arthritis, that's TRD for disease. This is an analysis of five Nordic PSA databases, almost over 14,000 patients, and the number of patients in there who discontinued a biologic or targeted synthetic two or more, three or more, or four or more was thirty six percent, eighteen percent, and ten percent respectively. So, only ten percent discontinued four or more of these advanced therapies.

But if you look at the definition of difficult to manage PSA, it's not like difficult to treat RA, it's not just how many drugs you fail, there are other caveats you must meet. The number of people who actually meet that definition is very low, two to three percent. And the number of patients who are treatment refractory, meaning they had to fail more biologic and targeted synthetics, three or more I think is definition, was zero point eight to one point two percent. So, again, this is a problem, we often say about ten percent of our patients may be that difficult to treat category, but meeting these formal definitions, maybe not so much. The people who do, meet that definition are more likely to be female, have depression, be on opioids.

In fact, those parameters go up with the number of biologic or targeted synthetic failures. Again, it's kind of similar to RA. A JAMA report this week looked at the, utility and success of mindfulness therapy in four fifty one patients in a randomized controlled trial with they had to have chronic low back pain getting in. These patients were from general practice. The study took place with a telehealth intervention where they received eight weeks of telehealth mindfulness versus, usual care without the mindfulness, instruction.

And they showed that a significant reduction in pain, intensity, and interference at six months was seen. It was statistically significant, but it wasn't clinically meaningful because they didn't get to the level of change that was beyond the MCID, the minimal clinically important difference of one point in their outcome measure. It failed to do that. So, the question is, I know we talk about mindfulness all the time. It is great for a lot of things, sleep.

It's actually great for weight loss, it's great for fibromyalgia and pain. It makes the cut on guidelines all the time, but I find it's hard to find people who do mindfulness training, and then it's hard to get patients to go. And the question from this kind of data is, is it worth doing? I got to think because the guidelines say so, I think we still should be striving for it, but if it's impossible, I don't think I'd lose sleep over it. What do you think?

An analysis of COVID vaccination is in our patients with, autoimmune inflammatory rheumatic disease, AIRD patients, showed that, a lot of our patients received the initial COVID vaccine, but the number of people who, went on to receive boosters and updates as they were available was forty one percent, seventy one percent, sixty nine percent. If they received boosters and updates, they were less likely to have forty one to seventy percent to have COVID related hospitalization versus those who did not receive these boosters and updates. So, again, the vaccine series is good, but should you advise your patients to get boosters and updates? For the patients who only had the initial vaccine series, the risk reduction was only five point six percent, whereas if they had the boosters and the updates, as I said, it's forty one to seventy one percent. This is a study of almost sixty one thousand United States, autoimmune inflammatory rheumatic disease patients who, had COVID nineteen between twelvetwenty and August 2024.

So, I think you should be advising your patients. Although right now it's kind of like, it's the flu, why bother? Well, aren't you recommending the flu in your RA, PSA, lupus patients? I am. And yes, I am recommending the COVID boosters.

A study coming out of Leeds, this is from Yuzefel, one of our great faculty covering UR and ACR every year. He did a study of forty four patients with idiopathic inflammatory myopathy were treated with rituximab and showed, guess what, a seventy percent response with four to six months of rituximab therapy. Now, you know there was a rituximab trial that failed in myositis, but there were a lot of problems in the design, and this is an open label, you know, uncontrolled, you know, no active comparator here. So, it's a skew towards the positive and it's a reporting bias, is it not? Anyway, the responders did have high total improvement scores of 50 versus 17.

They use a highly sensitive flow cytometry, at baseline in two weeks to show that the people who responded had significant lowering of memory B cells and plasmablasts. Question being, is there a role for B cell depletion in inflammatory myositis? Users data suggests, as measured by flow cytometry, it looks like there's a good correlation and we should be going down this path. A Swedish registry looked at ANCA associated vasculitis patients, four thousand three hundred and seventeen, over four thousand patients with either GPA and MPA, and showed they had a two fold higher risk of cardiovascular disease and a 2.5 fold higher risk of thromboembolic events. This was higher in males, who had a higher MI risk and both the cardiovascular and thromboembolic risk.

The highest risk occurred usually in the first three months of diagnosis. So, this points to the fact that, again, they said at the top of the podcast, these people probably do need to undergo cardiovascular screening, right? A Dutch study, single center study looked at over 5,500 ANCA tests done at their center between 2012 and 2023, two eighty six had a positive result, that's five point two percent positive. What, and of course they were being ordered because there was a suspicion of ANCA associated disease, but the bad news is, of that five point two percent that were positive, sixty three percent did not have ANCA associated vasculitis. The ones that did not have it, but were ANCA positive, were more likely to have another autoimmune disease, a malignancy, an infection, or possibly specific drugs.

It turns out that immunofluorescence and ELISAs were good first tests and had good negative predictive value, and that ELISAs were good second tests, and you can do a second test if there is a high suspicion and the first test is negative, but they did show across the board, a good, but not fabulous correlation between the titer of ANCA and actually having, an ANCA associated vasculitis. The same could be said for MPO and PR3 antibody titers, that also correlated with a higher, higher titers, higher risk. I like this report this week, I think I have two more reports here. ACP, American College of Physicians published an annals this week on the ethics of AI in medical practice. It's pervasive, it's all over the place, it's in, you know, it's everywhere you turn and it's in practice, you know, ambient dictation, office chatbots, AI assisted diagnostics, AI assisted, imaging.

So, the ACP came up with a formal ethical framework for you to consider. I like these, I think you need to look at these. What do they say about ambient dictation? Ambient scribes can reduce EHR burden during follow-up, but carry the risk of hallucination and bias. Hence, if you're going to use it, it strongly requires physician verification.

You need to review the notes. That being said, surveys of American patients show that they think, 60% of them think, that ambient dictation will worsen the physician patient relationship. I find that shocking because if you're using ambient dictation, you're not looking at a computer as I do when I see patients or, at a phone or taking notes. You're supposed to just talk to the patient. Anyway, that's what the data says.

What about, diagnosis? Clearly using AI for, imaging and certain diagnoses can improve accuracy. This is happening with referral notes, labs, and imaging. So, it is okay, but again, we need to have some degree of jaundice view about this. The real problem, I think, is in de skilling.

Because you're using AI, you're going to lose skills and that may hurt patient outcomes. That may hurt your relationship. So, it's an ethical issue, not just a competency issue. Bias and equity, AI trained on historical data risks reproducing known disparities, especially as far as age, race, socioeconomic disparities, about this where AI might be used if you're training data sets with AI. And then you have to disclose, you have to be transparent.

ACP recommends that you always disclose, either when they're checking in or when they go into the, office, you inform patients when scribes are active, that AI is being used. We make a declaration on RheumNow when AI is being used for publication. AI does not write any publications for us. The authors write it, but the authors may use it in researching and organizing their thoughts. Lastly, there was a really important paper published on Thursday in JAMA from Smolin, Kirsch, Baumer, Alitaha, and William Robinson.

It's a follow-up to their 2018 review of adult rheumatoid arthritis. It's an important document, it's in JAMA, it just came out, it's probably worth printing out and putting in your drawer. Key takeaways from this is that again treat to target is pivotal in care, that you must aim for a greater than fifty percent reduction in C. Dye at three months and remission or low disease activity at six months. Disease activity control drives mortality way more than seropositivity.

If they're seropositive, you can worry, especially if they're double positive, high titer positive, but seropositive just really mean that they need closer monitoring. Mortality risk is directly related to disease activity. Three months is the best and strongest predictor of future remission or LDA. Methotrexate plus short term glucocorticoids should be first line and achieves remission in forty percent of patients. I kind of agree with that.

Again, Smolin and colleagues and EULAR, driven by Smolin and colleagues, are big proponents for steroids being used at the outset and being used as bridging. They say it's both pragmatic and there's evidence to support it. They note that there's a strong difference of opinion, EULAR favors bridging steroids, the ACR says conditionally they're against it. Don't use steroids unless you have to, and then get off of them as soon as you can. Next point, add a biologic or targeted synthetic, don't switch.

When methotrexate is insufficient, adding a biologic or JAK inhibitor is superior to monotherapy. And last point is that JAK inhibitor guidelines differ by jurisdiction. The FDA says fail a TNF inhibitor and then go on to a JAK if you must. Again, based on the oral surveillance data of increased risk of MACI events, VTE signals, serious infections. Again, this is the guideline, a change the package insert for all JAK inhibitors.

On the other hand, the EMA and UR, say that you can use JAK inhibitors in earlier and in low risk patients if they are of low risk, meaning they're less than 65, less than 50, they're not smokers, don't have a cardiovascular history, that's a low risk patient. But they also are quick to point out, you must document their risk by the questions that you ask. The patient's at low risk for cardiovascular VTE and malignancies based on the history, that sort of thing. But again, there are differences in jurisdiction. That's it for this week on the podcast, hope you enjoyed it.

Check out the Room IQ quiz. It's been very, very popular, it's easy to do, it's every Saturday morning. 300 of you took last week's quiz, and got the highest score as a collective group that's been seen in a long while, but even though you were doing almost 80% correct amongst the eight questions that you were given, these are pretty fast, you can do these in four minutes. Less than half of you got this question right. The question was, the U Star Registry study on cancer in systemic sclerosis showed which antibody was most associated with a synchronous onset of cancer, same time scleroderma, same time cancer occurrence.

And the right answer was anti polymerase III antibodies had the greatest risk. We gave you other options, topoisomerase, PMCL, antibodies, and I don't know whatever, anticentromere or something like that, but it was anti, it said anti dash pol three. I think that many of you don't, you might have known it if it was called RNA polymerase three, the full spelling of it. Maybe that's why you missed it. Anyway, there's learning to be had if you take the quiz every Saturday morning.

Tune in next week. Watch for our content on obesity.