Here we go, 40 minutes of inflammatory bowel disease stands between us and lunch. All right. So first, here are my disclosures and a little background of what we're gonna talk about. We will very briefly discuss some basic pathophys of IBD. We'll spend a lot of time talking about risk stratification, treat-to-target approach and the drugs. We'll spend time talking about the drugs that are newer to market in the last couple of years, some kind of pro tips and clinical pearls we need to know about those medications, as well as reviewing some clinical guidelines and a little tickle of health maintenance at the end. So very basically, pathophys of IBD, we know that it's complex and it's a kind of conglomeration of things between immune dysregulation, environmental factors, the intestinal microbiome and genetic susceptibility. What happens in an inflammatory bowel disease is that the innate immune system recognizes bacterial products and their cellular signaling. This abnormal signaling pathways cause the dysregulation of the inflammatory response, which activates the adaptive immune system leading to excess pro-inflammatory cytokine production. And this excess pro-inflammatory cytokine production is important to understand. As we think about our therapeutic options and how they all work differently on either different cytokines or different pathways in the inflammatory cascade. So Jill talked about a lot of these in her talk about diarrhea, but when we're thinking about either patients with IBD or patients that you're trying to figure out, do they have IBD? Types of questions that we need to ask and also document, right? So number of bowel movements, a 24 hour period, but also as Jill pointed out, how often are you going to the toilet? Consistency of the stool, what's coming out? Tell me more about the blood. Is it a little bit when you wipe? Is it dripping into the bowl? Nocturnal awakening, so the need to have a bowel movement waking you up from sleep is considered an alarm symptom for either infection or inflammation. Patients with irritable bowel syndrome or functional diarrhea should not have nocturnal bowel movements or the need to have a bowel movement waking them from sleep. So that's why we point that out and ask patients about that specifically when we're trying to figure out our workup and the initial process of these diarrhea symptoms. Thinking about tenesmus. So patients sometimes when they come into your office, they might tell you, oh, I have diarrhea and constipation. Well, what does that mean? When you ask them more about their constipation, it's that they're going to the toilet 20 times a day. Stool is only coming out seven of the times, but they feel like they have to go and nothing is coming out. So it's actually tenesmus usually associated with proctitis or rectal inflammation, but patients might categorize that as constipation. Of course, we want to know if they're having nausea, vomiting, fever, chills, abdominal bloating, if there's any drainage from the rectum, signs and symptoms of fistula or abscesses, weight loss, changes in appetite, and of course, asking about extra intestinal manifestation. So joint pain, rashes, eye pain, and mouth sores. We know that inflammatory bowel disease is a systemic disease, and almost half of patients have symptoms outside of their bowels. Most common are joint, skin, and eye. We need to ask about these at every visit, every IBD visit, and up to a quarter of patients will actually have EIMs before the onset of their intestinal symptoms. So it might be that they're seeing rheumatology for arthritis symptoms, et cetera, before they ever have any GI symptoms. The pathogenesis of this is not that well understood. We think that genetics and smoking can increase risk of specifically skin and joint, extra intestinal manifestations and Crohn's disease, and likely a combination of the role of the microbiota. On the right-hand side, you can see some of the most common EIMs. I could give a whole 40-minute talk on EIMs alone, so we'll move on here. This graph has a lot of information on it. I'm not going to go over it, but I wanted you to have it for your references. So this is thinking about how we not only diagnose, but how we monitor inflammatory bowel disease. Of course, it is a tissue diagnosis, so we need biopsies to confirm diagnosis, but all of these other things can help us point us in the direction. Does our patient have IBD, and how are they responding to therapies? A note, we want to get, so if a patient comes into your office with diarrhea, bloody diarrhea, sounds like IBD, you're going to set them up for a colonoscopy. We still get a baseline fecal calprotectin, and the reason is we want to know what that calprotectin is at baseline. If that calprotectin is high, the patient is indeed diagnosed with inflammatory bowel disease, we can use that calprotectin and watch it fall over time to assess their response to therapy. If they have isolated ileal disease, they may never mount a calprotectin. Their calprotectin may always be normal, even with active inflammation. So it's important to know where we are at baseline so we know what we're tracking. Some patients may never mount a CRP response. We see this especially with limited left-sided colitis. Some patients will only have elevated platelets, they might be anemic, so knowing what their markers are. I also document this in my patient's charts. So if it's a patient who does not mount a CRP response, it's in my opening sentence. I put a little star with of note, patient does not mount CRP when flaring. Of note, calprotectin has always been normal. Of note, platelets jump when flaring. So those types of things to not only remind me, but any other providers that are seeing this patient so we know what our goals are. Then of course here, there are some imaging, CT and MR enterography can be useful for small bowel disease, colonoscopy and endoscopy, as well as capsule. And just a touch here on intestinal ultrasound. Many academic centers are doing this, but it is not readily available yet in the community. Hopefully in the next couple of years, access will increase and this will be something that is more into kind of everyone's guidelines, but right now it's certainly limited. We do not have access to it at my large community practice. So what does all of that mean? So we're thinking about patient's biochemical markers, where do we go? Why does it matter? So the graph here on the left is looking at both digestive damage and inflammatory activity in Crohn's disease. So the digestive damage over time is that red line. Inflammatory activity is the navy blue line that goes up and down. As we know, Crohn's disease is a relapsing remitting disease. So over time, as you have these ups and downs of inflammatory activity, as defined by CDAI, CDS and CRP, over time without tight control and monitoring, that digestive damage continues to go up. You can develop strictures, fistula abscesses, the need for surgery, and the potential for developing further strictures. What we have is called this window of opportunity. So at diagnosis, early in the disease state, if we are able to get tight control and monitoring of this inflammatory activity, we actually can change the natural history and trajectory of the disease. So over on the right-hand side, you see that blue line, the inflammation over time, right at diagnosis. But then with tight control and monitoring, that inflammatory activity stays low. And when that inflammatory activity stays low, digestive damage does not progress over time. Similar principles have been hypothesized in ulcerative colitis. We don't have as much data there yet, but this is why we're talking about risk stratification and treat to target. So when thinking about our patients with Crohn's disease and ulcerative colitis, we want to think about them as a person, but also about their disease. Who was someone who might be at low risk for rapid progression? And who was someone who was probably high risk for rapid progression? Patients who are at high risk for rapid progression, these are our patients we're going to get on advanced therapies early. So thinking about Crohn's disease here, Crohn's disease, high risk on the right, low risk on the left. Patients are high risk if they're diagnosed under the age of 30, if they've got extensive disease, if they've got perianal disease or severe rectal disease. If they have deep ulcers, of course, if they have a history of prior surgical resection and stricturing or penetrating behavior. For ulcerative colitis, similar, some things are a little bit different. Patients with ulcerative colitis are considered high risk if they are diagnosed under the age of 40. If they have extensive disease, so it's not just isolated proctitis, it's not just left-sided disease, but it is extensive. If they have these big, deep ulcers, Mayo score of three, you put the scope in, it looks like ground beef. It is bleeding by itself without even touching or biopsying it. Patients with a low albumin is a poor prognostic factor, as well as elevated CRP and SED rate, and are patients with ulcerative colitis who have been hospitalized. So when we're thinking about our patients and thinking about risk stratifying them, patients with these high risk features, again, are patients that we're not maybe gonna see if they respond to misalamine, give them six months to a year. We're gonna get them on advanced therapy early so we can control their inflammation and decrease disability, increase quality of life as well. So thinking about this treat-to-target approach, it wasn't that long ago, 15, 20 years ago, we thought, all right, you're feeling better, great. Diarrhea is better, rectal bleeding is better. We're moving in the right direction. Let's keep on keeping on. But now we know that we need to go beyond just symptomatic improvement or remission. It is not enough to feel better. We also know that symptoms very poorly correlate with inflammation, especially in Crohn's disease. You can see a little more correlation ulcerative colitis, but sometimes people feel great. You put the scope in and it's terrible. Sometimes people feel terrible and there's actually no active inflammation, but they've got an overlap of IDS symptoms. So we can't rely only on a patient's symptoms. We need to use these clearly defined objective biomarkers, including endoscopy and radiology in order to prevent this progressive bowel damage and complications. So yes, initially, do we want patients to feel better? Of course. Then moving into clinical remission, which usually in all of the trial definitions includes scope features as well, and looking at the mucosa. Then looking at steroid-free remission, so being off steroids. We know that remission is not remission if a patient is still on steroids. Then looking at mucosal healing, so normalization of that mucosa when we're looking at the scope. Moving into deep remission, which includes normalization of the biopsies. And the goal of all this after that is to reduce hospitalizations, surgeries, and change that course of disease. So here are our stride two recommendations. So your patient has active IBD and you choose a therapy according to risk. Now, all of the different classes of medications have safety profiles. We'll go into these a little bit later. But that safety profile changes on the individual patient and what other comorbidities or risk factors they have. So in each individual patient in a shared decision-making model, thinking about the patient with active IBD, choosing a therapy according to risk that makes sense for them and safety. Then we're looking at a symptomatic response. So yes, we want the patients to feel better. If that happens, then we're looking for that symptomatic response and normalization of the CRP or normalization of their platelets or their anemia or some kind of lab values to tell us that we're moving in the right direction. After that, we're looking at a decrease in calprotectin, which we usually only check about every three months because it can take some time for that calprotectin to change. In children, we're looking for normal growth rates. Past that, looking at endoscopic healing, meaning we put the scope in and things look normal. Also included in this target is normalized quality of life and the absence of disability for our patients. If along the way, we're not continuing to meet these targets in the short-term, intermediate, and long-term, we've got to go back to the beginning and we either need to dose optimize our medication or think about changing therapies. Looking at the future, likely future targets will be transmural healing in Crohn's disease and histologic healing in ulcerative colitis. We're not changing therapies based on biopsies alone just yet. That may be coming in the future, but just a note on that. So thinking about the IBD safety pyramid. So this has changed over the time and that top line has gotten crowded, which is great for us and great for our patients. At the bottom are the meds that have the worst or riskiest, if you will, safety profile. And I want to point out there that steroids are at the bottom. Then they go up in terms of safest at the top. And you can see that Vita-Lizumab, Ustekinumab, Rizankizumab, Mirikizumab, Gusulkumab, Ozanumab, and Atrazumab are listed at the top. Just under that are Upatacitinib and then it goes down to TNF and Tofacitinib and then combinations past that. We also know that sometimes surgery is the best option and surgery does not mean that we have failed the patient. Patients with isolated terminal ilea disease sometimes do really well with an ileocechectomy. You take out the disease portion, you take out that strictured IC valve, you get them into surgical remission and then you keep them there, typically on therapies after. Patients with complications, of course, might need surgery as well. The most important thing to remember here is that inadequate treatment and not treating our patients appropriately is an adverse event in and of itself. And we'll look further into kind of those patient-specific considerations that do influence the safety profile as well. A note here about steroids. Steroids should be as little as possible. I describe steroids as a necessary evil. Sometimes we need them. Sometimes we need them in short little bursts to give us some time to get our patients on an advanced therapy that is gonna control their inflammation. Steroids should only be used for induction of remission, not as maintenance therapy. And we also need an exit strategy. So if you're starting a patient on steroids, what are we doing or changing to get them off those steroids? Because if you don't change anything underlying, the inflammation is likely gonna come back when you taper those steroids off. So it's like a bridge. You need an island on the other side of that bridge or the steroids are a bridge to absolutely nowhere. It's also important that we counsel the patient and document that we've counseled the patient, both on short-term and long-term risk of steroids. And I have some listed here for you. So moving into choosing therapy, it is absolutely a puzzle. Types of things that we're gonna think about. Efficacy, is it indicated for what we're using it for, for either Crohn's disease or ulcerative colitis? How fast does it work? If it is a drug that might take a little longer to work that you really need to give it the full 12 weeks, does your patient have 12 weeks that we can wait for that? Is it durable? Thinking about the pharmacokinetics and if we need to do any therapeutic drug monitoring, which we typically only are doing with TNFs. Are you using it in combination with an immune modulator or as a monotherapy? Thinking about safety, the infection risk for that patient. If your patient has a cancer history risk or if there's a significant family history, is there a drug that has that? It might consider your thinking about the safety profile for that patient there. And then specific concerns by agent or mechanism. Thinking about the patient, how old are they? Are there any comorbidities and what they prefer? Are they needle averse? Do they really not have time to get to an infusion center? We have a patient who's a teacher and it was really hard for him to get to our infusion center at the end of the day. And ultimately, I hate that this is on the slide, but it has to be, but payer coverage is a part. And so the best drug is the one that we can get for our patients and the ones that they will take. Also looking at disease characteristics. So we talked about these high risk factors, the extent of disease, the behavior, complication. Is it stricturing? Is it fistulizing? How severe it is? And are there any extra intestinal manifestations? If there are, and or if your patient has psoriasis, for example, you might choose a therapy that also has an indication for psoriasis. So now we're gonna move into these slides. These slides have a lot of information on them. I am not going to talk through these slides, but I wanted you to have them as a resource for you. So I am gonna point out some things on each of the slides and we'll spend a little time towards the end on the medications that are newer to market. So steroids here, a reminder of steroids and doses. We talked about side effects. We talked about the exit strategy. A quick note here on Budesonide. So when you're thinking about Budesonide, you wanna think about what you're treating and where the release is. So Budesonide or Enticort is released in the small bowel and the right side of the colon. Whereas Budesonide MMX, which has this MMX coating or the brand name is Euceris is released in the colon. So thinking about which one you're prescribing and why, where the disease is. Reminder that steroids should only be used for induction of remission, not as maintenance therapy. There is also rectal steroids with hydrocortisone enemas that can be used for mild to moderate proctitis. Moving into amino salicylates. So this chart here, again, is gonna be a good resource for you, give you everything you need to know. An important part here about amino salicylates, it can affect a renal function. So you should have baseline labs, including a CMP, and also check that annually for a patient. Very rarely can cause interstitial nephritis or pancreatitis. So keep in mind if your patient's on misalamine. And we'll talk about later on, if we're starting a patient on advanced therapy, we might be able to pull off these amino salicylates as well. Immunomodulator therapies, thiopurines. So these now are used much less often as monotherapy, and really used in combination therapy, typically with TNFs, in order to prevent antibodies or to boost levels as needed, for example, patients who have severe stricture interfacializing disease. Reminders that they are weight-based dose, so you need to know your patient's weight in kilograms when thinking about the dose. You'll check a TP enzyme, enzyme activity before starting, and then you want to check the thiopurine metabolites a couple of weeks after. So these medications break down into two different metabolites here, and you want to make sure that one is in the therapeutic range, and the other one is not so high that we're potentially having hepatotoxicity. Thiopurines are safe in pregnancy. And then to methotrexate is indicated for maintenance and recovery. And then methotrexate is indicated for maintenance and remission of Crohn's disease, but there's really limited data in monotherapy. And again, typically in practice, we're seeing this typically in combinations with TNFs or in low doses as an add-on for a patient who's got persistent joint pain or arthropocies. You can use it for treating that as well. It can be given either subcu or oral. I find in practice that patients tend to have less side effects when it's given subcu. There is a fair amount of nausea with it. So if they are taking it orally, I recommend that they take it at bedtime. It is a black box warning for pregnancy. No pregnancy. Needs two forms of birth control and you need to wait three to six months after stopping before conception. It is not contraindicated for males who want to get their partner pregnant, but it can reduce sperm count. So keep that in mind in someone who's trying to conceive. All right, moving into TNF inhibitors. This class has been around for a long time. There is one new thing on the page that we're going to call our attention to. But reminders that these drugs include infliximab, adalimumab, sertalizumab, and golimumab. And infliximab and adalimumab now have a lot of biosimilars as well. The thing that is new is that there is a subcu maintenance option for infliximab. So the brand is called Zymfentra. It is 120 milligrams given every other week. So the subcu option is not weight-based dosing. It is a standard dose. Patients do need three IV induction doses before starting the subcu dosing. So they get their three standard IV dosing and then at week 10, they start their first injection and that injection is given every other week. For patients who are on stable infliximab and want to switch to the subcu dosing option, it should be given on the day that their infusion is due instead of their infusion and then given every other week. They do have data about patients who are on therapy at different doses. So in our practice, we're typically right now switching patients who want the subcu option who are on infliximab 5x per KQ8. Patients who are on 10x per KQ4 in one of their small clinical trials had about an 80% risk of a flare within six months of switching to subcu. Now, once subcu was dose escalated, almost all of these patients did recapture a response. But right now in the US, the only dosing that is approved is 120 milligrams every other week. So keep that in mind if your patient has needed dose escalation for infliximab. What's interesting about the pharmacokinetics of this is that with IV dosing, there are real peaks and troughs. So when we're checking an infliximab level, it is a true trough right before their next infusion. Subcu, overall, the levels tend to be a little bit higher than they are for their trough IV doses. And this is likely due to the more steady state with the every two weeks subcu dosing. Moving into anti-integrins, natalizumab is approved, but very limited use in Crohn's disease. And so we're going to spend the majority of our time talking about Vitalizumab. Vitalizumab is not new. It has been approved since 2014. It is approved for both induction and maintenance of moderate to severe Crohn's disease and ulcerative colitis. And the dosing is the same for both indications. What is new is that there is a subcu maintenance option. So there is a short IV induction period. So patients who are new starting this medication will do the 300 milligram IV dose at week zero and two. Then at week six, they'll start the subcu and do the subcu every other week. And it is 108 milligram and a pre-filled pen or syringe. The pen is really easy. Most of my patients choose the pen. For patients who are already on standard dosing, 300 milligrams every eight weeks, they will start their subcu injection on the day that their infusion is due instead of their infusion and then do every other week dosing as well. Vitalizumab is safe in pregnancy. There's a low immunogenicity rate and there is no black box warning as well. It is gut selective. All right, moving into the IL-12 and 23s, ustekinumab, also not a lot that's new here, but just to remind you, it is one IV dose, which is weight based, and then subcu dosing every eight weeks. And it blocks both interleukin-12 and interleukin-23. Moving on to the IL-23s, which are new and some late-breaking information. I changed these slides last night. We'll get to that. Rizin-kizumab is approved for both Crohn's disease and ulcerative colitis. The induction dosing is different by indication. The maintenance dosing is the same for both indications. So for Crohn's disease, it is 600 milligrams given over a one hour infusion at week 0, 4, 5, and 6. For ulcerative colitis, it is 1,200 milligrams, also given at week 0, 4, and 8. For maintenance, it is sub-Q and it is given by an on-body injector. What does that mean? Both doses, both the 180 milligrams and the 360 milligrams, it's too much of a volume to put in a pen or syringe. So they have this device called an on-body injector, which the patient basically tapes onto the syringe The needle goes in and it auto-injects or slowly injects the medication over five minutes of the sub-Q dose, then the device comes off the arm. The maintenance dosing is every eight weeks, but the first dose is at week 12 or four weeks after the last induction. I've seen this get confused a lot, the every eight-week dosing, but the first one is at week 12 or, again, four weeks after the last induction. The first one is at week 12 or, again, four weeks after you finish the IV induction. You should use the lowest dose that gets your patient into remission. In my practice, we always joke that we love meds and dose escalate everybody. And so in my practice, we're mainly using the 360 milligram for everyone. Some notes here, it is also approved psoriasis and psoriatic arthritis. So if your patient has one of those, you might think about using that as a first-line therapy. Moving into, before I do that, one more note. Rizin-Kizumab is the only interleukin-23 that had patients in their clinical trial who were ustekinumab or stellara failures. There were a small number, but they were allowed in the Rizin-Kizumab trial. The other two IL-23s, Miri-Kizumab and Goselkomab, did not have any prior stellara failures in their trial just because of the timing of their trials. Miri-Kizumab is also approved now for both ulcerative colitis and Crohn's disease. And these are different doses, so I'm going to talk out these very specifically. For ulcerative colitis, it is 300 milligrams IV given at week 0, 4, or 8 over at least 30 minutes. For ulcerative colitis maintenance, it is 200 milligrams sub-Q every four weeks. That does start at week 12 or four weeks after the IV induction. Right now, it is two 100-milligram sub-Q pens. So the patient does have to do two injections every four weeks. They obviously don't have to do them exactly at the same time, but it is right after another. And the two pens or syringes is the dose. For Crohn's disease, it is a 900-milligram IV dose also given at week 0, 4, and 8. And then for maintenance, it is 300 milligrams sub-Q every four weeks over at least 30 minutes. It is a 200-milligram sub-Q every four weeks, also starting at that week 12. The Crohn's disease is also two pens. It is one 200-milligram pen and one 100-milligram pen. Right now, the ulcerative colitis sub-Q, the two 100-milligram dosing, does have citrate in the formulation. So we need to counsel our patient about burning when the injections go in. The company that makes it does have approval, but I'm not sure the citrate will be out. But as of now, we need to counsel our patients. They can keep the medication out at room temperature for an hour, numb up the site with some ice before they do it, some things that they can do to help prevent that burning. Gucelcomab, these slides I just updated last night. If you don't have the updated one, it will get emailed to you on Monday. So the new thing was the Crohn's indication. I'll go to that shortly. For ulcerative colitis induction, it is a 200-milligram IV dose given at week 0, 4, and 8. For Crohn's disease, there are two options for induction. One is 200 milligrams given at week 0, 4, and 8 IV, just like the ulcerative colitis. Or you can do 400 milligrams sub-Q at week 0, 4, and 8, and then move on to the sub-Q maintenance. So there is a sub-Q only induction options for patients for gucelcomab for Crohn's disease. This might be helpful for patients who don't have access to an infusion center, et cetera. For maintenance, there are two different options for maintenance dosing, and it is the same dose for both ulcerative colitis and Crohn's disease. It is a 200-milligram sub-Q pen every four weeks. This starts at week 12, or four weeks after the IV induction. Or there's a 100-milligram sub-Q every eight weeks, which starts at week 16, or eight weeks after induction. Per the label, you should use the lowest effective dose for your patient. What is that? We don't know until we try it, right? There certainly is data that patients that have more extensive disease, pancolitis, and you see higher CRP and SED rate do better with the 200-Q4. There are varying kind of theories here. So one theory is that you could start a 100-Q8 dose escalate if needed, or you could start at 200-Q4 and de-escalate once your patient is in remission. I already shared with you that my practice loves meds. So we are generally using the 200-sub-QQ4 for most of our patients at this time. It is also approved for psoriasis and psoriatic arthritis. So thinking about that in patients as well. Moving into JAK inhibitors, tofacitinib is not new, but a reminder that it still exists. The induction dosing is 10 milligrams twice a day for eight weeks, and then it goes into five or a milligram twice daily. Maintenance will avoid pregnancy with TOFA as well. And it is a pan-JAK, so it targets all of the JAK inhibitors. And moving on to apatocitinib. So this is approved for both induction of maintenance of moderate and severe ulcerative colitis and Crohn's disease in adults. Per the FDA label, you cannot use either tofacitinib or apatocitinib unless the patient has failed a TNF. So it is post-TNF failure or exposure. The induction dosing is the same dose, but different time period. So for ulcerative colitis, it's 45 milligrams for every eight weeks. Crohn's disease, 45 milligrams for 12 weeks. Then the maintenance is 15 milligrams once a day. 30 milligrams can be considered in a patient who have refractory severe or extensive disease. If your patient has already failed a TNF, it's pretty likely that they have refractory severe or extensive disease. And so I'd say most people are using the 30 milligram for maintenance in their practice. Reminder that you do need to check lipids. There is some black box warnings, particularly about thrombosis. So think about this in patients and recommend vaccination with Shingrix or the non-live herpes zoster vaccine before starting therapy. Moving into S1Ps, so Atrazumab and Ozanamod. The dosing is different for these two. Atrazumab is the same dose for induction and maintenance. And Ozanamod does have a dose titration. Ozanamod is not off the market, but it is no longer commercially supported. And this was a business decision that the company made. So there is no problem with the safety of the medication or the class of medication. Because it is no longer being commercially supported, you're not going to get as much support for your patients who are commercially insured, like copay, savings card, bridge programs for new starts. They're keeping patients who are already on it in those programs. But Atrazumab is still commercially supported. What's most important here about these S1Ps is understanding the pre-med testing. These medications are not cardiotoxic, but they can cause transient AV conduction delays. So we need a baseline EKG to make sure our patient doesn't have an underlying conduction abnormality. We also need to check for varicella tigra before starting therapy. Around or near the start of therapy, we're going to get a skin exam and an eye exam. Our patients with inflammatory bowel disease should be having skin exams every year anyways. And the companies do have support in terms of testing to help your patients who are commercially insured get that done. OK, that was a lot. You have the tables. Moving on. So we have a lot of tools in our toolbox. We just talked about a ton of therapies. How in the world do we make sense of this? If we had a really easy algorithm, I would have just presented this algorithm and we'd be done. But unfortunately, it isn't that easy. There is an AGA clinical pathway for Crohn's disease. It's outdated. Likely a new one is coming this year. But basically for a moderate or high risk patient, you can use any of the therapies. Moving into ulcerative colitis. So the AGA living guidelines are new and they're going to be updated every six months with all of the big network analysis data. So with this, a couple of things I want to point out that in their recommendations, when they list meds all in the same, we recommend these options. They're listed not in order of efficacy, but listed in date that the drug was approved and then grouped by class together. So the definition for moderately to severely active you see is listed at the top and may suggest early use of advanced therapies or immune modulator therapy rather than gradual step up. So our patients don't need to earn their advanced therapy by failing a 5-ASA. They suggest that we can use these early. And the recommendation is any of the following over no treatment. You see the infliximab listed through there. And they suggest that you could use any of the following the Adalimumab, Mirakizumab. Filgotinib is not approved in the US. Note here at the bottom that biosimilars are considered equivalent to their originator and their efficacy. Sub-Q formulations might be considered as an alternative to most patients. And we talked about that. And patients might need extended induction or dose escalation depending on the therapy. They have really severe disease. So looking at advanced therapy, naive or first line therapies and then prior patients who've had prior exposure. Again, these are not listed in order of efficacy, but an order of approval. They suggest using a higher efficacy for patients who are naive. The green lines, the higher efficacy medications. Then you can see there the intermediate efficacy medications and then lower efficacy medications there at the bottom. So if you had to pick, you might start with a higher efficacy if your patient is first line or naive. Again, depending on patient preference, patient profile and what you can get for your patient, how they want their drug delivered. Upatacitinib has a star because it cannot be used in the US as a first line therapy. Then looking at prior exposure. So if your patient has had exposure to prior therapies, especially TNFs, down at the bottom, you can see the higher efficacy medications are JAX, tofacitinib and upatacitinib. Then moving into intermediate efficacy medications, Fogatinib is not approved in the US and then ending with lower efficacy medications there as well. There are some suggestions here about immune modulator therapy that they suggest against using thiopurines for inducing remission in patients with active disease. And if a patient is on combo therapy with the TNF and thiopurine, they recommend stopping the thiopurine if you can, but not stopping the TNF as well. So I got ahead of myself looking at combination therapies here and then looking at de-escalation. So in patients who have moderate to severe UC who have failed five ASAs and are now on an advanced therapy, the AGA suggests that you can stop those five ASAs. And patients with moderate to severe UC who are in corticosteroid free clinical remission for at least six months on a TNF and immune modulator, the AGA suggests against withdrawing the TNF and leaving them on immune modulator alone. So all of that to say, it's complicated. Our treatment landscape is drastically changing, but the safest drug here is the one that controls inflammation. I tell patients that the complications of untreated disease are worse than the side effect profile of any of our treatment strategies. Our positioning decisions should be patient centered, including clinical characteristics and informed in a shared decision making model. Consider safety, extra intestinal manifestations and patient preference for mode of delivery. A little teeny pearl here. Your patient's got some other things going on. Think of IL-23s for skin, JACs for joints. Health maintenance, we're going to move through this very quickly. The take home point is we all could be better at doing it. There are some tools to help, including the IBD Cornerstone checklist and the Crohn's and Colitis Foundation checklist. Reminder that we need to think about vaccines, cancer screening, managing anemia and vitamin deficiencies, as well as overall health promotion and prevention. Vaccines and cancer screening. These are in the common checklists. Anal pap smear might be indicated based on guidelines. I also subspecialize in anal HPV, so it's an area that's near and dear to my heart. But the anal cancer screening guidelines were published in 2024 in the International Journal of Cancer. Don't forget about DEXA scans once your patient's off steroids if they've been on steroids for more than three months. And a small tidbit here on pregnancy. The safest thing for mom and baby is remission before conception. We do recommend that our patients with IBD see maternal fetal medicine sometimes if only to convince them to stay on their therapies if they're safe, that sometimes obese try to take them off of. If your patient has a prior surgical history or perianal disease, C-section may be recommended. Mental health screening is really important. We should be screening our patients at least annually and referring to mental health providers if needed. Up to 20 percent of our patients with IBD have anxiety and depression and smoking cessation also key. So putting it all together, early diagnosis and treatment might be able to change the natural history of the disease and prevent future complications. IBD is a team sport. We need everybody, GI physicians, advanced practice providers, our primary care, derm, room, endo colleagues, as well as mental health providers and sometimes even our surgeons. And the best treatment is the one that the patient will take and that controls inflammation adequately. Thank you so much. And I'm going to pass it back over to Caitlin for Q&A.

Inflammatory Bowel Disease

pathophysiology

immune dysregulation

biomarkers

treatment strategies

systemic manifestations

diagnosis

patient-centered approach