EULAR Daily Recap Day 3 Save

Hello, everyone. Welcome to RheumNow's coverage of UR twenty twenty four. This is day three, and this is the day three recap where the faculty gets together and has a a bottle of wine. I hope we have a bottle of wine somewhere. And we discuss what we saw today at the meeting that we thought was new and important.

I'm Jack Cush, normally in Dallas, Texas, and I'm joined by Bella. Doctor Bella Menta from New York City, and doctor Anthony Chan from The UK. Alright. So we're just gonna go around the horn, give you our favorite abstracts from today. Why don't we begin with Doctor Chan?

Thanks. I want to start off by the the poster tour which I attended this morning. They are they are really nice things to attend first thing in the morning with some coffee and there are two posters that they're almost side by side but almost saying different slightly different results. That's his poster zero two six six and poster zero two seven eight. And this is looking at the question of cycle or swap.

Once patients fail the first TNF inhibitor, do you go to another TNF that's the cycle strategy, or do you swap? So, and these were the questions asked. The first one, sixty six is from the Italian group. There were three forty seven patients, two seventeen in the, continuous group, which is a cycling group and 130 in the swapping group. And basically the end of it they found that the, there was a slight difference in advantage with the switching group or the swapper group compared to the continuous group.

And I asked them the questions, was it because of inefficacy or was it because of side effects that made them switch and they said they haven't done an analysis yet. So I think again something to be considered when they really look at the data. Five years there was there was slight advantage of the the the swapping group compared to the continuous group. Almost adjacent to that at two seventy eight was the Dutch group also presented the same Kaplan Meier survival curve. This was also PSA patients four zero six this time.

Three zero seven in the continuous group and ninety nine in the cycling group and here this time they did look at whether it was in efficacy or whether it was side effects that made them switch and essentially the the bottom lines where they found no difference whether the switch was due to inefficacy or due to side effects they both groups did just as well whether they continuous or whether they were they were the swapping group but they only found a slight difference in male patients. Male patients did less well if they were swapped compared to female patients and but no difference in overall in terms of the deaths twenty eight CRP. So I thought it was interesting because it probably influences in some ways some of our own practice and we may often keep people in the same group cycle if they had what we call secondary failure and they've responded for a long time but then stopped responding after a period of time and in those who didn't respond from the outset sometimes we tend to swap.

So what were the drugs that were involved here? And usually in these trial in these studies

So, yes.

What we're talking about is cycling amongst the TNF inhibitors, you know, using one of the five and, and switching to another mechanism. IL-seventeen. IL-seventeen. Yeah. So this is t n f n f switching or cycling versus swapping to another MOA.

Correct?

Yes. Correct. And that's I l seventeen I I l seventeen inhibitor.

For treating what condition?

PSA, psoriatic arthritis. Okay. Are more studies of psoriatic arthritis.

Oh, okay. I got you. So this is basically an IL a a TNF versus IL 17 switch. And, you know, the the data on this for at least RA, there was a lot of it, and it always favored switching to another MOA. Meaning that, you know, when you and, you know, the story is that if you use a first biologic, like a TNF inhibitor in RA, you get a sixty, forty, 20 ACR, twenty, forty, 20, fifty, seventy response.

But if you keep staying within TNFs, it goes down. It goes from sixty, forty, 20 to fifty, thirty, 15, etcetera. And this is one of the rationales behind the swap to MOAs because you then get a second time around, get a sixty, forty, 20 with a new molecule, a new MOA. Up until recently, there wasn't a lot of research on doing this practice or these choices in psoriatic arthritis. It's interesting to see that they're kind of following the the observances of what's seen in RA.

Based on this data, do you does this change how you'll treat PSA patients when they don't respond to ultimately don't respond to their first TNF inhibitor?

I think the, the first group, as you say favoring the what we know which is to switch mode of action where they found that the people who swapped it better. But I think the second group probably what they were saying is that people who had responded to TNF for long periods of time and then say in a couple of years failed you probably could cycle in those patients. That I think is the kind of takeaway I've got from these two posters.

I guess, I mean, it was observational too. Right? So I mean Yeah. I don't know this showed us how many people were lost to follow-up. Like, you don't know what happened to those.

Yeah. We don't we don't have that detail. They just gave us the five year kind of survival curve.

Like five years is a long time for all these patients to be followed and not lost.

I think it wasn't it wasn't designed as a study, it was more an observational and they were doing it because of prescribing practices. So the second study they had a drug sort of a protocol that they had to follow. So in the first five years they were following the continuous strategy and then they had a change in their policy and then they went to a switch strategy. So this has allowed them then to do the two comparisons.

I I guess, are you guys doing, like, anti TNF antibodies? I mean, that's the rationale then. If you, like, take it for a long time, there's antibodies too.

So therapeutic drug monitoring to make decisions, not very much in vogue. I'm not doing it. I don't I don't find the point of it. Only recently have there been studies suggesting its utility in RA and PSA, but I can't say there's a lot of data to support it. The reason why this is an important, this kind of data, even being observational, important is that the longitudinal retention studies on our advanced therapies in psoriasis and psoriatic arthritis is abysmal, meaning that survival on those drugs is not very good.

That at three years, less than fifty percent are still taking the original, and sometimes like only thirty percent are taking the original biologic, whether it's an IL seventeen or TNF or a twelve twenty three. And so knowing what your next best choice might be to get the best success, really is gonna help. So we probably need more studies like this. It'd be better if they were a little better designed. But when the best you have is observational data, that is still the best you have.

So interesting. Bella, what's what what did you like from today?

You know, I like this, again, one of the studies from the poster tour. It was a poster number 0277. So this is canakinumab prophylaxis in patients with gout who are getting, methotrexate and pegilodecase. So instead of, you know, the the concept is that if you are in a gout flare, you give corticosteroids and then initiate methotrexate and pegilodecase. We know canakinumab is now approved, for, gout, for recurrent gout where patient cannot be treated with NSAIDs, corticosteroids or colchicine.

This is rather an expensive proof of concept study, sort of study, but they did this, in 12 patients who had gout flares, gave canacunumab, and methotrexate, initiated methotrexate, and then two or three weeks after give pegiloticase and then saw, you know, if they had any gout flares going forward. Again, you know, two or three patients of these 12 had sort of dropped out, had problems with serum uric acid rise, and thus pegilorticase needed to be switched off. So, basically, data from, like, the mirror RCT. But sure that it does work, and it does work well. And those patients where you absolutely can't do steroids, this might be a good option to initiate for gout flares along with sort of more prophylaxis treatment with

So how many patients ultimately benefited from this since there were dropouts? You know, so how many people did well in this?

I think, you know, out of the twelve, three dropped out, eight of them did well.

Okay. So, again, it's expensive double biologic therapy. Obviously, highly complex patients.

Highly complex patients. Like, it's one dose, one fifty milligram.

And and what's the timing here? So patients going on pegilodecase should be on an immunosuppressant, like methotrexate, mycophenolate, I I like azathioprine, and then you start the the peglodecase and so that they don't get the anti peg response that would limit its use. And when do you start the canakinumab, and how often do you give it?

They just tried to do it, like, once, like, during the flare. So they didn't I mean, at least in this study, they just did it once. How often? I mean, I hope not. Right?

Like, hopefully, the gout flare subsides, and you don't need to keep giving it.

But my experience with peglodecase is that when you give the peglodecase, they flare after every time. And my patients needed to be on I use had I use way too much steroids because let's say they were on, like, some low dose, you know, five milligrams a day, and then they get their peglodecase infusion, and I have to bump it up to 20 for five to six days and then hope to get them down. But and I was giving you every two weeks because these are people that had big time toe quality and total body urate. So they were constantly in this surge of flare and non flare that I must say wasn't always well controlled by steroids, and maybe canakinumab would be a great option, albeit an expensive one.

Yeah. Yeah.

And can you can you give it repeat did they have people where they gave it repeatedly?

Not in this study, but, like, we've we've given canakinumab repeatedly with biologics in in stilts, like, combined if we needed it to. So I guess we can.

Yeah. You know, if you can get get it get it approved and certainly is a new indication for the management of of of flares. This is pretty pretty novel. I I'd be really interested, in seeing how this goes forward and whether how it could be protocolized. Because once you get a protocol, then you better study it, can maybe get better, funded, and patients can benefit from it.

I can tell you my two patients where I had to use recurrent steroids were really bothered by the flares and the recurrent high doses of steroids. And I don't know if they were more bothered by peglodecase, which was benefiting them, but they were basically tied to it like someone with cancer has to go and be tied to chemotherapy and they don't like doing that on a regular basis. So, you know, while in the beginning they may be enthusiastic about what you're doing, when you're six months in and you're still doing infusions of peglodecase, they're not wild about it, and they still got a long way to go. And, you know, I must say it's it's these are really difficult, difficult cases to manage. So this kind of option could be could be really advantageous for some.

We've we've been doing anakinra, right, and gout for, like, these sort of, get us out of a tough situation where you don't wanna be on steroids a lot. I feel like when I have given pegloticase, it's maybe initially they've gotten flares, but then it it stabilizes and then flares stop happening. And the and the tophi also I mean, we know that with all the clinical trials and the data. I mean, it goes away. It does.

So

That was my impression going in, but the ones that I patients I got, they were I guess they had so much total body urate that it was just gonna be just an ongoing thing. So maybe I I had the wrong but, you know, in this when you're using piccoloctasis, these are always tough cases to manage. Right? They're never gonna be simple gout. And and gout is already kind of challenging in its own way.

But anyway, I like this as another option. So my abstract from today was a poster, POS one zero three five. It's a it's one of many studies at this meeting on interstitial lung disease, which is getting a lot of play. I mean, think some of the themes that I'm seeing at this meeting is a big theme on lupus that we talked about last night and steroid use that's playing out. There's a lot of action on direct to, I was going say direct to consumer advertising.

Instead, I meant difficult to treat RA. There's still some good reports on preclinical or clinically suspect arthralgia, but ILD is another one that's getting a lot of play. And this one I thought was important because it's a cohort study of one hundred and seventy two patients with rheumatoid arthritis associated interstitial lung disease. And in this cohort, you know, bad things happen to these patients, right? They get more infections, they certainly have more deaths.

And in this study there were forty four ILD related deaths, and seven patients went on to require transplant. And what they did was they looked at the this cohort was selected because they all had six or more serial assessments of PFTs and FVC measurements. And they then plotted out the FVC trajectories for these patients over time. And they showed that, about thirty five percent of patients had, a stable or improving FVC trajectory, but fourteen percent had a rapid decline in FVC, in the three years or more of follow-up, and over fifty percent had a slow decline. It turns out that it didn't matter whether you were a slow decline or a rapid decline, that the outcomes were kind of the same as to the bad stuff.

The bad stuff being the need for lung transplant. If you were to have a declining FVC, which it was very If you look at some of the graphs, it's very clear what it looks like over three years, but you can even make these distinctions about slow decline and rapid decline in the first year, right? Those patients had a 19 fold higher risk of having lung transplant. If they also were had a declining FVC, they had a nearly fivefold higher risk of ILD associated death. The point being, and there's a lot of the scary data about ILD at this meeting, is that bad things happen to them.

You need to identify them early. There's some hope that better treatment of the RA will lead to some better lung outcomes, and that's another story, maybe for tomorrow. But that I like that, this data comes from Jeff Sparks Group, in Boston that you can identify the slope of FVC in the first year if you're doing this every six months. And that should give you pause and concern. And it really tells me not being an ILD, you know, aficionado as many of my young fellows and young rooms are these days, I haven't been so vigilant about getting very early chest x rays, PFTs, and lung CTs to know where they stand.

And I think that if a patient, well, you have an RA patient and they have the slightest hint of any pulmonary issue, it's incumbent upon you to make sure they're not gonna be or that ILD isn't their biggest problem, and there's a number of other lung diagnoses that go along with RA, but identifying it early could be important in the management. Do you do you guys see much ILD, and and and what's your what's your assessment of it and how it impacts your practice? Bella?

I think I agree. I'm again, I don't screen everybody, but after all this data, I've been, like, at the slightest, like, shortness of breath, cough, something. I I start referring them and, like, getting testing done because it is pretty scary when they decline like that.

Yeah.

And and and sometimes, you know, the RA is okay, and, like, the patients can live with, like, not that great disease activity. They are not aggressive about it. But, like, when you see this sort of a thing going on in the lungs, then you can change the management options that you're doing with the patient.

Anthony?

Yeah. You know, I think the, the group that did less well, the one that you sort of accelerated and dropped in the FEV one probably are the group that, must be the rheumatoid factor positive or CCP positive presumably or might be smokers, but the the large majority of them even if you took those iris groups we're probably not you know diagnosing them early enough with ILD. The issue for us is that we're not doing these regular FEV ones as in the study suggests we're not even doing them, every six months. But I saw a poster which was, yesterday on the use of ultrasound and how lung ultrasound might be, less in less radioactive compared to CT certainly, but could be done very quickly and I asked them they said ten minutes you could do this and they had five lines that allowed them to not only find ILD but also bronchiectasis in the rheumatoid patients. So you know I think it's something that we could consider.

I know it's ultrasound and it's used already in looking at joints but something to consider if you're not doing regular CTs or lung function in our patients.

You know, Anthony, you mentioned about them these patients who are getting worse rapidly worse are probably gonna be seropositive. I think it was, two ACRs ago, maybe three. Jeff Sparks had a big analysis of all their patients and shocked me with the data that said that seropositivity wasn't the big predictor. I've always said it is.

Yeah.

That and when I was taught, it always is. That it's the patients the ones who get really bad RA ILD, you know, have really bad RA, polyarticular disease, erosive disease, extra articular disease, and strongly seropositive. They found it was a fiftyfifty split, and so much so that you can't think of seropositivity as the linchpin upon which you're going to be more concerned or do more vigilance. That's kind of changed some of my thinking and my approach to these patients. And I think it's paid off because the fact is that lung disease in RA leads to worse outcomes, more infections, more deaths, more, you know, everything.

So it's something that we need to worry about. All right, let's go, let's do our second round with Doctor. Chen leading the way.

Thanks. So, this was actually from yesterday, but I thought it was a new, agent that, worthy of discussion. This is a sonolizumab. Sonolizumab is a is a dual I l seven l seventeen a and l seventeen f nanobody and, this was presented by Ian MacInnis at the PSA, oral abstract session and, and this was slightly different from, our usual antibodies in the sense that they are molecular weight was small lighter is 40 kilo daltons compared to 150 kilo daltons from the conventional antibody and the idea that because of this and also it has an albumin binding domain. The idea is that this would bind tightly to the IL-seventeen ANF receptor and therefore result theoretically in higher efficacy.

As you know they only presented a twelve week, results and these studies are twenty four week, study at two zero seven patients and these patients had greater than three tender, three swollen joints for psoriatic arthritis and the dosage was sixty milligrams, one hundred and twenty milligrams with and without induction. They had a placebo arm and they also had a comparator adalimumab arm just as a control arm. It wasn't a compare head to head comparison and they went for the ACR fifty as a primary outcome measure and they were achieving in the range of forty six percent in the active treatment arm and thirty six percent in the half dose sixty milligram arm and the placebo was 20%. So and then the ACR twenty was seventy two to seventy eight percent. So it did meet its primary and secondary endpoint but of course it's only twelve weeks.

We don't have any structural data and we don't know what happens in the longer term but perhaps a kind of new kind of way of delivering some of our cytokine inhibition.

Yeah, so this is sort of on the coattails of bimekizumab and other dual IL-seventeen ANF inhibitor. And just to remind the audience, the story on that, of course, is that that works incredibly well in cutaneous psoriasis. Right? And the head to head studies on that are, you know, probably, you know, superior to everything else that's out there. And so they've been, that's been launched in psoriasis, that has not been launched in psoriatic arthritis yet.

They're waiting for the FDA. It probably won't happen till after December 2024. But it looks good in psoriatic arthritis, but will it be any better than what's out there? We don't know. And unlike in dermatology where they have head to head trials, we don't have head to head trials, but it certainly looks okay.

You know, yesterday had a long term safety and efficacy report that showed good data for bimekizumab. But this sonolizumab, sonolizumab, whatever, is looking like it's following the same path as bimekizumab with the unusual finding of one thing. And I think this is, and that being, from a safety standpoint, the dual inhibitors seem to have a little bit more of of candidiasis. Right? Do you remember the number that that they had in their trial?

They had two two candidates reported in two hundred and seven patients. Quite low, but it's only twelve weeks. So we have to kind of fully

Was that disseminated candidiasis or just no?

No. Oral oral candidiasis.

Yeah. And and that's the story with the bimekizumab. It's all, sort of nonserious, oral mucosal, never systemic. But in the derm world and looking at both bimekizumab, this one and another one, the percentage of just candidiasis complicating therapy in clinical trials ranges from about like nine to, I wanna say sixteen, seventeen percent. We don't see that with the other IL-seventeen inhibitors.

So it's much higher, but only in the derm literature. In room patients that get treated with bimekizumab, the numbers are single digit and kinda low. Think it's like, you know, less than six percent or something like that. But and and thankfully, it's not systemic. It's all that mucocutaneous stuff that's easily managed.

So it'll be interesting to see how that if the I mean, again, the issue is if it's biomechanistically different, is it gonna be is the efficacy or the safety gonna be different as well? And the only safety issue is this candidiasis, which I don't think is a serious one. And the efficacy clearly shows up in in dermatology, may or may not show up in in rheumatology that it's yet to be seen.

I mean, it's good to have some options.

Absolutely. Yeah. Absolutely. As we said before, too many patients with psoriatic disease, skin or joint, are cycling off of their biologics because they just don't seem to last. The question is, is that because there's so many options for treatment that people are quick to bail out?

Or is it because they really do have a higher than expected rate of secondary loss of efficacy? Doesn't seem like they have a, if anything, their safety profiles on IL-17s, especially and pretty much all the drugs in psoriasis look pretty good. The SIE rates and everything else are lower than what we see in RA. But I I again, I wonder why ask

when there's options, you try to sort of get rid of something that's not working.

Yep. Well, it makes it makes the switch easier. That's for certain. Bella, what what do you have second for a second, option?

So this is a poster, one one nine two looking at adult onset Still's disease patients, specifically looking at serum CRP and IL 18 levels. And this was interesting because, you know, even though I see a lot of Still's disease patients personally, I was not sending out I l 18 levels for logistical reasons or whatnot. But what I have started doing that, and the results of this study sort of are similar to what I'm seeing in my practice. So it was important to highlight it. They had around forty six Still's disease patients.

They were doing serial CRP levels as well as IL-eighteen levels, and sort of tracked outcomes in Still's as well as, flares. And, basically, they they came up with a threshold for CRP levels of, like, 10.8, above which there was a sensitivity specificity around eighty percent of predicting flares or, worse outcomes. Whereas IL eighteen pretty much tracked very, very well with any flares as well as development of a MAS. So even those patients who are not in flares and had a higher IL 18 levels, a level had higher likelihood of MAS or or sort of liver issues. So I I I think the point to take home from this is that I l eighteen is getting more and more available to do, and I think for Still's disease, it's gonna be pretty much the standard of care going forward.

I think it adds to the current, you know, practice, which is ferritin levels that we do.

So and I'm not convinced. I believe that they're both IL-one. Is an IL-one, predominantly IL-one inflammasome driven disorder. Right? And the mechanism by which IL-one gets produced is the same mechanism by which IL-eighteen gets produced.

And so by knowing that information, how is it going to make me better? You suggest that maybe it identifies people, one attracts better as a biomarker, if you will, and that maybe it identifies MAS. Is there anything else as to another reason as to why I should be doing this?

I mean, we do ferritin for Stills disease patients, right, to track if they are getting get into flares even before they get, like, a clinically full fledged flare. So this is how I think I l eighteen would also help with doing the same. See But much better.

Again, I'm a naysayer on too many things, and I gotta look into that. But

Uh-huh.

Ferritin is only useful in my mind, because it's as an acute you know, hyperferritinemia, is seen in fifty only fifty percent of patients in stills. And the only reason to identify rising ferritin or extreme ferritins, extreme hyperferonemia is because it is the doom of MAS. It's telling you MAS is here. It's coming. It's gonna destroy.

It's the only thing that really hurt a Stills patient. And that's why I'll do a ferritin. I still hang my hat on CRPs and sed rates, is going to again, how many cytokines can you order to feel better about what you're

doing? That

you know, we'd like to

It it even helps because there are iodine drugs in the pipeline. Right. And maybe you will, sort of, when you are out of options, I guess, and still sometimes can get difficult to treat, it will tell you that this is the right patient for that medication.

Yeah. And I'll I'll say what I've said before. I I think the best biomarker in Still's disease for activity is is aldolase. Aldolase with a normal CPK, but an aldolase that can range from 10 to 50. And it not just in Still's, but in other IL-one responsive auto inflammatory syndrome.

Follow your aldolase level. You'll be shocked at what it's doing. And if they don't have myositis, it's all coming from liver. And, and I learned this trick from the pediatric rheumatologist at UT Southwestern, who they learned it a long time ago, and it really, follows other biologic correlates like, you know, microarray stuff and whatever. So I like that.

Of course, it's a cheap test and maybe a little bit more accessible than IL-eighteen levels, which for many of us are gonna have to be send outs, because they're probably not gonna be done locally. All right, my last one for today, was a session that occurred at the end of today, where these, it's called UR points to consider. And in this case, this is a document, generated by a UR task force to look at the management of patients with inflammatory arthritis who also happen to have cancer. So this was presented by Professor Gottenberg, and they, you know, there's a lot of ways to discuss this, but I I I wanna just basically get into the hardcore stuff that what what they said. The bottom line is, that patients who are a cancer and that the cancer is treated and in remission, and now you have to manage their arthritis.

So that's either they come to you, they develop a cancer and it gets treated, what are you gonna do with your therapy, which therapies do you use, Or they come they they they have a history of cancer in remission. What can you safely use? We do know the ACR guidelines, which I think on this are totally crazy and make no sense other than the one statement which says that a patient who has a solid tumor, that could be pancreas cancer, that could be lung cancer, that could be skin cancer, that can be prostate cancer, breast cancer, colon cancer, that you treat the patient as if they didn't have cancer. The cancer does not go into the equation. Not at all.

That's the one thing the ACR got right. Their recommendations about lymphoma and hematologic, don't even wanna get into because they're kind of wrong. These UR points to consider are are getting closer to being right about this because and I and I say that because I study this and follow this. They have a a task force of 27 people. There were two patients, 25 rheumatologists, a bunch of cancer doctors, and people that were obviously Epi related.

They did literature reviews. And number one, they say that their point, the point number one is treat the treating arthritis in a cancer patient is important for both the arthritis and the cancer. Two, that you have to balance the risks of managing the arthritis with the drugs that you need for the arthritis versus the cancer and its potential pitfalls and or risk of recurrence. Third is that room should be part of a co management scheme that the rheumatologist needs to be actively involved in communicating with an oncologist about what should be done. Otherwise, you're letting arthritis management be done by people who know nothing about your disease nor your drugs.

And that's a bad situation for the patient. Number four, that a cancer patient in remission who is in need of anti inflammatory or or biologic targeted synthetic therapy, you start without delay. There is no, like, let's do something, let's wait, let's get an opinion. You start without delay. Number five was patients who have a history of cancer in remission that JAK inhibitors and abatacept can be used with caution and only after other alternatives have been exhausted or not available.

And the reason that they say that is that there's some early potentially questionable data, not because there's any indicting data about JAKs or abetacept here. Now we know about JAKs and the oral surveillance study, and that has some more to some well, some concerns. But remember, the cancers that were seen with JAK inhibitors were the cancers that RA patients get. Lung cancer, skin cancer, lymphoma. I mean, that's the story.

Inflammation gives you those cancers in RA and in PSA and other things. So I don't think it's a JAK inhibitor thing as much as it's an RA and inflammation thing, and that's my opinion on that. But they do say that, again, that, you know, you would you have options here, and maybe you should make Jack and Abba the first. Number six is like the ACR recommendation, a solid tumor. They say you should ACR says you should treat it as if they didn't have any solid tumor.

The UR recommendation is gonna say solid tumor should get an anticytokine biologic or targeted therapy, really a biologic. And the reason is that they're staying away from B cells because they believe B cells may be important in the overall success of cancer management. And then I must say that that information was a little weakly presented, so we're gonna have to wait for the paper. But they are making instead the strong point that I would always make is that the data is overwhelming about the safety of TNF inhibitors in patients with cancers. It's overwhelming.

I mean, we're talking about twenty to fifty thousand patients no negative story. And yet, you know, there are people who are saying use rituximab where there's no data at all. And it's just because it's approved for what lymphoma that's gonna work in all other cancers? I don't think so. Or be safer in all the cancers?

I don't think so. But they kinda lump in as anticytokine therapy, the IL-six inhibitors. And I don't know the strength of that data, and then we'll have to see that in the paper. Recommendation number seven, if they do have a history of lymphoma, they say certainly B cell depleting therapies for treatment of their RA would make sense. And lastly, shared decision making needs to be done between you, and the patient, and the oncologist if they're involved.

So I like these recommendations much more than I like the ACR recommendations on management that address the safety issue of cancer, But we'll have to see if it changes as it gets published. Usually when it's presented at ULAR like this, it'll be published in the literature hopefully in the next two months. Then And we'll be able to look at that and see if it still holds up. At least, I think it's going to hold up with what I've seen. How do how do these recommendations strike you, Bella?

I think, the TNF thing. Right? I've had patients who come to me, and they're like, the cancer is not a problem. Like, you know, I'll deal with it or I'll die with it, but the joints are killing me. And nobody wants to give them the right medication sometimes because everybody's scared.

So I think yes. Give them the TNFs when they need it, like, right away without being you know, because initially, there was a lot of scare about.

Yes. Lating's always a bad idea in pretty much any any decision making. Anthony, what do you think of this these recommendations?

I I I agree. I think we we should have moved away from the the fear of using TNF. It's certainly in the solid cancers as you say. When it comes to hematological cancers, lymphoma, we still currently use B cell rituximab. But is it your your what what do you do, Jack?

Do you are you happy to afford them to have TNF as well in this the hematology? Yeah.

Absolutely. Now now if they're getting as a part of their they're being actively treated for a non Hodgkin's lymphoma, for instance, yeah, I'll reserve using combination biologics in that person, because I do believe that will help them. But you know, there are registries, there's a registry, a Genentech registry of rituximab use in RA patients with cancer. And it's fraught with all kinds of, you know, ugly signals as well, because that's what you get when you have a background of cancer treatment. And it looked no better, no safer, than what you would get with other therapies.

And in my opinion, is that you use regardless of the situation, regardless of the cancer, you use the best drug available. And, and there's a lot of experience with TNF. So I'm free. I feel fine using, an anti TNF, or an anti IL-six. I have waited a little bit.

I've used some JAK inhibitors in patients with, active or past cancer, and only because there's not a lot of data out there. And I've also used rituximab as well. So, I think the idea is that it's a little bit to me like pregnancy, meaning the patient needs to be optimally managed for the best possible outcome for that thing, that pregnancy outcome or that cancer outcome. The best possible drug to manage their arthritis is really what you should be hanging your hat on. But I think we need to, sort of grow into these recommendations, because they are a little bit counter to all the warnings that we've had in the package inserts and, you know, FDA hearings and all this kind of stuff.

But, I still think this is just a forward step, on how we can better manage these people. Alright. I wanna thank my, discussions, for their review of a pretty active day here at EULAR in Vienna. Tune in tomorrow for our last day, day four recap. Same time, same place.

I think you'll enjoy that as well. Thank you, Bella. Thank you, Anthony.

Thanks. Bye bye.