Right now, I'd like to hand it over to Kimberly Kearns, and she's going to give us a presentation on the evaluation and management of inflammatory bowel disease. Kimberly Kearns is a nurse practitioner that specializes in adult gastroenterology for Dooley Health and Care in Hoffman Estates, Illinois. For the past 15 years, she has been providing both inpatient and outpatient healthcare specializing in adult gastroenterology. Her healthcare philosophy focuses on education, disease, prevention, and health promotion. She's currently serving as the co-chair for the Crohn's colitis diversity and inclusion committee and is a member of the Crohn's and colitis RN APP committee. Ms. Kearns is the co-founder of MidGut, a professional society dedicated to the education, mentorship, and collaboration of nurse practitioners and physician's assistants in the field of gastroenterology and hepatology, which I recently signed up for. So Kimberly, we'd like to give you the proverbial floor. Today we're going to talk about the evaluation and management of inflammatory bowel disease and in 30 minutes. So let's get rolling. Here are my disclosures. And our objectives this afternoon, of course, are going to be to identify differentiating features of inflammatory bowel disease, explore guiding principles of IBD management, review therapeutic agents used for the treatment of inflammatory bowel disease. We're going to have a quick discussion on therapeutic drug monitoring, and of course, provide some awareness regarding health disparities in inflammatory bowel disease. So inflammatory bowel disease consists of two subtypes, right? We have Crohn's disease and ulcerative colitis. IBD affects as many as 3.1 million persons in the United States. Diagnosis, we see that there's this bimodal type pattern, usually in the second and fourth decades, and also a noted increase in the sixth decade. IBD remains a significant cost to the U.S. health system, accounts for 1.3 million provider visits and 92,000 hospitalizations annually. Our biggest drivers of cost, therapeutics, which we're going to talk about a little bit today, comorbidities, of course, anemia and psychiatric illness, and of course, emergency room visits. So I know everybody's come back from lunch, and we just had an amazing lecture by Sarah, but I want to get things started as well. So let's start with a polling question. Your 23-year-old patient has just been diagnosed with small bowel Crohn's disease. During the visit, she asks, how did I get Crohn's disease? And you explain to the patient that the pathophysiology of IBD is related to genetics, environmental factors, microbiome disruption, overactive immune response, or you say to her, the underlying pathophysiology is not clearly understood, but theorized to involve all of these factors. Wonderful. Well, it seems I know after lunch is always tough, and I appreciate everyone here. And I agree, right? And we're going to talk about this further. The underlying pathophysiology is not clearly understood, right? What we do know, of course, is that IBD is a complex disorder with varying contributions from environmental factors, genetics, and the intestinal microbiome, along with immune dysregulation. So the table that you see here on the slide provides some further details regarding potential risk factors for developing inflammatory bowel disease. For example, patients with a family history of IBD are 3 to 20 times more likely to develop IBD. Smoking and appendectomy appear to offer protection from ulcerative colitis, but increases the risk of Crohn's disease. And as we can see all the way here in the bottom, diet, right? Diet does appear to play a role as well. We see an increase in dietary fat, right? So specifically more like a Western diet, has been linked with an increase for both UC and for Crohn's disease. Now, ulcerative colitis and Crohn's disease have many overlapping symptoms. So how can a provider distinguish between ulcerative colitis and Crohn's disease? So let's spend a little bit of time reviewing the differentiating features of Crohn's disease and ulcerative colitis. First of all, Crohn's disease can infect the entire GI tract, right? From mouth to anus, and is commonly located in the terminal ileum. Whereas ulcerative colitis is isolated specifically to the colon and almost always has rectal involvement, right? Now, what I also want to point out with Crohn's disease is that it's usually rectal sparing, meaning that it's not involved, but we do see perianal involvement, right? So that's another differentiating feature that I want to point out. How about inflammatory patterns specifically? Crohn's disease has a patchy pattern of inflammation with skip lesions, of course, while UC usually exhibits a continuous or circumferential inflammatory pattern of disease that usually starts from the rectum and then actually works or spreads proximally. How about also variants and clinical symptoms between the two conditions? Crohn's disease tends to be a little bit more insidious, right? Chronic pain, at times more common, I would think, to the right lower quadrant. We see weight loss, fatigue, malnutrition, and not always do we have to see hematokesia, which again is the definition, of course, is bloody diarrhea or blood mixed with stool. Now, let's look at our UC patients, specifically when it comes to symptoms. Patients usually will present with hematokesia, right? Increase in bowel frequency, stool urgency, and tinnismus. And if I could tell anybody about tinnismus, if you make a fist and kind of like squeeze your hand together, tinnismus, you know, usually I tell patients they know this sensation, they know this feeling. So I make a fist and I squeeze my hand together. And usually this is a key symptom when rectal inflammation is involved. And as you can also see here by the table, the complications vary between the two conditions, right? Crohn's disease, we've got fistulas, strictures, obstruction. We look at ulcerative colitis, we see toxic megacolon, hemorrhage, and of course, perfulation. And last but not least, extraintestinal manifestations. Now, I want to point out, extraintestinal manifestations listed can occur in either form of inflammatory bowel disease. But in Crohn's disease, there's a slight higher incidence in erythema nodosum, iritis, uveitis, arthritis, and even aftus ulcers, as I had in clinic this week. While incidence of pyoderma gangrenosum and primary sclerosing cholangitis appear a bit higher in our UC population. Now, let's talk a little bit about the endoscopic and histologic features of both Crohn's disease and ulcerative colitis. In Crohn's disease, patients may exhibit a cobblestone-like mucosal appearance, along with kind of segmental or skip lesions, along with a longitudinal appearing ulcers, as you can see by the image on the right-hand side of your screen that has that Crohn's disease. You can see those long ulcers and kind of those skip lesions. In contrast, patients with ulcerative colitis usually exhibit this kind of diffused superficial colonic inflammation, which usually continues, again, from the rectum, right, and spreads proximally. So there's commonly evidence of erythema, loss of vascular pattern, and, of course, spontaneous bleeding. Now, let's look at biopsy findings specifically, right? We know that both of them are going to exhibit inflammatory cells. But in Crohn's disease, inflammation is transmural, right? Patchy and a hallmark sign is usually the presence of granulomas. However, granulomas are only detected in about 15 to 36% of biopsy samples. So it doesn't mean if you don't have granulomas that you don't have Crohn's disease. So I just want to be clear with that. You can kind of see a picture of a granuloma here on the biopsy slide on the image here to the right. Now, ulcerative colitis biopsies are usually characterized by mucosal or submucosal inflammation, neutrophilic infiltration, of course, with cryptarchitectural distortion, cryptitis, and crypt abscesses. And, again, no evidence of granulomas. So how do we start moving forward with the diagnostic testing when we're considering inflammatory bowel disease as part of our differential? So diagnostics and IBD can be both noninvasive. So, again, we're looking here at stool test, a fecal calprotectin, which can be elevated even in Crohn's disease, but usually more in colonic Crohn's than small bowel Crohn's, right? In ulcerative colitis, we can definitely see that it's elevated, right? But the con, of course, of a fecal calprotectin is that it can be elevated even in infection and low even despite active small bowel disease. So kind of got to be cautious. Also, we have C-reactive protein, which we definitely see is elevated in Crohn's disease, but not always elevated in ulcerative colitis, right? But also the thing to point out specifically about CRP is that 40% of patients with mild inflammation don't actually mount a CRP or segregate even response. And there is even a population of patients that doesn't make CRP. You can also see here we've got hemoglobin and albumin listed as well with the pros and cons under each of the Crohn's disease or ulcerative colitis. Now let's move into some diagnostics, right? We've got CT enterography, which for Crohn's disease, you know, can actually help diagnose and follow small bowel Crohn's, but for ulcerative colitis can actually help rule out small bowel Crohn's. But with a CT, right, we've got the increased risk, of course, of radiation and IV contrast. So we have to be cautious with our patients who have kidney disease. How about MR enterography, which is kind of where I've kind of shifted my practice to in the last few years. Again, helps us diagnose and follow small bowel Crohn's disease. But of course, we use it in ulcerative colitis to maybe rule out that patients don't have small bowel disease. With, of course, MR, we have no radiation, which is great. We don't have to worry about our patients who have chronic kidney disease, but it's a pretty prolonged exam. And I'll tell you, I work in a community-based practice. You have to have a good radiologist. You know, someone who feels comfortable looking at MRE. And then, of course, we've got our tried and true colonoscopies, which help us make our diagnosis, gives us direct visualization. The con, of course, is this, is for our patients with Crohn's disease, there's minimal role in small bowel evaluation, and sometimes that can be a little bit complicated, right? So we do have capsule endoscopy, which can help us diagnose and follow small bowel disease, helps us rule out small bowel Crohn's disease, which I do a lot actually reading small bowel capsule. We have a lack of radiation. And again, some of the con, though, is that there is a bowel prep involved. And, of course, there's a small risk of retention. But I want to point out, it is a small risk of retention. Now, we've got all these diagnostic tools. And I think when we're considering what tool do we use, Kim, right, I think that you really should consider the diagnostics to really reflect your degree of suspicion, right, on how we're looking with our IBD patient. In a patient with maybe no alarm features, look at non-invasive diagnostics. Start with a fecal calprotectin, right? In someone with alarm features, right, they're having nocturnal diarrhea, they're having hematochesia, right, abdominal pain, weight loss. Go for more of a definitive test, right? First test, let it be a colonoscopy. So let's move forward and talk about our guiding principles of inflammatory bowel disease management. And what does this actually look like? And what I want to point out here is the image on the left, right? This is a classic image. I'm sure all of us may have seen this image at one point or another. So this is a representation of progression of digestive damage and inflammatory activity in a theoretical patient with Crohn's disease. So we recognize that structural damage is progressive in Crohn's disease. And I want to point out, within 20 years of diagnosis, close to 50% of patients with Crohn's disease will develop some form of an intestinal complication, whether that be stricture, fistula, abscess, or phlegmon. So the focus here should be adequate control of early inflammation, right? So we want that window of opportunity, which you can see there, right, on that image on the left-hand side. Look at that early disease, you know, patients, and, of course, getting into early inflammation control. So what we see here on the image on the right is that tight control and monitoring can alter our overall progression of disease, right, and change the course. And that's what we want, right? We think about these complications of disease for our patients. And again, starting off this discussion, our younger patients, they're 20, 30 years old, right? We want to change the course of this disease. So how can we do it, right? And again, this is a bit of a different approach than I think some of us are used to, right? We don't want patients to earn their drug. What we're looking at here is this window of opportunity. Get them early in disease, treat them early in disease, and don't make them earn anything, right? Have them change this course. So let's take a moment here to discuss, of course, treat-to-target in inflammatory bowel disease. As evidence does suggest, using the treat-to-target approach provides positive clinical outcome. Now, the guiding principle of treat-to-target is going beyond just symptomatic improvement or remission, right? As you can see represented by the image on the left, right, the multiple layers of the target that we have here. But we want to use clearly defined objective biomarkers, endoscopy, radiology, to prevent progressive bowel damage, right? Again, change the course of the disease. We're going to spend a bit more time discussing treat-to-target in practice, but first I think we need to kind of define a few terms to kind of help us describe this for us. So we often see disease activity and disease severity used very interchangeably in inflammatory bowel disease. So disease activity is a term that takes into account symptoms and diagnostics at a current point in time. It's like a snapshot, right? Disease activity is what changes between time points, and it's helpful in adjusting therapy to achieve a target, right? So improving symptoms, mucosal healing, we're going to get into that in a little bit. Whereas disease severity, on the other hand, looks at the patient's entire course in a longitudinal manner, reflecting on the entire course or the journey of their disease. It takes into consideration complication, prior medication therapies and failures, and prior surgeries. Now, disease severity is what really helps guide risk stratification, right? Hmm, new term here, risk stratification. Now, risk stratification is going to be one of our first steps to guiding these principles of guiding IBD management. So how do we risk stratify our IBD patients? Oh, I'm so glad you all asked. So let's look here at this graph here. We can see a low progression of rapid progression. For this is specifically our Crohn's disease patients. We can see low risk for rapid progression. You know, age of diagnosis is over 30, that they've got limited anatomic involvement, that they've got no perianal or severe rectal disease, that they've got superficial ulcers, no prior surgical resection, and no history of stricture and or penetrating behavior. Whereas we look at high risk of progression, age of diagnosis less than 30, extensive anatomic evaluation, that they have perianal and or severe rectal disease, that there's ulcers that are present, prior surgical resection, and of course, stricturing and or penetrating behavior. So again, what we need to consider is risk stratification. Where does our patient fit? Do they have a low risk for rapid progression or high risk? And this is what starts what we're going to talk about. We're talking about treating to target and, of course, the essentials of management. Now, let's look at risk stratification for ulcerative colitis. So our age at diagnosis for a low risk patient, greater than 40, their anatomic extent is just localized proctitis. Endoscopic activity, male one, they have very superficial ulcers, their albumin is normal, their CRP is normal, and they've had no hospitalization. How about high risk for rapid progression, age less than 40 at diagnosis, that they have extensive anatomic extent, so pan colitis, right? A male score of three, of course, or a UCIS score, which that, of course, is ulcerative colitis endoscopic index of severity score, right, of seven or more, that they have deep ulcers, that their albumin is low, that their CRP is high, and yes, they are hospitalized. All right, so now we talked a bit about, of course, risk stratification. Now, let's take a look at STRIVE-2 consensus. Now, STRIVE-2 recognizes specific treatment targets with the aim of, of course, improving clinical outcomes, restoring quality of life, and changing the course of the disease. And as we can see here by the image, right, we've got active IBD. Now, therapy according to risk, that's why we need to introduce risk to begin with. How do we risk stratify our patients? Now, let's look at our targets, right? We have a symptomatic response. These are our short-term targets, symptomatic remission and maybe normalization of CRP. Then we move on, we see a decrease in calprotectin, right, and normal growth in children who have Crohn's disease, and how about endoscopic healing, and, of course, normalization of quality of life and absence of disability. What I want to point out here in some points, even when it comes to treat-to-target, is this is a continuum, right, that we're constantly looking at our target. We're making sure we're meeting these targets, and they have active inflammatory bowel disease. We re-stratify these patients, right, and we move through this as a continuum. Also, things that we have to consider, and I will tell you as a provider, always have a plan in place as to how you're going to measure your target. One of the best words of recommendation I've heard is make an appointment with your patient before they leave your office. Do you want to recheck their CRP or their fecal calprotectin in six weeks? Have that appointment set. Make sure you do that. If you want to repeat their colonoscopy, again, a year after you start their biologic or six months, make that appointment before they leave. The other thing that I wish to point out as an advanced practice provider is that we need to ensure that our targets and our patients' targets align because we know that this ultimately provides the best patient outcomes. So this is my favorite part, and I know everybody always gets a little, you know, humdrum when we talk about pharmacology. I love pharmacology, and I think the reason that I point this out specifically in this lecture is because when patients are going to be started on therapy, guess who they're going to see? They're going to see us. We're the ones that have to talk to them about safety, evaluating them for any side effect profiles. When the patients want information about how drugs work, we need to know how it works. So let's dive into some pharmacology. So we're going to start with corticosteroids, which are effective in inducing remission in both ulcerative colitis and Crohn's disease, but not intended as maintenance therapy. Corticosteroids are used, of course, to, corticosteroids that we use, of course, include methylprednisone, prednisone, and hydrocortisone. Of course, we have non-systemic formulations as well as budesonide, which are commonly used to treat mild to moderate IBD. When we talk about our non-systemic formulation, this high-potency or local corticosteroid has a targeted delivery and has an extensive first-pass hepatic metabolism, which reduces systemic side effects. Of course, we know that there are multiple risks involved with systemic steroids. Some of them include, of course, infection, diabetes, hypertension, sleep disturbance, which I see a lot of, weight gain, and osteoporosis. So some quick considerations. Remember, when you start a patient on steroids, there should always be an exit strategy. Steroids are short-term, okay? They're not maintenance therapy. Kind of, I always kind of consider the use of a non-systemic steroid first, and bone density and vitamin D testing should be performed on patients that have been on steroids longer than three months. Now, how about aminosalicylate to our 5-ASA agents? These are indicated for induction and maintenance of mild to moderate ulcerative colitis. 5-ASA agents have been suggested to have a weak or ineffective kind of outcomes in treatments for Crohn's disease, and so technically used as off-label, but I can tell you it's definitely seen in clinical practice. So the dosing of all the 5-ASA agents are listed here. This is a labor of love for all of you, so you can have this and see them, you know, and use this kind of as a reference. We're not going to go through them all for a time element issue, but studies have suggested that, you know, that there's an improvement of efficacy for left-sided ulcerative colitis with the use of both oral and rectal therapy. So I'm going to tell you, double dose those. Use those at the same time. The mechanism of asking the 5-ASA is they act topically, decrease inflammation by modulating chemical mediators, which are involved in an inflammatory response. So for starting therapy, start with a baseline renal function, and I always ensure that I check a renal function annually. Some common side effects include nausea and headaches. Less common side effects include interstitial nephritis, the reason, of course, for checking this renal function, and 3% of patients are intolerant or allergic to 5-ASA therapy, and there's even a small subset that may report worsening of diarrhea, so discontinue at this time. And even as Sarah pointed out, I think, you know, earlier we were going to talk about some of the medications that can cause some other problems, but sulfasalazine, of course, is reversible for male infertility, so there is some data on that, but kind of keep that in mind. So I think this next slide is something that I've used well over time, looking at our agents of delivery. Again, this is more for your visual use, but again, choosing a 5-ASA medication should be based on delivery location matching the disease location. So if you have a patient who has, you know, proctitis along with left-sided disease, again, using dual therapy. So I always find out where is the disease located and choose a therapy, of course, that will, that coincides with that disease process. All right, let's move on to some immunomodulator therapies. So we have azathioprine and 6-mecaptopurine. So these are both indicated for the maintenance and remission of Crohn's disease and ulcerative colitis, whereas methotrexate is actually indicated for the maintenance or remission of Crohn's disease, even though it can be used in UC. All are considered to be steroid-sparing agents and utilized in combination therapy with biologics to potentiate effectiveness and reduce immunogenicity of biologics. So, of course, the focus on this slide is azathioprine and 6-mecaptopurine, and, of course, the mechanism of action is to exhibit immunosuppressive effects by inhibition of purine and protein synthesis subsequently limiting lymphocyte proliferation. You can see the dosage here for you. I'm not going to review all those, but you can see the dose for 6MP is actually lower. And that's because, of course, we think about the metabolism of the thiopurine. And I will say, you know, checking a TPMT level, because TPMT is the principal enzyme in the regulation of thiopurine metabolism. So looking at the genotype and phenotype helps actually identify those patients who are at higher risk of developing toxicity and can also guide individualized treatment plans. So lab monitoring. This is what we want to know, right? This is how I do it. CBCs and LFTs every two weeks for one month. If they're stable, then I do CBC LFT monthly for two, right? And if it looks good after that, then I continue to do it usually every six months. If you've got your dose of thiopurine at 2.5 milligrams per kilogram per day, check a thiopurine metabolite level in four to six weeks. Once your dose has been optimized, again, check labs every three months. So side effects of thiopurine, GI upset, myelosuppression, and as Sarah mentioned, kind of got a little ahead of myself, pancreatitis, right? So this is something that I have seen. If a patient complains of GI upset, please, please, please check enamelase and lipase. There is a risk of lymphoma, especially those over the age of 50 and in use of combination. There's a rare side effect of hepato splenic T cell lymphoma, specifically in males and under the age of 35. And with combination therapies, we're talking about immunomodulator and biologic. So some final considerations, of course, immunomodulators take a slow onset of effectiveness, four to six weeks. Normal TMPT screening does not preclude bone marrow and or liver toxicity. So make sure you continue to monitor these. They are safe in pregnancy. And as we know, no effect on male fertility. All right, let's move on to methotrexate. Of course, we use this in combination with biologics to potentiate effectiveness and reduce immunogenicity of biologics. Methotrexate is a folic acid antagonist, so inhibits lymphocyte proliferation and also suppresses T cell function. As you can see, the dosing is oral or sub-Q. What do we do beforehand? Check our labs. You can see them here, specifically pregnancy test and a folate. What do we do during treatment? Again, every two weeks for one month, I check a CBC of U.N. Cranin and LFTs and then monthly for three months. What we need to know specifically about methotrexate is the longer that you use it, there is a buildup for that. And LFTs can actually change. Please make sure you continue to monitor LFTs. Specifically, we're looking at hepatotoxicity, necrotoxicity for our side effects. Methotrexate should not be used in patients with underlying liver disease. Some considerations, of course, it's contraindicated in pregnancy. We recommend two forms of birth control. Wait at least three to six months after you discontinue before you consider conception. And of course, this should be documented at every single visit. There's a slow onset of effectiveness, as we talked about before. And of course, if they have a really big issue with nausea, you can actually premedicate with antiemetics. That actually helps. And please make sure that you give them folic acid. Now let's move on to our biologic therapies. The role of anti-TNF therapies, of course, is to help balance our overactive response, of course, to TNF, right? So our current therapies include infliximab, which is indicated for Crohn's disease and ulcerative colitis, etalumumab for treatment of Crohn's disease and ulcerative colitis, sertalizumab, which is for Crohn's disease, and galumumab, which is for ulcerative colitis. Specific dosing for each of these is listed in this table for you. We talk about lab testing. And again, prior to initiation of any of our advanced therapies, again, we should be checking for active or latent TB, hepatitis B screening, CBC with a differential. And I usually order a CMP. Throughout maintenance therapy, of course, I usually check in about week eight, making sure everything is stable, and then every six months, along with an annual TB monitoring. Common side effects, of course, include headache, nausea, upper respiratory infection, and also include infusion-related hypersensitivity. And there is a box warning, as I'm sure we all are aware of, which, of course, includes serious infection or reactivation of latent infection. Of note, of the limited number of patients diagnosed with a lymphoma, majority of them have received treatment with concomitant immunomodulator anti-TNF prior to diagnosis. What I want to talk about in regards to consideration specifically about TNF, right? This is the most effective therapy we have to treat our IBD patients from what we have in regards to our complicated patient, right? Effective specifically in our Crohn's disease patient with fistulizing disease. And it's got a rapid onset of action. Combination therapy with an immunomodulator yields the best clinical outcomes, right? So make sure that we keep that in mind. It also helps lower our rates of antibodies and loss of response. What I want to just point out quickly is that biosimilar therapies have become available for infliximab. There's also biosimilars for adalumabab that are right around the corner. Current data suggests that biosimilar therapies do not exhibit any clinical meaningful difference in efficacy, safety, or potency. So please be aware of that. Now let's move on, of course, to our anti-integrants. Oops, we went a little too quickly. So we've got Intivio and natalizumab for essence of time. We really don't use natalizumab as much as used for patients with Crohn's disease. It has a black box warning. And, of course, you have to be enrolled in the TOUCH program. So let's turn our focus to vetalizumab, right? It's indicated for Crohn's disease and ulcerative colitis. It's currently the only gut-specific biologic treatment approved for ulcerative colitis and Crohn's disease. We can see our dosing that is listed here on the slide for us. Prior to initiating therapy, again, we've kind of talked about that. I'm not going to belabor that point. We do do TB testing, even though it's technically not necessary. And, again, from routine monitoring, you guys can see that here on the slide. Some of the most common side effects that I see sometimes can be hypersensitivity reaction, but arthralgia. I do see that a lot, joint discomfort, fatigue, headache, and a little bit of nasal pharyngitis. Now because natalizumab is gut-specific, right, the safety profile doesn't include the side effects that are usually associated with systemic immunosuppressives. So when I think about this therapy, I may consider it in an older patient who maybe I'm worried about risk of, of course, infection. Also, the natalizumab appears to have low immunogenicity rate, and it's got selective. So, again, might not treat all of our extraintestinal manifestations, so keep that in mind. How about biologics when we talk about our IL-1223s, right? So first one we're going to talk about is Celara, or I'm sorry, ustekinumab, which is used for our treatments with ulcerative colitis and Crohn's disease. So it's a human monoclonal antibody that binds specifically to the P subunit 40 and inhibits interaction with IL-12 and IL-23. So, of course, we have an ion induction, single IV induction that's weight-based, followed by subcutaneous dosing every eight weeks. Again, we've talked about our initiation labs prior to initiation and during therapy. What I want to point out is that there's no required monitoring. Common side effects include nasopharyngitis, UTI, bronchitis, sinusitis. And again, rare, of course, is posterior reversible encephalopathy syndrome, which we'll see in one patient's post-marketing in Crohn's. Consideration, safety in pregnancy, low risk of infection and malignancy, low immunogenicity rate, and consider as a monotherapy. It's also been approved for flaccid psoriasis as well. Now, as we move on to our IL-23, rizekizumab. So, again, induction and maintenance for our Crohn's patients and adults. Monoclonal antibody that selectively binds to, of course, our IL-23. So it's IL-23 specific. You can see our dosing here. We've got IV induction, of course, at 0, 4, and 8 weeks, with a maintenance of 180 or 360 sub-Q at week 12, and then every eight weeks we have an autobody injector. What I want to point out, and I'm sure this is the question, most people stay at 360 until maintenance, you know, and then they've got some kind of remission is proven, and then they can decide decreasing it to 180. As I want to point out here from a lab perspective, slightly different, right? Prior to starting, when you liver function test, including that of a bilirubin, lipid profile, and again, everything else is the same. But during therapy, there is a requirement here that during induction, for at least up to the first 12 weeks of treatment, that we do recheck LFTs, including a bilirubin. Traditionally, when I, you know, in my practice, we do it at week 8 or at week 12, and I also recheck a lipid profile at week 12. So again, routine labs, of course, have a CBC, LFTs, and real functioning every six months, along with, of course, our active evaluating for TB annually. Some considerations here, we've got an on-body injector, low risk of infection and malignancy, low immunogenicity rate, and again, a small, thinking about it as monotherapy. Moving on to our small molecules, right? We've got tofacitinib, which is approved for UC, who are intolerant or had an inadequate response to TNF. So tofacitinib is considered a panjack, so it kind of targets all of the jack inhibitors. So as you can see here, our dose induction is 10 milligrams twice daily for eight weeks. You discontinue this 16 weeks if there's been no therapeutic benefit. Our maintenance is between 5 to 10 milligrams daily, and we use our lowest effective dose to maintain response. We look at our labs here, we need baseline CBC at weeks four and week eight, and then every three months. And of course, we check our lipids at week four and week eight, as we do see LDL and HDL increases have been noted. We also check liver enzymes every three months, and TB testing, of course, as we've been discussed before. What I want to point out specifically that we've seen here with our jack inhibitors, right, is that in 2019, the FDA issued a black box warning for tofacitinib in patients who are taking this 10 milligrams daily. There's an increased risk for blood clots and even death. This recommendation came from a post-marketing study in an RA population. And, you know, they have done some additional evaluation, even in the tofacitinib group, but this black box warning lives here. So one thing we have to consider, of course, is evaluating our patients for any kind of thrombotic risk. And again, we have actually seen, you know, serious infections, including that of herpes zoster. So we do need to make sure we recommend a zoster vaccine. Considerations, it's a rapid onset of action, improvement in three days, right? There's no apparent immunogenicity, no therapeutic drug monitoring is needed, but we do need to avoid it in pregnancy and, again, avoid in patients with a high risk of thrombosis. And again, we do not recommend use in combination with other jack inhibitors or biologic therapies for ulcerative colitis or immunosuppressants. So we look at oopdacinib here, of course, newest kid on the block, right? Induction and maintenance, of course, for our UC patients who are intolerant, who had inadequate response to TNF. And this is supposed to, oopdacinib has a selective and more preferential inhibitory effect on MorbJack1. As you can see, the induction is 45 milligrams daily for eight weeks. And then you can go to maintenance of 15 milligrams once daily or 30 milligrams once daily for patients with refractory or extensive disease. Labs prior to starting therapy, again, CBC, LFTs, and a lipid profile. Pregnancy test is important and, of course, risk screening for thrombosis because it carries that same kind of risk. And again, oopdacinib cannot be given if it's for patients who have an intolerant or inadequate response to TNF, just like TOFA. So during therapy, of course, we want to check our lipids, CBC, and LFTs at week 4, 8, and 12. And then, of course, CBC and LFTs three months thereafter. And you can see here there's some specific holding restrictions in regards to your CBC with differential, which I'm not going to get into because I see I'm already out of time. This is what happens when I get too excited about looking at all of my pharmacology. Again, there is a black box warning here. So, again, looking specifically at thrombosis risk. Some considerations specifically with oopdacinib, there's a rapid onset of action, symptoms improving as early as day one, there's been some data out. No apparent immunogenicity, there's no therapeutic drug monitoring, but avoid use in pregnancy. And again, recommend vaccination with the Shingrix vaccine. And last but not least, our S1Ps. And specifically we're looking at ozanamide, you know, S1P receptor, which blocks the capacity of lymphocytes to aggress from lymph nodes, reducing the number of lymphocytes in peripheral blood, resulting in a reduction of lymphocyte migration into the intestine. So you can see our dosing here. What we really need to point out is, and I examine patients with a history of uveitis or macular edema and check your varicella and zoster virus before starting, right? And if they're not immune, that they need to be immune. Of course, considerations, we want to do a CBC LT every four weeks, routine lab monitoring, and of course, we want to evaluate for active or latent TB. Of course, let's look at some contraindications here. You guys can see all the side effects. Wait three months after discontinuation before considering any kind of conception. And contraindications include prior cardiac history in the last six months, Mobitz type 2, second or third degree AB blocks, six sinus syndrome, or if the patient has any kind of issue with a, you know, they have to have a functioning pacemaker if they have sinus block. And of course, there has been an increase in systolic pressure that has been observed about three months after treatment. So avoid any foods with very high tyramine content, because that can affect the blood pressure. So a little bit of therapeutic drug monitoring. I think in the essence of time, we're going to skip this, but let's talk a little bit about reactive and proactive, right? We know a little bit of difference here, but a reactive monitoring rationalizes and better directs the management of, of course, primary non-response and secondary loss of response to biologic. It can be more cost-effective than empiric dose escalation and is associated with better therapeutic outcome compared with anti-TNFs. What about proactive monitoring? Well, it's been associated with better therapeutic outcomes compared with empiric optimization and or reactive therapeutic drug monitoring for anti-TNF. Can optimize model therapy instead of combination therapy. And last but not least, infliximab de-escalation, or when we want to consider stopping. Here's a proposed drug concentrations, which again, more for your own personal reference. And in my opinion, I think that these are great to kind of keep in mind when we're looking specifically at our drug monitoring for our patients. And do we have room in order to optimize our patient's therapy? Here's some factors that can influence pharmacokinetics. So when we're looking specifically at these drug levels, and if we want to optimize our patients, let's keep in mind specifically what influences the PK on these monoclonal antibodies. Specifically, we're starting with a patient with a very low albumin level. Well, we already know that this increases clearance and worsens clinical outcome. So do we need to consider a higher dose? How about body size? If they have an increase in BMI, high BMI can increase, of course, drug clearance. And of course, what I always think about too is that concomitant immunomodulator. We know that this can increase our serum concentration, and we know that this is the best option when we're using it with biologic therapy. So there's so many tools in the toolbox. What do we do, right? And I think that this is a tough kind of thing to discuss, because there are so many that are coming in the future, right? Ooctocinidib hopefully will be approved for Crohn's disease by mid-2023. Risinkizumab hopefully will gain approval for ulcerative colitis in 2024, right? And not to mention, we have new S1Ps, atrazumab, here before we know it. So before we move on to evaluating possible positioning, it's important to recognize there are multiple factors that go into selecting a therapy for our IBD patients, right? We talked about evaluating disease activity, disease severity. Evaluating safety considerations. Looking at extraintestinal manifestations. Of course, looking at individual risk factors, right? Choosing the right therapy for the right patient. And most importantly, it's having a patient-centered, decision-making discussion, right? We know that patient-centered decision-making actually improves adherence, satisfaction, and cost. So what I want to point out first and foremost is that this is kind of a, there's no head-to-head studies, or, you know, they're very limited head-to-head studies, I should say. And this is an adaption from the AGA pathway, right? So we've got our Crohn's disease patient. We risk them, right? We look risk stratified. Low-risk patient. Mild patient. So consider use, right, of budesonide, with or without azathioprine, tapering course of prednisone. If they have diffused left-sided disease, right, consider prednisone with or without azathioprine. So we look at our patient who's got moderate to severe risk, right? So our considerations, and these are options, again, in no particular order. Anti-TNF monotherapy. Anti-TNF plus a thiopurine or an immunomodulator, right? Or methotrexate for those who don't tolerate a purine. We also have ustekinumab, vialuzumab, and risinkizumab to consider. Now how about positioning our treatments for UC? And, again, this is an adaption. We look at our patients. We risk stratify them. Low-risk of colectomy. Look at their disease. Where is it located? Oral 5-ASA, right? Should we use a rectal and or in oral 5-ASA? Oral budesonide? And or topical endorectal steroids? Then we evaluate. Are they in remission? Okay, we'll keep them on their therapy, right? The biggest point here, too, is make sure that we, of course, what we want to do is taper those steroids, okay? How about high-risk for colectomy? That's a moderate to severe patient. Consider a short course of steroids, right, with or without a thiopurine, right? And this, again, is for ulcerative colitis. We could use vitiluzumab. We could use an anti-TNF. We could use ustekinumab. And, of course, we could use ozanamide because we don't need to fail a TNF for that drug. Now if they're not in remission, then let's look at our options we have here below, right? Did we not start with a TNF? We could use a TNF plus or minus a thiopurine, right? If we had them on a TNF, should we use a thiopurine? Should we add it? If they're just on thiopurine, can we maximize that? And, again, looking at drugs like vitiluzumab, ustekinumab, right, we have TOFA and ooptocinative if they're intolerant to TNF. And, of course, last but not least, surgery is not always the last option. So these are our last few slides here. And data, of course, suggests that IBD population does not receive the same preventative services, right, that the rate of general population does because of the fact that our visits are usually disease-focused with a low priority, right? It's unclear who the responsibility is. Is it ours or is it the primary care doctors? And, of course, there's just a lack of knowledge. What I put on here for you, of course, is just a little check sheet that's available free. It's at cornerstones. A, helps you with vaccines. B, helps you with therapy-related testing that we moved over. And C, of course, talks about our highlighting, of course, our IBD maintenance for our patients. Last but not least, if I don't talk about health disparities and IBD sitting on all these committees, it would be ill of me not to do so. But there's been an increase in incidence in IBD among races and ethnicities in the United States and across the world. Over the past four decades, the IBD incident rates for individuals from non-whites compared to white race has increased by 134 versus only 39%. So in order to promote health equity among patients with, of course, IBD, we have to be able to recognize these. And I think as we, as advanced practice providers, we definitely need to have a deeper understanding of the role of race and ethnicity in the care of patients with IBD. You can see over here on the right-hand side of the screen, there are many reasons that we have treatment disparities in IBD. Genetic, environmental, phenotypic, provider-making, delay in diagnosis, right? All of these things lead to, of course, our treatment disparities. One of the biggest things, of course, is access to an IBD specialist. What we see here, of course, are mechanisms of inequity. And to promote health and equity among patients with IBDs of different races and ethnicities, we must understand the multiple factors that lead to disparities, specifically social determinants of health. This is a great visual representing the upstream social determinants that ultimately lead to downstream health outcomes. Some of these downstream health outcomes include delayed diagnosis, increase in disease severity, and, of course, increase in ED visits, hospitalizations, and prolonged stay, and even increase of mortality. So what's our role as the advanced practice provider? We need to ensure that we expand our knowledge on health disparities of inflammatory bowel disease, as this becomes increasingly imperative as our population is diversifying, right? Also, I'd like to point out using the current and appropriate language when referring to racial and ethnic groups and sexual identity and orientation and use of gender-neutral language in terms that are inclusive of all gender and identities. Now, putting it all together, I know we're out of time, so I'm going to kind of breeze through this here. I've got a 20-year-old female with iron deficiency anemia. She was initially diagnosed here, and I'm going to move through these. I'm so sorry. Her fecal calprotectin was elevated and ends up getting diagnosed with Mayo 2, right? So in here, we look at her. We risk stratify her. We put her on betalizumab, and now we use our treat-to-target method. And using this, you can see here, right, we've got our symptomatic response at 8 weeks. We look at our DQs in fecal calprotectin from 1,300 to 138. We've got endoscopic improvements, right, with a Mayo of 1. We're looking at our quality of life, right, which is important, of course, in stride guidelines, and then we have a normalization of her fecal calprotectin. Here are some great APP IBD practice resources. All of the drug monitoring that you saw came from this BRIDGE Consortium. It's a great resource. Also here, the Crohn's and Colitis Foundation has many, many, many resources that you can all look at, and they are free, F-R-E-E. You can download letters for appeals, so on and so forth. I'm sure you all have plenty more. Please put them in the chat. Last thing, practice pearls. Early treatment with use of treat-to-target strategy is key to changing the natural history of disease and prevention of complications. Targets are continually changing. Make sure to reevaluate and monitor these targets. Risk stratification provides guidance regarding the tool that we can select in our ever-growing toolbox. Patient-centered shared decision-making regarding treatment improves adherence, satisfaction, and cost. Expand personal knowledge on health disparities and IBD, and use your APP practice resources. Again, work smarter, not harder. With that, I do apologize that I went over, but I thank you all for your time covering this very, very diverse and ever-changing topic. Thank you.

inflammatory bowel disease

Crohn's disease

ulcerative colitis

therapeutic agents

treat-to-target approach

pharmacological options

health disparities

management