A Day of Infamy (9.11.2026) Save

It's the 11th of September, 2026. This is the RheumNow podcast. Hi, I'm Dr. Jack Cush, executive editor of RheumNow.com. Let me say it again. 9/11/26. That date will live in infamy.

This week on the podcast, we were pretty much into it full throttle on obesity. And obesity management as 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 tempered as the durability of GLP-1 agents may not be as great as we'd 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 the 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. We have a lot of content. I think we did a really great journal club this past week discussing the STEP 9 trial of semaglutide in NASH, showing fabulous results. And then 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 M 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 and non-pharmacologic management. But there's this tendency right now to go to incretin therapy, GLP-1s, GIP inhibitors — 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 inflammatory disease — both the skin inflammation of psoriasis and the arthritis of PsA.

What we found out from many of these studies is that 5% is the minimum threshold that can lead to substantial reductions in disease activity, especially in PsA. Secondly, it's dose dependent. If you lose 5 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 of almost 20%, and very high MDA responses — MDA responses comparable to TNF inhibitors and biologic responses. 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 who have disease with normal weight or diet resistance. Changing their diet can lead to disease improvement. So these trends that we're seeing here are really interesting.

But are they affecting kids? Well, there's an Epic Cosmos study looking at the number of GLP-1 receptor agonist drugs prescribed amongst 3.5 million kids ages 8 to 11. Very few were given these GLP-1 drugs — it was about 20,000 kids — but the interesting thing was in 2019 it was only 0.3%. By 2026, it had risen to 9.6% of kids between 8 and 11. That's a 31-fold increase. Whoa. More likely in older kids, females and males, and kids with obesity. And the other thing was most of the GLP-1 treated kids did have severe obesity — it was almost 94%. So this is something that's happening in kids as well.

Another report looked at what's the influence of BMI on achieving a 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. Is that because maybe infliximab is dosed according to weight? They did not see BMI impairing responses to IL-17 inhibitors, IL-12/23 inhibitors, ustekinumab, and the IL-23 inhibitors or JAK inhibitors, although I think we had a report last week saying it does affect JAK inhibitors. So it depends on who we're looking at. Again, this is a longitudinal cohort of almost 1,300 patients with a BMI of almost 30 to 29. So again, the odds of lowering the chance of getting MDA were significant, but only 3% 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 who are treated with GLP-1 drugs for obesity stay on them. So this was looking at semaglutide and when it's given to 157,000 first-time drug initiators, this is in the Danish population, followed for 12 months. Over 12 months, nearly half of them discontinued the therapy within the 12 months of follow-up. 13% at 3 months, 27% at 6 months, 39% at 9 months, and then again at 12 months it was 77,000 out of 157,000, a little less than 50%.

Discontinuation of these drugs — the incretin therapies — is more likely in younger people, men more so than women, low income patients, patients on GI drugs who already have 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 157,000 prescriptions written by doctors — I assume for obesity — how many of them were familiar with these drugs and how they should be dosed? You got to start low and go slow. You 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 Klareskog's group in Sweden looked at 1,000 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, 56% of that 197 had three problems with healthy lifestyles. And when they were followed for 3 years, it was largely unchanged. It went from 56 to 58%. 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 changed.

Non-smoking — meaning teaching patients not to smoke — went up from 77 to 83%. Small but sizable. Counseling patients on healthier alcohol consumption went up from 85 to 97%. But changing the patients' habits on physical activity was 84% at the start and went down to 71%. Lifestyle modification is a major challenge in rheumatology, and not just as regards weight. It regards pretty much all the comorbidities that we manage.

So we sometimes cover hidradenitis suppurativa. This week we covered it as an example of what happens when you use an IL-17 inhibitor. IL-17 inhibitors are effective in hidradenitis. And in a meta-analysis of 24 studies, 3,000 patients with HS, they found that — all the patients in this study were taking IL-17 inhibitors — colitis, either new colitis or worsening colitis, was actually quite rare, and really no difference between those treated with IL-17 inhibitors or placebo. On IL-17 inhibitors, the risk of IBD was 0.23, or that is 23 per 1,000, out of 2,500 patients. There were no IBD events in 1,660 patients who were taking placebo. But it's really no difference in the first 16 weeks of management.

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-17. I think this is open for debate.

I like this report this week about difficult-to-manage 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 36%, 18%, and 10% respectively. So only 10% discontinued four or more of these advanced therapies.

But if you look at the definition of difficult-to-manage PsA, it's a lot 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, 2 to 3%. And the number of patients who are treatment-refractory — meaning they had to fail more biologics and targeted synthetics, three or more, I think the definition was — 0.8 to 1.2%. So again, this is a problem. We often say about 10% of our patients may be in 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, and 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 451 patients in a randomized control trial. They had to have chronic low back pain to get 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 6 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 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.

An analysis of COVID vaccination in our patients with autoimmune inflammatory rheumatic disease (AIIRD) 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 41%, 71%, 69%. If they received boosters and updates they were less likely — 41 to 70% less likely — 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 5.6%, whereas if they had the boosters and the updates, as I said, it's 41 to 71%. This is a study of almost 61,000 United States autoimmune inflammatory rheumatic disease patients who had COVID-19 between 12/20 and August of 2024. So yeah, I think you should be advising your patients, although right now it's kind of like, ah, it's the flu, why bother? Well, aren't you recommending the flu vaccine 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 Usefel, one of our great faculty covering EULAR and ACR every year — he did a study of 44 patients with idiopathic inflammatory myopathy who were treated with rituximab and showed, guess what, a 70% 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, uncontrolled, no active comparator study, so it skews towards the positive and there is a reporting bias — is it not? Anyway, the responders did have high total improvement scores of 50 versus 17. They used highly sensitive flow cytometry at baseline and at two weeks to show that the people who responded had significant lowering of memory B cells and plasmablasts. The question being, is there a role for B cell depletion in inflammatory myositis? This 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 — 4,317, over 4,000 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 thrombotic events. This was highest in males, who had a higher MI risk and both the cardiovascular and thrombotic risk. The highest risk occurs usually in the first 3 months of diagnosis. So this points to the fact that, again, as I said at the top of the podcast, these people probably do need to undergo cardiovascular screening.

A Dutch study, single-center study, looked at over 5,500 ANCA tests done at their center between 2012 and 2023. 286 had a positive result — that's 5.2% positive. And of course they were being ordered because there was a suspicion of ANCA-associated disease. But the bad news is, of that 5.2% that were positive, 63% 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 ELISA were good first tests and had good negative predictive value, and that ELISA 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 higher titers, higher risk.

I like this report this week. I think I have two more reports here. ACP — American College of Physicians — published in Annals this week on the ethics of AI in medical practice. It's pervasive. It's all over the place. 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 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 jaundiced view about this. The real problem I think is in deskilling, because you're using AI you're going to lose skills, and that may hurt patient outcomes and 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, and socioeconomic disparities are concerned. Think 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 Smolen, Aletaha, 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: treat to target is pivotal in care; you must aim for a greater than 50% reduction in CRP at 3 months and remission or low disease activity at 6 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 seropositives 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 40% of patients. I kind of agree with that. Again, Smolen and colleagues and EULAR — driven by Smolen 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 the 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 MACE events, VTE signals, serious infections. This is the guidance that changed the package insert for all JAK inhibitors. On the other hand, the EMA and EULAR say that you can use JAK inhibitors earlier and in low-risk patients — meaning they're less than 65, less than 50, they're not smokers, they 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 patients 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 RheumNow 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, a 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 3 antibodies had the greatest risk. We gave you other options. Topoisomerase, anti-PMSCL antibodies, and I don't know, whatever anti-centromere or something like that, but it was anti-pol 3. I think that many of you — you might have known it if it was called RNA polymerase 3, 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.