ACR24 - IL - 17 Save

Hi, everyone. Jack Cush. I'm on the floor of the ACR Exhibit Hall. It's ACR convergence twenty twenty four. We're in Washington DC.

This is day one, morning one. We're excited to be here. Looks like a lively meeting. Lots of folks, lots of buzz. The exhibit floor and our booth is really happening.

If you're here at the meeting, come by, visit us. We'd love to meet you. Say hello. Give you one of the new RheumNow pens. Hope you like that.

I wanna talk to you about what I think you should be doing and what's new at this meeting. You know, the meeting is is really the same meeting. Right? It's face to face and that's what people want. Some things are new.

And we have the same old sessions, the great debate. This morning they had the the year in review. We're gonna have knowledge bowl and other highlights including a wrap up at the end. But plenary sessions are have flipped. They're in the morning at 09:00, and the posters are beginning right about now at 10:30.

So that's something that's new. I think for you watching this video, how am I gonna learn the ACR? I'm gonna give you a few pointers that I think you should pay attention to. Number one, come to the meeting. See us at the booth.

Go to your favorite sessions. Number two, if you're at home, I'd recommend that you follow us on Twitter. On Twitter, you're gonna get this constant stream of information and what's happening really right to the minute. And it's almost like watching a ticker tape of what's going on at the meeting. I think that's kind of exciting, but maybe you're not a Twitter person.

And maybe you want to get a feel for what happened at the meeting. I'm gonna give you three ways that you can do that. Number one, that is at the end of every day at 6PM eastern time. We're gonna livestream the daily recap where it's gonna be me and three or four of the faculty And we're gonna review the happenings of that day and what was notable, exciting, and something you wanna take home. Number two, starting next week when you get home, you can view the video that's gonna be called the lupus topic panel or the RA topic panel or the PSA.

We have topic panels with me and four experts in lupus, RA, etcetera, and we're gonna do RA, PSA, SPA, lupus, JAK inhibitors, TIC inhibitors, and IL seventeen drugs. And so that's like six different videos that you'll be able to look at. And the third way that makes the most amount of sense is this go to the RheumNow website and you might already subscribe and get a daily email or a weekly email. But if you're an RA person or a lupus person, we have an email list and you can sign up, check the box. I want the topic email list that'll come out once a week.

And if you check the box on whatever topic you like, you're gonna get an email after ACR and all the lupus stuff that we produce. So you'll have that in your inbox to review. By the way, everything I just said that's in video form will also be in podcast form. You can listen to the daily recap podcast. You can listen to the topic panels in a in a podcast.

And you can also listen to podcast, accumulated podcast reports from all our faculty who are here covering the meeting for you. Hope you enjoy this meeting. I'm going to. We'll talk more.

Hi, this is Eric Dine from ACR Convergence Day three. Here's what I'm looking forward to today on our last full day in Washington, D. C. I'm looking at the IL-seventeen data. There's a lot of information about some of the new medicines like bimekizumab and also some data about some of the older medicines like secukinumab.

We know that one of the benefits of IL-seventeen is its efficacy on enthesitis. One of the abstracts being presented today is 2,586 looking at the tissue effects on an in mesial tissue. The EBO study is looking at minimally invasive ultrasound guided biopsies of enthesitis, particularly looking at the lateral epicondyles of patients with active enthesitis. What they do is they established a baseline ultrasound guided biopsy and then they repeated it after at least three months of being on fecacitinib therapy. They had 10 patients enrolled in the study.

They had nine of them that they got the secondary biopsy to complete a before and after. And found what was they found that there was definite improvement in that tissue inflammation in the amphesus after initiation initiation of of the the IL-seventeen inhibitor. They found that neutrophils, CD4 plus T cells and IL-seven was decreased with a particular benefit of the IL-17A fractions of cell types being decreased in patients on an IL-17A inhibitor. So this is very useful information. They showed major effects on the transcriptional states of the resident endothelial cells.

So it's good to see in practice, in actual data in the tissue, to see that when we give an IL-seventeen inhibitor that we see that inflammatory response actually decreasing in the target in those entheses. So definitely great data to show that our agents for IL-seventeen are helpful for addressing our active enthesitis. Lots of great coverage here at RheumNow. Stay tuned for more information.

Hey everyone, it's Brian Jaros here. I'm reporting live from ACR convergence twenty four here in Washington DC. Today I'll be telling you about abstract number seventeen fifty six. Now this is an abstract, that's being presented with the ankylosing spondylitis therapy group. It's out of, a group from Europe and their question is really interesting.

They're looking to see whether patients who were previously exposed to TNF therapy had longer times to remission when they used another TNF inhibitor or an IL-seventeen inhibitor compared to those that had never been on TNF treatment before. And in order to do this they had a very clever design where they used a bunch of registries from across Europe in order to really gather a strong pool of patients to help answer this question. And I think this is a really important question to ask because our most recent guidelines out of EULAR and ASAS suggests that after failing NSAIDs, either TNF inhibitors or IL-17T inhibitors in addition to JAK inhibitors may be used for refractory symptoms, not providing specific guidance whether TNFs are preferred first or IL-seventeen agents are preferred first owing to a lack of head to head data about these agents. And so this study might be interesting to tell us a little bit more about patients who fail TNF inhibitors first line, whether it's beneficial to class switch and go to a different agent like IL-seventeen or to stick with the TNFs. So let's get into the data of the study.

And so as I mentioned, they used about 13 registries. They excluded patients who had been on other biologics besides TNF inhibitors or IL-seventeen inhibitors and their primary outcomes were the time it took for the patient to achieve low disease activity or I'll refer to it as LDA and they defined this as an egg spa disease activity score of less than 2.1. The other primary outcome was looking at durability and so once people achieved low disease activity, how long did they stay in low disease activity until a subsequent visit where they became active? So in total they had over fifteen thousand patients who initiated TNF inhibitors and over 2,000 patients who initiated IL-seventeen agents, largely with similar baseline characteristics between the groups, although with more biologically naive patients in the TNF group. And the results are really interesting.

So they showed that the mean time to achieving LDA or low disease activity increased based on the number of exposures patients had had to TNF inhibitors previously. It was shortest if they'd never been exposed before and that was around an average of thirty three weeks for the TNF agents and thirty seven weeks for the IL seventeen agents, and increased all the way up to 51 and forty six weeks respectively if they'd used two or more agents. In some ways this is not surprising. It might suggest that people who have failed a previous treatment have more refractory disease or a more severe phenotype in general, but it was interesting that both TNF inhibitors and IL-seventeen inhibitors suffered from this delayed LDA in those that had tried just a TNF before. Now, the other outcome that I mentioned was the duration of the low disease activity.

So how long it actually lasted once they achieved and this finding was even more interesting. It showed that the patients who were switched to IL-seventeen therapy actually had a shorter durability of low disease activity in the patients who had previously trialed TNF inhibitors. And this was different than the patients who were prescribed a new TNF inhibitor and actually maintained durability. And I thought this was quite surprising. Know, oftentimes we think about patients failing agents and the idea of class switching, which is switching to an agent that has a different mechanism with the idea of trying to target inflammation, to target different disease from a different way.

But this study actually suggested people who stayed in the same class, stayed in TNF inhibitors performed better in terms of staying in that low disease activity. So in some ways this gives us a little bit of insight into maybe using additional TNF inhibitors before switching to IL-17s but I think it also is one of those studies that actually raises more questions than maybe it gives answers. It'd be really interesting to see if the group went back and sorted these people from primary failures, which is, you know, no response to the TNF up front versus secondary failures where they responded to the TNF and then had a, you know, wearing out effect over time to see whether the class switching to IL-seventeen had a more profound effect in those with secondary failures since this is something that we often think about when we're making our clinical decisions in practice. That's all I have for you today. Tune into RheumNow for more.

This is Catherine Bakewell. I'm reporting to you today, 11/18/2024 on the best thing that I saw today in psoriatic arthritis at ACR. Today, I'm actually gonna take you on a rapid fire tour of several different abstracts that I found really exciting. I wanna start with this one, which is two five eight three, and it's titled Apremilast Reduces Axial Inflammation in Patients with Psoriatic Arthritis as assessed by Candon MRI Scoring Results from a Phase four Study. So what is very exciting about this trial is that Apremilast has not been considered for axial disease.

It's one of the things that we say absolutely new in ankylosing spondylitis, and we're considering it now, though, potentially effective in axial psoriatic arthritis because of the results of this phase four trial that demonstrated by the CANDON MRI scoring system, which is a very detailed anatomy based comprehensive scoring system for inflammatory lesions, pardon me, both at the vertebral bodies and at the posterolateral elements, demonstrated significantly reduced inflammation at both twenty four and forty eight weeks. So this may change the way that we think about a cremolast in this domain. The next abstract I want to highlight is this 2584, which is looking at a new agent, TAC-two seventy nine, an oral selective TYK2 inhibitor, and it's entitled Achievement of Remission and Additional Improvements in Disease Activity in Patients with Psoriatic Arthritis Enrolled in this Phase two b trial. This element or this new novel agent, this tac two seven nine, did demonstrate higher rates of remission and low disease activity as assessed by both DABSSA, PAZDAS, and DAS twenty eight CRP at twelve weeks, and we'll move forward now to phase three. So excited to see more on that.

The next one is twenty five eighty two, which is efficacy and safety of sonolocumab, a novel a novel IL 17 ANF nanobody. These are the little bitty tiny antibodies, potentially better tissue penetration and lower vascular areas like the enthesis. This was active psoriatic arthritis, twenty four week results from a global randomized double blind placebo controlled phase two trial. This is Ian McGinnis. It had very nice looking results with ACR 50 scores up in the sixty percent at twenty four weeks, which again is not normally what we see.

No unexpected safety signals again moving forward to phase three trials. Fantastic. Next abstract is going to be twenty six thirty eight, defining sonographic enthesitis in psoriatic arthritis, developing a data and expert driven diagnostic criteria for the inflammatory enthesitis at the single enthesus level. This is Andre Riviera. What I can tell you about this trial is that they were dialing down on what increases experts said, like, confidence that what they are looking at ultrasonographically represents enthesitis in arthritis and the results were that a two plus power Doppler very important or four or more elementary lesions so that would be hypoechogenicity plus thickening plus enthesophyte plus Doppler one plus for example.

Enthesophyte is not specific seen in the healthy population, so the heel spurs, as we all know, it's not going give you a diagnosis of spondyloarthritis. Last abstract for you today, 2635. This is Doctor. Jessica Walsh's group out of the University of Utah, Direct to patient screening for psoriatic arthritis patients with psoriasis. Appropriateness of rheumatology referrals and treatment outcomes.

This is important because she mailed out surveys to patients with a psoriasis diagnosis, asked them to undergo the PEST screening questionnaire, and they self referred to rheumatology for a positive PEST screening. Questionnaire. About a third of patients got a new psoriatic arthritis diagnosis, really underscoring how exciting this is as a method of finding these psoriatic arthritis patients in the community. So with that, that's all I have for you today. Thank you for your time and attention.

Hello, everyone. Leahy Heather here from, the University of Toronto reporting from RheumNow. This the abstract that I decided to present today, number 603, cycling versus switching after first failure of TNF inhibitors in patients with axSpA. So this is a very relevant question to us because of the limited options that we have. This is a study from a big check registry that evaluated patients who failed their first TNF inhibitors, and they evaluated whether persistence on a TNF inhibitor versus IL-seventeen inhibitor is better in one or the other.

The bottom line is that there is really no difference. The retention was similar for TNF inhibitors and IL-seventeen inhibitors, but uniquely there was a difference in response. So the study did have information about ASDAS in response to treatment, and they showed some superiority of TNF inhibitors compared to IL-seventeen inhibitor. On the other hand, there was a little bit of more safety issues, including severe adverse effects in the TNF, inhibitor group compared to the IL-seventeen inhibitor group. So even though the retention was similar, there were some differences in terms of efficacy and safety.

So I think for us as clinicians, both options are available, either switching to a different mode of action or staying within class of TNF inhibitors, but we obviously need to take into consideration issues like safety, and some patients might benefit from IL-seventeen inhibitors if safety issues are a major concern. Personalized treatment still remains intact until we have biomarkers that could help us predict response. Thank you.

My name is doctor Philip Meese. I'm a rheumatologist from Seattle, Washington and director of rheumatology research at Providence Swedish Medical Center in that city. I'm delighted, to report on an abstract about bimekizumab. Bimekizumab is an IL-17A and F inhibitor that has been previously approved in the treatment of psoriasis in The United States and has recently been approved for the treatment of psoriatic arthritis and axial spondyloarthritis. This abstract reported on major patient reported outcomes that are of great importance to patients.

One, of course, is pain, but the other is fatigue. Fatigue ends up being a big deal to our patients partly because it is a phenomenon that occurs in an increased amount in inflammatory diseases and it has central brain mechanisms and can be improved by treatment of the underlying immune disease. And thus, we saw both in pain and fatigue very significant improvements in the both biologic naive population or B optimal and the B complete trial, which is in bio experienced patients. So for example, improvement in pain. One of the ways in which pain results are reported in the pain literature are 30% or 50% improvement in pain.

30% being something that the patients can tell and is meaningful and 50% being a really significant improvement in pain. And what was shown was that about sixty percent of the patient achieved an MCID, of pain, and about forty percent had this really substantial, benefit. We know that this is a highly important outcome for patients, and showing, that the majority of patients did achieve this is is great. In terms of, fatigue, there was an instrument known as the facet that was used to measure this. It has several questions.

It's a composite measure. And there too, we found that a highly important improvement in fatigue occurred in at least fifty percent of patients. And this was sustained over time, over the course of two years, as was the sustainment of, pain response, suggesting that not only, was there a substantial effect that occurred relatively quickly, but it was durable. It lasted over time. Plus, this gives us important information to support the use of an IL-17A and F inhibitor in achieving goals that are very important to patients, improvement of pain and fatigue.

Hi, my name is Doctor. Philip Meese. I'm a rheumatologist in Seattle, Washington and direct the Rheumatology Research Division of the Providence Swedish Medical Center there. I'm very glad, to present data, from an abstract on integrated safety across all of the trials of bimekizumab in axial spondyloarthritis and psoriatic arthritis. These were all the 2B and phase three studies as well.

So it gives us a very comprehensive picture of patient safety in over fifteen 100 patients observed for up to two years. What we saw were relatively low rates of infection, about one point three or one point four events per 100 patient years in both the axSpA and PSA studies. We saw relatively low rates of candida infection. This is something of interest because we know that IL-seventeen as a cytokine protects us from surface candida. So there were occasional cases of thrush, for example, usually just occurring once and easily treatable with topical treatments for the most part.

Only occasionally were we to see patients with recurrent episodes, more than one. So this rate was also low, and there were no systemic, fungal infections noted, nor any cases of tuberculosis. Another area of interest is inflammatory bowel disease. This was seen in very low rates in the axial spondyloarthritis population more than the psoriatic arthritis population. Again, this is something that we have seen with this mechanism of IL-seventeen inhibition.

Usually these are cases in patients who have a past history of inflammatory bowel disease and there's a flare. Occasionally we have seen some new onset cases. So this happens, the frequency is low, we do need to talk to our patients about it. Another issue that is being monitored for in current trials of psoriasis and psoriatic arthritis is the issue of depression and suicidal ideation because these are issues that are more prevalent in a patient population with these diseases. Again,

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the rates were low. There were slightly more patients in the bimekizumab arm that reported let me start that one again. Again, these rates were low, and I think if anything, what this reminds us to do is to talk to our patients about their mood, to talk about depression openly, and be ready to care for this issue if the patient is meaningfully depressed or has potential suicidal ideation. Another issue that is of interest, especially in a group of patients who have a proclivity to obesity, is the potential for liver transaminase changes because sometimes if a patient has underlying fatty liver or is on methotrexate, we may see perturbations in LFTs. This was seen on occasion, so we do occasionally see upticks in liver trans aminases, but these were generally transient and would return to normal and generally did not lead to any concern about the ongoing use of bimekizumab.

Another topic of interest is that of uveitis. We know, for example, that when we use a monoclonal TNF antibody that we can see reduction, in uveitis flares, which can occur in patients with PSA or axial SpA. The rates of uveitis, in this integrated safety analysis were quite low, and so it doesn't look like there's, in any case, a significant increase in number of cases of uveitis, and overall, the rates were very low. We saw no signal, for malignancy, no signal, for, cardiovascular disease of concern. So in general, this report underlines the relative safety and tolerability of bimekizumab and IL-17A and F inhibitor, a dual mechanism that has been recently approved for the treatment of psoriatic arthritis and the full spectrum of axial spondyloarthritis.

Hello, I'm Doctor. Philip Mees. I'm Director of Rheumatology Research at Providence Swedish Medical Center in Seattle. It's been a busy and interesting ACR meeting for me. One of the highlights was the data on the phase two trial of Sonalocomab.

Sonalocomab is a novel IL-17A and IL-17F inhibitor, so a dual mechanism, which is a nanobody construct, so just 40 kilodaltons. It binds to IL 17 a and f, as well as to albumin. The albumin binding, as well as its small size, allows it theoretically to penetrate difficult to reach areas, and be highly effective in covering the IL17 family. So, we saw phase two twelve week data for the psoriatic arthritis program previously. In that twelve week data, we saw ACR 50 response in approximately forty six percent of patients, treated with the sixty milligram or one twenty milligram monthly dose of this medication.

We also saw MDA or minimal disease activity criteria achievement in approximately forty four percent of patients. Now we're looking at twenty four week data. There were some changes in the groups that patients were in. For example, if they weren't responding to placebo or to a sixty milligram dose, they might shift upwards. But we saw some really exciting outcomes.

For example, the ACR fifty response in the sixty and one hundred twenty milligram groups went up to about sixty two percent of patients achieving an ACR fifty, and the minimal disease activity criteria, we saw a rise from forty four percent up to about sixty percent of patients, achieving this composite holistic way of evaluating psoriatic arthritis in all of its domains. So very effective. In terms of safety and tolerability, the one item to mention is that because we know IL-seventeen protects against surface candida, we did see a couple of cases in the sixty and one hundred twenty milligram arms each in the twenty four week program. These were generally mild and easily treatable. Otherwise, there were no unexpected findings relative to the IL-seventeen mechanism.

So this is a neat, new molecule, a new approach by having an antibody and more complete coverage with IL 17 a and f inhibition. Thank you so much.

Hi. Marina Mayagre from Case Western Reserve University once again reporting for RheumNow at ACR Convergence twenty twenty four. Great meeting so far and a lot of exciting data. And today, I attended it was a session for difficult to manage AxialSpA, which has been a very hot topic at this meeting. This session, you know, doctor Dennis McGonigal from UK did a very nice discussion about difficult to manage AxSpA.

And the take home message from that, what I got was, what he mentioned was these patients that are difficult to manage, first thing one needs to know is go back to the drawing board and make sure that these patients have a right diagnosis. Because sometimes it may not be the right diagnosis, and that's why these patients may not be responding to the therapeutics as we expect them to be. So so maybe they don't have XBA. Maybe they have degenerative arthritis or some other form of arthritis that needs to be taken into account. He also mentioned about some anecdotal reports of using a combination biologics in these patients.

So what he showed was that patients, you know, particularly those patients with psoriatic disease, there have been some reports, if using combination biologics like an IL twenty three inhibitor along with the TNF inhibitor. However, it seems, you know, to be determined, and we need actual clinical trials to show the efficacy of these combination biologics in these patients. Thirdly, the point he emphasized was that these patients may have other reasons for being in pain, and they may have central sensitization, other, you know, other causes for pain, sleep deprivation. So these need to be thoroughly also looked into these patients and make sure that those areas are also addressed when trying to manage these patients. So that was the take home message from that session.

Another abstract that I like today that was presented was it was an poster actually, was this group tried to look at it was a French group trying to look at the time to low disease activity in patients that have been previously treated with TNF inhibitors. And what that abstract showed us that those patients that were previously treated with TNF inhibitors, either one, two, or three, then they switched to another TNF inhibitor, it the duration to reach low disease activity was longer. So the bio naive patients took lesser time to reach low disease activity compared to those patients that were previously treated with TNF inhibitors, whether they started a new TNF inhibitor or they started an IL seventeen inhibitor. They also looked at the durability of, you know, the low disease activity in these patients, and they found that those patients that switched from a TNF inhibitor to IL seventeen inhibitor, the durability of low disease activity was decreased. However, the durability of low disease activity was not decreased in those patients who are naive or switched from a TNF inhibitor to another TNF inhibitor.

So the take home message from this abstract was that those patients who now show inadequate response to previous TNF inhibitors. And when we are switching treatment to them, I think it may be it may be advisable to let our patients know that it may take longer for them to reach the low disease activity. So they need to be more patient, you know, stay on the treatment rather than cycling treatments from one class to another. It may be better to wait and give them more time till they attend attain low disease activity. Thank you so much.