Chapters Transcript Video Recurrent Pericarditis: Standard of Care and Upcoming Trials Dr. Abbate discusses management if acute and recurrent pericarditis, risk stratification, and clinical trials. No, thank you for the invitation, the kind introduction. This is really a field that it's very close to my heart, and allow me the terminology. It's really an evolving field. I mean, I've been passionate about inflammation and cardiovascular disease since I was a medical student, but the pericarditis research really took off in the past decade. And if you're not following closely, you may have missed some of really the step forward. So I look forward to telling you about the new upcoming trials because I think they will be very informative, but I wanted to start with reviewing what we've learned mostly in the past 10 years because the field has changed both from a diagnostic prognostic approach to a therapeutic approach, mostly. Um, I'm going to start and then I'm going to pause a little bit, uh, take some questions about the standard of care, and then introduce you to the exciting new drugs coming. Hopefully they will give us, uh, give our patients more opportunities. So these are my disclosure. I collaborate with many different companies. I'd like to bring the treatments to the patients. The slides have been reviewed for accuracy. I'm going to cover information is public domain. Hopefully you'll find this not biased presentation, and I'm also a clinical like Dr. Tresa. I'm a clinical investigator of some of these ongoing trials that I will share with you at the second part of the presentation. So I've been interested in inflammation and innate immunity for, for many, many decades. The the figure here on the right is from one of our radio articles on Jack for a few years ago. It was one of the first figures that showed the central role of this star-like structure that you see here in the middle of the screen, that is the inflammosome. When, when I went to medical school, I had not learned about the inflammosome. I think the term first appeared in the literature in Mid 2000s as this multi-molecular macromolecular structure that aggregates in inflammatory cells and allows for the processing and release of key inflammatory cytokines like interleukin 1 beta. So we had known interleukin 1 beta for more than 50 years. This is Charles Diorrello work. We know 1 beta is the inflammatory cytokine mediates. and the systemic inflammatory response. But how did the cells go about to decide to produce L1 beta and particularly in large quantity was a little bit of a mystery until we understood this macumolecular structure. And what is unique about this structure is that it responds to a variety of stimuli because we know we can have fever due to many stimuli. It could be a virus, but it could also be an autoimmune response. It could be injury. We know different viruses, different bacteria, different fungi can give us an inflammatory response. And so this structure is able to sense injury and dangers from a variety of stimuli, and we've learned recently that some of these stimuli are not infectious at all, like cholesterol crystals or gouty crystals. And so today I'll show you how this cascade fits. Into the management of pericarditis. Also, until recently, we didn't really have any guidelines for the management of pericarditis outside of the European Society of Cardiology guidelines of 2015, but none from our societies here in the United States. No American Heart or American College statements. Um, in 2024 and then in 2025, the American College of Cardiology came out with two statements that I, um, recommend you uh read through. Uh, one on the top is heavily focused on the use of multimodality imaging, but it also integrates biomarkers and treatments. The one on the bottom is a concise clinical guidance from experts in the field on how to diagnose and manage um pericarditis. So I guess we have some additional guidance in this, and I'll show you some images on how the approach has changed over the years. Uh, the, I've mentioned the European Society guidelines for 2015. 15, actually, in 2025, just a few months ago, uh, the new guidelines came out um and they actually introduced us to a new terminology that we'll see if it, if it takes um the uh the, the central role in this field as a preferred terminology of inflammatory myop pericardial syndrome. I view, I personally view pericarditis and myocarditis, uh, largely distinct, uh, diseases, uh, with, uh, different kind of challenges and complications, but there's an overlap between these two. And so, uh, in these guidelines, uh, Doctor Imazio, who led the guidelines, decided to. Focus more on the overlap uh rather than on the uh the differences, and so the guidelines cover both micocarditis and pericarditis. You may enjoy reading this here. So in the first part, I'm gonna go uh rapidly through the definition and diagnosis of pericarditis. I think this is something you know. Well, I want to talk about the initial management and particularly the management of recurrences that are more complicated. I will review some special cases, some of the zebras that uh we are going to see at our large hospitals because we're referral centers, and then I'll pause you, I'll pause for a second and then I'll tell you about the clinical trials that are ongoing. Why I'm excited about these new therapeutic strategies. Um, so what is this pericarditis? We know this it's an inflammation of the pericardial sac. We rely on clinical presentations and then EKG and imaging to define this inflammation. I'll show you. The American College of Cardiology consensus has identified some criteria that need to be met. Um, and I will start by saying that in many cases, we don't know what caused the pericarditis. Um, it, it, we associate it with viral um infections, but it's not really clear, um, which virus. can do it, which virus cannot do it. It may be variable in the individuals. A lot of times, more than viral illnesses are more post-viral syndromes, meaning the patient has actually recovered from the acute illness from like COVID or from the flu, and then a week or 2 weeks later starts having more chest pain. So it's more of an immune mediated. Uh, response rather than viral, uh, growth in the pericardial, uh, layers. Uh, we should not forget that the ischemia is very common and acute myocardial infarction can cause pericarditis. Usually it's the large transmural infarct that give what we call ischemic, uh, pericarditis, but, There's also an immune mediated pericarditis after MI, which we refer to, to, to as the Dressler syndrome. You can see that also after cardiac, uh, surgery, and that's delayed by a few weeks. Uh, many drugs and radiation and trauma can cause pericarditis. Pretty much anything that irritates that cirrhosa, that shouldn't be, um, perturbed in any way. Um, and, uh, I, I will, uh, I will say that, We see many cases related to, um, uh, EP procedure, for example, ablation, radio frequency or cryoablation, they can irritate the pericardium and cause pericarditis. And then, as I mentioned, some of these are clearly immune mediated. You can have it in the setting of autoimmune disease like lupus, or, as I mentioned earlier, to address the symptom as a post injury, immune mediated process here. Um, To, to the left here are some notes. You know, the pain is usually characteristic, um, when you, when you, you know, we are, um, we are cardiologists that, uh, I'm, I'm sure many of you like me have been trained to recognize chest pain as a sign of acute myocardial infarction. So we are, um, have been, um, how do you say, uh, programmed to react rapidly to acute MI and recognize angina. And so this is pain that is different from angina. It's kind of positional. It can be worse with breathing, worse with laying flat. It's intense. It doesn't seem to respond much to narcotics, but it responds very well to anti-inflammatory drugs. Allow me to term, these are kind of pain that is a little atypical for an acute MI, but worrisome. Enough that the patient may be seen in the emergency department with a concern of a heart attack. If you have a rub on exam, that's actually diagnostic, but the rub is not always present. It can be positional. You may have to have the patient lay back, uh, in the, in the bed or lay, lean forward to elicit the rub. Sometimes it's loud and you can't hear. If there's a fusion, you're less likely to hear a rub, but if you hear a rub, you pretty much have your diagnosis because the rub is not a normal finding on exam. The EKG is usually what kind of prompts the diagnosis. There's PR depression or ST segment elevation. I would, I would like to remind you that PR depression is much more common than ST segment elevation. Um, and so, you know, pay attention to that PR interval and see if it's pulled down. Uh, there may be an indication of you're having some pericardial irritation. Um, the laboratory tests are not, you know, none of these tests are specific for pericarditis. Um, there are more nonspecific inflammatory, um, markers or myocardial involvement that would lead you to more a, uh, a myo pericarditis or perimyocarditis. Um, but, You need to check them, and, you know, in the new guidelines here on the right, in the European studies of cardiology actually tells you that C-reactive protein elevation can be one of the criteria that you use to validate pericarditis. So I get it at every, uh, patient I'm evaluating for a chest pain and it may help us, help me define whether the pericarditis is hot and flared at that time. The echo is not a requirement of diagnosis, meaning that if you have a, uh, an exam, uh, symptoms, an EKG, you have your diagnosis, but, uh, you should get an echo in everybody because you want to see, uh, in the presence of pericardial effusion, which supports the diagnosis, but also, uh, make sure you don't have complications like a large effusion or, or, uh, constriction. But remember, a normal echo may not exclude a pericarditis. In the new EC criteria, they changed it from the prior and said that you need to have pain or pain equivalent. Sometimes it's a heaviness, tightness, constriction, and you have to have two or more of these criteria to be a definite, one or more to be positive. Dr. Rea just shared. That sometimes we only have patients with pain, we don't have any other supporting findings. Those become unlikely or undefined pericardial syndrome because they may not really have pericarditis, even if they had an episode in the past. But if you have pain and you have 2 out of 5 of these criteria, 2 or more out of 5 of these criteria. You are very likely to have pericarditis, and I think the new kid on this block here is the pericardial edema T2 signal or LGE at MRI. I know we're doing a lot more MRIs. I'm sure you guys are doing more MRIs. We're also doing more CT scans, and so we're picking up this pericardial thickening, this pericardial effusion, this LGE on MRI that supports that actually there is injury to the pericardium and supports a diagnosis here. How do we treat this, you know, if you ask everybody, everybody will say it's NSAIDs, and yes, NSAIDs do treat the pain, and they should be started promptly in patients who do not have contraindications, but I'll say there's really no good data to say which NSAID. for how long, and there's no data to show that NSAIDs actually change the natural course of the disease. Like in many other conditions, NSAIDs are pain medicines, and they should be given, but you need to, you need to consider that the first line treatment for pericarditis is colchicine. If you're not utilizing colchicine for pericarditis, you're missing an opportunity. I'll show you some data here. The colchicine changes the natural history of pericarditis, reduces the recurrences and complications. Uh, of course, there are some contraindications to to colchicine if you have severe. Renal failure or you're on medication with a very narrow drug level target level, but in general, most of the patients can tolerate some level of colchicine, either 0.6 mg once or twice daily. Um, I want to go back to, I, I'd say that, you know, the past 10 years have been really hot for colchicine, but we got to get a shout out to Doctor Imazio in Italy, who started this research longer than 10 years. This, this trial actually is now 20 years old or more. And he showed that adding colchicine to NSAIDs significantly reduced the rate of complications. In this slide here you see that he went on to repeat this trial some years later in patients with first recurrence in the CORP trial or multiple recurrences in the CORP 2 trial, and you know, it consistently showing that adding Colchicine will reduce complications, and so I would say that colchicine should be your first line. There are some additional trials from the Imao group looking at patients after surgery, uh, pericardectomy or cardiac surgery, and again, um, a clear benefit of colchicine, and I borrowed this slide from Dr. Amasu some years ago that the number, Needed to treat for colchicine benefit, it's, you know, between 3 and 5. So again, this is first line. It should be used and you're going to get a great return on your investment with colchicine. But what about the more complicated cases, the ones who don't respond to colchicine, the ones who cannot get colchicine? You know, when I started this research, My impression was that that pericarditis was pretty benign. It wasn't really a big deal. Yeah, it can cause pain. Yes, you know, it can lead the patient to the emergency department, but my impression was, was kind of like most patients do fine. Well, I was really wrong. I think most patients may get lost in the in the follow up or they don't get good recognition. So when, when I started doing research in this area, I actually pulled cases from our court at DCU. We started with about 500. Cases over the prior 7 years and we follow their course into our electronic health record. We actually found that these patients had a high number of complications here. The publication on the left is showing that about a third of the patients had some sort of complication after the pericarditis, with recurrent pericarditis, tamponade, uh, constriction being the ones that are most concerning. Um, the one on the right is actually a sub-analysis where we, uh, we said, well, maybe some of these patients who are doing so poorly is because they're really, really sick, uh, to start, uh, and you know, you may diagnose a pericarditis as someone who's in the medical ICU with sepsis and now has pericarditis associated with the bed staph pneumonia. Um, that made bias. Well, we looked at the, at a more clean case, 240 cases of patients that were really not, um, no high risk feature outside of the pericarditis related disease, and then we started to find that based on how large the effusion it was, whether they had symptoms for more weeks or they had constriction, and if you took these patients with only pericarditis, no other major disease at that time. And you look at those with complicated course now, you know, 30% were having recurrent pericarditis, but even the ones who we saw, we considered low risk, so no, you know, no high risk feature for complications, still a 9% recurrences or other issues, you know, for within a few months. So you know, again, my The idea that pericarditis was rather benign was wrong. It's actually they are very common complications, and now I've I've learned to follow these patients closely. If those who have an effusion, I get a repeat echo within a week, and then I get an appointment in clinic within a few weeks to make sure they're actually responding to treatment. They don't need an intensified treatment. Um, and, um, and what, how do I stratify these patients? Well, you know, this year are some retrospective analysis from our court and others, you know, persistence of pain, elevated levels of biomarkers, subacute onset. I'll show a slide later that if it's a part of a systemic illness, they do worse, of course, but really what has been the new addition to the field is the use of gasdolinium. MRI looking at late gadolinium enhancement and you clearly see here this is one way to grade the gadolinium enhancement, the white line around the pericardium sac here that if you have a severe, you know. Circumferential thickened pericardium, that really tells you that the pericarditis has been going on for a while and this is high risk. There's anatomical abnormalities there, and so this is unlikely to heal quickly with a short course of treatment, whatever treatment that may be. So, uh, what have we learned at this point for those patients who are complicated? You know, we said earlier that pericarditis can happen after any kind of insult. It can be a viral illness, it can be an ablation, it can be trauma, it can be ischemia, but, you know, months later, for this to be recurrent, something has changed. At this point, the initial insult is gone. And so what we're seeing now is an auto-inflammatory loop where the initial injury is given inflammation. Now it is the inflammation itself that is perpetuating the injury, and we know that the inflammasome and LL1 are central in this cascade. This is a slide that Dr. Klein, who's, you know, one of the world experts in pericarditis from Cleveland Clinic, has put together a few years ago. Really shows how when there is injury to the pericardium, you release alarmins from the cells. Among those there's interleukin 1 alpha that is released outside and triggers an inflammatory response in the neighboring cells and the inflammatory cells that activates that star-like structure we called earlier the inflammosome, particularly LLRP3 inflammosome. And that stimulates a large amount of interleukin 1 beta to be released. This is the fever molecule. L1 beta now activates the entire inflammatory response. It activates the endothelial to recruit more white blood cells. It gives these white blood cells, give more injury to the pericardium, release more alarmins, including L1 alpha. L1 beta is also the one that stimulates. The cyclooxygenase 1 and 2, so the fever, and it produces interleukin 6, which gives a secondary mediator acute phase response like C-reactive protein. So when we're measuring C-reactive protein, really measuring IL-6 and IL1 activity. And so what can we do once this is now recurrent and this loop is ongoing? Well, until recently, all we had was steroids. There was nothing else, and you know we have all used steroids to treat pericarditis because there's nothing else to do. We know that steroids are really an effective anti-inflammatory therapy across a wide range of diseases, but we've all learned very well in our training that they're associated with significant side effects and complications. And in pericarditis, we also learned that low dose is better than high dose, although there are no good clinical trials, it's all retrospective analysis. So steroids have been used as second line treatment for a long time at a low moderate dose with a very slow taper and monitoring for complications, but we should be careful about not using this as in everybody's second line. I'll show you there's a new class of drugs that actually is taken. An equal role as second line treatment or a rapid third line treatment after a short course of steroids. Now there are, this is a review from Dr. Imao from some years ago. There are some cases where you're still going to use steroids, and particularly if it's associated with autoimmune disease. If you're treating a patient with lupus that has ulcer pericarditis, well, steroids are still the first line treatment in many rheumato. Biologic diseases, and I have another slide on this, but I want to go forward and, uh, uh, and tell you about the new class of drugs. This year, it's important consideration of use of corticosteroids. I am quite sure you've heard this multiple times, and if you haven't learned by now, you may never learn it, but, you know, we, if you put someone on steroids, you need to be monitoring for toxicity and side effects, and you need to stratify a patient who may have more complications with steroids, but, Along these lines, the past 10 years have really revolutionized the way we treat this disease as we've gone from a pretty blunt instrument of anti-inflammation like corticosteroid to a targeted cytokine-specific treatment like in many other rheumatologic disease that is going after interleukin 1, which is that central. mediator that in the auto-inflammatory loop. So here I'm sharing with you 3 clinical trials that was done at 3 different times in 3 different regions of the world with 3 different IO1 blockers, and it's really a unique opportunity to see this, how it's a consistent signal of benefit. I'll start with the one on the left. This was the pilot study done in Italy, mostly and other parts. Of the Mediterranean, these are the sickest of the sickest of the patients with pericarditis. They had failed, uh, colchicine, and they were all dependent on steroids. So these are the patients, you put them on prednisone, they were doing fine. You tried to take the prednisone out, they would flare again, and so now they're on long term. Steroids and these patients were all treated open label with an I-1 blocker and Akira, which is interleukin 1 receptor antagonist, the recombinant form. This drug has been approved for 20 years or more for many auto-inflammatory disease and rheumatoid arthritis. And then once they were in remission, meaning they were pain free, they were off the steroids, they were randomly assigned blinded to either continue the I1 blocker and the kid ra or switch to placebo, and you can see that once you, you switched to the placebo, you took the I1 blocker out nearly every single patient. Occurred within a time of about 90 days where the patient on Aquino did fairly better, much better. So this was the first proof that keeping someone with the worst type of pericarditis on an R1 blocker could keep them in remission. The trial in the middle was done mostly in the United States. And this was with a different one blocker, Riloni. Riloni is a recumbent infusion protein that works as a trap and binds circulating L1 alpha and beta, so it traps it in the in the blood rather than blocking the receptor. Very similar design in this study. The patients were very sick as well. They had multiple episodes of recurrent pericarditis, but not quite as sick as the Atrop. Not everybody was on steroids, and here they all were. Treated open labeled riloice, then randomized to continue Rilo or placebo in a double blind fashion. Again, here very, very strong number of recurrences in the placebo and maintenance of the disease with Ronice. Here to the right, there's another drug. This is actually not available in the United States. It's very structurally similar to Ronice. It's also a trap. In this case it was done mostly in the Russian republics and They were also started on the flu cassette and then randomized and you can see again very similar path of the curves. So in my mind this is a very strong support. This is a class effect of IL-1 blockers in recurrent pericarditis, and it seems to be working in different continents. So that's very reassuring. And so along these lines now, IL-1 blockers in the United States we only have riloni and And Akira and Rilona actually has recurrent pericarditis in the label, um, are now considered either second line or third line after a course of prednisone. I'll show you a slide where, um, the more we know, we, we think this should be more of a second line, particularly in those patients that are unlikely to respond to a short course of, uh, uh, of steroids. There are additional immunosuppressive therapies that can be used. Some of these are still in the guidelines. The evidence supporting these immunosuppressive therapies outside of specific rheumatologic disease is pretty limited. So if a patient is not responding to um an IL-1 blocker or a steroid, uh, they may have a rheumatologic disease that requires targeted therapy. So if you have not engaged a rheumatologist yet, you need to engage at that point. Or they may not have pericarditis. And then pericardectomy is reserved for very severe cases. This should be radical pericardectomy. It's a, it's a pretty intense surgery, and I generally reserve this for patients who not only have pericarditis, but have also constriction and constrictive pericarditis that has not responded to therapy. Uh, in this, uh, concise statement that I mentioned earlier, there's this introduction of the concept of inflammatory phenotype. Remember that until recently, 2nd line treatment were steroids and you know and for many years IO1 blockers were kind of used as a rescue, as a 3rd line or 4th line regimen, and here you can see is that the trials with Rilona and Ainra and Gofi have really shown that these are effective treatment. To keep patients in remission with a pretty good safety profile and so particularly in those patients who have an inflammatory phenotype, meaning they have chest pain, elevated inflammatory biomarkers, evidence of inflammation and imaging like T2 signaling or LGE. Um, those are the ones that have been enrolled in trials, and they do really well with I1 blockers. Those who don't have that phenotype, uh, really don't know how to treat them at this point. And so I1 blockers may work, but those were not really studied well in trials. Steroids may work, but these are difficult to treat when we're going to need more, uh, more research in that case. And so we're transitioning to I1 blockers. So it's kind of second line treatment, especially in those with that uh auto-inflammatory phenotype. Uh, before I stop telling you about uh the standard of care, I need to remind you that what I just showed you were cases of recurrent pericarditis that were not related to another specific disease. We call this also idiopathic recurrent pericarditis. But in this article that just came out of Heart and BMJ this week, I believe, we went and summarized some conditions that are not the classic recurrent pericarditis. They need a little special attention. And, uh, it is not like often is in medicine, not one size fits all. So I'll start with this acronym. A, B, C, D, E. A, you know, when you are assessing these patients, if these patients have an autoimmune disease, they have lupus, rheumatoid arthritis, systemic sclerosis, you need to coordinate the treatment with the rheumatologist. And honestly, there's the rheumatologist is going to guide the initial treatment, and you can then jump in as a cardiologist, Just to assess the damage to the pericardium, add additional pericarditis specific treatment. You can add IL-1 blocker on top of other treatments, but if you don't get the underlying disease controlled, you're not going to succeed, and you may miss other life threatening complications. So in any patient, you need to do a head to toe assessment and say, is this, is this isolated pericarditis or is this part of a systemic illness? And when in doubt, you should, uh, consult with your rheumatologist. If the patient you start treatment, they don't have anything else outside the pericardium or they develop symptoms, uh, uh, afterwards, you should pause and refer to the rheumatologist, um, because again, this can be part of a systemic illness. Um, rare in the United States, but very common around the world, uh, bacterial pericardio. You know, that is something we, I dread, of course, because I don't want to suppress the immune system if they have tuberculosis or they have a bacterial, uh, other form of bacterial pericarditis. So when you're assessing the patient, you should ask yourself, is there a chance this is infectious? If it is infectious, can I tap the fluid and, uh, uh, and see what am I dealing with? Um, if you start the treatment and the fluids, grows larger, or the patient shows any systemic, uh, signs of infection, you know, pause and, uh, and readdress. Again, this is pretty rare, but you will see it if you see a lot of pericarditis patients. Uh, I put in the third category, cancer related. I do also cardio oncology, and I think all of us will need to do cardio oncology because there's more and more cancer survivors. And there are specific aspects of cancer and pericarditis. One, cancer itself can give pericarditis by invading the pericardium or impeding the drainage from the, uh, pericardial sac. A lot of chemotherapy are toxic to the cirrhosa, like the mucosa, so pericarditis is common. Radiation is a trigger. So, you know, you should identify these patients as not having just idiopathic recurrent pericarditis. Um, you know, the treatment may be similar, but for example, if you're, Received an immune checkpoint inhibitor, steroids are still first line in that case. Um, under D, we put damage in drugs. Again, there's other drugs that can induce pericarditis outside of, uh, chemotherapy. We talked about myocardial injury from ischemia. We talked about procedures. Those are all inflammatory triggers, and you can identify them, and, uh, uh, they may need a little additional imaging, make sure there's no scarring on the myocardium. Make sure that your myocardial marker, Troponin is not elevated. Finally, under E, endocrine and metabolic, it's kind of like a little bit of, uh, other, uh, section. Sometimes you have these patients that the, uh, pericarditis or the effusion is kind of difficult to treat, and, you know, don't forget if they have thyroid disease, particularly hypothyroidism, they have uremic syndrome, they have amyloidosis, they may have additional mechanism of pericardial injury that may be interfering with the response to treatment. So it's just to say, That many of our cases of pericarditis and idiopathic, uh, thankfully 2/3 of those may respond to first line treatment, especially if you have a good first line treatment with colchicine. A 3rd may become complicated, and some of these patients may actually have a more complex case of pericarditis, whereas pericarditis is just one of the symptoms or one of the manifestations of the disease, and it's important to remain vigilant. So the uh the actual more trials are coming out with more IO1 blockers. And so, um, you know, why, why do we need more I1 blockers? Well, this is, this is a trial that's actually sponsored by the same company that makes one of the current uh I1 blocker, loo Arlis, and this new IL1 blocker is a different mechanism of action. In the schematic here on the bottom here, there are uh the one on the left here, the L1 receptor. antagonist, this is the anakinrainret that I showed you earlier. So this drug here competes with the receptor and it works. There's no doubt it works. However, it is a competitive antagonist. So you, you know, if there's more signal to from natural IL-1, it may have problems competing. So in some other diseases you actually Have to escalate the dose in pericarditis, there's limited data on that. And then this is given as a daily injection under subcutaneous because it's a short half life of the of the molecule. I'll skip the one in the second one for a second. I'll come back. The third one is the trap that I showed you earlier, so the riloice and goflika. These are common infusion proteins that look like the receptor for IL-1 beta and alpha. They have an additional part that kind of gives them stability in circulation. And so the half life of these drugs is somewhere between 7 and 10 days, and they trap the circulating IL-1 alpha and beta and prevent it from signaling. And we've shown that this also works in pericarditis and And other diseases, all of these drugs have multiple indications across different inflammatory conditions. These are usually given a subcutaneous injection once weekly, and they certainly have a benefit. Now we have learned that antibodies are actually a great way to target cytokines and other mediators. One of the advantages of the antibodies. They last in circulation a long time, so they're usually given once monthly or every 3 weeks. And in this case, the company is developing a fully human immunoglobulin G2 monoclonal antibody against the IL-1 receptor 1. So they're targeting the receptor, blocking the receptor for IL1, so alpha and beta, so it cannot signal. So we We are excited to see this because we think that this strategy should be very efficacious and should allow also treatment less frequently than once weekly, maybe every 2 weeks or every 4 weeks. And, uh, um, and so we're going to a new, uh, class of drugs that we're very familiar with across the spectrum of, uh, of medicine, including in cardiology, we've been using as PCSK9 inhibitors. Uh, I will pause. I will actually go back here to the second one, which is I1 beta monoclonal antibody. This one here, the, the clinically available one in the United States, is called caneinumab, and you probably have heard about it because of a study in the CNOS trial, and that's also a monoclonal antibody, but in this case it's directed at one of the two isoforms of IL-1 against IL-1 beta. In the CTOS trial, you know, blocking this has reduced cardiovascular events. However, this does not block I1 alpha, and we think that in diseases that are acute and associated with injury, there may be an additional benefit of blocking I-1 alpha. That's why this strategy is going against the receptor rather than one of the two isoforms of IL-1. These trials are ongoing. There's actually two different trials that are kind of a similar concept in a slightly different population in. I'm sorry, here it's kind of uh summarizing again what kind of what I was telling you earlier. The antibody here binds the receptor, prevents the signaling. So this is what we uh what we reviewed here, and here I'm going to review the two trials here. So one trial here is um uh is the uh labeled with a kind of a weird name, KPL 387C211 is Looking at patients who are having a flare of pericarditis or recurrent pericarditis at time of screening, so these patients have to have the pericarditis, and then they are randomly assigned to one of four arms of this drug at different doses at different intervals, and then they will transition to long term treatment with this drug. And at some point, once we, once the study has enough data on which is the preferred dose, they would actually go into a blinded randomization to placebo or active drug like we've seen in the prior, in the prior studies. So this is seeking what is the efficacious dose. This is the phase two part, and then whether that is actually. Efficacious in keeping patients from recurrences. That's a phase 3 part. So I look forward to seeing the results of this study. So if you have a patient that you think you would want to use an H1 blocker, you can certainly refer Dr. Theresa or to me to consideration for this trial. As you know, trials have very strict inclusion, exclusion criteria, so we'll have to see if the patient qualifies. There is Second trial with sorry, what's going on here, there's a second trial with the same drug it's actually transitioning from one treatment to another treatment. So this is actually for patients who are already on treatment for recurrent pericarditis. They can be on any of the IL-1 blockers and so you're now transitioning from the existing IL1 blockers to this. newer I1 blocker once monthly injection to see if we can keep them in remission because if the drug is shown to be successful, we'll want to know how to transition from one drug to another. And again, the greatest benefit here may be this drug may be more powerful by blocking completely the receptor and it may allow for less frequent administration. I'm sure our patients will like more. Another trial that is ongoing with IL1 blockers is actually not available in the United States at this time, but it may be on our radar at some point. It's with the other IL-1 trap, the goflia, and these are also looking at a different extension and seeing how efficacious the drug is and may seek enroll. In the United States at that point, at some point, but not right now. Moving on to other targets, the inflammasome inhibitors. If you remember earlier I showed you that this star-like structure here in the middle of the picture is the inflammasome. The inflammosome senses the injury from sources and activates. Interleukin 1 beta interleukin 1 beta is released. It does also other things. It actually mediates inflammatory cell death that stimulates more injury and more inflammation. So there are different companies that are looking at inhibiting the inflammasome structure itself. This is one of the drugs. It's from Aventix. It's now been purchased by Lilly. Uh, and, uh, um, there is an ongoing phase 2 trial for patients that are having an active recurrent pericarditis flare. I think I have a slide after here. Where in here in the bottom, you'll see that in this phase 2 trial, the patients are receiving this oral inhibitor pill twice a day, and they're initially getting treated. Everybody's getting treated and see if there's beneficial, and then those who respond will continue an extension period. This is again is a pharmacokinetic pharmacodynamic study, phase 2, finding the dose, and I would expect that they Follow with a phase 3 randomized double blind placebo controlled trials. This company has other inflammosome inhibitors. You can see the 2735 is what the company shows as being investigated in recurrent pericarditis. There's another one, it's 3232, that is slightly different molecule. It also penetrates the brain, and the company is exploring it in other indications. Why am I showing this to you? Because they just recently presented some of the data with this inhibitor in patients with obesity and cardiovascular risk factor. This was a studied not on pericarditis, but it was on patients who had elevated inflammatory biomarkers. They were obese, and they were 2 by 2 study with either this drug or semaglutide, the active ingredient of Ozempic or Regovi, and what they found here was that this drug Was efficacious in reducing the C-reactive protein, which is the readout of the systemic inflammation here as shown on the left as percent change and on the right as absolute reduction. Again, a different disease, but at least shows you that these drugs are active on the the inflammation. Amosome, IL-1 beta IL 6 cascade. So hopefully we'll see if they work in pericarditis. There's another trial ongoing as well with cannabiodiol. CBD is the non-psychoactive component of cannabis, so this is not what gives you the high. Many people have been studying CBD as an anti-inflammatory drug or inflammatory modulator. Um, it's actually available over the counter as CBD oil, but this here in, in the trial is a pharmacological grade CBD, so it's very pure and very effective, and there's a phase 3 trial ongoing for patients that are currently on IL-1 blockers. And how does this work? Well, it's a, it's a Small molecule. It's an oil. It interferes with the membrane fluid, fluidity and signaling. We've done some of the research in Virginia here in our labs showing that this actually modulates some of that upstream signaling like TLR signaling that primes the inflammasome, so it kind of fits in the same cascade here. This is again another summary from another publication where it shows the potential role of the CBD in red, uh, mostly we've, we have shown mostly the TLR signaling involved, but it may affect in multiple areas of this cascade. There was a pilot study that was finished and it was presented already and the publication is coming out soon. We were involved as one of the centers. In this pilot study, patients were having an active pericarditis episode. And they were treated open label with the CBD oil, and escalating dose, and what we found in that study was that there was a response in terms of pain and C-reactive protein uh with this treatment. Again, there was no placebo in this arm, this study, so we have to be careful about drawing too strong a conclusion, but certainly uh suggests there's a biological reason to Expect the benefit of this of this treatment here. That was the prior one was the pain here. The second slide here is the C-reactive protein. We rely on the C-reactive protein to look at the activity of disease and so certainly promising here. And the current trial is for patients who are on stable IL-1 blockers. So we have seen in trial that I-1 blockers are very effective in keeping patients in remission. Uh, I've not shown you the slide, but we have data now that shows that when you take patients off IL-1 blockers, there's a high risk of recurrences. And so we, uh, because the disease may still be active and it may last several years, so our job is to stratify patients and figure out who may be ready to come off an I1 blocker. We often do a tapering strategy. It's actually a publication from our team. It came out this month. About how to increase the interval between the doses of L1 blockers, and this trial is looking if adding the CBD oil may actually help come off an L1 blocker when the patient is felt to be been well controlled and possibly on the healing phase of the disease. So we're enrolling in this in Charlottesville. My colleagues are enrolling also in Richmond at VCU. I don't know if Dr. Theresa is enrolling in Norfolk, but this may be another opportunity for our patients. So I think this brings me to the end. I'm happy to take more questions. I hope that, you know, I'm sure the definition of disease was easy. The diagnosis was pretty easy. I think understanding that the risk is not as low as we thought, and we need to identify high risk patients, complicated cases like the one with constriction we heard earlier. We need to make sure we know that the colchicine is part of the initial management always or almost always. Of course there's some contraindication to colchicine, and for recurrences, I1 blockers are likely the preferred second line, particularly if you have an anti-inflammatory phenotype. In some cases, however, you need to identify them and you need to put them back on steroids or start on steroids because they're special cases that need steroids to treat in systemic autoimmune disease. And uh please refer to clinical trials. If we didn't have clinical trials in the past 5 years, we'd be still doing steroids for most of our patients and that is not doing them a favor. So please refer to Doctor Teresa or to me in Charlottesville or to Doctor Thomas in Richmond. There's plenty of trials going on. Thank you. Published May 4, 2026 Created by
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