Welcome. Thank you guys for having me here. I'm going to go over a case series regarding steroid-dependent chronic eosinophilic pneumonia and using anti-IL-5 antagonists to treat this disease. So I'm from the University of Chicago. These are the objectives. So just for some background, chronic eosinophilic pneumonia is a very rare idiopathic disease, interestingly very female predominant. As opposed to acute eosinophilic pneumonia, this is more often associated with nonsmokers. And it presents as this kind of unresolving pneumonia, refractory to kind of antibiotics, like they get better after they come off antibiotics. And what's pathognomonic for this disease is this photonegative pulmonary edema where the infiltrates are upper-low predominant and peripheral as opposed to bilateral and bibasilar. It's a diagnosis of exclusion, so once many other things have been ruled out, oftentimes you'll find the BL as eosinophilic predominant, and you have some peripheral as eosinophilia. Some patients have elevated IGEs. So back in the 1960s, this is when the disease was first defined, if you will, as this very steroid-responsive pneumonia. You'll have a patient come in with bilateral infiltrates that is, this is at the time of tuberculosis where they would get tuberculosis therapy and many other things. And just as a last-ditch effort, they would try steroids and find, within 48 hours, resolution of all symptoms, and then within five weeks, complete resolution. And then when the patients come off steroids, they have a recrudescence of their symptoms. It's very refractory in that regards to coming off steroids. And this was a series that looked at whether extending the course of steroids will help calm down whatever the etiology of the inflammation is from three months to six months. And they found that there was no difference. If you extend the course to six months, the patients still have relapses. And again, there's no significant difference. So while the etiology of the disease is unknown, the cell type that's kind of partly responsible for the pathophysiology is the eosinophil. And as you're all aware, there are multiple biologics that target different activating pathways of the eosinophil. And one thing that I didn't disclose but wanted to discuss is I'll be discussing off-label use of mepolizumab and benoralizumab. Restolizumab is an IV. It requires patients to come into the clinic, so we didn't include that in our case series. So not that what I'm doing is novel. Many other groups have used these as ways to get patients off steroids who are kind of steroid-dependent. So this group looked at mepolizumab and benoralizumab and were able to show that patients who are on chronic steroids, if you start these therapies with these, you can wean them off their steroids. So our study is a single center retrospective kind of case series that was looking at how out of our patients, how many of them were able to come off steroids. And some secondary outcomes was just using biomarkers to look at eosinophils. And what we were interested in kind of the secondary outcome is how willing is insurance to pay for this off-label in these patients who are steroid-dependent with all the side effects that that entails. So this is kind of an overview of our patient characteristics. Let's see if the pointer works. So you'll notice most of our patients were obese, hypertensive with concomitant OSA. Again, is this a sequelae of the chronic steroids? Can't say. But for those who received BAL, most of them had eosinophilic predominant cell count and peripheral eosinophilia. A couple of the patients required supplemental oxygen. Interestingly enough, those who had IGEs drawn, all of them had low IGEs or undetectable IGEs. And this is our primary outcome for most of the patients. Similar to what was seen in about three other case series, these patients are able to come off steroids, most of them completely. And then this, our biomarker, you can see the drop in peripheral eosinophilia from in the thousands down to the tens. So what is also interesting is, as you know, a lot of these are younger patients, younger female patients who don't want to be, want to have this chronic disease. They want to come off their medicines. So a couple of our patients asked, can we just come off our mepolizumab or benrolizumab and see what'll happen? And interestingly enough, for the past three years, one patient tried three times to come off her mepolizumab when it was unable to come off just with recrudescence of their symptoms. And this is just for how fortunately all of our patients were able to get it approved, off-label by insurance companies. And obviously some insurance companies will require their formula biologic and other ones, the pharmacy benefit won't cover it. So our wonderful pharmacist was able to get this covered. And for the last couple of minutes, I'll just go through how similar to like steroids, this is very responsive. So this is kind of the classic image of chronic eosinophilic pneumonia, the upper low predominance of it. And you'll see on your right, this is before and after mepolizumab initiation. You can see kind of complete resolution. Also, what's quite interesting is three out of our five patients had this kind of central bronchiectatic disease that was kind of filled with mucus plugs. And that's why we would have multidisciplinary discussions whether this is overlap with asthma. And you'll see what the bronch looked like, just diffuse mucus plugs, similar to what you'd see in a severe eosinophilic asthmatic. And you can just see after the initiation of these biologics, just resolution of these mucus plugging. And this patient actually went resection of the slope just because of how severe her disease was. But again, another example of these patients who don't meet the criteria for asthma, but do have this eosinophilia on their BAL and this disease. So in conclusion, this is a very rare disease diagnosis of exclusion. Again, the comorbidities are probably a sequelae of the chronic prednisone use. And again, not that we're showing any novel, but from a mechanistic standpoint, targeting the eosinophil is an effective way to kind of use it as a steroid sparing agent. But again, the patients are now on the mepolizumab, which again, better side effect profile, but getting at the etiology of the disease is unclear. And one of our main impetus for doing this study was to kind of expand the case series for having this approved as an indication for using these biologic therapies. And this work wouldn't be possible without our wonderful pharmacist who is very dedicated to ensuring our patients get equitable health care. Thank you. Any questions for Dr. Shama? Yes. I noticed in those scans, some of your patients after mepolizumab, there's bronchiectasis that are present. Is that common that you see in these patients? You know, in three out of our five patients, they had this phenotype. So in looking at the literature, specifically the radiology literature, they do comment on central bronchiectasis. That's why there's this overlap. Our radiologists read these initial studies as ABPA, like consistent with ABPA. But as you are aware, the IgE levels were undetectable. I didn't include this, but the aspergillus serologies were negative. So I took this out of the slide, but there's significant overlap with ABPA other than the aspergillus overlap and the IgEs. So to your point, as you know, most of these diseases are on a spectrum. So is this on the spectrum? Is there some environmental irritant that's causing this chronic eosinophilia? Not sure. But it is noted, the central bronchiectasis. So Dr. Pablo, in Texas, what does it look like for patients who visit all of the Bronx? Bronx extensive, like AFBs, fungal cultures, everything. And it was oftentimes just colonized with pseudomonas, staphs, and occasionally rare things. These patients underwent multiple bronchs just because these patients were referred from the community oftentimes, who their pulmonologist did extensive work up and wasn't able to find the diagnosis. So we repeated the bronch and you'd get things. So to your point, nothing like pathognomonic in terms of what grew on their cultures, but just typical things in bronchiectasis. Thank you. Yes. I have one more question. Do you feel that when we're talking about counseling patients first, initiating them, or are there silos that we should be having conversations with them about how this probably will be, or at the very least, can be a lifelong therapy for them, rather than something that will be a trial for a couple of months or a couple of years? How does that factor into your discussion? Certainly they have the disease and this is their option, but they're not going to say no in prepping patients that this is something that could be a lifelong thing, like insulin or fluoroxan that they'll have to take. And oftentimes, these patients are hesitant to do self-injections with these therapies. Wonderful question. I mean, 50% of patients who have CEP are able to wean off prednisone and do well. So this is very uncharted territory. So initially, I would counsel patients that will give this a shot to get you off your prednisone. And then that's why we've had these multiple attempts to see if we can get them off their biologics. And going forward, I would counsel them that you might be on this for lifelong. We'll need to move on to the next speaker. I'm sorry to cut you off there. Our next speaker is Dr. Gandhi, and he's coming from University of Arkansas. He's going to talk about combination therapy with profenadone and intenitive in IPF, a systematic review and meta-analysis. Hello, everyone. Thank you for having me here. My topic is a systematic review and meta-analysis that we conducted to evaluate the use of profenadone and intenitive as combination therapy in patients with idiopathic pulmonary fibrosis. I'm a third-year internal medicine resident at University of Arkansas, and I have nothing to disclose. So moving on, idiopathic pulmonary fibrosis has been a known chronic progressive fibrotic type of interstitial lung disease, where in 2014, nintedaneb and profenadone were approved as antifibrotic agents to slow the decline in the forced vital capacity amongst patients with IPF. Now, traditionally, they are used alone. However, there is some data regarding the fact that they have different mechanisms of actions along the fibrotic cascade, and that provides some rationale to using them together as combination treatment. However, the literature on the same is very sparse. So we conducted a systematic review through three databases and included patients who had IPF and were placed on combination antifibrotic therapy using profenadone and nintedaneb. And we looked at two main outcomes, namely the safety profile of this treatment. We looked at the frequency of adverse events, which were defined as events secondary to the treatment, looked at serious adverse events that led to hospitalization, life-threatening events, or death, and looked at the efficacy of this approach. I also have a QR code to get the PRISMA flowchart for this systematic review for those interested. So what we find was there were a total of seven studies that were included in this review involving about 240 patients who were predominantly male and were around the age of 68 years. They were placed on nintedaneb and profenadone therapy, received this combination therapy for an average of about four and a half months, and the average duration of follow-up was about seven and a half months. The slide here is really busy, and it's a summary slide of all the studies that were included, but what I would like to draw your attention to are three main things. One is the study designs. So about three of these studies were retrospective observational cohorts, and the remainder were clinical trials. Most of them were conducted in Southeast Asian countries like Japan and South Korea, and a couple of them were multicenter studies. And about three studies provided direct comparison with the monotherapy group as well. So when we looked at the safety of this approach, we found that about 80% of the patients actually experienced at least one side effect, and subsequently we compared patients on monotherapy and those on combination therapy, and we found that this was no different between the two groups. Next, we were looking at the adverse event profile and what these patients were experiencing, and we found that gastrointestinal symptoms were comprising the most common adverse events that these patients experienced, with diarrhea being the most common at about 41%, followed by nausea, vomiting, loss of appetite, and fatigue. We also looked at the number of patients who were experiencing a serious adverse event, and we found that this was very low in the combination group. It was about 3% people who experienced a serious adverse event. And again, comparing that in the monotherapy and the combination group, there was no statistically significant difference between the two groups. However, what was curious to see was that when we were comparing the combination group to monotherapy group, a higher proportion of patients experienced an adverse event that led to discontinuation of therapy from combination to monotherapy. So it was about a quarter of the patients who experienced something like this, and we compared the same in the monotherapy and the combination group, and there's where we find a significant difference, where monotherapy was just about 10% patients who experienced that. Now, looking at the efficacy of this approach, five studies looked at that, and overall, it looks like combination therapy appears to be more efficacious, and the metric that we used was looking at the rate of FVC decline. Each study reported it heterogeneously, some reporting it as milliliters, some reporting it in percent predicted. However, what you can see is that there is a trend where combination therapy group has a lower rate of FVC decline when compared to their same monotherapy cohort, and this was statistically significant in two out of five studies. However, the number of participants was overall very low. So to conclude, combination therapy and monotherapy appear to have very similar profiles in terms of adverse events. However, patients on the combination therapy were more likely to experience an adverse event that led to discontinuation from combination to the monotherapy. The preliminary data that we have so far does suggest a possible benefit of using combination therapy to slow the decline of FVC amongst patients as compared to the monotherapy with antifibrotic agents. However, there are several limitations to this systematic review, and one of them is the high degree of heterogeneity amongst the studies that were included, and that there were very few studies with few participants. Thank you so much. I had one question actually. So in some of the observational studies, do you know how they accounted for the exposure to the medication, just to account for immortal time bias in those? They just provided a mean duration, and it wasn't always, so there was a loss of data as well. There were patients that they weren't able to account for the exact duration they were on because there were periods where they weren't receiving that, and then there were periods where they were placed on that. So they just reported, each study just reported it as a mean duration. Any questions for Dr. Gandhi? All right. So we can move on to Dr. Fauldi, who's coming to us from Mayo Clinic. He's going to talk about treatment with Ivacopin for ankyl-associated vasculitis with DAH. Good morning, everyone. It's a pleasure to be here. As introduced, I'd like to share a case series of patients with ankyl-associated vasculitis who received Ivacopan in the context of diffuse alveolar hemorrhage. I have no disclosures. In terms of objectives, I'd just like to revisit diffuse alveolar hemorrhage in the context of ankyl-associated vasculitis, introduce Ivacopan and its current applications in ankyl-associated vasculitis, as well as summarize this novel case series of patients. As you all may well know, DAH is the most common subset of immune-mediated capillaritis that cause diffuse alveolar hemorrhage. It has a variable presentation with about half of patients that present with hemoptysis, with estimated mortality in most recent literature of around 10%, although historical literature would say that the mortality is higher, with respiratory failure occurring in anywhere from 10% to 60%, favoring the higher rates of respiratory failure. Bronchoscopy with BAL demonstrating sequentially bloody return, or a high proportion of humans that are in macropages more than 20%, is the gold standard for this diagnosis. And in terms of treatments of ankyl-associated vasculitis, traditional remission induction strategies are now favored via the new ACR and ULR guidelines, with PLEX no longer being favored at this point. The alternative complement pathway in the context of ankyl-associated vasculitis has developed increasing recognition. The alternative complement pathway is a really powerful chemotactic agent recruiting neutrophils, myeloid cells, to name a few. It magnifies the intensity of immune inflammation and drives not only complement deposition, but other inflammatory cascades. That ultimately mediates necrotizing vasculitic manifestations of ankyl-associated vasculitis. The role of Avacopan in the context of DEH is somewhat less clear, however. Avacopan, to introduce it as an agent, is a complement C5a receptor antagonist. It's approved in the context of AAV with severe manifestations. And there's increasing literature to support its role, especially in those with severe renal involvement. Although the phase 3 clinical trial data available only reported 12 patients with DEH and excluded those that had prolonged mechanical ventilation. And so the role is less clear in that subset of patients. And so we sought to explore that in our case series. So this was a retrospective, multi-site, single-center trial conducted across the Mayo Clinic sites, including Florida, Arizona, and Rochester. We included patients that were 18 years of age or older, who had either GPA or MPA by Chapel Hill and ACR-ULR criteria, and had a diagnosis of DEH based on BAL with hemocytopenia and macrophages of greater than 20%, progressively bloody return, surgical lung biopsy. And in one specific instance, with patients that had severe manifestations of ankyl-associated vasculitis that were biopsy confirmed with clinical features consistent with DEH. Avacapan was, of course, used in the context of remission induction strategies for all of these patients. And in terms of describing these, we ultimately identified 15 patients that met these inclusion criteria. The median age was 66 within a quartile range of 52 to 72, predominantly female, largely overrepresented by white ethnicity. And the majority of these patients had ankyl-associated vasculitis at diagnosis, with a fairly balanced population of those that were PR3 positive as compared to MPO positive. And by phenotype and classification, these were predominantly GPA rather than MPA. In terms of the organ manifestations and disease severity, the median BVAS-WG or Birmingham vasculitis activity score for Wagner's granulomatosis, which has been validated in the context of both MPA and GPA, was 8, with an interquartile range of 5 to 10. The majority of these patients had generalized manifestations. A small minority had nervous system involvements. ENT involvement was fairly common. And we saw a confirmed renal involvement in 60% of patients. The vast majority of patients received methylprednisolone. Everybody received methylprednisolone. The vast majority received rituximab. About a third received plasma exchange during the course of this remission induction, with three patients receiving cyclophosphamide, which two of those had overlapping rituximab and cyclophosphamide administration. What's been also described in the DEH and ankyl-associated vasculitis literature is just a parameter describing degree of hypoxemia on presentation, which was obtained at the first ER or admission encounter, with the SpO2-FiO2 ratio, which was 449 in these patients. And in terms of severe involvement and organ dysfunction, two developed renal failure and three developed respiratory failure, which was defined as requiring high-flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation. Diving into the outcomes a little bit more from a pragmatic standpoint, only seven of these patients, or 47%, received Avacopan during their index hospitalization. The lag time between the initiation of Avacopan as it related to the diagnosis of ankyl-associated vasculitis and diffuse alveolar hemorrhage and the initiation of traditional remission induction therapy was 18 days. Barriers to initiation, especially while hospitalized, was cited in at least four patients with a lack of inpatient availability or difficulty obtaining the Avacopan while hospitalized. We follow these patients for a median time of 21 weeks. And remission was achieved in 14, or 93%, of patients. And I'll describe the one patient that didn't achieve remission with complete remission, which was defined as a BVAS WG of zero, completely weaned off prednisone, in 10 patients. Avacopan was discontinued in two patients for cost, in one patient just due to kind of perceived completion of therapy. Serious adverse events were described in two patients with serious infection, with death occurring in one patient who suffered a, who was infected with severe meningoencephalitis. Relapse was seen in zero of these patients. And kind of further describing these patients and kind of characterizing their glucocorticoid use during their hospitalization and as remission was achieved. I think I'd just like to point out the significant heterogeneity across this case series of patients. Four patients were completely weaned off prednisone by week four. I think highlighting that two of these patients, in fact, received no prednisone after traditional remission induction therapies. And so in conclusion, Avacopan appears relatively safe in patients with ankylosocial vasculitis and dibeocephalic hemorrhage. Enteral access, which wasn't, remains a barrier in critically ill patients. And that was seen in this case series as well. And more rapid glucocorticoid tapers need to be standardized as there was significant heterogeneity seen in this case series of patients. Thank you. Any questions for Dr. Falde? Yeah, so major trials would kind of standardize kind of the achievement of complete remission, which would be a VVAS WG of zero, completely off prednisone, at 28 and 52 weeks. And in this case series, you know, and the rates are generally around 60 to 70% by about 28 weeks. I think in the advocate trial, that was achieved in around, in about that time frame. And so, again, these patients were followed for a shorter period of time as compared to that. But certainly we saw remission, time to complete remission, was quite a difference and shorter in this subset of patients. Yeah. You know, you know, so really interesting, we kind of delved into that patient a lot. You know, they, that patient specifically had received at least two remission induction therapies. There were, they were, they kind of were transferred from an outside facility where they received traditional remission induction and plasma exchange. And then again, kind of cyclophosphamide and rituximab, it, you know, in discussions, it's, it seems less likely that that's, that's correlated with the evac plan as, as, you know, the biggest concern would be as you're targeting the complement pathway, that's, that you could, you could target the membrane attack complex. However, this patient had a viral meningoencephalitis rather than a bacterial one. So I think that that's, it's hard to say, obviously there's, there's, there's a fog of war within that data set and obviously it's, it's just a case series level data. So challenging to say, but certainly it was reported. We can take one last question. It was the same question actually. Yeah. Okay. Thank you. All right, we can move on to the next talk. Dr. Limper from Mayo Clinic is going to talk to us about the impact of Nintendib dosing on clinical outcomes and analysis of real-world data. Okay. Wake up. There we are. Okay. So I'm going to talk a little bit about Nintendib dosing and looking at a real-world data source. This is OptumLab Data Warehouse Analysis. Thank you for letting me be here. I'd like to make one thing. As far as my disclosures go, I want to specifically say this is not industrial-supported in any way. This work was funded by a grant from Three Lakes Foundation, which is an independent philanthropy that provided the work. So we wanted to look at clinically meaningful outcomes in patients that are retreated with, are treated with lower-dose Nintendib, 100 mg twice a day as far as a traditionally tested 150 twice a day. And as I said, we used claim-based OptumLabs data and we looked at mortality and hospitalization and we did a one-to-one propensity matching for comorbidities and severity indices. Now we all know that Nintendib has impact antifibrotics such as Nintendib, slow FEC progression in IPF. We also know from our real-world data that Tim Dempsey and I published a few years back that this does impact mortality and reduces hospitalization rates. I'll show you some of that. We also know, I love your slide, it looks like the Pepto-Bismol guy, you know, in the pink outfits having all that diarrhea and cramping and stuff. But those side effects limit it. And you know, empirically, clinically, all of us, anybody in this room ever reduce the dose of Nintendib from 150 to 100 twice a day empirically? What data were you doing that on? Anybody had good data? No, the data doesn't really exist. That's why we did this study. Now this is all Impulsa's study data looking at decline FEC, Impulsa's 1 and 2 for Nintendib. We know that Nintendib slows that rate of decline. So I wanted to take a real-world data approach. We work in the OptumLabs data warehouse. We've had a great relationship with them. It is really 320-plus covered lives. These are all people that have private insurance and Medicare Advantage and it's across the whole country. And I won't go through all the details with this. It is a diverse data set. We have good data for diagnoses, for hospitalization rates, for outcomes, you know, and it's led to a whole string of publications by colleagues and analysts at the Mayo Clinic Group across a whole variety of data. Mayo Clinic was a founding partner with OptumLabs to set this up. The cons are, though, it does not have the whole Medicare fee-for-service. Within the last year, we now have the whole Medicare fee-for-service. I'm in the process of looking at that. We have done some analyses in that for the efficacy overall, but I won't be showing that data today because this is too new. So Tim Dempsey, when he was a fellow in my group, wanted to look at whether the antifibrotics impacted mortality. And in fact, across the OptumLabs data warehouse, if you're on any antifibrotic compared to no, you do have statistically improved mortality over about two years that then goes away because the disease progresses. But that was actually first demonstration. There have been similar demonstrations of improved mortality short-term out of registry-type trials. The impact on hospitalization is more lasting. Whether the antifibrotics keep people out of the hospital and that effect seems to persist. Both antifibrotics have equal efficacy across the board. When we compare them head-to-head, there's no difference. So how do we do these studies? You're not going to read that, but we took all the people that were on 100 twice a day and 150 twice a day, and then we took out of the 150 twice a day, which was the bigger cohort, we propensity matched them. So we had similar comorbidities, similar illness levels, severity was by oxygen use and amount, and we were able to do a one-to-one propensity match, and we had 345 in each arm, either 150 twice a day or 100 twice a day. And we looked at mortality, and there is no statistically significant difference at the reduced dose. Now I look at the lines, you look at the lines, you say, well, the 150 looks a little bit better, and there's 346, which is actually a good sample size in each one. However, it is possible that when we go back to the whole Medicare fee-for-service, that may or may not hold up. The findings, I think, are actually more of equivalency or more striking for hospitalizations. The curves are intertwined. So at least on this preliminary data, you could be a little rest assured, this is not definitive proof, I'm not making more out of this than it is, but we all put people on 100 milligrams twice daily because their guts don't tolerate it. They live in the bathroom. They don't want to live that way. And so we are looking into larger data sets, including the whole Medicare fee-for-service. So in this real world, these are docs all across the country. Some of your patients may well be in these data sets that I'm reporting right now, wherever you're at. And we actually saw equivalent rates of mortality and equivalent rates of hospitalizations on people on reduced dose Nintenoneb, 100 milligrams twice a day, compared to the traditionally and the RCT, randomized controlled trial study, 150 milligrams twice a day. And I'm going to say, this is not randomized controlled trial data. I doubt that Barringer is ever going to do 150 versus 100 milligram head-to-head trial, but it does give us some ground to start to look at this. And as I said, we're taking it to our Medicare fee-for-service data. And by the way, in that data set, we could do the immortal time bias analysis you were asking about. And we just published, or in the process of publishing that, on the whole outcomes, not the dosing outcomes in the ERJ. And with that, I'm going to finish up. Hopefully I was on time. Thank you. Questions for Dr. Limper? Hi. Charlotte Molasky from the Bronx. It's sort of hard to derive from that, but would you advise doctors to prescribe the higher dose initially to optimize the patient and then de-escalate, or just from the get-go? So I'll just, I could tell you what I do. I always start 150 milligrams twice a day. Not everybody gets intractable diarrhea. I tell them to self-treat with a low-peramide Imodium, have it there before they start it. And I have a lot of people that get by with a couple of low-peramides Imodiums a day. If they have intractable symptoms, they're losing weight, they're living in their bathroom, or other GI or other intolerable side effects, then I reduce the rate, the dosing at that point. So that's what I do. So I'm basing it upon what I know from this study, but I always start at full dose because that's what was studied in RCT. Any other questions? Yeah. Any experience with making doses, like 100 in the morning, how does that work? Yeah. That's a great question. I actually went through our data sets, and the numbers start to shrink. So I got to the point that it was not worth doing an analysis. So great question. Maybe out of the whole Medicare fee-for-service. I think there was one here and there. I'm sorry if I may have missed it, but the patient data set included only IPF patients? Yeah, no. These were IPF, defined IPF. We've done a validation trial that was published in BMC using our coding that does show that our coding analysis with appropriate exclusions work well, but these are just IPF patients, thanks. Good question. It's a great question. We are actually going through all the available parameters now to see for both drugs, right? I mean, how do you pick which antifibrotic you use? To me, it's kind of a coin flip based on the side effect profile, but not everybody gets the side effect from either drug. So we're trying to determine exactly that, and whether there's some clues from the electronic records that we have. I think it's a great question. We have lots to do for a while to do it on. So, out of the first paper, these are people that were on the drug really for pretty much the duration of the time we were studying them. I think that the disease tends to progress despite the drug. It's slowed with the drugs, and that's true for either profenadone or nintendinib. I think as we start to glean into the Medicare fee-for-service, we actually go from having We basically have 95,000 IPF patients across the country. We're going to be able to do that finer detail on people, do people that are on it longer. But obviously, if somebody doesn't tolerate the drug or either one, they come off the drug, they don't tend to do well, or they go off as they're deteriorating. I think it's a great question. We just don't know. Yeah, great question. Because we don't have lung function for all the patients. And so that's why I said we look at severity by oxygen utilization time and such. Because we don't have lung function. Now, within the Medicare fee for service out of the 95,000 that I was talking about that we're in the process of starting to analyze, we do have lung function and complete record data on about 10 to 20%. That'll still give us a pretty big cohort of 9, 10,000 IPF patients that we can do exactly what any card-carrying pulmonologist would want. Where's the lung function data? I will say one last thing, though. When I prescribe antifibrotics, which I do, not to every patient with IPF. We always talk about it. My patients don't really care what their FEC does over time. They want to know, what can I do? Am I going to be able to walk? Am I going to be able to stay alive? And am I going to be able to stay out of the hospital? So to a certain extent, these are kind of clinically relevant things to patients. But I agree with you. We're going after the lung functions, but we don't have them yet for this data. Great question. Thank you. All right. Next up, we have Angela Montes from MUSC. She's a medical student there. She's talking to us about methotrexate versus mycophenolate in treatment of cardiac sarcoidosis. Hi, everyone. This is a presentation on treatment outcomes with methotrexate versus mycophenolate mofetil in cardiac sarcoidosis. My name's Angela Montes. I'm a fourth-year student at MUSC in Charleston, and I have no disclosures. So just some background. Cardiac sarcoid is a major cause of morbidity and mortality, and its treatment typically requires high doses of prednisone. So steroid-sparing agents have been increasingly used in its treatment, but it is unclear which second-line therapy to use. There really haven't been any studies directly comparing the steroid-sparing agents methotrexate and mycophenolate in its treatment. However, there have been past retrospective studies showing that methotrexate and mycophenolate have both been proven to lead to a decrease in SUV uptake on PET scan, as shown on the slide here. So our study aims to compare clinical outcomes, which we defined as the change in SUV uptake on PET scan, and steroid-sparing effect in a retrospective cohort of cardiac sarcoid patients treated with these medications. This was a retrospective cohort study. Patients had to be at least 18 years old, seen at our institution. They had to be treated with either of these medications between May 2017 and May 2022, and then they had to have two PET scans. PET 0 was prior to starting the medications, and PET 1 was 90 to 365 days after starting. So then we had our outcomes. We had clinical outcomes, medication outcomes, as well as combined outcomes. So starting with the clinical outcomes, we defined that as the change in SUV uptake from PET 0 to PET 1. A positive clinical outcome was any improvement by at least 20%, and that was a decrease in SUV uptake by at least 20%. This was then subdivided into a partial metabolic response and a complete metabolic response. Anything less than that was a negative clinical outcome. So this could be a 0 to 20% increase or decrease in SUV uptake, defined as a stable metabolic disease, or anything greater than 20% increase in SUV uptake, which was a progressive metabolic disease. So to the left, we have our medication outcomes, which is the change in prednisone dose from PET 0 to PET 1. So anything greater than a 50% prednisone dose reduction was a positive medication outcome. Anything less than that was a negative medication outcome. We then attempted to stratify these patients by creating four categories of combined outcomes that prioritized clinical outcomes over medication outcomes. So we have our strong, moderate, fair, and poor treatment effects. So strong is a positive in both outcomes. Moderate is a positive clinical negative medication outcome. Fair is a negative clinical positive medication, and poor is a negative clinical and medication outcome. And then these were just some of the statistics that we used. So we did originally start out with 165 patients that had qualified. We did have to exclude 89 of them due to things such as insufficient time on medication or PET scan that was outside of the timeframe. We ended up with 76 remaining patients, 43 on methotrexate, and 33 on mycophenolate. Some of our demographics included a median age of about 58, 59, and then we had mostly white males. In terms of baseline characteristics, the most common presenting feature at cardiac sarcoid diagnosis was palpitations. We had about 40% of patients that had biopsy-proven sarcoid, and then our baseline SCV uptake was around 4.0. So for our first outcome category, our clinical outcomes, 67% of all patients had a positive clinical outcome. And then overall 30% of total patients had a 100% reduction, and it is more commonly observed in the methotrexate group, but again, not statistically significant. In terms of our medication outcomes, 75% of patients overall had a positive medication outcome, but again, no statistically significant difference between the two groups. And then finally, for our combined outcomes, 57% of total patients had both a positive clinical outcome and positive medication outcome. So they were put into the strong treatment category. There isn't any significant difference between the two medication groups again. However, there is a trend suggesting that more patients on methotrexate had a strong treatment response when compared to mycophenolate patients. Some of our side effects, the majority were GI related, and then more patients reported total side effects in the methotrexate group than mycophenolate, and this was statistically significant. So in conclusion, both medications had a significant steroid sparing effect. Both medications resulted in a significant decrease in SCV uptake on pet skin, and again, there is a trend that more patients on methotrexate were in the strong treatment response than mycophenolate. And then in terms of side effects, mycophenolate is generally better tolerated. Some of our limitations is that this was a single center analysis. We had a small sample size of around 76 patients. We only looked at short-term outcomes, and then less than 50% of our patients had biopsy-proven sarcoid. And then these are our sarcoid team members, and these are my references. Thank you. question. Yes, please. Sure. I'm actually not quite sure of the specific doses that we looked at in here, if I'm not mistaken. I believe it was just like more of a yes or no, like a yes or no whether they were on the medication or not. But I can definitely double check on that answer. Very nice study. I guess a question or comment, I guess the question is we usually do both PET as well as cardiac MRI, of course, because the PET is picking up active inflammation, the MRI may cause or show with late gadolinium enhancement scarring. So as the inflammation goes away, it could be scarring. And MMF actually has antifibrotic as well as anti-inflammatory. So I guess my question is really twofold. One, do you know if the PET scan was actually protocoled the same, because usually you need 48 hours of low-carbohydrate diet to adequately read a PET. So usually we call them cardiac PETs and not just so it's protocolized. And two, did they have any really MRI data in these patients? In terms of the first question, I'm not quite sure what the protocol is. I can get back to you on that. But in terms of the second question, in this study specifically, we don't have any cardiac MRI data. However, we have another study that's overlapping, that has overlapping patients. And we do have some cardiac MRI data that we can pull out. There's a question at the back. Great talk. Just curious, do you know why a certain patient's heart hydroxyapatite is not a good thing? and methotrexate and mycophenolate, so that was used to support in the decision of both of those medications. And then when talking to the attendings, I believe that they were using, I believe, mycophenolate because a lot of the transplant attendings were also using that, so that overlapped in their decision as well. All right, great job. We'll move on. Thank you. Our last speaker is Chengu Niu, talking about risk of diffuse alveolar hemorrhage with direct oral anticoagulants, a 10-year retrospective report. Still loading? Okay, good. So today we're going to talk about the risk of diffuse alveolar hemorrhage with the DOAC. So this is a 10-year retrospective study from the FAERS database. So I'm part of team on behavior, I'm Dr. Vavilasavi. So our authors has no disclosure for this presentation. So with increasing use of DOAC for various indications, there has been increased report of DOAC associated with diffuse alveolar hemorrhage. With limited data available, so we aim to explore the association between the DOAC and diffuse alveolar hemorrhage. And characteristic and the clinical future use this pharmacal database. So this is observational, retrospective, and pharmacal study based on the U.S. Food and Drug Administration Adverse Events Reporting System database. It was performed between the January 2013 and December 2022. So pulmonary diffuse alveolar hemorrhage was identified using the terminology in the medical dictionary for regulatory activities classification. So the five FDA-approved DOAC available in the U.S. are PaxBan, BatraxBan, Dabigatrin, and DoxBan, and RavaxBan was included in this analysis. So adverse events associated was performed by calculating report ulcer ratio and within 95% confidence interval. So the ulcer ratio was considered significant when the lower limit of 95% of confidence interval was more than one. So our studies show there's almost 3,000 drug-induced diffuse alveolar hemorrhage from the total of 18 million events reporting the FARS database from 2013 to 2022. So among them, there's 462 were DOAC-associated diffuse alveolar hemorrhage reports. So highest occurrence was seen at age 65 to 85 years, and within mostly they are male compared with female. So they are 61% versus 32%, respectively. Atrial fibrillation, deep vein thrombosis, pulmonary embolism were understandable. The most common reported indication for use, so you can see the number was 240 and 67, respectively. Death occurred in 0.4% of all DOAC-associated diffuse alveolar hemorrhage, but 388 of them need hospitalization and were deemed life-threatening. It's pretty remarkable outcome. So among the adverse events, so rivaroxaban was associated with the highest diffuse alveolar hemorrhage rate, 47.8% followed by apaxaban. And odds ratio for DOAC-associated diffuse alveolar hemorrhage was 12.84. That was pretty high. And with regards to each DOAC, apaxaban had a higher odds ratio than rivaroxaban through the entire association in the 27% cases. And surprisingly, dabagetran and apaxaban had the highest odds ratio, and this 13.47 and 21.43, but result are likely from relatively small rate of adverse event from this unpopular DOAC when calculated against the adverse event report in the database. Odds ratio was not calculable for betraxaban given no report in the adverse event in the database. So the main finding of DOAC-associated diffuse alveolar hemorrhage is higher in older adults. Male and frequently required hospitalization were life-threatening. Among cases reported, the most common DOAC encounter were rivaroxaban. Lastly, the fact DOAC present nearly 13-fold increase associated with diffuse alveolar hemorrhage is an important finding that cannot be ignored. So this database comes with definitely some limitation. FDA does not require casual relationship to prove or give the use of other drugs cannot be delimited, and this should be explored further real-world data. And with the recent increase in trend of DOAC-associated cases being reported, particularly the higher use of DOAC, so extend beyond the non-alveolar atrial fibrillation, caution for major bleeding-related events should be used. So clinical implications of diffuse alveolar hemorrhage is serious and potential fatal complication often require admission to ICU for supplement oxygen ventilation. So based on our database analysis, DOAC has strong correlationship with diffuse alveolar hemorrhage and this needs further study, I believe. So thank you so much.

diffuse alveolar hemorrhage

DOACs

US FDA's Adverse Events Reporting System

atrial fibrillation

deep vein thrombosis

pulmonary embolism

hospitalization

rivaroxaban

odds ratio