ACR 2024 Preview Podcast (11.15.2024) Save

Hey, everyone. It's 11/15/2024. That's right. It's the day before ACR opens tomorrow, Saturday the sixteenth in Washington, DC. I'm going to be at ACR Convergence along with many of the RheumNow faculty reporters and prospective videographers who will be reporting on the meeting and things that we like, things that we think you need to know.

You can follow us daily. We'll be doing emails twice daily that will direct you to the content, the written content, the tweets, the videos. If you're a RA person, sign up for the RA week, weekly email. You'll get an end of week, end of ACR email, all the RA content. Same thing for PSA and anti rheumatic and drug safety and SPA and lupus, etcetera.

Okay? There are a lot of ways to learn ACR content from RheumNow. You know, we recently did a survey of 450, rheumatologists, 60% from United States, the rest were ex US. And we asked you, the rheumatologist, of all the things that we do at RheumNow, what's your favorite? And I was shocked to see that number one on the list was RheumNow's coverage of ACR and EULAR.

Rated as highly as the weekly podcast, which many of you also seem to like. So I think that we're doing something right. I just shot a video that you can find on the website about how to master and conquer the ACR in a new and digital way. It's basically the RheumNow model that we use. Today, I want to cover again, ACR convergence twenty twenty four, and give you what I feel is the ACR p preview.

A few abstracts that I think are worth looking for and learning from. And, and then a few other bits of guidance on what sessions you should be attending if you're gonna be at the meeting, either live on-site or even virtual, because they are doing virtual this year. So my first one I wanna talk about is, a Sjogren's abstract. It's abstract number two five two seven. It's the efficacy and safety of nipocalimab, a, neonatal Fc receptor monoclonal antibody in patients with primary Sjogren's.

This is a phase two multi center trial called the DALIA study. This became the basis of this week, the FDA granting breakthrough status for, NIPO, I'll call it Nipocalimab, and it being used in Sjogren's syndrome, okay? Adults with Sjogren's syndrome. This is a phase two trial, that was done in patients with moderate to severely active primary Sjogren's syndrome. It was one hundred and sixty three patients who enrolled and were randomized to either receive, Nepo or placebo.

And when you compare the groups, they were the same going in. But in the end, I think the week, the endpoint was here, week 24. It was the Nepo group at fifteen milligrams per kilogram, that had the best performance on its endpoint was towards was the s SPRE, I think it was, the Sjogren's endpoint, where the data was, actually the primary endpoint was the difference from placebo and least square mean. So it was greatest, obviously, for the drug. You're gonna have to look at the data.

I didn't write it down right. But the bottom line is it led to significant improvement in the, clinical SDI score. That's the primary endpoint in the study, at week 24, and the drug was well tolerated. Again, this is remarkable because generally nothing works in Sjogren's syndrome. And I've been saying that for years.

This is now a phase two trial, and it looks like this may work. We've got a lot of drug studies coming up, a lot of companies working on drugs for Sjogren's syndrome, and I think that's a great thing for us rheumatologists who manage this. The other abstract I want to talk about is, abstract number nine eighty nine, the malignancy risk between JAK inhibitors and TNF inhibitor therapy across multiple indications. It's a network meta analysis, 196 studies over 123,000 patients, one hundred 33,000 patient years of exposure. They took all the data, reported data, in phase two, phase three, and phase four, placebo controlled randomized trials, and even long term extensions.

And when they look, and these are patients who got either a JAK inhibitor or TNF inhibitor, regardless of the indications. That includes RA, psoriasis, psoriatic arthritis, axial spondyloarthritis, and IBD. Overall, they showed that TNF inhibitors was associated with significantly lower risk of malignancy compared to both JAK inhibitors and compared to placebo. Now that's important because that's kind of the story behind the oral surveillance study. Not that JAK inhibitors had more cancers, but that TNF inhibitors were better at preventing cancers.

That's been shown in multiple studies, going back for multiple years. But in this network meta analysis, they're comparing, TNF rates to both placebo rates, and it was lower, and also to JAK inhibitor rates. No difference between placebo rates and JAK inhibitors. So that's really another important point. The other important point, I think, had to do with whether you included skin cancers, non melanoma skin skin cancer, or whether you looked at hematologic malignancies, and some of the same trends we're seeing here.

But again, I, there's awful, I get a lot of questions, from the audience about what do I do when a patient who's got cancer? The ACR guideline from 2021, I still think it's the best guideline that says, if they have a solid tumor, treat them as if they didn't have a solid tumor, treat them with whatever you want. TNF inhibitors, they do very well. Yet the old data, the old recommendations on cancer management was stop the TNF inhibitor. That's so wrong.

That's, I mean, I've never done that, okay? My next abstract is a late breaking abstract, L16, dapirlizumab pegol being used in patients with systemic lupus. This is a phase three study that's going to be presented on Tuesday, November 19. And daprolizumab is basically a fab fragment linked to a polyethylene glycol, moiety for durability and half life. And this targets the CD40 ligand.

For CD40 ligand, it's involved very much in co stimulation, is very much involved in a lot of what ails lupus and other diseases for that matter. This is a phase three trial in patients with moderate to severe SLE. The number of patients in the study, think was one hundred and seven, and patients either received placebo or daprolizumab, for forty eight weeks. The primary endpoint in the study was the bilag responses. I think it was a Bicla.

Bilag, so no, it was a Bicla response at week forty eight, and that was significant at p point zero one. So they, everybody in the study was on standard of care, and half got placebo and the other half got the anti CD40 ligand, and Biclo response was achieved in fifty percent of patients on dapro, and thirty four-thirty five percent on placebo, and that was significant, okay? Side effects looked to be nothing big. There was significantly less flares in the patients that were getting the investigational dubbed dupirozumab. And again, altogether, it looked like a successful trial.

There was one small caveat though, that I will need to go by and look at what the data was, but there were more opportunistic infections with the CD40 ligand inhibitor at two point eight percent. And that is like three times the amount seen in placebo population, zero point nine percent. So I need to see what were the opportunistic infections. Again, this is a, an early, phase, I think I said it was a phase two trial. And, you know, we need to probably see more studies on this to know what the true safety of this is going to be.

But nonetheless, I think this is I'm sorry, this is phase three trial. So this has been, we've reported in the past about dupirilizumab, also showing success in lupus in other trials. So that's good news, I guess. The last abstract I'm going to cover, I think is an interesting one. It's an abstract about abstracts.

It's abstract thirteen fifteen. It's a poster going to be presented by Sherena Gandhi on Sunday, November 17, at the Poster Hall, poster session B. What they did in this was that they looked at all the posters presented at ACR twenty fifteen, sixteen, seventeen, and eighteen, and they determined the fate of that presentation. Meaning, should I really pay attention to any of posters or any of these plenary sessions? Because do they ever make it to publication?

Maybe they don't. So what they did find was, a total of, let's see. It says here, 1,658 abstracts or 55% from 2015. And 1,625 or 56% from 2018 were published within nine or six years respectively. So almost 60% of the abstracts are ultimately ending up in publication.

By the way, that's all abstracts in those years, and it was kind of consistent from year to year. However, plenary session is different. If you are a plenary session, the rates of of of ultimate publication was ninety four percent in twenty eighteen, eighty one percent in 2015. That's pretty impressive. Also, concurrent sessions, again, are podium presentations, also had a higher likelihood, sixty seven percent versus, and fifty five percent 2015 and 2018.

So, the good news is that the majority of the abstracts that you'll review at ACR will be published, more so if it's a plenary. Also, a little bit more likely if it's a podium presentation and a concurrent session about RA, or a podium presentation, for instance, like late breaking abstracts. I think that that's worth noting. You know, I got another one. I I got an interest in seronegative RA, and the Mayo Clinic has a really strong, abstract.

There's a poster. It's abstract number four, five, eight from the Mayo Clinic on Saturday. Long term outcomes of seronegative RRA patients. They're going to tell you their eleven year follow-up of one hundred and seventy six patients have complete data on. One hundred and seventy six patients who are seronegative RRA for both RF and CCP.

Almost seventy percent were female, a median of eleven point eight years of follow-up. The story is that thirty two patients out of one hundred seventy six had a change in diagnosis. Forty percent went into remission drug free, not forty percent, forty out of the one hundred seventy six, that's about twenty five percent, went into drug free remission. And thirty ultimately needed a biologic or targeted synthetic to treat their disease. So the ten year cumulative incidence of a change in diagnosis was fifteen percent.

The ten year cumulative incidence of being in drug free remission was twenty seven percent. And the ten year cumulative incidence of going on to DMARR, advanced DMARR therapy, nineteen percent. It didn't matter whether these seronegative what criteria were met amongst these seronegative patients. Right? And the ones that went on from being seronegative to having some other diagnosis, what do they have?

Eleven had spondyloarthropathy, six turns seropositive RA, five OA, three crystalline arthritis, three CTD, that's a non diagnosis, one infection related, one paraneoplastic, one RS3 PE, if you believe in remitting seronegative symmetrical polyarthritis as a diagnosis, and one sarcoidosis. Ronan Kavanaugh said a long time ago that something he learned from a colleague, every time you see a seronegative is your opportunity to rethink the diagnosis of that seronegative. This says that it pays off at least fifteen percent of the time. Some other reports say it pays off as much as 30% of the time if you follow people going out further. Some of those stay seronegative, some will be other things.

All right, what should you be seeing? I strongly recommend the year in review. That's on Saturday, November 16, Hall E, 07:45 in the morning. Get up early, show up. It's going to be Michael Pillinger in a in a pit match against Lou Bridges.

Michael Pillinger from NYU is going to be giving you the year in review highlights from the clinical spectrum of rheumatology. And then, Louis Bridges from Hospital for Special Surgery is going to be covering the basic science advances in the last year. I'm going to be there. I hope that you're going to be there. The next big thing on Saturday, starting at 09:15, is the plenary session.

It's, an hour and a half. It's got a whole bunch of stuff. I like the first one. It's, data was presented at EULAR. It's the SELECT GCA study.

It's abstract seven seventy, the safety and efficacy of upadacitinib in patients with giant cell arteritis, the results of a phase three double blind randomized controlled trial. I think you'll like that study when you see the results. At 1PM, the FDA is going to update a very large audience of rheumatologists about safety issues that they've dealt with in the last calendar year. This is always a big thing. It's a product of the Drug Safety Committee, headed up by Michael Weissman, and then previously by Artie Cavanaugh.

Used to be on that committee. This is something they started a number of years ago. It's very popular at the ACR. Two thirty Curbside Consults. I don't if you've ever gone to one of those.

They get, an interesting case presented by a KOL, and then they get a discussant. I've done it once. And they don't tell you the diagnosis, but they make you go through it almost like the New England Journal CPC. And then there's voting by the audience before and then after, and you get to convince the audience that you're right and whatnot. It's kind of a fun clinical session.

I recommend it. Sunday, plenary session again at 9AM. You may want to be there. One of the leading abstracts, I cut off the numbers. I think it's four forty two.

It's eight forty two, probably. Eight forty two, urinary biomarkers predicting the histopathology in lupus nephritis. Again, a hot item in the last two years, at our meetings. Also, abstract eight seventy seven, zazocitinib, another, TYK2 inhibitor, being studied, and this is a drug from Takeda. It looks like it seems to be effective.

And then abstract 08A2, Brepocitinib, a selective TYK2 JAK1, being used in dermatomyositis. A clinical trial of dermatomyositis with a JAK TIC inhibitor. What? Be there. I think it's going to be cool.

They also are going to cover in that session, treat the target as a rationale for better outcomes in RA patients who are pregnant. Really good data. Later on in the morning, the Klemper Lecturer is going to be from a real giant at the NIH and in the auto inflammatory and pediatric rheumatology community, Raffaella Golbakmanski is lecturing at 10:30. The Klemper lecture, where she's talking about children with rare auto inflammatory syndromes, and recent things that have been learned in their research at the NIH. At 1PM, I like this great session on synovial fibroblasts, in RA.

You know, that's where all that's the one thing we're not treating. That's where all the damage comes from. We need to understand what's going on here. It's going to be at 1PM. The lecture is going to be by Nunzio Bottini from Cedars Sinai.

He's going to talk about synovial fibroblasts in RA. It's in Room 145 AB. 1PM is Knowledge Bowl. It's the final round. I must say, I've never had the time to go by this, but I know people religiously go to this and love it.

And then the next great big session that I started many years ago, The Great Debate, It's at 03:30PM. They're going to have a great debate on, drum roll please, MCTD. Really? Didn't you see my dead Rheumatology Word Society video where I said MCTD is a dead word? Well, Lisa Lisa Christopher Stein is going to argue in front of in favor of MCTD, and she's from Hopkins.

And Peter, is merely from NYU is gonna argue against the use of MCTD. I'm Peter, I'm on your side. And although I like Lisa, she's great in everything she does. I'm sure it's going be a great session. Monday, the third day, begins with a 9AM plenary session.

This is where they're going to present that, DALIA data on Nipocalimab, in Sjogren's syndrome. They're also going to present abstract 2,532 about, mortality in, autoimmune patients who get checkpoint inhibitor therapy. Whoo, what does that mean? Is it up? Is it down?

You're going to have to show it, show up. I'm not going to tell you here. At 10:15 is the long awaited ACR twenty twenty four guidelines on the diagnosis and treatment of lupus nephritis. Oh, this is going to be a good one. We got lectures by Lisa Samaritano from Special Surgery on guideline development and key recommendations.

We've got, Maria Dallara, talking about, the updated guidelines in various classes of lupus nephritis. Maria from UCSF. We've got Anka Eskenazi, she's a nephrologist who's going to be talking about applying the guidelines to membranous nephritis. And then we're going to have guidelines addressing pediatric lupus nephritis from Mary Besson. I think it's going to be a fabulous session.

You better get there. That one's going to sell out. It's going to be standing room only. So that's on Monday. Tuesday, as you know, is a half day, 8AM, late breaking abstracts.

I think you want to be there. That to me is one of my favorite sessions. It's a two it's almost a two hour session. It's an hour and a half session, eight, 08:30, 09:30. And then sort of like the clinical year in review, Grace Wright and Christopher Richland will tell you about some of their favorite abstracts from this meeting to wrap up the meeting.

So I hope I see you at ACR. If not, follow RheumNow and enjoy our coverage. And we'll be back on the podcast next week where I'm going to give you my big ACR overview. Other things to look for in RheumNow's coverage every day, starting Saturday, Sunday, Monday, Tuesday at 6PM. We're going to live stream the day one recap report, the day two recap report.

And it's either 6PM or 7PM Eastern Time. Check on, on the RheumNow website. Those are great discussions with the faculty, right? That's every day, we're going to recap the highlights of the day. And that's at the end of your day if you're at home.

After we get back from the meeting, we're going to have our topic panels where we'll have the lupus faculty talk about the lupus highlights, the RA highlights, PSA, SPA, IL-seventeen, and Jack. We've got a lot of different panels. And then, next Friday, Artie Cavanaugh and I will do the famed Rheumatology Roundup, where we give you our best of the best meeting. Take care, enjoy.