ACR24 - Day3a Save

Hi this is Doctor. Jiha Lee, a rheumatologist from Michigan at ACR Convergence in Washington DC. I'm here with Doctor. Elam from Augusta University to talk about her abstract number seventeen forty six looking at incidence of osteoporotic fracture in RA population and its relationship to disease activity. As we all know, patients with rheumatoid arthritis are at an increased risk of osteoporosis and it affects their mobility and function especially in older adults and it's an important comorbidity that we need to address.

And so Doctor. Ellum, what are the traditional risk factors that we consider about and what tools and approaches do we have and what made you think that we need to look at disease activity as a measure when we think about this population?

Sure, great questions. So traditional risk factors that we usually think about when we're risk stratifying for fracture are participants age or people's age. The older you get, the more at risk of fracture you are. There's also race and ethnicity factors as well as your sex, but those are things that aren't modifiable. So the more important things to look at to me are modifiable risk factors.

Things like smoking, alcohol use, glucocorticoid use and then having RA is a risk factor. At this point we haven't got to the scientific level where we can prevent RA from happening but there is some data that if you have higher rheumatoid arthritis disease activity, so more active RA, that leads to less bone density or a weaker quality of bone and then also leads to fracture. So that's what made me interested in wanting to, use RA disease activity to maybe help us predict or at least know the incidence rates of fracture by how active the RA disease is.

And we do know that the goal is to go for remission or lose disease activity because not only does it hurt RA related outcomes but other comorbidities and the FRACS score only asked for the yes and no but you're trying to get at the more granular level. And when you looked at this, what kind of trends did you find?

Right. So what we saw was that for the two different fracture outcomes we looked at in our study were the two fracture outcomes that we use in the FRACS model, which are hip fracture and major osteoporotic fracture, which a composite of distal forearm, upper arm, spine or hip fracture. And so we looked at these two outcomes and we saw that for hip fracture if you have high disease activity level compared to someone in RA remission, you had higher rates of hip fracture. And then for major osteoporotic fracture, we found that whatever level of disease activity you were above remission. So low, moderate or high disease activity level compared to RA remission had greater rates of major osteoporotic fracture.

And how do you bring this into the conversation with the patient when you're trying to talk to them about how to mitigate the risk, whether it be in terms of lifestyle or thinking about how you approach RA treatment?

Yeah, so I think that it's usually not hard to convince an RA patient that they want to be on treatment usually because a lot of them are having joint pain symptoms that make them want to get treated but there are some patients who maybe don't see the benefit of doing a biologic therapy over the medicine that they're already on and this can add to the data that we have to suggest that really reaching that remission target has benefits even outside of what they're perceiving on the day to day in their joints. And then also something that this study didn't look at but something we're planning to look at in the future is the issue of glucocorticoids which we know to be a strong risk factor for fracture and something that is still used to control RA. And so this just gives us kind of makes the thinking more complex here. Is it that if we control RA but we're controlling it with glucocorticoids, but those are bad for bone health maybe we need to make sure we're controlling it with something other than glucocorticoids and that's sort of the next steps in what I want to look at with this project.

Wonderful so as you said we know that RA patients have a higher risk osteoporosis for two to three folds so as Doctor. Alam was saying it's not just about the unmodifiable risk factors but what we can play a role in is in the modifiable risk factors particularly when it comes to disease activity because that is where our skill set lies. Aim for remission and treat the patient especially when it comes to older adults.

Hi this is Bella Mehta reporting from ACR24 for RheumNow and I came across a very interesting abstract, abstract number seventeen eighteen. It is discussing whether to hold or not to hold JAK inhibitors or IL seventeen agents when patients get COVID nineteen injections. So I get this question a lot in my clinic. You know, patients with RA or spondyloarthritis, they've they message saying, do we need the boosters? And most likely, we'd be like, hey.

These guys are immunosuppressed enough. We'll give them boosters, but should we hold them? So this was a study by Jeff Curtis and colleagues using the COWA study, which is a multicenter randomized control platform trial. And they took patients with rheumatoid arthritis as well as spondyloarthritis. And they use the energy research network, so a pool of rheumatologists who are interested in research and contribute data.

And there was a one to one hold versus not hold randomization where some patients were asked to hold their medications and some were not. And what they found was that when they so the the group that held the biologics were more likely to flare than those who are not. And, also, they did measure, like, the antibodies, and they found that the antibodies antibody response groups were pretty much similar. The JAK inhibitors probably lower, but still enough that I don't think they recommend holding either JAK inhibitors or IL seventeen agents when giving COVID nineteen boosters. So that's a big take home message, especially useful in clinical practice.

And last year, the same group talked about TNFs, and they they decided, looking at the data, that even TNFs and abetacept both don't need to be held during the vaccinations, especially boosters, which is gonna be a yearly thing with our patients. I hope this helps. And with that, I'm signing off here. Please follow us on RheumNow and follow me on Twitter at Bella underscore Mehta. Thank you.

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, slightly 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 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, here 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 transaminases, but these were generally transient and would return to normal and generally did not lead to any concern about 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.

I'm Anthony Chan. I'm reporting here for RheumNow here in Washington DC at ACL twenty twenty four. And on in this ACL, we have seen there's a global reach to rheumatologists across the world. And on the first day, there was a global session looking at rheumatology in other countries. And one of the sessions, which was session one forty ten, was a global summit looking at rheumatology care across the world.

And one of the places that really struck me was the rheumatology in Ukraine. And I just wanted to hear more about this, and I'm very happy that professor Martha Juice from the university in in Ukraine, professor of nephrology. She also works in Saint Michael Hospital. He's able to join us here today. Welcome.

Thank you, Anthony. I am working in

So it's a big it's a big hospital and major teaching hospital as well. Yeah. And so for give us give us a bird's eye view from the sort of insight looking out because, obviously, we have not been able to get there to see what's it like. What kind of patients do you see in your clinic?

Our disease exists in our patients, and they feel more pain than normally before the birth starts.

So you have seen maybe a shift in the population that you probably were seeing before, And, also, some of it might be related to, as you say, due to the stress or the pain that they're experiencing. So what has you know, in terms of your your clinical practice, what are your challenges for you at the moment?

Especially those patients who are at the frontline areas. A lot of patients move to other areas and they are looking for a new rheumatologist. So it's difficult for us, rheumatologists, and it's very difficult for our patients who are in need of specialized treatment.

Yeah. So you're doing a you're doing a good a challenging job in a challenging time for us. But that's that's been a really useful insight into us trying to understand, you know, from the outside looking in firsthand experience of what's it like to to work there. So thank you very much for sharing with us today on firsthand information about working here in Ukraine and what what's it like and the change in the in the demographics and also the the patients that they see. So I'm Nt Chan reporting for RheumNow here in Washington.

Hi. This is Eric Dine from New Jersey here at ACR Convergence day two. We just wrapped up a great day and I'm here to talk about some of the oral rheumatoid arthritis abstracts that were just presented. So, we had a wonderful afternoon session where one of the things that we talked about, the first abstract was seventeen forty three which looked at the difference between low disease activity and remission. The goal is we love having patients in remission, but, you know, from the guidelines, we often say that that low disease activity is good enough that we got them pretty close so we don't need to up titrate their medicines to the highest degree.

But is there a difference between LDA and remission? The study looked at LDA, which is, again, that C. Diffeile less than 10, remission less than 2.8, and they also had another group of very low disease, which is between the two point eight and six, kind of the lower part of the very low disease. What they found is that, particularly when you look at that higher level of the lower disease activity between six and ten, the patients did not do as well as those patients in remission or very low disease activity. They were not feeling as well.

Their patient reported outcomes, their fatigue, their pain were notably higher. It's not a surprise, of course, that they're not quite as good, but it did have significant impacts and it showed that they were utilizing health care more. They were using ambulatory devices like canes more. And so this is a suggestion that says maybe we should have a little bit of a higher target. Maybe we should be going for a little bit better disease control.

If not remission, maybe a C. Diff of under six for a very low disease control. So, I I think that is something that that we can change our practice with and and take into account when we see someone who's kind of has that C. Dive eight or nine doing kind of okay, but, you know, maybe not well enough for what we want. The next oral abstract that came just afterwards was seventeen forty five which was taking a look at the oral surveillance study again.

So, we've talked about the oral surveillance a lot over time. They did another post hoc analysis, but I think this one really adds a little bit more color to what we've heard. Of course, with the oral surveillance, we know that the main takeaway was tofacitinib was not non inferior to TNF inhibitor that that JAK inhibitor showed that there was the higher MACE events. One question they had though is what if we specifically look statin usage? Does that make a difference?

And what was interesting was first of all, at baseline, there was not enough statin usage in the group. Only, you know, less than a quarter of patients were using satin. And of patients that had the known risk factor of MACE events, it was fifty percent of them. Half of them were not on appropriate treatment for someone who has had a history of a MACE event. In the patients that were on a Saturn, they did as well as the patients on TNF regardless of if they were in the TNF or TOFA category.

So, that provides some reassurance to me that if you have a patient that has been doing well on tofacitinib and they're worried about their MACE risk, then maybe you can still do it as long as you're doing the other preventative things well or secondary prevention by having them on a statin, you know, for appropriate care. And this is something that I think is helpful, give some more information as to why patients may not do as well on the TOFA. Again, you know, they weren't on the appropriate background therapy with a statin. And so, you know, there's always more information we can glean when we go into those numbers from the oral surveillance. So I thought those were two of the highlights from that oral session and a lot more that me and my colleagues will be having on RheumNow.

Hi, this is Catherine Bakewell reporting to you for RheumNow. I'm in Washington DC for ACR twenty twenty four and I wanted to tell you about the best thing that I saw today, which was related to sex differences in psoriatic arthritis. We started off the day with session 17S08. It was a combined session by Laura Coates and Leahy Adder. And we learned that females have a significantly different baseline characteristic profile as well as response to therapy.

So females by and large are going to report more pain and disability. They're going to have higher overall composite disease activity scores. They're going to have lower drug persistence, AKA discontinued drug more often and more adverse events related to medication, which again you would assume is a correlate to that as well. Whereas males are going to have higher CRP levels, higher levels of dactylitis, PASI scores, aka worse skin psoriasis, and more radiographic progression. But the good news for them is that they tend to have better treatment response.

Interestingly, they also highlighted some data around ultrasound that, of course, I as a lover of ultrasound found particularly fascinating, which was that men tend to have higher ultrasound and the site of scores both by grayscale and color power Doppler, whereas women tended to have higher clinical and the site of scores. And to me, this underscores not only the importance of objective measurement, aka with ultrasound showing us true inflammation, but we need to better understand why is it that our females in general have more pain reporting, more pain in general. Those are probably a gender related difference in our gender expectations around the stoic man not reporting his pain, whereas it would be more okay for the woman to talk about her discomfort. But also we know that hormones significantly impact immune function and pain processing itself. So Doctor.

Ader showed us a slide showing us that microglia in the level of the spinal cord in men regulate pain signaling whereas in women it tends to be more T cell regulated. Doctor. Ader also showed us a meta analysis of 54 different randomized controlled clinical trials looking at ACR responses in psoriatic arthritis and specifically looking at ACR20 responses. Only nine of the 54 RCTs reported sex disaggregated data, AKA showing us how men responded differently to women. But when analyzed, it did appear that there was a tendency for the men to respond better to biologic therapy.

All of them examined TNF inhibitors, IL-twelve twenty three, IL-twenty three inhibitors, IL-17s, whereas there was less of a gender discrepancy for the targeted small molecules of JAKs and TYK2s. One possible mechanism for this, she also showed us a study that demonstrated that women have higher immunogenicity to at least infliximab, so maybe there is an issue there. But regardless, we need more data. Nine out of fifty four is not good. She shows us how they don't separate women based upon whether you're 20, whether you're 80, it's all lumped into one pile and again a minority of these trials differentiated by men versus women at all.

Last abstract I want to highlight for you, this is seventeen oh nine entitled Sex Differences in Serum Proteomic Profiles of Males and Females with Psoriatic Arthritis. This was presented by Stephen Dang and it did demonstrate that men had an over 20 fold increased level of protein deregulation relative females. That unfortunately, they did not measure estrogen and testosterone levels, but they did break down the women into premenopausal and postmenopausal status. So there is some hope that we're gathering more hormone related data, but we do need to be studying our females more closely, both for hormone levels throughout the menstrual cycle, but also pregnancy, nursing related, and of course pre or post menopausal status. We also need to be gathering data around gender and the impact that that can have on response to therapy in psoriatic arthritis.

So a call out to those in industry to please join us in this fight. I will mention Doctor. Adler one last time that she is running the SAGE trial, examining sex and gender related differences in PSA response. And that's all I have for you today. Thank you.

Hi. This is Eric Dine with RheumNow from ACR Convergence day two. I'm here with doctor Harry Hurley who just gave a presentation in the scleroderma oral abstracts about single versus double lung transplants for patients with systemic autoimmune disease ILD. Tell me before we get to your study, I'm not familiar about how do we choose who gets a single and who gets a double lung transplant?

It's a great question and it's a constant area of scrutiny. There are multiple considerations. One is indication. Some patients can only get a double lung transplant, like if you have cystic fibrosis or pulmonary artery hypertension, you have to get two lungs. A lot of other indications are fine with one, but we've always wanted to know, like, is it better to give a patient two lungs?

The benefit of having a single lung transplant, of course, being another patient can get one too, and it is a less morbid procedure.

And tell me, for patients with systemic autoimmune disease, what did you find about the difference between single or double lungs?

So we examined mortality at one year as well as thirty days and three years, and we saw no difference in mortality in SARDA ILD patients after whether they received a single or a double lung transplant.

And

this is for all all comers. So you looked at it was you said mostly systemic sclerosis. Were you able to look within that pop within those groups more specifically or this is just all patients with systemic autoimmune?

So we lumped them all together. We had the greatest sample size that way. Had done some, like, didn't present it, but I had done some subgroup analyses and they seemed pretty consistent.

And so that's reassuring that patients may not need the second lung. So if you're counseling a patient that hopefully that can help them get lung sooner or at least have more lungs available for our patients that need them. So, I think that would be really useful for our transplant patients. That's wonderful. I think this is a really useful study.

I think it's an area that we have a lot of patients that we send them to the transplant. We're not sure exactly how they're best managed and what to do. So I think this is really useful, helpful information. Thank you very much.

Thanks for having me.

So look for RheumNow for more coverage throughout ACR convergence and beyond and for information about scleroderma.

Hello, I'm Doctor. Philip Meese. 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 sonolizumab.

Sonolizumab is a novel IL seventeen a and IL seventeen f 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 IL-seventeen 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 arise 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 that IL-seventeen protects against surface candida, we did see a couple of cases in the sixty and one 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 a nanobody, 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 Axelspa, 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 therapeutics as we expect them to be. So so maybe they don't have XPA. 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 of 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 active 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.