RheumNow Day 2 Recap: ACR Convergence 2024 Highlights Save

Hello, everyone. Welcome to ACR twenty four. This is our daily recap, second day of the meeting. We're all here in Washington, scouring the meeting and looking for all the good content. And we get together at the end of the day, myself and three faculty, and sort of recap what we thought were the highlights of the day.

I'm joined by the RheumNow faculty. I'm Jack Cush from Dallas, Texas. I'm joined by, I'll let them introduce themselves, Doctor. Day.

I'm Renalini Day. I'm from London in The UK. I'm a clinical fellow there.

Anthony.

Hello, I'm Anthony Chan. I'm from Reading, United Kingdom.

Eric.

Hi, Eric Dine, I'm a rheumatologist in Summit, New Jersey.

Okay, so the ground rules are we're each going to present our favorite abstracts. We're going to do two rounds of this. We're going to cover at least eight of what we think are the best abstracts of the day. I wanna remind you that we do this daily recap, every day of the meeting. We did yesterday, today's day two, tomorrow day three, and day four all at 6PM Eastern Time.

We livestream it. You can watch it either on Zoom, YouTube, Twitter, Facebook or LinkedIn. So why don't we begin and let's begin with MiniDay.

Yes, so I'm gonna highlight an abstract that was actually in the health services research segment today. And this is abstract number seventeen nineteen and it's on steroid exposure and major adverse cardiovascular events, MACE risk. So this is something we've heard described many times, but this was actually a really large match nested case control study done in the veteran affairs cohort. So it's known that approximately seventy five percent of our patients with rheumatoid arthritis are on steroids to manage their RA symptoms at any given time. And this was basically looking at the effect of cumulative steroid use.

So there was about seven hundred patients in this cohort of about nineteen thousand who had incident MACE. And it was found that greater cumulative steroid use was associated with incident MACE. And crucially, that did not, that was regardless of whether patients had baseline MACE risk. So I just felt this was a really important study because obviously it adds to our growing evidence on comorbidities, cardiovascular risk in our patients with rheumatoid arthritis. And just really brings home the fact that we really need to be trying harder to get our patients off steroids and onto steroid sparing agents much more quickly and more effectively.

Yes, we had a highlight yesterday from the TAPERE study in GCA, which is also about weaning people off of steroids and that was probably a good idea. Steroids seem to be a common topic. What did you guys think of this research? Anthony?

Yeah, thought it was great. In fact, I joined that talk as well. But I think one of the issues was around how do we identify the risk factors. In this meeting it looks like a lot of the risk calculators that we are using is probably not as good as we like them to be and I think a lot of message was going back to just assessing traditional risk factors, addressing those and then trying to minimize steroid use as much as possible.

Eric?

Yeah, I would just draw attention to my favorite session that was related to this that was the session today by Doctor. John Stone, Michelle Petrie, and Beth Wallace, where they looked at if there's a future for if steroid free is a future, and they looked at ANCA vasculitis, lupus, and rheumatoid arthritis. And I can't do it justice in a short summary, but really kind of looking at all of them and how much we've been able to bring down steroids for each of those and looking to see in the future how little we can bring. I think there's always going to be time where we need some, but hearing those kind of three super experts at what we've done and take the historical long view is quite amazing.

So Doctor. Day brings up this issue of MACE and obviously a big issue. Eric, is there more from that session that you think we could add to this discussion? Everyone's told to minimize steroids, either at the start and certainly at the end, it's one thing to say, it's another thing to do it. Did that session on vasculitis RA and lupus give any greater insight other than be more vigilant?

I think certainly if you've heard Doctor. Petrie talk, you've probably heard her say that the P for prednisone is poison. You know, And she she did give some hints that in terms of things that we we often do, we bridge them by giving them kind of a nebulous length of prednisone that if we can avoid that, having, you know, the using a sub I'm injection of triamcinolone instead of oral prednisone, having less side effects, but also having them not have those pills that they can stockpile at home, making sure they're on the background therapy. But I think also just an understanding that there's not necessarily safe doses of prednisone and some of the data that she showed, including just increasing by one milligram increases risk of, I think it was MACE events, three percent. And so if you go up by three milligrams, that's nine percent increase.

So that even these things we think of as low risk or low safe doses have a cost.

So I want Doctor. Day to wrap this up, but I'm going to give a shout about another steroid abstract on Tuesday, 02/1973 and it's from British Columbia where twenty eight thousand people with RA are on steroids and they talk about the risk of again cardiovascular events and infections, serious adverse events. And that the bottom line is for every year of corticosteroid use, both of those deaths from CBD and infection go up seven percent. For every year you stop GC use, the rate of mortality for CBD goes down one point three percent and goes down almost five percent for infection. So obviously they're making a point and what I have to go and find out is if you stop steroids, does the risk ever go away or do you carry that risk lifelong?

And we'll find that out on Tuesday. So, Doctor. Day, you bring up a really good topic. There's tons of research about this. What would your summation for the audience be?

I mean, yeah, we're so lucky in rheumatoid arthritis. Have effective drugs. Now there's really no reason from that point. Also say that, you know, in the aging session, it's patients who many of them are not on DMARDs and many of them continue on steroids in late onset RA as well. And so I think we need to consider comorbidities, age and, you know, polypharmacy and everything in that steroid discussion.

And, yeah, I think this just adds to that growing burden, a growing base of data that really brings brings that home and, you know, clear reason to bring down the steroid use.

Excellent. Alright. Let's move on to our next one from doctor Chan.

Yeah. So along the lines of the steroid, I really like the plenary session this morning. It's abstract sixteen forty seven and this is from the Rotterdam group who looked at time to conception or time to pregnancy. And there are two cohorts, the para cohort which is the original cohort which were treated in a lot with anti inflammatories, NSAIDs, prednisolone, kind of before the biologic era and the sort of pre care cohort which is the cohort that receive treatment to target strategy and they had early use of hydroxychloroquine, sulfasalazine and TNF. Any steroids were required very low dose of steroids but avoiding anti inflammatories and the bottom line is in the treatment to target group, the time to conception was eighty four days on average compared to the older cohort which was one hundred and ninety six and my reading of this is we need to treat the disease more So keeping the rheumatoid arthritis under good control is important for fertility and secondly avoiding prolonged use of anti inflammatories or steroids in these patients and moving towards more targeted therapies in these patients should result in a better outcome.

Yeah, is, I like this. This is presented at ULAR, again presented here a little buffed for this meeting. The interesting thing about this was it was just really a reflection of two eras, right? The power cohort was how we used to do things. You know, where we worried about, you know, or we said things like RA made patients who were pregnant go into remission.

We know that's actually not true. Know, it may be true in about a third of patients, but there's really a third who get a lot worse and a third who can bounce around. So old days we said these things and we really didn't have much of a plan. This pre CARA newer cohort that was treat to target did much better. Did they say how good they were at treat to target in that pre CARA newer cohort that led to these better outcomes, meaning more pregnancies, faster time to pregnancy?

Did they say how good they were at the treat to target?

I think a lot of them were able to achieve low disease activity and fifty percent of them were on TNF and very few were on prednisolone. So I think it's more the reduced prednisolone burden and improved disease activity that probably resulted in the results that we see.

Yeah, that's excellent. Anybody else have a thought on this?

Yeah, I think it's a great project. It's not too surprising to me that patients who are doing well unless state of inflammation do, you know, do reach their goals of fertility better. You know, I know there's been data for men that their sperm counts are better when their RA is under control. But I think it is something that is very useful, and we have a lot of patients who are uncertain about, you know, treating with medications, even medications that we know are safe. But I think this tells us that if we can control them better, we can help them reach fertility goals.

So I think it's wonderful.

Agree. I think this was a really important piece of work, to be honest. And as Eric was saying, like during the pregnancy period, it just means that there is less stress for the treating team and the patient and their family about also the drugs that they're going to use during the pregnancy. And also, think it really brings home the fact of multidisciplinary clinics, preconception counseling, and all of that side of things as well, and how important that preconception period actually is. And that includes the treat targets aspect as well.

This is a good time to call out the ACR's efforts and its reproductive guidelines, a tremendous document that's at all our disposals when we're managing patients for pregnancy. And then I like, we always like to say that what it'd be known from medical school, organogenesis ends at week, is done by week eight. If you really wanna be crazy, you know, week twelve. But after that you can use anything you want. The baby's already made, you know.

It's already in the oven. And, I've started patients on all biologics including abataceps and all immunosuppressives. I don't use mycophenolate at all during pregnancy. It's the only threat agent. But all of them during pregnancy, all the effort to control them.

And I think it's the smart way to go. All right, Eric, what's yours to talk about?

Yeah. So I was going to talk about abstract sixteen eighty nine, which was a study by Kamani Guchinad in Oregon Health and Sciences where she was looking at racial disparities with pulmonary function testing, which is, you know, we know that there's so many healthcare disparities that affect our patients, particularly in the scleroderma population, which is what the study was looking at. And one thing I didn't think about very much is the role of PFTs. You likely have heard about EGFR being something that has been thought to have potentially racial bias, And same thing with the PFTs. So some of the factors that go into PFTs are age, height, sex, and race.

There's not a good physiologic reason for race to be included for it. Certainly, height, we know that there is a good reason for that, but there's a higher percent predicted for people who are deemed on the calculator to have an African American or black race. If we use a race specific equation, they have different results than these race neutral equations for PFTs, particularly, again, the FVC. So what they did was they looked at company Cush, Cush, looked at looked at these, the Hopkins scleroderma ILD patients and found, you know, looked at various benchmarks for what they would consider would meet trial eligibility, immunosuppressant, or lung transplant, and found that it changes drastically who's in the group. So for example, trial eligibility by their threshold, sixty nine percent of patients would meet it with a race neutral calculation for African American or black patients, that sixty nine percent goes down to fifty seven percent.

So it's drastic difference. White patients are more likely to have access to a lot of these things or have more aggressive treatment approaches because when you go race neutral, it will remove some of those patients. So it just shows the way that we're thinking about things, you know, even if you're trying to attack all the health disparities, you may not be thinking about the numbers that we're using, the things that seem the most objective or influence.

So, Erica, it sounds like they're looking at this from the effect of the calculation on the outcome side it, and how it affects the outcomes, but the calculation must exist for a reason. Why why not test the the race component in the calculation against the gold standard for lung function?

Yeah, you know, that's something that I actually asked about afterwards is because, you know, where does this FVC calculation comes from? And there's really not a reason to, you know, there's not kind of a gold standard. We kind of use the PFT data as the gold standard for what lung function is, and this is based on a calculator that comes up with the FVC score. And there was kind of a presumption when this was first made that black populations have higher reserves, higher function, but that's not based on any evidence. You know, I kind of asked outside of the talk, do blacks, you know, a general healthy population, do they have higher baseline FECs?

And that doesn't seem to be what the evidence shows. So it's unclear how that kind of got put in there, but it's been in there for as long as we've been looking at pulmonary studies.

I must say this, I find this surprising. I was not aware of this issue. Anyone else have an opinion about this?

I think it's important to study this especially with a lot of our connective tissue patients perhaps there was more, the racial distribution might be you know more predominant in certain races. I think the key thing is to kind of avoid overtreatment or under treatment. So you might be denying somebody or you might be over treating somebody if you're using lung PFTs for monitoring of treatment response or longer term follow-up of these patients.

Yeah, I was just thinking that I work in a very ethnically diverse area of South London and I'm certainly gonna be, I wasn't aware about this either before coming to this meeting. So I will be thinking about this now when I treat those patients who this applies to. And I think it's really important to think about those downstream effects because actually as the authors have correctly pointed out, may be denying or otherwise prescribing immunosuppression to these people for these kinds of reasons. So, yeah, quite important.

Something to consider. The thing is the PFTs arrive without explanation and with or without know, a a race based calculation. That may change, I guess, based on this kind of research. So it'll be interesting to watch where this goes. Alright.

I I was I was gonna talk about abstract seventeen forty five presented this afternoon by John Giles. It has to do with the effect of statin use on MACE outcomes in the oral surveillance study. A really nicely done presentation by doctor Giles from Cedars Sinai. You know, The oral surveillance study is four thousand three hundred patients, and we know the outcomes that JAK inhibitors were not non inferior to TNF inhibitors with regard to cardiovascular and malignancy outcomes, which is to say that TNF inhibitors were better than JAK inhibitors or that JAK inhibitors were worse than TNF inhibitors. And that's a whole argument unto itself.

But the issue is, we know that JAK inhibitors certainly will increase statins, sorry, will increase lipids in a proportion of patients. These patients who are already enrolled because of their age and being high risk, whether or not they were on statins was kind of a key issue. So in their analysis, some analysis of the data I'm trying to pull it up right now and I don't know why am I okay. So there it is. The number was twenty three percent of the total population study were on statins.

Fifty three percent of those with significant cardiovascular histories, atherosclerotic cardiovascular disease, half of the ones who should have been on statins were on statins. And of those, only fourteen percent were on the high potent statins. A lot of them were on lower doses and whatnot. Again, the patients who had a high predicted risk of events, only twenty seven percent were on statins and of those only three point two percent were on the high intensity. So the idea here is that a lot of those events might have been actually prevented.

So in the different arms, we had two TOFA arms and a TNF arm that the patients that were on tofacitinib were more likely to start statins during the study. Again, another big red flag. So again, the bottom line on this was that the patients, it's already a high risk population, but they were really being undertreated regarding statin use and that might've colored the outcome. So much so one of the moderators asked Doctor. Giles at the end, well knowing the data that you know now, would you modify the recommendation so an older person with cardiovascular events who had an MI as a smoker, you would say don't use a statin, don't use a JAK inhibitor, it's not a good idea.

Might you consider that if the risk factor was just atherosclerotic risk and whether or not they needed to be on a statin, putting them on a statin since many of those patients needed statins anyway, would that change some of your guidance? And he said it clearly changes the equation where you could now consider it. I thought this was very interesting and as Doctor. Giles said, it's the last nail in the coffin of oral surveillance, at least as far as cardiovascular risk, so that we now know pretty much all that we're gonna know. What did you guys think of this data?

I I thought I I was laughing a little bit when when you started to say it because I I was about to actually bring up that abstract. I was worried that too many people had oral surveillance fatigue after all the analysis. But I thought this really adds quite a lot because I think I agree with what you said that the baseline numbers that people were not taking Savants as much as they should be was surprising and the most modifiable thing that we can do. But I feel really reassured that patients who, you know, we think will benefit from being on a JAK inhibitor, particularly Tofa, that if we're managing their comorbidities as best as we can and if we're having them on primary or secondary prevention with things like a statin, we can probably safely use tofacitinib a bit more than people may fear. And so I think it's important that I wouldn't necessarily take these medicines off the table.

We have to have kind of risk benefit discussions, but this is reassuring that if we treat the comorbidities, we can use these medicines and control their inflammation, which will make them healthier.

I still think that the trifecta of age, smoking, cardiovascular events, is still one that you should avoid a JAK inhibitor, but if it's just cardiovascular risk, the statin might be the right intervention. Any other comments?

I found this abstract quite alarming actually. Because as you say, the rates of taking the statin are quite low and the types of statins as well, the differentiation between them. I think we all know that there's a cardiovascular risk in our patients with rheumatoid arthritis. And I personally would quite like to know why that rate is so low. Is it simply people are not prescribing it or is there a patient factor in there that maybe they don't want to or there's a difficulty taking this tablet at night by itself.

I don't know. So yeah, the numbers really did alarm me a little bit.

Anthony, what do you think?

Yeah. I think we should be using more of it. Don't think we, going back to my earlier point, I think we don't address a lot of the traditional cardiovascular risk factors well enough and our focus has been mainly on trying to treat the rheumatoid itself and not maybe addressing some of the comorbidities as we have, should be. And I think this is probably why we are probably under prescribing a lot of statins or hypertensive treatments for patients.

Well, to me it says two things. One is that patients in clinical trials have one intervention and they don't do comorbidity management in clinical trials. So if you come into the play with comorbidity, it's in play. Right? And the clinical trialist is not the primary care doctor and may not be the treating rheumatologist.

And so that's why this goes under managed. And the second thing is Jeff Curtis, I was involved in a project with him a long time ago and he's continued to work on this idea of how good a rheumatologist and physicians in general at doing health maintenance things that they should be doing. We're not that good at statin use. We're not really following guidelines and whatnot. And the problem is a lot of our patients don't usually, are not seeing primary care as they should.

So it's between their primary care that they may or may not be seeing in us, a lot of people fall through the cracks. Alright. Our next round is gonna be what we call our our, quick hit round, so that we can get in a few more, goodies from the day. Doctor. Day, what do you think?

So this is abstract seventeen sixteen in the epidemiology section, plenty of good abstracts in this session actually. But this is basically looking at serious infection risk with different biologics and targeted synthetic DMARDs. We have a lot of data in this area again, as you can see, I really like micro comorbidities. And this was basically trying to do a head to head comparison in a real world setting. And essentially, it found that treatment with rituximab, JAK inhibitors and anti IL-six drugs had a higher risk of serious infections relative to anti TNFs where I think the most data is really in this area.

So it just added again to that evidence base about serious infections and biologic use actually.

There's a lot, was this the jackpot data?

Oh, sorry, didn't quite.

Was this from the jackpots dataset or what was the cohort from?

Oh, this particular cohort was, I don't think they actually mentioned to be honest. I don't think it was Jackpot though. Don't think it was Jackpot.

Relative to a TNF inhibitor and they found that the other ones were increased as far as serious infectious events?

So rituximab JAK inhibitors and anti IL-six relative to TNFs, but there was no difference with, I think it was abatacept, IL-seventeen and IL-twenty three relative to the TNFs.

Yeah, I could argue, talk about this kind of data forever and a lot of it has, you know, order of use bias, right? You know, TNF inhibitors get used first when the patient might not be as bad as it may be later on. Apotacin gets used because it's got the label of maybe being somewhat safer drug. When you're looking at large population data or claims data on these regards, you're gonna find that that serious, warning, black box warning, being backed up by this data. And I think that's fair, but I don't know.

I worry about that also impeding people who need these drugs from getting these drugs. I mean, on what you saw, is it gonna change the way you use any of those drugs, whether it's rituximab or tocilizumab or JAK inhibitor?

I don't think so. Because rituximab already we know the serious infection risk. And to be honest, as you say, abatacept would be my go to in terms of safety, in terms of infections. So on that regard, probably not. I mean, there's less data in the IL-seventeen, IL-twenty three and IL-six maybe, but yeah, overall, probably not.

Any other quick comments?

Yeah, just with these studies, I just have to watch out for channeling bias because you think that these drugs may be a bit safer than TNF. You put them on it. You're going to pick up that they will have you know more infection within the small population. Kind of reminds me of our time during COVID we put everybody on sulfur salazine. It turns out sulfur salazine was the risk factor but in fact it was because our decision making was to channel everybody to sulfasalazine during the pandemic.

Eric?

Yeah, no, agree with with your thoughts there exactly. I think it's it's great that we can use these large database and and put a whole lot in, but it's always hard when we're kind of extrapolating.

Right. Alright. Let's move on. Eric, Anthony, you got another quick hit?

Yeah. Quick Hit is a fourteen sixty seven. It's a poster. I love the posters. These, this is a study of risankizumab.

One of the criticisms about the IL-twenty three is that it takes a very long time for it to work. But, here they have, did a post hoc analysis of keepsake one and keepsake two study where they have keepsake threes are in. They've looked at the bio naive patients in this cohort and they were quick so within thirty five days they were getting AC sort of 20% response and fifty seven days they were getting 50% response. So it's just that because we tend to use the IL-twenty three quite late and maybe that is why we don't see a quick response but it's quite interesting this is the first of its time that shows it works quickly in the bio naive patients.

And did that study also show that again that the bio naive response was equal to the bio experience response?

They had a small population of the that also were bio experienced. The BioNaive did better.

Okay. I'm kind of kind of expect that. Yeah, I think that's that's valuable data and Ryzogizumab IL-23s are a major force in this area. So Eric, what'd you think of that data?

Yeah, no, I think that's really useful data that Yeah, because that's the thing that I think really slows down whether or patients do it because it's a great medicine, but that time to work is such a critical factor.

Okay. All right. Eric, do you have a quick hit?

Yeah, I can go quick for seventeen forty three, which is looking at really helping to answer what do we do, how do we talk to patients who are in low disease activity, of patients that remission is what everyone loves, but low disease activity is a great place to be. It's what the guidelines say we should at least strive for, and that we don't need to titrate all their medicines up to the max. But what do you do with those patients that are kind of on the higher levels of the LDA? So this study looked at remission versus low disease activity, and they actually separated that out into very low disease activity, which is between that 2.8 to six is where they drew the threshold, versus six to ten. And the patients who are in remission and very low disease activity did roughly about the same, but the patients who are in low disease activity, again, C.

More than six, did not do as well. And it's not a surprise that they weren't quite as good, but some of the patient reported outcomes in terms of pain, fatigue were definitely different, healthcare utilization and things like ambulatory devices, like using a cane, were impaired in this patient population. So we may not just want to accept that patients who are just kind of in that low, not quite moderate range of a C. Seven, eight, nine every time you see them may not be doing as well as they should be or we should have a lower threshold to maybe tweak the medication dosing interval or add a CSD mark or do something to try to get them a little bit lower down?

The problem I had with this data was that the way that they present it and the way that the title is, it makes it look like it's a comparison of the outcomes in patients in LDA versus those that are in remission. And that's what it is. It's a comparison, but it's a cross sectional analysis of a cohort that's treated in a continuum, it's not like it's a clinical trial and they had two groups with two different outcomes. They selected their groups from a large number of outcomes and then said, well, yes, the remission patients clearly had an advantage. I think that that's inherently obvious to anyone who treats rheumatoid arthritis.

But, the question that I don't know is still is answered is how hard should you push? So it's almost like you need an LDA group who gets observed, and you make believe that you're doing something constructive, but you're really not messing with their meds. But that there's another cohort that's randomized to where you're messing with their medicines and a treat to target fashion or some fashion that you, and then you see what happens, whether it's worth treating. And I would like to know the answer to that. I don't know, Eric, does the study really answer that question?

Yeah, I think on the face it's kind of obvious that patients who are in remission are doing better than ones who are not in remission and you know, the patient reported reflects that. I thought what was interesting was some of those other metrics of things like using a cane that shows that there are some kind of objective differences. But again, it comes back to the risk benefit of do we add methotrexate on or go up on doses? And that, how much juice for the squeeze of going up on immunosuppressants? Is it worth it to get them into that category?

That's not answered.

This gets into, first off, we're dealing with the better end of the spectrum, right? We're dealing with people are doing pretty good, right? It's not like we're having a discussion about the difficult to treat patients, the recalcitrant patients, and how you treat them. So, yeah, I like the idea of aiming for remission. Minnie, do have any ideas about this?

I think as you said, there's a reason we have remission. I think one thing which has not been touched on is that we know that patients even with the slightest disease activity, mild disease activity, which is not in remission, are also at risk of those extra articular manifestations as well. So we're not just, it's good that they looked at PROs and it's good that they looked at the joint outcomes, but we have to remember as well that not getting into remission has its other risks as well. Yeah.

All right.

I would add in quickly that there was a study right afterwards that talked about fracture and patients in remission have less fracture than patients who are in low disease activity. So there is a difference.

Good to know. Very good to actually, I like that data. One that I liked was from Andreas Kirschbaumer, Abstract July. Is that right? I think I got that.

Maybe it's 1772. He had a presentation today about placebo responses and, what they mean, over time. And know, Kirschbaum works in Austria with Smallen and colleagues and those of us who've done trials for many years have noticed this creep of placebo response rates. You know, I remember back when I was a fellow in the 80s, placebo response rates were often single digit, sometimes fifteen percent. Usually was like thought of maybe twenty percent.

And then I did a study of a CD5 immunotoxin and We had a fifty percent placebo response rate. The question is what's the deal with placebo and it can certainly screw up the clinical trial results. He showed a graph over time showing that there really is this increase in placebo responses, when you go over a twenty year period where it was common to be ten to twenty percent back in the 80s and now in the 2020s, it's really, you see some as high as sixty percent. So one, placebos have gone up over time. Two, the really cool part of the study was where were the trials done in the eighties, nineties, February, 2020s.

And he shows a global map and shows United States lighting up in the 1980s with a little blip in Western Europe. And that as time goes on the map changes in color, color indicating how many people are enrolled in trials, showing that there's been this gigantic shift to worldwide recruitment and recruitment in small countries and in big countries, all throughout Europe and into Asia and into South America. So therein also lies that a lot of the newer patients are coming from countries where one, they don't have a lot of options. The one thing that was taught to me in learning clinical trials, again in fellowship, was a lot of what you see in placebo responses have a lot to do with how many options that patient has remaining after that study. So patient went to the trial in my practice for psoriatic arthritis, it's got lots of options.

But if you're in Chile and enrolling someone, maybe this is the only option they have. So they stick in there, they report that they're doing better, they have greater hopes and they get a real placebo response. So the other thing that they showed, the last point they showed that's really cool is this inverse relationship between placebo response rates and the gross national income of the country involved. So if you have rich countries, you have lower placebo response rates. If you've got really poor countries, you've got really high placebo response rates.

So it helps explain the last forty years of my life, but it also helps anyone who looks at clinical trials to understand why, especially like in lupus now. You see lupus studies where you might see a 27% placebo response rate, You might see a 50% placebo response rate. How do you get there? They all had lupus, didn't they? So I think it helps explain things and whether it's going to change the way trials are run, I don't know.

Minnie, what do you think?

I think this is fascinating data. And I think, as you say, I think really maybe when we're designing trials or interpreting trials, maybe we need to pay a bit more attention to the socio economic factors behind that as you were describing.

It's a reflection of the provision of health services in a lot of these parts of the world, But it also raises the question that you know standard of care done properly can actually be a good thing for our patients in these places. You don't always have to go with the big guns or the big drugs that just providing basic care for a lot of these patients could be the way forward just as a start.

Well that's a whole new can of worms but I think that's very very appropriate what you just said. Eric, last sight.

I agree. I I you know, I think, again, it's it's placebo plus conservative management or or standard of care and and inpatients just getting them into the medical system and and potentially in the developing country. I think it's very thought provoking. I think it's, you know, challenging because we don't know exactly, you know, these are big countries and and there's rural sites, academic sites, cities. And so it's it's hard that we can't get more granular on the data.

So it it would be great to learn more, but it's totally thought provoking for for how we're doing studies.

Alright. I wanna thank the faculty for a great discussion of some great abstracts here from ACR twenty four in Washington DC. Tomorrow, tune in at 6PM eastern time. We're gonna do it again with three other faculty from the floor.