Dr. Kinnucan: I would love to walk us through. A lot of what Jordan already talked us through in terms of STRIDE is really going to just bring those points home is we have patients who have symptoms. We prove that there is inflammation using a variety of modalities, and then we need to assess response.

What are the STRIDE guidance? One, led to STRIDE-II. Hopefully, we will be seeing some STRIDE-III guidance shortly. STRIDE-II really incorporated not only symptom response but biomarker monitoring. It is really, again, bringing the points home about checking C-reactive protein at baseline, getting that follow-up assessment, both short-term, intermediate, and long-term, fecal calprotectin. It emphasized individual goals and focused on the importance of mucosal healing.

When that patient is meeting some of those other targets but has the persistence of inflammation on endoscopic assessment, the opportunity to optimize that patient, either within the current therapy that they are on or when do you consider moving on so that you can give that patient not only short-term success, prevent that relapse, that may happen in the next three to six months, but also give them long-term success.

We know that undertreating inflammation is what puts patients at risk for the adverse outcomes that they definitely want to avoid, right? They want to avoid that unpredictable relapse. They want to avoid being hospitalized for their disease. They would like to avoid having emergent surgery for their disease. They would also like to avoid complications that we know are associated with persistence of inflammation, like precancerous changes in the colon.

Those are all definitely important things that you want to talk through with your patients.

STRIDE-II: Dynamic Treat to Target in IBD

This next slide really depicts that same thing in a visual format. It is talking about that early overall therapy response, looking at symptomatic response. Now looking at overall improvement or normalization of C-reactive protein and fecal calprotectin. Then at what point? Usually I am allowing patients time on therapy.

The worst thing we can do is to take a patient and look too early, right? Do a colonoscopy at three months. That is probably too early to see a response. I am usually having that patient assessment, especially if they are meeting our first two targets: clinical and biomarker improvement or resolution. I am usually doing a colonoscopy at six to 12 months. With ultrasound in the practice, we can sprinkle that in throughout that as well.

Now we are talking about what are the targets that have been defined. It is based on evidence to show change in outcomes. We are starting to understand a little bit more about the extra credit. When we get transmural healing in patients with Crohn's disease, so patients can have an endoscopy that shows absence of ulceration. You get that enterography and you see persistence of thickening.

Does that mean that they have failed? Have they not reached their target? According to STRIDE-II, they have reached their target. They have absence of inflammation. When we get that extra credit, when we get that transmural healing, that deeper level of healing, we know that is going to be associated with likely longer-term success. Should we change their therapy if they have not achieved that? That is really where STRIDE-III is going to really help us.

The same thing with ulcerative colitis. When we see patients with ulcerative colitis and we have a Mayo score of zero, we have reached endoscopic healing. We have reached that target. Histologic healing, the presence of histologic normalization. I call that extra credit. If patients reach that, we know that that is associated with longer-term success. I do not know that I would change their therapy to be able to achieve that if they have achieved all their other targets.

We are going to learn more as we start to study those particular outcomes. Does histologic normalization lead to longer term success if we are able to maintain that? I do not know that we have the data to suggest that we should be reaching for that target if we have achieved the targets that are already defined by STRIDE-II.

Treat to Target: Defining the Target in IBD

This is again another way to think about that same approach, at overall, from the bottom-up, is looking at clinical targets, looking at overall improvement in quality of life. We want endoscopic targets. Then looking at some of these other extra credits that might be defined in our STRIDE-III guidance coming up.

Then future perspectives is reaching different molecular targets of healing, which right now is wishful thinking. We do not necessarily have specific biomarkers to be able to follow commercially in our patients right now.

Treat-to-Target Strategies in IBD

I am not going to go through this. This is mainly for you to have this for your own future reference, ulcerative colitis. Looking at what are some of those targets along the way? What has been defined by guidelines so that you are looking at that, but it does require you to check those things.

I will meet patients that come into our practice that have never had a C-reactive protein and never had a fecal calprotectin. We know that that is something that is very important as part of our evaluation and monitoring of these patients. It really just helps you to find what are those target values that you are looking for.

Goals and Timelines for IBD

Last, it is really reiterating these goals and timelines for IBD, when we should be looking at improvement and resolution of symptoms within the first three to six months. Clinically, I check biomarkers quite frequently, especially in my really sick patients. I often time them with their therapy.

If I am starting a patient on an IL-23, I have got a baseline CRP, I have got a baseline fecal calprotectin. Likely in my practice, I have a baseline intestinal ultrasound. Then I am going to be bringing them back at that eight week mark to get a C-reactive protein of fecal calprotectin and another intestinal ultrasound, so that I can follow their progress as well as how they are doing clinically.

Then endoscopic evaluation, we talked about six to 12 months and whether we are going to do cross-sectional imaging depending on that patient. Then obviously practical implications for ongoing monitoring. If we are moving in the right direction but we have not reached that target, making a plan with your patient. We are going to continue to give you a little bit more time. Maybe they are a delayed responder to that therapy and they are not following the classic clinical. They were not enrolled in the clinical trial. They are not following that classic 12-week mark or looking at that 52.

Maybe they just need a little bit more time as long as they are moving in the right direction. We are looking at data trends over time.

Role of Biomarkers in Crohn’s Disease

Again, these are looking at roles of biomarkers. Again, I am not going to go into this slide. These slides are available to you and they should be referenced. Print out this slide which is the role of biomarkers and evaluating them in Crohn's disease and really providing guidance on what those deltas should look like.

Role of Biomarkers in Ulcerative Colitis

As well as in this next slide, where we are talking about the role of biomarkers in ulcerative colitis. When they have reached those biomarkers versus when they have persistence, how are we going to be approaching that patient? What are we going to change? If nothing changes, we cannot anticipate that patient to reach that target, if only time. Maybe sometimes time alone.

Oftentimes we are usually augmenting something in their treatment plan. Maybe it is not an FDA-approved therapy, maybe it is dietary modification. Maybe it is improving their sleep quality. Maybe it is addressing other comorbidities like obesity. We are starting to learn the impact on obesity in terms of inflammation.

Maybe it is cutting out some of the things that have been shown to be more pro-inflammatory. Maybe we are doing some more adjuvant type approach to this particular patient's care, plus time to give them that opportunity to meet those targets.

CALM: Tight Control vs Clinically Driven Management for Patients With Moderate to Severe CD

We saw this word come up previously in one of Amy's slides talking about the CALM study. Essentially the takeaway here, this is talking about tight control, looking at biomarkers versus clinically-driven management of patients with moderate to severe Crohn's disease.

Patients were taken with moderate to severe Crohn's. We can extrapolate some of this data just thinking through ulcerative colitis. Ulcerative colitis patients were not included in this study. They were randomized to tight control, meaning biomarker-driven decisions versus assessing the patient's symptoms.

Now, of course, we know that patients in their symptoms and their inflammation do not always match. If we are basing our decisions on symptoms alone, we probably are going to miss the mark. We looked at primary endpoints of patients at week 48 with mucosal healing without ulcerations, and then some key secondary endpoints: patients in remission, patients in biologic remission, complete mucosal healing, endoscopic response at week 48.

The take-home here is that the greater number of patients in the tight control group were able to achieve endoscopic healing, a really important target that we have talked about several times throughout the webinar today. Another important target, corticosteroid-free remission. Obviously, there was more treatment escalation because we are using tight control as opposed to basing it on symptoms alone. This really was helpful to put data to what we were already doing in clinical practice, which is that we were really trying to target those biomarkers.

We also think is really key is that this resulted in reduced hospitalization and need for surgery or disease-related complications. Things that are important to us as clinicians as well as important to our patients.

CALM: Outcomes

I apologize, my screen froze, so you did not get to see some of the data, but much of what I just said is now outlined here in this slide. I apologize about that.

Novel Tools and Improved Monitoring Will Advance IBD Treatment Goals

What overall are we headed towards? This is really a great image depiction of looking at STRIDE-II and seeing it and thinking about what might be happening in the future. Just thinking about your patient. This is a great thing to show a patient because this is helping them understand along their journey where they might be and where they may not be, and what targets have they reached so that they can really follow along on their particular journey.

Looking Beyond STRIDE II: Future Considerations

Looking beyond STRIDE-II, which I already alluded to, is talking about that transmural healing, normalization of all bowel layers in patients with Crohn's disease and ulcerative colitis, working towards improved and normalized histologic measurements in IBD disease activity.

Patient-centered goals, really incorporating quality of life metrics to be able to do that in clinical practice. We probably need to be sending patients survey-based questions, looking at quality of life, other than just asking them a question in clinic, and then really thinking about emerging therapies, the role of novel biologics as well as small molecules, and the impact that that not only may have in terms of clinical outcomes for our patients, but where would that have in terms of long-term outcomes for our patients?

Key Takeaways

Really key takeaways from today, and then I will hand it back to Amy is patient-centered care. Engaging patients with empathetic communication, really learning to understand their perspective, tailoring those treatment discussions to that patient sitting in front of you. We know that it is not a one-size-fits-all approach, and including how starting effective therapy early can not only improve important things around their disease, but also their quality of life.

Really emphasizing treat to target goals. Symptom remission is important, and we want that for our patients. Symptom remission often misses patients that may have some subclinical disease. We need to talk to patients about biomarker evaluation and looking for mucosal healing, and how important that is to predict how they are going to do in the next coming years.

Also thinking about as we learn more about therapies that we are using now, but also what might be coming down the pipeline in terms of novel treatment approaches.

With that, I will hand it back to Amy.

Skill Building and Feedback: Patient Case 3—Priya, 38-Yr-Old Woman With Ileocolonic CD

Amy Stewart: Thank you so much. We are in the homestretch here, so stay with us. Let us meet Priya, who is a 38-year-old woman with ileocolonic Crohn's disease. She was diagnosed with ileocolonic Crohn's disease. She is having eight to 12 bowel movements every day with abdominal pain. Her fecal calprotectin is elevated at 2100. Her CRP is elevated and her colonoscopy showed deep ileocolonic ulcerations. She is currently on ustekinumab. She has previously been on TNF in the past and that therapy failed her.

She does have meaningful symptom improvement at 16 weeks. At 16 weeks now she is going three to four times a day with occasional postprandial abdominal pain. Fecal calprotectin is 820. CRP is still elevated. She is off prednisone and the MRI enterography shows persistent ileal inflammation, no abscess or obstruction. And Priya has not missed any doses.

What are we thinking about Priya here? So we are better. Are we where we need to be? Are we giving Priya more time, or are we moving on adding, augmenting? What are we doing here?

Dr. Axelrad: Like you said, what are we doing here? What do we know? We know that she is improved, right? We know that the patient started quite sick, elevated biomarkers, colonoscopy, deep ulceration. This is someone who had already failed anti-TNF therapy or at least had been exposed to earlier anti-TNF therapy. A little bit of a different category of a patient that maybe at week 16, you may not be expecting normalization, but you would certainly want to see improvement. We have seen that. We have improvement here.

The question is, is this enough improvement, right? Is this enough improvement that we should still just say, okay, continue on, or is there something we can do to optimize that may improve the current situation? That is gauged by the same factors of when you start medication. It is gauged by how the patient is feeling right now and what is the disease activity right now?

You already know, yes, it is improved. Calprotectin is still pretty elevated. It is 820. The patient is still symptomatic. He is much better but still a little symptomatic. Patient is off of prednisone. That is good. You now have cross-sectional imaging that they are still persistent radiographic activity. Where do you go from here? It is a little bit of an open question to an extent, but improved, but maybe not good enough yet.

Dr. Kinnucan: Again, I would agree with you. The question is, is more time at the same dosing. This is a case from now. I probably in this particular patient would not be choosing ustekinumab. I would be using an IL-23. We did not make this decision. You are seeing this patient now. Somebody else made this decision. Obviously there is off-label dosing that could be considered in this and that has been looked at. It will potentially capture a percentage of patients that do not respond to standardized dosing.

You are in a place right now that it may be worthwhile to give her time and optimization and maybe even, again, some of those adjuvant things that might be contributed negatively to inflammation in her body to consider and then have that really short turnaround to look again and make sure because if you have not met target by six to 12 months, more time is not going to give you any benefit at that point and we should be having a low threshold to move on.

We do know patients exposed to ustekinumab can respond to IL-23 therapies. Some of them were enrolled in some of the clinical trial programs. Also we have looked at this in post real-world data that patients who are exposed to ustekinumab can be put on an IL-23 and have success, even though it is in a similar class.

Dr. Axelrad: Yes, I would probably put this evaluation as someone who has improved, but not meeting all the targets that Jami reviewed, not meeting biomarker normalization, not meeting symptomatic normalization, not meeting radiographic normalization, certainly improved. So you definitely know the patients partial response.

Poll 9

Amy Stewart: Thank you both so much. With that, we are going to move on to poll nine. Which interpretation is most appropriate?

1. She has achieved the treatment target because symptoms improved and prednisone was stopped;
2. She has partial clinical response but has not met treatment targets;
3. She has primary nonresponse and should switch treatments; or
4. Biomarkers are not useful since her reported symptoms have improved.

Dr. Kinnucan: I feel like we led the witness.

Amy Stewart: 86% of people chose B, that she is a partial clinical response but has not met treatment targets. It is really important to understand what our treatments are, what we are looking for as we are thinking about assessing response here.

Faculty Discussion

With that, in a patient with symptomatic improvement but persistent objective inflammation, what findings would lead you to continue therapy, optimize therapy, or switch to a therapy with a different mechanism? We have talked about this. Any other points to add here?

Dr. Axelrad: This is someone that you reasonably could either optimize, right? Maybe try to go to ustekinumab every four weeks potentially versus just switch them over to an IL-23. In 2026, I probably give a little more thought to the IL-23 utilization. Certainly optimizing ustekinumab if the patient is already not on a Q4 regimen with partial response is certainly something to consider.

Posttest 4

Amy Stewart: Perfect. Thank you so much. To keep us on time, I am going to keep moving us along here to posttest question number four. A 29-year-old woman with ileocolonic Crohn's disease initially responded to anti-TNF therapy but lost response within six months. She was subsequently switched to mirikizumab and achieved clinical remission, which has lasted for the last six months. She asks if she can stop therapy. What would you do for this patient?

1. Continue therapy given sustained remission and safety profile;
2. Continue therapy with consideration to de-escalate if remission remains durable;
3. Gradually increase the dose interval until discontinuing at six months; or
4. Discontinue therapy with close monitoring of fecal calprotectin and CRP.

Okay. In pre-test, 38% of people chose A and 46% of participants chose B. Moving on to post-test, we have 37% of people choosing A and 55% choosing B.

Posttest 4: Rationale

In our treat to target scenarios, we did not talk about de-escalation, right? We talked about meeting targets and staying there. In this patient, we would continue therapy given sustained remission and safety profile.

Quickly because we are running into questions here, but when do you consider de-escalation with remission if ever in this scenario?

Dr. Axelrad: Yes. This is a complicated question. We have very poor data to guide our management of de-escalation strategies. Usually before I consider de-escalation, one is that the data suggests that de-escalation is not a successful strategy in the majority of patients over time. I just want to put that out there.

In patients in whom I would consider de-escalation, these are patients who have had year after year after of real deep remission, normal radiography, normal colonoscopy, normal biomarkers, no symptoms. I would even go as far as to say normal biopsies. This way you know that if you are going to consider de-escalation with monitoring, you are not setting the patient up to have a problem with normalization on all of the other factors that Jami touched on from STRIDE guidelines.

Dr. Kinnucan: De-escalation does not always need to be de-escalation off.

Dr. Axelrad: Right.

Dr. Kinnucan: It could be in a patient with ulcerative colitis who previously required escalation to advanced therapy or biologic therapy or small molecule therapy in the right patient with complete histologic normalization off of steroids without complications. You might have conversations, especially if it is not driven by preference, but actually medical requirement of considering mesalamine. It does not always have to be to nothing. It could be to escalation to a different therapy.

Dr. Axelrad: Yes.

Poll 10

Amy Stewart: Thank you so much. Two quick polls here before we move on to Q&A. Do you plan to make any changes in your clinical practice based on what you learned in today's program?

1. Yes;
2. No; or
3. Uncertain.

I will give that one a quick minute.

Poll 11

Then our last open-ended question. Please take a moment to text in one key change that you plan to make in your clinical practice based on today's education session?

Dr. Axelrad and Dr. Kinnucan, thank you so much. We are going to go into some quick Q&A, but I think that was so robust and such good conversation.

Q&A

I have an interesting question here for you. What are the most common mistakes that clinicians make when escalating or switching biologic therapy in IBD?

Dr. Kinnucan: I think I touched on that. The number one mistake that I see made is that no objective assessment for inflammation in a symptomatic patient. The assumption is patients having symptoms, they have inflammation. Then the therapy is changed, specifically with their anti-TNFs not doing therapeutic drug monitoring to assess overall why that patient may have lost response or have active symptoms despite being on therapy.

Really, it is this misunderstanding that not all symptoms equal inflammation and not all inflammation equal symptoms. We have patients out there with no symptoms and inflammation. We have patients that are symptomatic and have no inflammation. Really focusing treatment on the right thing, whether it is inflammatory or non-inflammatory.

Dr. Axelrad: Yes. Keeping in mind, APPs are a first-line providers, and many practices worldwide, APPs are doing the heavy lifting of evaluating the patients, getting the right studies done, evaluating the data from those studies and then talking about what is the next steps.

Understanding exactly how to assess disease activity, how to have the conversations with patients around what their options are, and choosing wisely based on patient preferences that Jami went through and our data. Really critical steps for the management of complicated IBD patients.

On one hand, we have many options and on the other hand, we actually do not have that many options. Right now in 2026, there are options, but there are not so many that it is overwhelming. That allows us to have a good understanding of which therapies to think about and which patients and how to assess for response and partial response and nonresponse.

Dr. Kinnucan: I actually have one more thing to follow-up with that, Jordan. That is an excellent point. The thing is phone a friend. I have many of the area APPs in my region who have my cell phone and know when to ask for help. These patients are complicated. They are complicated. As many resources as we have at Mayo Clinic, they are complicated.

If you are feeling like this is a little bit where you feel comfortable taking care of these patients, there are places that are more than happy to see these patients as a second opinion referral and help in terms of partnership and co-management. I think do not do not feel that you cannot reach out and phone a friend. That is another key thing is do not do this alone.

If the physician that you partner with is not specialized in this particular area, then reach out to a specialized physician and they are more than happy to see these patients. Many of us can see actually virtually. We can do it as a tele visit. It does not even have to be the patient travelling somewhere.

Dr. Axelrad: Yes. I would also add to that, especially for APPs working with other providers that maybe are suggesting more prednisone, more mesalamine, doing the wrong things when we have many more effective and safe options. Remember that the most unsafe things for patients are uncontrolled disease and unnecessary corticosteroid exposure, specifically prednisone. Whatever we can do as providers to really mitigate that is super critically important.

Amy Stewart: Thank you so much. Completely agree. It can be challenging, certainly as an APP, working with physicians, when we are going to conferences and learning the up-to-date data, and not everyone is there. Also printing out these slides and having them in your clinic as a resource and sharing the data and sharing the head-to-head studies, right, to get all of your team members on the same page can also be important.

Say a patient has a partial response to risankizumab, but is having some breakthrough symptoms two weeks leading up to the next dose. Insurance denied every four-week dosing. Would you consider switching to another IL-23 in this case?

Dr. Axelrad: I would add that that is a common scenario, is that we want to dose escalate if a patient has been initiated on risankizumab. The payers may say no. Sometimes that could be successful on an appeal. There is data that has been published on risankizumab dose escalation.

The other is that most drugmakers have programs that if there is a denial, even for if it is an FDA not approved dose, because we know every four-week risankizumab is not FDA label, they can still potentially access that drug through the drugmaker. There may be drug programs, assistance programs, bridge programs and so forth that patients may be able to access that if that is what you want.

The other question of, well, would you just move over to guselkumab in that patient? Yes, that is a consideration, and that is certainly something I would consider, particularly if the patient was a partial responder to risankizumab wanted to stay on IL-23 or had multiple indications for an IL-23 therapy. That is something I would definitely consider.

Dr. Kinnucan: Yes, that is excellent advice. I would like to put it from a practical approach. If you are not using open evidence, which is accessible, open evidence rates are really great letter of medical necessity. Asking for a therapy that is off-label for FDA in terms of optimization, 100% of the time, you need to include the patient's clinical data and you need to include a letter of medical necessity, otherwise it will be denied. You can optimize your chances of getting approval.

There are also some really cool AI programs out there. We are currently using a program called Tandem. No conflict of interest there. That has been really great in terms of streamlining approval processes. I know it is a heavy lift, but peer to peer and letter of medical necessity have been very successful.

I will say that many times we have optimized dosing. We are at like a 98% approval because of some of the resources that we are using.

Amy Stewart: Thank you for that. To close us out with our last question, how can I, as an APP, most effectively collaborate with other healthcare providers to deliver comprehensive IBD care for our patients?

Dr. Axelrad: I will let Jami start with that one. That is a big question.

Dr. Kinnucan: It is a big question. The first step is already being taken. Anybody who is on this program today has taken that step towards getting deeper education into this space. I know, Amy, you are really involved with GAP[?], which is an incredible organization that is ensuring the sustained education up-to-date across the APP practice, knowing that very few APP providers out there are in the IBD specialty space only.

What we understand is you all are doing what I cannot do. I am not a generalist. I am not your go-to person for non-IBD-related stuff. It is getting involved with conferences like this. This is pretty comprehensive today. I am going to those conferences nationally, Crohn's and Colitis Foundation, AIBD. If your physician partner in your practice is not a specialist in this, or maybe he is not practicing evidence-based medicine, these slides are an option. Maybe hosting a journal club where everyone is up-to-date and reading some of the newer stuff, but find that phone a friend, identify who that person is for you that you are going to be able to connect with that can help you co-manage these really complex patients, knowing that many of us are doing it already.

If you have not found that phone a friend, Amy, your moderator today has a huge network and as well as GAP of different physician providers who really love to partner with APPs in managing these complex patients in the community.

Take that one, Jordan. I am just kidding.

Dr. Axelrad: I have nothing to add. Obviously what is really important is not just the therapeutic relationship that you have with the patient, but a therapeutic relationship that you have with the whole care team. APPs are like such a crucial part of that care team, especially in a complicated multidisciplinary disease like IBD. It is not just doc and APP and patient. There is RNs, we have psychologists and psychotherapists and psychiatrists and nutritionists. We also work with radiologists and rheumatologists and dermatologists and APPs across those disciplines.

There is a care team that needs to work in symbiosis with all the other parts of this landscape. Also the pharmacy team. We talked about all these medications, but patients being able to obtain those medications is obviously a huge link as well. Everyone needs to be working together for the ultimate goal of improving the life and taking care of a patient.

As long as the goals are aligned there, then using the information that hopefully we have provided a little bit of can help in that management strategy.