EULAR 2026 Daily Podcast Day 4a Save

You're listening to a RheumNow podcast coming to you from London in ULUR twenty twenty six. Enjoy.

Hi. I'm Sheila Reyes from The Philippines reporting here in London for ULUR twenty twenty six. Joining me today is professor Marina McGray from, K. Western. And to in in this video, she will be talking about two of her abstracts, which she presented in the oral abstract sessions on the safety and, major adverse cardiovascular events of biologic DMARDs and JAK inhibitors in patients with, AS and psoriatic arthritis.

These will be abstract zero p zero one zero six and, abstract zero p or o p rather zero one eight one. Doctor Magrath, thank you very much for joining us.

Hi, Sheila, and thank you for giving me an opportunity to present these abstracts, which were two oral presentations. These abstracts, they were actually some real world data, which, work we had done, answering some real world questions. So the risk of, you know, cardio major cardiovascular events in patients with psoriatic arthritis is high. There was actually a meta analysis done several years ago. We showed that the risk was around, like, forty percent in the psoriatic arthritis patients on major cardiovascular events.

We have multiple therapeutic classes now available for treatment of psoriatic arthritis. However, you know, there is no direct compare to, you know, studies in real world showing their, cardiovascular safety profile. So we decided that we're gonna, compare the cumulative MACE risks between the biologic classes like TNF inhibitors, IL seventeen inhibitors, IL twenty three inhibitors, IL twenty three, IL twelve inhibitors versus JAK inhibitors. And the reason we chose that is because there is always a concern of increased, MACE risk with JAK inhibitors based on the oral surveillance study, even though the study was in RA, but those results are then extrapolated into other, in rheumatic diseases. And so that was the reason why we wanted, to look at these data.

So, we used the TriNetX database, which is a large federated database and has, medical records from at least, more than 100 healthcare organizations, and Subhout has more than 100,000,000 patients in it. So, our main question was to look at cumulative MACE risk of these, in medication classes versus this, and our primary outcome was incident MACE. The MACE was defined in this study as myocardial infarction, stroke, pulmonary embolism, and venous thromboembolism. So we combined them together. We did not include, sudden cardiac death in this because those data were not available in this database.

And in order to balance the baseline characteristics of these subjects since it's a large database. We did inverse proportional treatment weighting because, to balance these groups. It was a large, group of patients, about, 21,000 patients together, and predominantly majority of them, at least 11,000 to 12,000, were on TNF inhibitors, followed by IL-seventeen inhibitors, then IL-twenty three inhibitors, and there were about six hundred patients on JAK inhibitors. We matched the baseline demographics. However, in the JAK inhibitor group, still, there were more females than males.

There were about sixty nine percent females, and then and only 30% males, so that kind of remained as a bias that we could not balance that, which also balanced their baseline, comorbidities, hypertension, diabetes, anticoagulation use to make this, cohort uniform. Interestingly, what we found was that up to two years, there was no difference in cumulative MACE risk between, IL-seventeen inhibitors, TNF inhibitors, IL-twenty three inhibitors versus JAK inhibitors. However, based on time to event analysis, the risk for JAK inhibitors increased, and over time, the risk accrued for all the medication class, but the most accrual was for JAK inhibitors compared to TNF inhibitors or IL-seventeen inhibitors, and this accrual was seen after two point five years of JAK inhibitor use. So, we concluded that saying that the risk of MACE events increases over time in these patients, and JAK inhibitor was most commonly associated with these events, particularly after two point five years of use. Now the city does have some limitations.

You know? Obviously, there has there was we tried our best. We have very strong team of, you know, clinical, these statisticians with clinical research training. We tried to use mutually exclusive datasets. We included patients only that were only on one class of TNF inhibitors, but there is definitely there had to be some residual confounding, and we did not account for adherence to the medication.

Mhmm. Okay. Thank thank you for that, doctor Nagre. So since these are real world data, right, I was wondering if based on your results, how could how could these results translate to considerations in clinical practice, or are there implications in clinical practice?

So, you know, one one thing I wanna make clear is that the it's just an association, not a causation. So from these data, we cannot imply that this is, the JAK inhibitors are cause of it, just an association. So, we thought that with the, with this, you know, answering this question would enable clinicians for a risk stratification at the time of treatment initiation and choose which patients would be appropriate for JAK inhibitors and which patients would not be appropriate.

Okay. So it still, is important to do risk stratifications for our patients and considering individualized treatment and what associated risk or comorbidities that they may have.

Exactly. Yeah. I think it's very important for a clinician to, you know, take into account these factors, as you mentioned, comorbidities, age, other risk factors, smoking, and then have a good you know, it should be a, like, a good discussion with the patient, and, it should the decision should be made, both taking into account patient's preferences, where the patient understands the risk and benefits, and then combined decision between the two would, you know, make it a better way of treating our patients.

Correct. And, do you have any plans to further institute research on this area or, like, make more? Mhmm.

This since this database is a it's an electronic medical record database, most of these, comparative safety studies in real world have been done out of claims database. So we wanted to do it out of real EMR. But still, these, you know, these are not, like, prospective studies. So they are basically hypothesis generating studies, and I think it's worthwhile, like, with you know, now that we saw these these results from this database, it's worthwhile doing a proper prospective study and seeing if this you know, is this information going to be same as what we saw in this retrospective cohort study.

I agree. And, so let's go on and, discuss, your next abstract, which is on, real world data now comparing the safety and adverse event adverse event profiles of biologic therapies and targeted synthetic DMARDs in patients with ankylosing spondylitis. So what can you say about your study, the results, and, its significance in clinical practice?

So in in ankylosing spondylitis, we do use the same database, but here, we want compared the safety profile and adverse events between the TNF inhibitors, IL-seventeen inhibitors, and JAK inhibitors. And, the, you know, we are the primary outcome was, again, looking at overall safety profile, onset adverse events between three months to five years after treatment initiation. We again selected the patient population. These had to be patients greater than 18 years of age with a diagnosis of ankylosing spondylitis based on ICD 10 code of 45 it's 45.9. And then these patients had to be only treated with a single class of medications.

There was no, crossover allowed between the groups. If a patient was had taken more than two classes, they were not included in the study. Within that treatment class, they could have used multiple medication. Like, if they were on TNF inhibitor class, they could have been on dalimumab, changed to internship, but they could not have crossed over to, like, an IL-seventeen inhibitor or a JAK inhibitor. And then we also wanted to make sure that these patients, adhere to their medication.

So medication adherence was also accounted for, and how that was done was these patients had to have at least two exporters to the same medication class, and at least the second prescription had to be ninety days beyond the initiation of the treatment.

Mhmm, I get

And those patients, yeah, who actually had more than, two classes of medications were excluded, and we also excluded those patients who had infections, like oral infections, pneumonia, skin infections, candidiasis that happened either before the start of the medication index date or within ninety days of medication initiation. And these patients that they who that had, like, you know, these adverse events of interest, like if they had had myocardial infarction, stroke, DVT, PE, they were all excluded before the treatment, so if they had them in the past. So, we at the baseline, the cohort, you know, included mostly TNF inhibitor patients, followed by IL-seventeen and JAK inhibitors. And the patients were, the TNF inhibitor and the, IL-seventeen, that the TNF inhibitor had, had, age group was lower compared to the IL-seventeen inhibitor and JAK inhibitor group. The JAK inhibitor and IL-seventeen in older patients, and, they were also predominantly males in those two groups.

So, we then tried to balance these baseline characteristics by doing a propensity score matching between the two groups. And, time to event analysis was also done using a Cox proportional hazard ratio and, Kaplan Meier curves, and what we found was in these propensity matched scores, the adverse events between the three therapeutic classes were variable. So those patients that were on IL seventeen inhibitors, that they actually showed a lower odds of, major cardiovascular events compared to TNF inhibitors. The odds ratio was point six four. So there was about, six percent patients on IL-seventeen inhibitors that showed an increase.

The MACE risk was six percent in these patients in IL-seventeen inhibitors compared to nine percent in TNF inhibitors. However, there was no difference in all cause mortality, malignancy, depression, overall infections, candidiasis between IL-seventeen inhibitor and TNF inhibitor group. On the other hand, the MACE risk was higher in JAK inhibitor. The odds of MACE were higher, two point four, compared to TNF inhibitor group, but there was no difference, again, in all cause mortality, malignancy, depression, infections between JAK inhibitors and TNF inhibitors. And then in time to event analysis, we found out that the the even though, IL seventeen inhibitors had shown lower odds of MACE compared to TNF inhibitors, but in time to event analysis, we did not find a statistically significant difference between the two groups.

So the Crocs proportional hazard, the hazard assumption failed. And, but in contrast, the JAKs over time continued to show an increased hazard, compared to TNF inhibitors, the hazard ratio was around 3.4. So in conclusion, we said that in this real world study in patients with, you know, using a real world ankylosing spondylitis population, the risk of MACE increased over time, and the risk was more in JAK inhibitors compared to TNF inhibitors. However, there was no different among the classes in all cause mortality, malignancy, depression, and infections. And, again, you know, the study has some limitations.

You know, in the earlier studies, like any retrospective cohort study, there is still possibility for residual confounding. We tried to account for medication adherence, but the cohort of JAK inhibitors was small, and, it was only two forty five patients in that group. And so that kind of limits this generalization of these results. And, even though and then we only included infections after ninety days of treatment initiation, which also lowers some generalizability. Mhmm.

Okay. So it and the the results are still interesting. And, you've mentioned about infection. So, was were there any particular infections or safety signals that stood out in your, in the study, in the patient and the participant?

We looked for pneumonias, specifically skin infections, candidiasis, and none of them showed any difference between the treatment groups. There there was not one one more than the other. They were there was no increased signal showing in any of those treatment groups, which is reassuring us as clinicians and patients saying that, you know, there is there is not one has a more more risk than the other, at least. The association, we would say there was no association of those infections within this. So that was kind of a that is reassuring for us,

both Okay.

And to telling our patients. It was only the association with, major cardiovascular events and deep vein thrombosis and pulmonary embolism. That was the only thing that, was higher with JAKs. The with the other groups, we did not see an association to that.

K. That's very, reassuring to know. I was actually gonna ask about, was were there any incidents, or were there any signals on the occurrence of TB or hepatitis in these sets of patients, but I guess there were none.

We know we didn't check. We didn't look for that. So we didn't look for TB or hepatitis. So that was not, you know, in our study question.

Mhmm. Okay. But thank you for thank you, Marina, for sharing your study results with us today. And I think this will add more it will it will add more how do you call it? Like

Yeah. Definitely, there I would say, you know, as you're you're alluding to what I was gonna say, that these are very hypothesis generating ideas. It's Yeah. You know, trying to give us tell us that there may be there may be an association, and this needs to be studied further to evaluate further.

Yes. To evaluate further and to have more robust data that we can get generalizations from. But, again, I I guess the main message here is that we really have to prioritize individualized treatments, risk stratify our patients, especially since patients with SPA and with PSA have an increased risk of developing cardiovascular disease. So it's really important that a shared decision making is made between the physician and the patient, taking into consideration, again, their individual risk factors, other fact comorbidities, and even patient preferences, and as well as the local availability of these treatment options. Yeah.

So before we end, Marina, just a quick, like, a a quick message that, you know, our viewers can, use as they go back to clinics, based on your study results.

So I don't mean, you know, that as you already mentioned it, you know, shared decision making is very important for treatment of patients, and, we need to, you know, make our patients feel better. We need to improve their quality of life, and we need to treat them, you know, with available therapeutic classes. But, we have to thoroughly discuss the safety profile, adverse events with our patients so they are aware of it and then have the shared decision and, go ahead and treat them.

Okay. Well said. Thank you very much again for joining me, and, we look forward to more, to more researches in this field. And so as I end the interview, follow me on Rheumatra at sorry. Follow me on x at Rheumatra, and tune in to RheumNow for more updates of EULAR twenty twenty six.

Bye. Have a

nice evening. Bye, RheumNow. Thank you.

Hi. I'm doctor Janet Pope reporting at room now at EULAR 2026 in London, England. I wanna talk about how many CAR Ts, cars do we need to test drive? And the reason I'm talking about this is there was a lot going on at this meeting on CAR T therapy. And in fact, I searched and there were 93 abstracts at ULAAR twenty twenty six that had CAR T in the title.

I also went to a wonderful session on June 5 on the What is New or Win session by Doctor. Hector Chanoi, and he talked about CAR T and inflammatory myositis. And many of the concepts that he talked about, I've tried to internalize to update all of us. So with this many abstracts, I think we know lots, but we have more questions than answers. So one of the first questions is, who should we select for treatment for CAR T?

I think in general, the consensus would be certain diseases might do better than others, such as lupus, maybe myositis, would do better than maybe RA or systemic sclerosis. But I'm just giving you a gestalt, we really don't know within an individual. The other thing on selection that's important is we would like someone in general, the perfect candidate would be younger and not having comorbidity, high disease activity, low damage, and they haven't failed everything, but they have poor prognosis. So we know the writings on the wall say in a lupus nephritis patient who hasn't responded well at all in three months of triple therapy for lupus nephritis and is adherent. Then the next question is, well, what do we want to inhibit?

So there's a lot of CARs out there. So CD 19, CD 20, BCMA, NK cells, dual targets, even a triple target. I learned something called an armored CAR, which is a CD nineteen CAR T therapy, but also giving cytokine inhibition, which is supposed to increase the durability of the response. So which target to choose? I don't actually know, and I don't think that in these trials we know who will respond to what better.

Then do we prime with chemo or not? And do we give leukapheresis? And leukapheresis will depend on the type of CARs. So if you're giving the traditional one that was around the longest autologous, you have to get the cells, cell sorts, so you get the CARs made against say CD19, if that's the target, and then you give chemo to get rid of all their cells, at least in the circulating compartment and some within organs as well. So that's autologous and there's no graft versus host or anything like that because it's your own cells.

But there's a timeframe where you wait. If it's not made right and the patient's off therapy, they might be flaring more or not because they've been primed with chemotherapy. There's allogeneic and it's kind of attractive because it's off the shelf. So we would assume in something like that, let's say again, we'll say the target is CD19, that it would be a CAR that would look like most people's CD19 that they could basically be distributed and destroy the CARs, the the CD nineteens within the patient. Then there's this new concept of endogenous.

So in vivo, where you're popping it into the patient. It could be in vivo with mRNA vector or even with viral delivery. The next issue really is safety, the short term and the long term. It's So important to know the timing of reactions. So cytokine release syndrome or CRS takes a few days to a week or two to occur in general.

The ICANS that's immune effector cell associated neurotoxicity syndrome, That's more severe. The patient can be obtunded having other neuro side effects. And that problem might actually need tocilizumab either CRS or ICANS might or might not need glucocorticoids. Then there's a new problem that's been described called LICATS, that's local immune effector cell associated toxicity syndrome. LICATS is a mouthful to think about, but it's more in our autoimmune connective tissue disease patients where they might have an organ wake up for a while that is transient, and the thought is it's when cells are coming up and then more normalizing over time.

But I'm not exactly sure why occurs. Then what do we do if there's a recurrence? Do we have frozen, if it's autologous? Do we have frozen cells? Is the patient going to be resistant?

How long will it work for? And what will it work for? Will it work for every manifestation or just some? Will it work for lupus nephritis and not maybe for pain and fatigue? We don't know all that.

Then what to select in different diseases? Is there one optimal route of admin of like the autologous versus the allogeneic? Is it whatever you can get your hands on? Are we priming? And with that comes the new expectations.

So when I naively heard about CAR T therapy, when it first came in oncology more than a decade ago, I thought, wow, this is amazing. It's a cure. It's quite a neat immune way to mop up a lymphoma or leukemia that has been recalcitrant to everything. And so the idea in CAR T back then was immune reset. Now they're talking about a new buzzword phrase.

I hadn't heard it till this meeting called immune dimming. And what that means is the immune system has improved, but you're not getting a patient say to remission and certainly not in drug free remission that you might have to restart something. Then a final long term concern, not for everybody, but there have been reports mostly again coming from the oncology literature of an increased risk of cancer years after getting CAR T therapy. But in oncology literature, the biggest risk of cancer is having had cancer. The next biggest risk is having had huge cocktails of chemotherapy.

So I think we have a lot to think about, but if there's 93 abstracts just at this meeting, this is still a really exciting field. And right now, I don't know how many CAR Ts we need to actually test drive. Please follow me at JanetBurdope and follow RheumNow. Thank you.

Hello. I'm Jonathan Kaye reporting from EULAR twenty twenty six in London, England. This is the second day of the EULAR meeting, and there were a number of interesting abstracts presented today. I'm gonna talk about abstracts o p zero two zero six and o p zero two zero seven, which were about optimizing treatment of rheumatoid arthritis with methotrexate. At the American College of Rheumatology meeting last fall, there was an abstract presented as a plenary from India of a clinical trial that compared split dose methotrexate twenty five milligrams given in a split dose once weekly to single dose twenty five milligrams of oral methotrexate.

And they found that split dose methotrexate was more effective than one single dose of methotrexate twenty five milligrams weekly, probably because the methotrexate receptors in the gut are saturated at a dose of fifteen milligrams weekly, and doses higher than that are not absorbed as well. So this abstract, o p zero two zero six, reported on the SCOOT study, a study comparing oral split dose methotrexate to subcutaneous parenteral methotrexate in patients with active rheumatoid arthritis. This study randomized two hundred and fifty two patients with rheumatoid arthritis that was in at least moderate disease activity, one to one to receive either parenteral methotrexate twenty five milligrams subcutaneously weekly or oral split dose methotrexate twenty five milligrams once weekly in two divided doses, fifteen milligrams in the morning, and ten milligrams in the evening. And this was a noninferiority study with the primary noninferiority outcome being minus fifteen percent noninferiority margin for achieving a EULAR moderate or good response at week sixteen. This study failed to demonstrate noninferiority of oral split dose methotrexate to subcutaneous parenteral methotrexate, indicating that probably parenteral methotrexate is the way to go when you need to use doses of methotrexate more than fifteen milligrams once weekly.

The oral split dose methotrexate also had a higher incidence of elevated ALT and AST compared to the parenteral methotrexate. So not only was the parenteral methotrexate more effective, but it was also safer or at least better tolerated. So this study suggests that when one is escalating methotrexate above fifteen milligrams orally weekly, it's better to go to perennial methotrexate administered subcutaneously despite the preference of many patients to take an oral medication rather than a parenteral medication. The other abstract that was presented at this session that I'm gonna discuss is zero p zero or o p zero two zero seven, which was a study from Montpellier in France that looked at dietary fiber supplementation in addition to methotrexate to see if dietary fiber supplementation might improve methotrexate clinical response. The rationale for this was that dietary fiber supplementation increases short chain fatty acids, which may decrease t h 17 cells compared to t regulatory cells, decreasing the pro inflammatory effect and also alter the microbiome, perhaps leading to a change in the metabolism of methotrexate resulting in greater efficacy.

This study randomized forty nine patients who were randomized essentially one to one to receive either twelve grams of inulin daily as fiber or placebo, which was a different powder. The primary endpoint was the EULAR moderate response at thirty days. In this study, the patients who received inulin fiber had a greater response to methotrexate than those who were given placebo, suggesting that the administration of fiber with methotrexate improves the clinical response, and the exploratory analysis of the microbiome showed changes in the microbiome with dietary fiber supplementation compared to placebo supplementation, suggesting that this might change the metabolism of methotrexate, resulting in greater efficacy. So taken together, these two abstracts, OP zero two zero six and OP zero two zero seven, suggest that there are ways to change the way in which we administer methotrexate, giving doses of fifteen milligrams or higher once weekly as a single subcutaneous parenteral dose rather than split dose oral administration, and that perhaps administering dietary fiber supplementation with methotrexate may alter the microbiome, increase short chain fatty acids, and decrease t h 17 cells, increasing the t h seven or decreasing the t h 17 to t regulatory ratio, thereby improving the efficacy of methotrexate.

So these two rather straightforward alterations in the way in which we administer methotrexate, subcutaneous rather than oral at doses of greater than fifteen milligrams once weekly and along with dietary fiber supplementation, may potentiate the effect of methotrexate, which is our anchor drug and which is incredibly important in the treatment of rheumatoid arthritis for virtually all of our patients. For this and more from EULAR twenty twenty six in London, I'm Jonathan Kaye. Go to rheumnow.com, and I look forward to seeing you again soon.