Chapters Transcript Positioning Newly Approved Therapies in IBD Course: Eleventh Annual NYU Langone Advanced Seminar in Psoriasis and Psoriatic Arthritis Thanks for the invite. Always good to see, uh, friends and colleagues in the audience. So another GI talk. So hopefully you guys won't, uh, fall asleep, um, but I'm gonna talk about how we position some of our newer therapies in IBD and really focusing on twenty-threes and jacks and hopefully that could generate some questions and some discussion. I know we're gonna have afterwards on similarities and differences on how we manage, um, our patients. Uh, these are my disclosures. So first, I just wanna talk about our the goals of treatment, um, and what we speak about in IBD where obviously we want our patients to feel better and feel better quickly, um, right? There's a significant impact on the quality of life with urgency and even showing up to work or school each day, but we're really shooting for those deeper goals, right? That we're having mucosal healing when we do a colonoscopy, it looks great. And if possible, which isn't attainable in the majority of patients, is histologic remission. And this we sort of stole from uh you guys, uh, this, this concept of treat to target. So we have our stride to guidelines now and the key here is whatever therapy, whatever advanced therapy we're starting is we wanna make sure we're monitoring both clinically and objective markers of inflammation. So when we start a new therapy, we're monitoring them symptomatically within, you know, those first few weeks. We're looking at biomarkers. We use CRP more and more, we use fecal calprotectin, stool marker of inflammation. So it really helps differentiate, right? Is the, um, the symptoms of inflammation driven by IBD or something else. We're using more and more intestinal ultrasound now. Um. Um, in our practice, you know, busy almost every day now monitoring patients, seeing those early changes within the 1st 1 to 3 months after starting therapy, and then eventually repeating a colonoscopy or an enterography around 6 months to making sure we're hitting our target. And the concept is, and I know similar um with er room, we want to treat early, right? And for IBD why this is important is that, and this is probably the spend the most time speaking to um my patients about is symptoms don't always correlate with disease activity. And what happens with IBD is the symptoms could fluctuate up and down, but inside that irreversible bowel damage, that fibrosis is slowly building. And if we're able to treat early, we could prevent those complications of strictures, fistulas, surgery. And one of the newest studies to really uh show this, and this probably could only be done in a pediatric patient population, this is called the profile study, and they actually got pediatric patients on combination TNF and an immune modulator within 2 weeks of diagnosis. And looking at the steroid-free remission at the end of a year, and this is the highest rate we've seen, right? 80%, right? So the importance of treating early, um, in this, now I don't think we could do this in adults, but you know, if you look at any of our data, anytime somebody has a major clinical trials, you have disease duration of 8 to 10 years, those are gonna be the lowest rates of remission. You do a trial when somebody has disease within 2 years, the numbers are even better. Pediatrics are even higher post post-op, so early is the key. And I think for all of our therapies if we start early enough it probably doesn't matter so much what therapy we choose. We also have a lot more agents now, right? This is dramatically changed, right? If you go back 56 years, we had TNF, uh, vitolizumab was approved in 2014, used to kinumab for us in 2019, and then until recently now we have this influx of medications, and we expect a lot of newer therapies, both similar mechanisms, uh, different modes of delivery, and newer mechanisms of action in the next three years as well. So how do we make a decision? So, it all starts with efficacy, right? The rest is a moot point. If it's not gonna work, why put your patient on it? Um, but these are all the other things we talk about safety, right? Age and comorbidities, how quickly is this gonna work, right? If you have a patient going to the bathroom 10 times a day with urgency and it's gonna take 23 months to kick in, that's not gonna do the trick. Pregnancy, we just heard a great talk from Lisa, um, on this, and I agree with her completely that pretty much the most important thing is disease control. So as IBD docs, we keep patients on all our biologics throughout pregnancy, breastfeeding, and if we need to with our jacks, we do, um, EIMs and then adherence, but. I think no matter what therapy I put patients on adherence is gonna be tough across the board. And when trying to make these decisions, we don't, you know, the gold standard is head to head trials, and we really don't have that many head to head trials yet in IBD. More are coming, so we have one head to head in UC and we have two in Crohn's. Otherwise we're looking at placebo controlled trials. There's the two main, the way they're mainly done in IBD, they're either randomized withdrawal, so patients that respond after the end of induction will then re-randomize, so you have to take that. One year, uh, number remission rates with a grain of salt, and now we're having more of those treat through study designs, which is. You know, more practical, when you see a patient in the office, you start them on therapy. How are they, that one patient, how are they gonna be doing at 3 months, 6 months, a year later? Real world evidence, which is very important. There was a nice study done now, I think 7 years ago, showing at least for IBD when we're trying to the patients we see in the office, less than 50% would actually qualify for these clinical trials. And then there's more and more data, uh, in our world and these network meta-analyses, very complicated statistical analyses that I can't explain. But the concept concept is if we have, you know, a study head to head comparing drug A to drug B and another head to head comparing drug B to drug C, we can make these indirect comparisons. These studies I always take with a grain of salt. These are churning out now every couple months in a major journal. There's another network of meta-analysis, but it's really what you put in is what you get out. So let's start with ulcerative colitis. So our first, uh, great. So, uh, one of our new mechanisms of action, uh, which doesn't overlap is our S1P receptor modulators. Um, so this was the, um, studies, the elevate studies that were done in moderate to severe UC. Um, for us these are pretty good deltas or differences between drug and placebo. We really wanna see those numbers over 20% now. I think some of our older studies we would accept 10%, 15%, but with these newer agents what I'm looking for is over 20%. So you see that here. We also a big, uh, thing I look at in our clinical trials are how many of these patients were bio exposed versus or advanced therapy exposed versus advanced therapy naive and how do those look. This study effective therapy, but if you actually look, actually look at the patient population, about 70% were bio naive. So these really fit only fit into our practice more moderate patient, not sick, um, but it's a nice oral option, right? So the real benefit with this, it's one pill a day. Why this hasn't really been taking up as much, I would say, um, in IBD is there's a lot of baggage around it, right? It's very easy to put somebody now on a TNF on a 23 on used toinumab. Here you need to get an EKG. You have to have them see um a dermatologist, an ophthalmologist, all this around the time of start of therapy. And if you think, right, every, our offices are super busy and trying to coordinate all of this to get somebody on a pill isn't always practical. But I do think it's a very effective therapy again for the more moderate um patient and somebody that would much rather take a pill. It's a great option. So what about our IL 23 and 1223 inhibitors? So I just put the dosing strategy, so they all vary, uh, for IBD whether it's UC or Crohn's and whether it's induction or maintenance, and we have 3 selective IL-23 inhibitors. Um, just one addition, uh, guelumab now has a subQ induction for ulcerative colitis as well. That happened in, uh, a little more recently, so we have both subQ versus IV induction. And just to highlight, um, some of the different data, um, in ulcerative colitis, so mirikizumab, this was the first selective IL-23 inhibitor approved for ulcerative colitis, and just this is looking, these patients were re-randomized. This is looking at one-year outcomes. And what I wanna highlight here is whether you look at patients that were advanced therapy naive versus advanced therapy exposed, the deltas or the differences between drug and placebo are pretty similar, right? So just support that the selective IL 23 inhibitors and IBD do work very well first line but also as a second or third line agent. This is looking now at risenkizumab, which um there's overlap, um, uh, with you guys, um, and looking at their data, this is the 2nd, uh, IL-23 inhibitor approved for ulcerative colitis. Really, at least where the data shined is in this bio naive or advanced therapy naive patient population with patients re-randomized, but in the advanced therapy naive group, 70% um remission at the end of the year. When you look at the bio-exposed patients, they didn't really separate as well, right? That's in the for risen casesumab for ulcerative colitis. It's unclear why that is. Um, I think a lot of the part of it is probably just the patients that were included, rather that this therapy doesn't work in bio-exposed, but this is the data we have. This is our most recent um therapy approved for uh selective IL 23 inhibitor approved for ulcerative colitis. So this is looking at theelumab, and you could see here, um, at week 44, really nice deltas, right? You're seeing close to 30% clinical remission, and when the clinical remission endpoint in IBD trials is both symptoms, so stool frequency, rectal bleeding, as well as how the colonoscopy looks. So either perfect or close to perfect. So really nice deltas, and then if you look at the bottom right, this is an absolutely perfect colonoscopy. And we really see nice differences between drug and placebo, even in these really um advanced or more complicated patients, refractory patients, in the bio um and jack failure patients, so very effective agent. Um, I think Lisa was alluding to this a little bit, but, and this is a very safe therapy, right? So when we're talking to patients, I usually say the biggest risk with this therapy these classes of therapy is whether it's gonna work or not, right? Very low infection risk. We're not worried about cancer risks. So then we have eatocitinib, our JAK inhibitor, and this is pretty much we're 95, 99% using this over tofacitinib, um, now, um, for our IBD patients. And this is really where we started seeing deltas of 30%, right between, um, drug and placebo. And I think all of us in IBD that have used this therapy, we've had very sick patients where we're talking about surgery and we put them on eatoid, and not all, right? Not all patients respond, but we've seen pretty remarkable recoveries. Uh, with that, and this is looking at, uh, just looking at some of that data. This was a nice study, a head to head study, um, done at Mass General, just looking at eatocinoib versus tofacitinib. Again, our real world experience, one pill a day versus 2 pills, and just we think this therapy works better, and this is a nice study looking at different endpoints showing that eatocidoib has better clinical outcomes and endoscopic outcomes, um, than tofacitinib. So again, the only patients I'm really using Tofaci in a bar is if they can't um chew a pill or some insurance. I just can't swallow a pill or some insurance issues. The bigger issue with our um JAK inhibitors are the safety, right? And that's why um it hasn't been taking up as much and not really first line therapy. Uh, this is your data, right, that I'm presented to you, but the small increased risk in um. Uh, cardiac events and clots, um, and this was that select, uh, patient population rheumatoid arthritis over the age of 50 with underlying heart problems. So that led to all these different guidance. But most recently, um, for yatoinoib, there was an update with the FDA where the language was changed a little bit. It hasn't really translated to insurance yet, but hopefully that will. That now, it's, you don't have to fail or be exposed to a TNF or they say if a TNF is not advisable, or sorry, if an advanced therapy is not advisable. So what does not advisable mean? A lot of room for argument there. So we've been trying to just if you, um, you had to sit in the first line. It gives us a little window of an opportunity to argue with um insurance for that. So that little, that slight change hopefully will benefit. Probably the biggest reason why my patients stopupatocinonib is acne, right? And so we call it acne. And this is, we've seen pretty severe cases or even more mild cases that are just very problematic for our patients. We have a lot of younger, um, patients as well. So this is a meta-analysis over 25 studies across multiple, um, anemia conditions, uh, showing that about 16% develop acne, and this is dose dependent, right? So this is something that's very common. I've learned from my derm colleagues we're talking about different over the counter creams before I start this therapy, prescription strength creams, and again, can we lower the dose and sort of stay on top of it. But again, this is probably the most common reason we have to stop our JAK inhibitors, not infectious complications or cardiac issues. All right, moving to Crohn's disease. So here's our, again we have all um 3 selective IL 23 inhibitors FDA approved for Crohn's as well as used toinumab um again for bulkumab, um, just to separate that we have both a subQ and an IV induction, and I think that's sort of, you know, we can answer any questions which ones you like better. I think bottom line you see more and more bulkumab being used because it's much easier to get one authorization versus two getting an IV to a sub Q. Um, I do wanna highlight this, um, uh, one study, the rescue study, so this was presented, um, last year at our European Crohn's and Colitis, um, meeting. And essentially, um, as you know, our IBD docs, we like to give more drug, we like to give drugs more frequently, double the dose, right? So a lot of our patients for tainumab, our standard dosing is you get an initial IV infusion and then 90 mg every 8 weeks. But a lot of our patients need every 6 weeks, every 4 weeks, and we're doing this with our IL-23 inhibitors, um, as well now. Now with the IL-23 inhibitors though, should we be optimizing use tokinumab or should we just move on? So that's what this study was looking at. So it was a prospective randomized trial. They took patients that had an initial response to use tokinumab and then lost response, and they randomized them to all getting a sec another IV induction dose and either randomizing them to every 4 week dosing, subQ 90 mg, or every 8 week dosing. And bottom line, looking at steroid-free remission at the end of the year, they only recaptured about 20% of patients. Right? Um, and there was no difference between the two dosing regimens. And, you know, they looked at drug levels and the pharmacokinetics and levels went up as you gain more drug, but again, didn't lead to clinical outcomes. So I think, you know, outside of dealing with insurance biosimilars, if a patient is losing response to ustainumab, I'm really moving them to a selective IL 23 inhibitor now. We're not pushing that dose anymore for the majority. Just to highlight, um, some data from our, um, selective IL-23 inhibitors, so this was risenkizumab, first, um, therapy we had that was FDA approved for Crohn's, and here it's, which was different, uh, than you see, this worked very well in our bio naive and bio-exposed patients, right? And this is probably the first study, uh, with a therapy in Crohn's to show that, um, and all with really nice deltas, right, 20-30%. So we, this is our first study, we hadn't really seen this in Crohn's disease before the study with the risenkizumab. This was a more refractory population with still so these were patients that almost the entire over 95% were exposed to advanced therapies in the past with really nice data. This was our one of our head to head trials um in Crohn's, um, so this took patients with moderate to severe, so it's called the sequence study, moderate to severe Crohn's patients that failed anti-TNF, and it was a head to head comparing risenkizumab versus eustainumab and bottom line, whether you're looking at clinical endpoints at the end of the year, um, risenkizumab outperformed eusoinumab 60% to 40% and similarly with the endoscopic outcomes. So really, this has been shown, I'll show you some other Crohn's data, but I think we're all very aggressive about pushing the IL-23 inhibitor in Crohn's. You see, we don't have this data yet, um, but I think that will be coming. Um, this was mirokizumab's, um, data, again, similar, really nice deltas, um, bio naive versus bio-exposed, 20 to 30%. However, in this study, they did not, um, show benefit over use tokinumab. Now, again, maybe this is study design, this included bio naive patients. The sequence study did not, um, but this did not show benefit over use tokinumab. And then this is the gelumab data. So here, very nice deltas over 30%, um, tree through study design. So, you know, 50% of patients are doing great at 12 weeks in remission at the end of the year. So really nice data there and there was benefit over use tokinumab, and this is both bio naive and bio-exposed. So again, with Crohn's disease, we're seeing this pretty common theme that our IL-23 inhibitors, um, work better than, um, eustainumab. And this is just one more study on the IL-23 inhibitors just showing the subQ induction, um, showing that very similar numbers and a common question we always get is there a right patient for IV versus subQ induction? And really if you're looking at the data, post hoc analysis, really breaking it down, there doesn't seem to be yet any clinical data on who's better for IV or subQ. and I think the vast majority now we're mostly using subQ induction for all of our patients. Um, eupatocioib again a very, very effective therapy. Same thing with Crohn's disease. This is just data looking at bio failures, right? And again this is very impressive numbers, uh, response or remission rates in a very refractory Crohn's patient. And then the last data slide I'm gonna show, this is just perianal Crohn's, and this is probably one of our biggest unmet needs and our most refractory patient population. And these are small numbers, um, and outside of infliximab we don't have any. Uh, prospective, um, randomized trials yet. And so now with this data in our clinical experience, if you're failing an anti-TNF or complicated perianal Crohn's, the next step we're using apato synonym now. Another big benefit um of this therapy is the EIMs, and we've done a lot of work here, working with our rheumatology colleagues trying to, you know, quantify how often we're seeing arthralgias, arthritis, spondyloarthropathy, sacroiliitis, and if you look at the IBD data, right, it's anywhere from 10 to 50%, meaning that we just don't have good data. And as GI doctors, we don't ask the question the right way. Um, we're not very good at that, but. You know, I think this is gonna be an important part as we're talking about positioning therapies that we're evaluating uh patients for these extraintestinal manifestations, these joint issues, because this is gonna help, right? Decide what therapies we should be putting these patients on. And lastly, I just wanna highlight this cause I know there's studies coming, um, coming down the road, um, for you guys, for Room and Durm, and this is the really big topic now in IBD is combination therapy. So this is our one prospective study we have called the Vega trial. This is a phase two trial looking at combination of guzumab and golibumab, right? So a 23 and a TNF versus either one alone. Similar numbers when you're looking at clinical endpoints. Um, we see a nicer difference when you're looking at endoscopic endpoints. But this is where I think we're moving towards. So we're doing this more and more off-label, right? And there's more and more sort of real world studies coming out. There's also ongoing phase, there's, we're about to start phase 3 trials with this, this similar type of combination. There's also other companies are doing their own combination studies. So this is where, um, the field's moving. And I would say now the real question is when do we start it, right? A lot of these times we're doing in our office are these are very refractory patients. They failed multiple therapies, and now we're, you know, trying to think of something else to do and that we're getting added benefit, but I think we're still waiting too late, right? And we should probably be using these combinations, um, earlier on. So just to summarize some practical tips for S1P receptor modulators, this is a great oral option for our ulcerative colitis patient, uh, that are on the more moderate end. If you, um, failed previous therapy, probably not the right therapy for you and a little bit of baggage getting patients started, but it is a very safe therapy. For IL-23 inhibitors, there is some um variable differences in mechanism of action. Um, and there are clinically meaningful uh differences when you're looking at our IL-23 inhibitors versus eustinumab. Are there differences between selective IL-23 inhibitors? We'll find out. There are gonna be head to head trials coming in IBD comparing different IL-23 inhibitors, so we could better, um, answer that question. And now in clinical practice, we are switching from one to the other. So we will see, but I think the main thing that's driving this now is subQ induction, right? Rather than we think one is gonna be so much more efficacious than the other. Um, again, losing response to us tokinumab, we're not messing around anymore. We're just moving to IL 23 inhibitor. We don't add an immune modulator, right? This is a big thing we're doing with our TNF agents, more for immunogenicity and drug levels. We're not really doing this for our non-TNF biologics. Um, combination, usually the base of the combination is a safe therapy, so that's gonna be an IL-23 inhibitor or vitolizumab, and usually when we're talking about combination, it's those two combined with either a JAC or a TNF. And these are, even though there's a lack of data and a lot of our patients ask, these are completely safe in pregnancy, we spoke about the global consensus. So I just tell the patients stay on it, there's no issue at all. For JA JAK inhibitors, they work well, they work fast. They have some data in IBD that within 24 hours, it improves rectal bleeding and stool frequency scores, um. There are these concerns, but I think what we're seeing, at least what I'm seeing now in the IBD world, is that these people are waiting too long to start that JAK inhibitor because they're concerned about the safety, and I don't think that's something we should be doing, right? It's in my elderly patient. I have many elderly patients on JJAK inhibitors just talking with their primary care, their cardiologist, make sure the cholesterol is under control, their blood pressure is under control, but we shouldn't be avoiding them because they work very well. So what, um, how do we use these therapies again first line, anything works, right? So if you start early enough, um, and I'd say mostly for UC we're using either vitolizumab or IL 23 inhibitor for Crohn's, mostly IL 23 inhibitors. 2nd and 3rd line TNF, IL 23 inhibitors or JACs, severe disease. So anything we're concerned about, they're either getting infliximab or eupatoinnoib. Um, overlapping EIMs, psoriasis, obviously the selective IL-23 inhibitors were great, spondyloarthropathy, we're still really focusing on infliximab oreatoininib, um, and then not for this talk, but surgery is also important, especially in Crohn's disease, and I think a lot of times we delay too much. So, you know, at our center here, if somebody has signs of irreversible bowel damage, we push for early surgery and then starting on one of these agents to prevent recurrence of disease for better long term outcomes. So thank you for your time. Published December 19, 2025 Created by
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