0:04
Hi everyone, it's David Lou here again for the fourth time this meeting, the fourth and final time for the daily recap ACR Convergence 2026, summing up everything good that's happened in Orlando.
0:19
The meeting doors have closed. We're done.
0:23
But the last day, even though sometimes the attendance tail is off, some of the really really good stuff is there.
0:30
It's my favorite day personally. Late breaking amongst everything else.
0:35
This is where the fun is. So I'm glad to be joined by the esteemed panel of four.
0:43
We've got some really experienced minds here to give you some insights into what's going on.
0:50
I'm going to go around the room for these old hands.
0:54
Minnie. Yes. My name is Minnie Day. I'm a fellow in rheumatology and internal medicine from London in the UK.
1:00
Jiha. Hi, my name is Ji Hali. I'm a rheumatologist from Michigan with a passion for aging in rheumatology.
1:08
Richard. I'm Richard Conway, rheumatologist from Dublin, Ireland.
1:16
And Lisia, the incoming president of the Brazilian Society of Rheumatology, I understand.
1:24
Yeah, I'm Lisia Ma, rheumatologist from the University of Brasilia.
1:28
I'm professor of medical science and molecular pathology at the University of Brazil and the elected president of the Brazilian Society of Rheumatology.
1:35
It's a great pleasure to be here with you tonight. Congratulations. Congratulations.
1:39
So, let's get started. Minnie, what caught your eye today?
1:43
What's a big hitter? Yeah. So I went to the late breakers.
1:48
Specifically, I'd like to highlight the ALBAGIA trial.
1:52
So this is LB24 and this was looking at efgartigimod in autoimmune myositis.
1:57
So some very exciting results for a disease that, you know, it's very difficult to treat and we have very few options for currently.
2:03
So this was a positive phase three result for FcRn blockade, with particularly important findings in immune-mediated necrotizing myopathy specifically.
2:13
So for people who are not aware, FcRn blocks the recycling essentially of IgG antibodies, which increases their breakdown, and this provides a way of reducing potentially pathogenic antibodies without directly depleting B cells.
2:32
And so the question here was sort of whether that would translate into actual clinical improvement.
2:37
So the trial randomized 175 adults to weekly subcutaneous efgartigimod or placebo alongside background treatment for a period of 52 weeks.
2:47
92 had immune-mediated necrotizing myopathy, 54 had dermatomyositis, and 29 had polymyositis.
2:57
The main reported efficacy analysis combined the IMNM and the DM subgroups.
3:04
The study also included a protocol-mandated steroid taper as well.
3:08
So the primary endpoint was something known as the Total Improvement Score.
3:12
So this is a naught to 100 composite score incorporating muscle strength, physical function, and other measures of disease activity.
3:20
And essentially a score of at least 40 is what we're looking for, which represents moderate improvement.
3:25
So at week 52, the mean score was 54.4 points higher with people receiving efgartigimod than placebo, with a 95% confidence interval of 6.3 to 24.5.
3:42
And most participants achieved at least moderate improvement by that definition.
3:49
Improvements were also seen in muscle strength and patient and physician global assessments.
3:55
So essentially, in IMNM specifically the treatment difference was 14.8 points and that was statistically significant, but in the DM patients it was 14.5 points but that wasn't actually statistically significant.
4:08
No new reported safety signals in this particular analysis, no deaths reported either.
4:15
And so essentially, yeah, this is the first successful phase three trial in necrotizing myopathy. So exciting stuff.
4:24
That is super exciting when you have a disease where you don't have registered therapies — you're shooting in the dark.
4:32
We've got something now. Obviously dermatomyositis also important.
4:37
Not like we are overrun with therapies there, but it can be so disabling.
4:42
Can you — so we saw early in the meeting there was a bit of discussion about the nipocalimab data that came out, another FcRn inhibitor, same mechanism, phase two, maybe not quite as impressive.
4:59
Any ideas as to why there's a difference, or is this just the way things go?
5:05
Chance, and I guess smaller phase two numbers not leading to significant outcomes.
5:09
Difficult to say, I think. But yeah, I think numbers are the key thing.
5:14
Of course these are often quite a severe set of diseases that we're dealing with as well.
5:22
But yeah, I'm interested to see what my colleagues think of this as well, actually.
5:26
Yeah, and I'm interested — does anyone have any opinions on the safety of this as well?
5:31
I guess where we land with this. I guess it's easy to think about FcRn as, you know, plasma exchange in a bottle and that it's relatively benign, but I guess there is a little bit of — there are some safety things to be aware of with FcRn inhibitors, aren't there?
5:49
Yeah. I mean, yeah, I guess — um, do they discuss that at all in the abstract?
5:56
That really wasn't the focus of this particular abstract.
6:02
Overall kind of positive things put forward here.
6:05
And I guess also it was testing efgartigimod against placebo alongside background therapy.
6:11
So we don't actually know about, you know, compared to IVIG or rituximab — what is the superiority both in terms of efficacy and in terms of safety?
6:21
So just something to — it's very hard to know the difference.
6:26
I guess they're monitoring immunoglobulin levels and we know we've seen drops with that, and I guess they're still poring over the data, aren't they? Yeah, exactly.
6:38
I guess I'm not sure if anyone else saw any other of the myositis data at this meeting.
6:44
It's quite a productive meeting for myositis.
6:49
I think the big challenging thing here for me at least is we have so many of these drugs coming through now in myositis and how do we decide which drug we use?
6:58
Like, they're all positive trials. There's no head-to-heads.
7:04
We can't be giving them all to the same patient.
7:08
So I don't really know how to parse that out.
7:12
Has anyone got any thoughts on that? Because I mean, I guess as well, you know, we are working towards this world where we'd like to move to an antibody-mediated, kind of descriptive view of myositis in general, and we'd like to move away from the days of polymyositis to this kind of thing.
7:33
But then I guess you look at this and this is something that cuts across.
7:36
I think it came up in the questions about anti-SRP and whether that broke down with this as a cause of IMNM, and it seems like from what they've looked at it kind of cuts across it in general.
7:51
So we're not quite at the point where the antibodies are what's going to pull that apart, but I guess there's a lot that we could tell from muscle tissue or other biomarkers. There's a fair bit to come.
8:01
All right, Richard, what have you got? Yeah, so I have another late breaker which is LB19.
8:10
That was by Park and colleagues from Korea.
8:15
And I will say at the start of this that I am — this is a study of stem cells essentially being injected into joints and I have been an absolute naysayer about injecting anything into joints other than steroids.
8:30
So stem cells, PRP — haven't believed any of it.
8:32
I will also say that on the positive side I love a good practical interventional study that might change our immediate clinical practice of something like osteoarthritis.
8:43
So this was a phase 2A study. It was of a single joint injection using this — which I presume is a proprietary combined product — where they've got umbilical cord blood-derived mesenchymal stem cells combined with a cartilage acellular matrix, and a multi-centre study from Korea.
9:11
The other thing I like about the study: their primary outcome measure seems to be a VAS pain, which I like because so many of these studies now are coming out with these composite measures that I don't really know how to interpret or I have to go look at what they're actually composed of.
9:29
So I like that there's a nice simple one for me to talk about.
9:32
They also did look at all the standard osteoarthritis measures — so WOMAC and some functional scores, couple of MRI scores as well.
9:42
And the results here really surprised me.
9:46
So month one to month six, single injection.
9:49
In terms of VAS pain, it was a phase two study so there are two doses for this product — I'll just talk about one of them.
10:00
So there's a 44-point improvement in the VAS pain score out of 100 with the product that they're calling Oscar, and that compared to a 14.8-point improvement with the placebo.
10:15
So those are huge numbers — very big delta there.
10:22
All of the secondary outcome measures kind of fell in line with that, so WOMAC, the functional scores, the MRI scores — they all kind of held up and supported it.
10:33
So it's a phase two study; be nice to see phase three data, but I was both surprised and encouraged by this.
10:43
I'm curious, what are your thoughts on these studies using placebo as a control, because the real contender — like prednisone and hyaluronic acid being so cheap and quite effective — I feel like in the real clinical setting that's what all of these new agents or injections have to measure up to.
11:00
So I think if I can play the role of the authors — who were largely a pharmaceutical biotech author group, which is important to remember — but we have studies of steroid joint injections compared to placebo which are no better than placebo. I think that would be the argument.
11:23
Yeah. And I mean I guess when we've looked at the critical meta-analyses of all these products including stem cells, and we've looked at randomized controlled data of just stem cells by themselves, we've seen nothing in osteoarthritis.
11:39
So to have this — and I don't know, we don't know if it's this combination, if this allogeneic stem cell product, whether it's this added porcine cartilage acellular matrix added into that, something to do with a magic combination — but those numbers, I mean, those are retarutide numbers, right?
11:54
That's the kind of thing we're looking at there.
12:00
And I guess as well I don't know, Richard, whether there was much talk about — there's a bit of talk about this whole tissue repair business.
12:09
I guess, you know, you take it with a grain of salt.
12:12
What do you think about the MRI signals of tissue repair and biomarkers?
12:17
Yeah, I mean, before looking at this study I would have said this is all nonsense, trying to come up with a justification for this product.
12:27
I don't know — this has challenged me. I say it is a one-off.
12:32
We've very much seen, as you said, lots of other studies which have been negative.
12:36
I can't imagine — the magnitude of it is so high, it's very hard to say that this is a chance thing.
12:42
But I guess we'll see in phase three. Yeah.
12:44
And then in the questions they were talking about going out to five years, maybe benefit out to five years after those first two injections.
12:53
I mean, this is quite something. I don't know — who — let me go around, let me ask the group here: who injects knees with steroid?
13:05
I mean, that's me. I'll say that. We all do.
13:10
What about anything else? Anyone else game to say that they inject anything else?
13:12
Hyaluronic acid? Anything? Yeah. Hyaluronic acid.
13:17
Stem cells? Anyone? No. Nope. I think we're very evidence-based people here.
13:25
But so I mean this is really quite a frame shift and a half across.
13:29
And I guess we'll see what the further data is.
13:32
Is anyone else kind of skeptical about this, or maybe even excited about this?
13:39
No. Or a bit of both. I feel like I'm a bit of both.
13:43
I think Ji is both skeptical and excited from the look on her face.
13:48
It's more skeptical than excited, to be honest with you.
13:50
It sounds too good to be true, right? That's it.
13:55
Yeah, it does. We will see more in the phase three as you say.
13:59
Jiha, what have you got from today? I have abstract number 2929.
14:06
This is from the RA abstract session and it's basically — we've seen over the years some replications or trying to recreate or look at how ORAL SURVEILLANCE stands up.
14:14
So this is similar to that. So it's the real-world cardiovascular mortality outcomes in JAK inhibitors versus TNF.
14:20
And what I liked about it is that they are looking at a myriad of anti-TNFs as well as JAK inhibitors including baricitinib.
14:29
So just to set it up, they're using the Trinetx data, which is expansive, and they recruited patients over the age of 18 with RA on either medications between 2013 and 2022.
14:43
So it's over a 10-year period of time. And they matched patients based on demographics and comorbidities — 16,000 each in the JAK versus the TNF group.
14:55
And the outcomes they're primarily looking for using survival analysis is all-cause mortality and MACE, the major adverse cardiovascular events.
15:03
And they're looking at three- and five-year follow-ups, and secondary outcomes like DVT, PE, stroke, A-fib, and serious infection.
15:10
So I'll just run through the results because basically the bottom line is they showed what ORAL SURVEILLANCE does in the sense that with JAK inhibitors you have a higher risk of cardiovascular disease.
15:21
But the reason I pointed it out was to really look at more of the design elements of it.
15:25
Basically what they are showing is that when it comes to all-cause mortality, at the beginning they're very comparable — sorry, in terms of the
15:35
three and five years — but the MACE is interesting: within the first three years there's no big difference between TNF versus JAK, but the
15:43
differentiation starts from year five out.
15:44
So it may be that in earlier stages the mortality and the MACE events are for more non-medication-related reasons and more for RA disease activity.
15:54
But I think what we do as part of RheumNow is we're trying to be critical readers of these sciences and these papers.
16:00
And there was a session with the journal club meet-the-editors where it was Dr. Dan Solomon talking about cautious use of AI and study replications and really understanding study elements.
16:11
So you know, you're trying to really be as rigorous as possible to get to an RCT understanding of the constraints of real-world data.
16:19
So although they did try to propensity match on demographics and comorbidity, perhaps as part of the limitation of the data, we know disease duration
16:27
is an important factor, we know prior drug exposure is important, and also what wasn't really clear is that we sequentially prescribe these meds, right?
16:34
Like you go from TNF to JAK, and it wasn't quite clear whether patients could contribute to both observation arms, and if so, if they have varying follow-up time, what does that mean in terms of how do you attribute these events based on what treatment group you're in?
16:49
And even though they were looking at new users, which is really great, and the index date was the first drug used, they didn't really match on drug exposure period, because again this is a 10-year period of time.
17:00
The first FDA warnings came around in like 2019 and we've seen that changes prescribing behaviors.
17:06
Also this kind of overlaps with COVID time, and at one point baricitinib I believe was being used for COVID, and that may have conflated things — and there is a wider confidence interval when it comes to their baricitinib outcome numbers.
17:19
So I think it's nice to know that we have real-world data that allows for studies that involve like 32,000 patients to be able to replicate some of these studies.
17:31
But I just wanted to bring the caution: when you read these papers, really try to pay attention to what are some of the biases and the limitations.
17:39
And I think also as researchers, really understanding some of the data limitations and the construct — to know what data source are you going to use for these studies.
17:49
So that's why I wanted to highlight this one.
17:52
Yeah, that's a good point. Yeah, sorry. Yes.
17:56
Could I make an observation? What really caught my attention in this study was the striking difference in mortality across individual JAK inhibitors, particularly the hazard ratio of almost five — 4.48 — for baricitinib.
18:14
So it was interesting, but could you really interpret those differences as drug-specific effects?
18:22
So that really caught my attention, the difference in bars mentioned.
18:26
So when you look at it, out of those 16,000, like 10,000 of them are on JAK inhibitors but only 3,000 are on baricitinib or upadacitinib.
18:33
So it's a smaller sample size as well. And like I mentioned, baricitinib — if during that time it's one of the later market entry
18:40
users, so they could have had more drug failures, but also this particular one was potentially being used for COVID, which could have conflated your
18:48
mortality and MACE outcomes entirely and have nothing to do with RA-related factors, but just confounding by indication.
18:54
So I think that's why — it's interesting, but like you said, you notice that number immediately, and in order to interpret that you really have to pay attention to the study design and some of the context that could have played into this but didn't enter the study design as well.
19:08
So Jiha, do you believe that result? I guess after all that — I mean I think, let me just add as well, we were
19:17
meant to see an RA-BRANCH poster here at this meeting, which is looking at the phase 4 head-to-head randomized controlled trial for safety between baricitinib
19:27
and TNF inhibitors — the postmarketing requirement that is the equivalent to ORAL SURVEILLANCE for baricitinib.
19:35
It was withdrawn. I've got an article coming about that if anyone's interested.
19:41
But I mean, you know, we really want to look at those data.
19:44
We saw a 7-minute version of those at EULAR.
19:47
Do you believe this baricitinib versus TNF inhibitor mortality with a hazard ratio of 4.48?
19:52
And obviously there are a lot of reasons why you don't think the magnitude is there. Is there anything behind it?
20:00
I don't know. I think — I'm a little bit, again, I think by nature you're learning that I'm on the skeptical side of things.
20:06
Oh, that's a good thing. Yeah. So I'd be curious to see what that article shows, and I don't know so much about the withdrawal or the reasons behind it.
20:14
I'd be curious to follow that story. I don't know if you have some hints or a preview of that right now.
20:20
Mainly a wince. But I think, you know, this makes it so hard.
20:25
There are a lot of Trinetx abstracts at this meeting.
20:28
It's a lot easier to get access to Trinetx now.
20:33
It can be done well, it can be done badly.
20:33
You can get a very exciting headline out of this.
20:38
Yeah, some really great points there, Jiha, about how to navigate this difficult space — and who better to give that advice than Dan Solomon as well.
20:49
Okay. All right. So next, Lisia, do you want to talk a little bit about what caught your attention today?
20:55
From the same session — the rheumatoid arthritis abstract session.
21:00
So I chose abstract number 2934. That's an abstract about discordance between synovial pathology and ultrasound scores in early versus refractory rheumatoid arthritis.
21:11
It's from Milan Smith, and I thought this was a particularly interesting study because it challenged an assumption underlying rheumatoid arthritis management: does ultrasound-detected synovitis always reflect active histological inflammation?
21:29
Or, in other words, are we always treating inflammation when we escalate therapy based on ultrasound findings?
21:38
So I thought this was a fascinating question raised by Melania and her colleagues.
21:44
They compared ultrasound findings with synovial histopathology in 60 patients — 29 patients with early DMARD-naive rheumatoid arthritis and 31 with refractory disease.
21:55
Greyscale ultrasound correlated with histological inflammation in both groups.
22:02
But here's the interesting part: power Doppler correlated with histological inflammation only in early rheumatoid arthritis, but not in refractory disease.
22:12
And even more intriguingly, some patients had high ultrasound scores but minimal histological inflammation.
22:20
Those samples frequently showed reactive tissue with features of proliferative scarring.
22:25
And this raises for me the possibility that persistent ultrasound abnormalities in refractory rheumatoid arthritis may reflect more than active immune-mediated inflammation.
22:37
Of course we need to be cautious — the sample was small, some biopsies lacked identifiable synovium.
22:45
So maybe we have a sampling error — an important alternative explanation for this.
22:52
But the clinical implications are potentially significant.
22:54
So in difficult-to-treat rheumatoid arthritis, we often face the dilemma of whether to escalate immunosuppression in patients with persistent symptoms or imaging abnormalities.
23:05
So my key takeaway is that ultrasound activity and histological inflammation are not always equivalent, and that brings us to a provocative question: are we sometimes escalating treatment against imaging abnormalities rather than underlying biological processes?
23:24
So I thought it was a very provocative question.
23:27
Yeah, I mean, that is a very provocative question.
23:31
Great abstract. So do you believe this? Would you — I guess we've always thought ultrasound is an extension of our hands, sold to us as an extension of our clinical acumen.
23:45
And you see it there on the screen, you're sitting in that darkened room, you see the red come up — it's very hard to ignore that in terms of disease activity, right?
23:57
But maybe not. Would you escalate on now?
24:02
Does this change your thinking? Would you escalate on the basis of a power Doppler signal, especially in someone who's failed a couple of biologics, say?
24:12
No, usually not. So I think specifically this study has several limitations and it's very important.
24:20
So it's very small — as I said, a small sample size.
24:25
The study was cross-sectional, so we cannot determine whether these discordant findings predict treatment response or long-term outcomes.
24:34
And in my practice, I coordinate a cohort of rheumatoid arthritis patients.
24:40
We do not escalate therapy based only on imaging — not ultrasound, not MRI.
24:45
So I really think we have to consider a lot of information, not just the imaging in rheumatoid arthritis.
24:54
And to add to Lisia's point about limitations — I think one of the things that I noted is that they took their ultrasounds mostly from the wrist and the knees, and those are very two different joints.
25:06
And when they saw Doppler signals they noted that it was a lot of extra-capsular, but the significance of those extra-capsular versus intra-articular signals is very unknown.
25:15
The other thing — isn't it interesting? They were more concerned about consistency of the pathology read, so they had three pathologists read per slide.
25:23
However, only one ultrasonographer read those images.
25:24
And there's a lot of, you know, operator variability there.
25:28
So they recognize those as limitations. In fact, I think the author said they're actually working on making two or more ultrasonographers verify so they can get consistent images to verify against and match the biopsy site with the imaging as well.
25:42
So I think even before we get to the clinical implications we need a little bit more solid evidence.
25:47
Yeah, sure. Well, and Jiha, let me ask you: how much do you believe the biopsy correlates with what we should do in terms of therapy?
25:59
How much should that direct us? It's really challenging, right?
26:03
Because again, sampling issues — this was a core needle biopsy.
26:06
And I mean, what was it, a couple of years ago at EULAR where they were trying to do precision-based medicine based on biopsy and looking at chemokine profiles and doing things like that?
26:16
I don't think we quite have the evidence.
26:18
I think we're still at the point where we have disease measures, global measures to go on, and even then when they have that degree and they're reporting — is it coming from the pain, fatigue, function?
26:28
So I think there are still so many things to parse out that it's hard to pin your decision on biopsy alone or even ultrasound alone to make these decisions.
27:06
Yeah. I mean I guess we've had these — you know R4RA and those other studies have really used, tried to use it to direct — to try and understand what phenotype rather than disease activity — and even that is far from absolutely perfect.
27:06
I mean, certainly it's a positive result but far from absolutely perfect in picking your therapy.
27:06
And then in terms of talking about actual active disease, like you say, there are just so many things that might get in the way of that.
27:10
But at the same time, I don't know — should we be doing more biopsies in practice?
27:17
Let me ask both of you that, or anyone else. Minnie, you shook your head there.
27:21
Yeah. I feel like that's a valid shake of the head.
27:25
Why not? No, I think the evidence for — you know, it's an invasive procedure.
27:29
We still don't know kind of how it guides escalation of biologics alongside clinical symptoms and ultrasound obviously.
27:37
And so yeah, I think the evidence is not quite there for routine biopsy performance in clinical care.
27:45
I agree. Not routine. I think for selected patients in very select situations — you know, I think I particularly like it in older adults where they have other reasons for pain, right?
27:57
And it's really hard to differentiate whether that's truly inflammatory.
28:01
And I've had more benefit there than in any other population, potentially for differential diagnosis basically.
28:08
Not for escalation. For example, in our practice in Brazil, we have a lot of infectious diseases — endemic infectious diseases that can simulate in every aspect rheumatoid arthritis.
28:20
Sometimes when we have a very refractory disease we revisit our diagnosis making with the biopsy, but sure, not for all patients.
28:30
But I thought that this abstract was really trying and very provocative.
28:35
So that's because of that that I decided to bring it here. Great choice. Great choice.
28:40
Now I've got one of my own. I've got my phone out so that I can read to you a quote from ACR 2023, three years ago.
28:48
And I remember where I was sitting, I remember the way the light was hitting, I remember sitting there and exactly who got up to sit there.
28:58
This was in the late breaking session at ACR 2023.
29:01
This was data from the molecule that was known at that time as TLL018, which was a dual JAK1/TYK2 inhibitor from China, and it had a head-to-head phase 2 of this molecule — this JAK1/TYK2 — versus tofacitinib.
29:20
And you've got to remember this is in the aftermath of ORAL SURVEILLANCE; everyone's thinking about safety.
29:27
TYK2, obviously — we have deucravacitinib as a TYK2 inhibitor by itself, pretty good safety profile.
29:32
What are you going to gain? It's not something we use in rheumatoid arthritis.
29:37
And you know, on those phase 2 data, TLL018 was absolutely smashing it somehow.
29:44
And Roy Fleischmann in his very dry way got up and said, "This is a spectacular compound, unbelievably spectacular."
29:52
And the suggestion was, well, why don't you go back and bring some phase 3 data, and then maybe we can talk.
30:03
Three years later, they brought the phase 3 data, and it smashes it again.
30:07
So this is fascinating stuff. This is the TYRA study, and the molecule now has a name: gerosertinib.
30:15
It's still the same Chinese investigators, the study is entirely conducted in China.
30:20
And the numbers — the numbers — let me kind of...
30:26
I guess we used to believe in the 60-40-20 rule, right, where ACR 20 gives you 60%, ACR 50 gives you 40%, ACR 70 gives you 20%.
30:38
And those have shifted over time as where we've done studies and background treatment has changed.
30:47
But we're talking ACR 20 91% for gerosertinib versus 75% in tofacitinib.
30:53
ACR 50 73% instead of 49% for tofacitinib.
30:56
And then ACR 70 44% versus 25% for tofacitinib. The safety profiles are very similar.
31:04
This is an appropriately sized study — 229 in each arm.
31:13
There are some limitations. I think one of the ones that's pointed out previously and now is that just having a previous tofacitinib failure did not exclude you from the study.
31:23
So you could have had an inadequate response to tofacitinib and then get randomized to tofacitinib again here.
31:28
Still the numbers are very high, but that may reflect the population they were taking from.
31:35
I think one of the controversial criticisms — which is sometimes said out loud, sometimes whispered — that I don't necessarily have an answer to, is how relevant are these data, all from China, for our patients who are not in China?
31:51
And I think we haven't seen as much of this in rheumatology, but I look at my oncology colleagues for example, and the rate of research development that's happened in the last 5 years in China — the way they can turn around studies in oncology particularly is incredible.
32:10
There's just a volume that they've got, and I guess there's been some greater confidence in the way that their clinical trial infrastructure has developed over that time as well.
32:21
So the headline is super impressive. We also have a JAK1/TYK2 inhibitor in the form of brepocitinib now as well, and I guess there's a question as to whether that should be part of a rheumatoid arthritis development pipeline or not.
32:35
But I'm really interested in what all of you think about whether this is something that's actually going to enter our clinics, or whether this is just going to be a little asterisk in the history of late breaking abstracts at ACR.
32:46
David, I have a question or a thought on the China-based criticism.
32:52
Like, do you think that's coming out of a question about generalizability to our patient populations, or is it some perception that the regulatory or trial processes are not up to scratch in China?
33:07
Because I mean, I don't think either of those things are particularly valid.
33:12
Especially after vamorolone, we really shouldn't be criticizing other parts of the world saying they can't do trials properly.
33:20
And the generalizability — I might think differently if it was this molecule against placebo, but they're comparing two JAKs.
33:27
I find it really hard to believe that a different patient population will see markedly different responses to different JAK inhibitors.
33:37
I think those are the questions that we're all thinking, and we're very conscious — we should be very conscious — about not discriminating against data just because we didn't come up with it.
33:54
I think there are arguments on all sides.
34:00
We perhaps don't have exactly the same transparency into what happens in China at the same time, and we're far from faultless in studies run out of the US and Europe and elsewhere.
34:17
Has anyone got any other thoughts? Would this be something you'd use in practice?
34:21
I may have missed it, but was there anything much about long-term safety?
34:28
So I mean we only have the clinical trial data here that goes out to 24 weeks.
34:34
The safety was similar between tofacitinib and gerosertinib.
34:40
There was only one venous thromboembolism, which was in the tofacitinib arm.
34:44
In that short period of time there was no malignancy or MACE.
34:50
And I think importantly in a Chinese population you might have a moderate background risk of opportunistic infection and tuberculosis, and we did see one opportunistic infection in the gerosertinib arm and none in the tofacitinib arm, and no TB at all.
35:10
So from that side of things it's a short follow-up.
35:14
And this is not the cardiovascular-enriched population that we saw in ORAL SURVEILLANCE.
35:18
We're far from getting to that level of data.
35:22
I think people will want to pore over the full data properly in a full paper, which I think is another one of the critiques of this whole situation.
35:31
And I guess the question will be as well: will the FDA or the EMA or other correlating jurisdictional regulators accept these data in and of themselves?
35:45
Big questions. I don't think they will. They're going to want a western-world study to support it, I think.
35:52
For sure. For sure. They fall back on the kind of two-trial thing that the FDA are increasingly wanting.
35:59
Did either of — what you said about the tofacitinib failures — do you know, did either this study or the previous one — did we ever find out how many patients actually failed tofacitinib?
36:10
No, not that I'm aware of. And I think that's a very interesting question.
36:14
There was a bit of a question as well about — I think where upadacitinib sat on that — and I think in one of the other questions they dealt with that, about kind of trying to understand and stratify that out.
36:31
They said that in terms of that it was broadly the same between the groups, but once again, I mean, you have to think that that is a detail we would like to see, and that if it were any study going to the regulator, they would certainly scrutinize that.
36:45
So we're going to — but at the same time, if I had a therapy where these numbers were real and it was available to me in practice, it would genuinely change the game.
37:01
So yes, we will see. Maybe in two years' time we'll be talking about more data.
37:06
Maybe sooner. Maybe this year — 2026, three years from ACR 2023.
37:12
That's right. That's right. It has some beautiful symmetry to it.
37:16
Let's do some quick-fire around the group here.
37:18
We'll go in the same order. Minnie, I think you've got a good one.
37:22
So fire away. So I've got 2942. So we've seen a lot of GLP-1 data at ACR 2026.
37:29
So this was a highly anticipated TOGETHER-PsA study.
37:33
52-week data, phase 3, randomized open-label trial, just over 270 patients with active psoriatic arthritis with obesity or overweight, comparing ixekizumab with tirzepatide versus ixekizumab alone.
37:50
So at one year essentially it was just under 45% of patients receiving the combination who achieved ACR 50, compared with 15.7% on ixekizumab alone.
38:00
So obviously quite a wide percentage-point difference there.
38:04
Also improvements in physical function, weight, metabolic outcomes.
38:08
There was discontinuation because of adverse events, but those were comparable between the two groups.
38:16
So yeah, another abstract showing the role of obesity treatment in the management of PsA as a whole, which we have talked about previously on previous ACRs and EULARs as well. So yeah, positive data.
38:29
Yeah, fantastic — really exciting to see that kind of benefit sit there.
38:35
Richard. So I have 2931. This is a rituximab study.
38:40
And this interested me because I use a lot of rituximab in my practice — I specialize in ILD and vasculitis, so we are heavy on the rituximab.
38:50
And this kind of reflected what I see in my own practice.
38:52
So this was looking at repeated cycles of rituximab and how that affected gamma globulin — so causing hypogammaglobulinaemia.
39:02
And essentially, with this very long follow-up out to like 30-40 cycles of rituximab, what they found is there was this slow steady decrease in IgG over time.
39:16
And ultimately, the lower it went the higher the infection risk was.
39:19
And I think that's something we do see, and it kind of reminds us all that these patients — some of them can be more and more at risk of infection the longer they're on rituximab.
39:29
And also if you stop rituximab at some point, it can have a very persistent effect even after it's been stopped for years sometimes.
39:39
Yeah, absolutely. Great point there. Jiha, so I have a fun one.
39:47
This is abstract number 2965. We were talking about injections earlier, and we've all probably learned from simulations and things like that.
39:52
This is a simulation for patients on how to teach them to do a joint exam, because we know there's a lot of discrepancy between what we do and what patients report — particularly when it comes to swollen joints, right?
40:03
Tender joints we rely on patients, so that's not the issue.
40:04
And in the admin — I don't know about you, like 25% of my clinic is still virtual.
40:08
And it's interesting trying to say, okay, press on your hands, which one hurts, trying to get a gauge of the disease activity.
40:14
What's awesome about this is a really cheap, low-fidelity way of doing it.
40:18
So they got a skeleton, put some Play-Doh or Mod Podge on it and then covered it with latex gloves to simulate what a swollen joint would look like.
40:27
And so they gave it to patients with video training and then basically taught them how to do a joint exam.
40:35
And what's awesome is that it's small — right now they've tested it in 17 patients — but their confidence skyrocketed.
40:41
Like only 6% said they were very confident before; now 25% say they are.
40:45
And in terms of just the confident group, it went from 25 to 56%.
40:49
So like three-quarters of the patients are now saying they're very confident in measuring their swollen joints.
40:54
So I thought it was really patient-empowering, a really accessible way of doing things, and just a really fun way to bring patients into the whole process of the care continuum. So I thought it was really cool.
41:06
That is a fun one. But yeah, I mean we spend so much time trying to learn how to detect synovitis — that seems like a fun way to help our patients. Lisia?
41:18
I chose abstract 2933. That was about large-scale plasma proteomics that identified orosomucoid 1 as a circulating predictor of difficult-to-treat rheumatoid arthritis.
41:29
I thought it interesting because the question is: can we predict difficult-to-treat rheumatoid arthritis years before it develops?
41:40
So they studied large plasma proteomics.
41:43
They screened 270 proteins and identified five potential biomarkers, and orosomucoid 1 emerged as the most promising candidate.
41:55
The samples were collected years before difficult-to-treat classification, suggesting that orosomucoid could really help identify patients at risk of difficult-to-treat rheumatoid arthritis earlier in their disease course.
42:09
But I think there's a very important question: orosomucoid is an acute phase protein.
42:17
So is it identifying a specific biological pathway associated with treatment resistance, or simply reflecting persistent inflammation?
42:28
So I think there's a bias there, but it was a very interesting study of molecular biology.
42:33
Oh, that's fascinating, and you can imagine how that might flow through into practice.
42:37
That's cool. I — my quick one — there was a temptation to talk about biomarkers in combination therapy in the AFFINITY study, or there
42:59
was a really interesting study from Germany about how large language models might help us in trying to figure out everyday practice things — the
42:59
answer being: just slightly quicker.
42:59
But actually I'm going to talk about something not from the conference itself but that came out this morning as breaking news.
43:04
So this is actually — you might have heard — that there have been some real issues with Novartis's CAR-T product Raphal — Raphael — um, there were three deaths reported.
43:14
It's really coming out in the news this morning.
43:16
Gay Ghahramani has commented on this. Novartis is still running their investigation and no details have come out.
43:24
And he said, and I quote — here's my phone again — "This is very sad for the community," and that they've tried to piece it all together, and that they're going to submit — they've submitted, sorry — an article to the NEJM to discuss this.
43:42
So I think this story is far from over. I do feel a bit sorry for Zel, which did present a late-breaking poster yesterday and had the news come at the same time — but a very different problem, and I think one that's very workable.
43:57
Thank you all for joining us on these daily recaps.
44:02
Four wonderful panelists here today — Minnie, Richard, Jiha, Lisia — thank you so much for your insights.
44:09
It's been a great discussion, and thank you to you listeners out there for hanging on throughout our ACR Convergence coverage.
44:18
I may not be as witty as Roy Fleischmann, or indeed anywhere near as wise as Roy Fleischmann, but hopefully I've helped you ask the right questions as well.
44:27
So thank you so much for joining us and make sure you catch all the rest of our coverage. You know where to go — RheumNow.com.
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