Transcript
Announcer:
This activity, titled “IBD in Practice: Case-Based Insights on Treatment Optimization and Switching Strategies” is provided by Global Learning Collaborative.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
Dr. Iroku:
Welcome to this patient-clinician connection. I am Dr. Ugo Iroku, an Assistant Professor at Mount Sinai Hospital and on the National Board of Trustees for the Crohn's and Colitis Foundation.
Dr. Odufalu:
Hello. I am Dr. Florence Damilola Odufalu. I am an Assistant Professor of Medicine at Keck School of Medicine of University of Southern California.
Dr. Iroku:
In taking care of IBD patients, starting medical therapy is only the beginning. We don't just treat, we treat to target, proactively assessing a range of endpoints to achieve progressive levels of inflammatory control. Some of our patients will go on to achieve clinical and endoscopic remission, but others may have a primary non-response to therapy or lose their response over the months or years to come.
These inflection points are critical. Knowing how to respond to symptoms, how to adjust current therapy, when to consider alternative therapies, and which ones to choose requires clear counseling, shared decision-making, and a pre-determined game plan to achieve deep remission.
Dr. Odufalu:
Today, through case-based examples, we'll examine the practical strategies for treatment optimization, switching mechanisms, and longitudinal follow-up in IBD care.
So let's begin with our first case.
Mr. David Stone is a 65-year-old man with newly diagnosed Crohn's disease. He presented with diarrhea and abdominal pain. This all occurred in the setting of increased life stressors that precipitated onset of his symptoms. His medical history is notable for a pheochromocytoma that has been in remission for several years. He is an avid biker and enjoys long-distance biking on the weekend.
His initial presentation was notable for elevated inflammatory markers and a fecal calprotectin of 4000. His initial colonoscopy showed patchy inflammation throughout the colon and the examined portion of the terminal ileum.
His treatment approach included starting prednisone to initiate a clinical response and starting vedolizumab. Once a symptomatic response was noted, prednisone was tapered. He's presenting for a follow-up, and we are discussing the plan of care.
Dr. Odufalu:
So, David, how are you doing today?
David:
Honestly, I'm feeling like myself. I'm not running to the bathroom all the time. I'm not planning my day around where the next restroom is, and I just feel normal. I can get back on my bike and go out for hours and not worry about it. So to me, I feel that remission is just not worrying about my gut all the time. I'm not in pain, I'm not having diarrhea. It just feels like this thing is behind me. So I'm wondering if I'm feeling this good, do I need to stay on this medication?
Dr. Odufalu:
Excellent. I'm so glad to hear that you're feeling this well. That's exactly what we want. What you're describing is what we call clinical remission. That means that your symptoms have resolved and you're feeling good. For us, remission goes a step further. In addition to how you feel, we also look at objective measures, like your labs and what we see on colonoscopy to make sure that there's no ongoing inflammation. When all of those line up with no symptoms, normal biomarkers, and no visible inflammation in the colon, that's what we call deep remission.
David:
I see. So what are next steps?
Dr. Odufalu:
Our approach is what we call treat to target. That means we're not just treating how you feel, we're targeting that deeper level of remission because it helps reduce the risk of future flares and future complications. That's why we started vedolizumab. It's effective for your type of disease and has a strong safety profile, especially for disease in the colon. The goal is not just to get you feeling better, but to keep the inflammation controlled long term.
Even though you're doing well, I'd like to keep monitoring you with labs and at the right time a colonoscopy or advanced imaging to make sure everything stays under control.
David:
Sounds good.
Dr Odufalu:
In IBD, remission encompasses several clinical and objective targets. Symptomatic remission involves the reduction of symptoms of inflammation within the GI tract, including resolution of abdominal pain and diarrhea, and importantly, patients will report normal stool frequency and no urgency. All of this improves a patient's quality of life.
Deep remission involves endoscopic remission, where there is normal-appearing mucosa on ileocolonoscopy. In addition, objective markers of inflammation have normalized. And in pediatric patients, there is normal growth and development.
Functional remission puts all of this together. Patients are able to achieve normal function. They can go to work or school without symptoms. Extraintestinal manifestations have resolved, and mental health is addressed and not triggered by ongoing GI symptoms. These three aspects incorporate remission and is a goal when treating patients with inflammatory bowel disease.
Although remission is our goal, disease progression happens, and if you treat enough patients with IBD, you will see this in your practice. However, disease progression can occur for several reasons. There can be an inadequate dosing or an incomplete response to their therapy, where some patients may need dose escalation in the case that they may be rapid metabolizers. Sometimes clinical symptoms that occur just prior to the next dose or in between dosing can point to an incomplete response. In the right setting, therapeutic drug monitoring, proactively or reactively to new onset of symptoms, can help to answer this question.
Infections can occur for a number of reasons and can be a cause for potential disease progression in patients who were previously well. It is important to always rule out infection before making major changes in pharmacologic therapy. However, in some cases, even with adequate treatment of infections, disease progression may still require a change in the therapeutic plan.
Lastly, there can be non-response, which includes primary or secondary non-response. Disease progression may be caused by a mechanistic failure when inflammation does not improve despite adequate dosing with their chosen immunosuppressive or biologic treatment regimen. In the case where patients were previously well and the patients seem to lose response, this may suggest the occurrence of anti-drug antibodies that may indicate a secondary loss of response.
Going back to our case, at 10 months his colonoscopy showed endoscopic remission, and now after being in deep remission for 18 months, the patient is back in clinic voicing concerns about safety of long-term treatment.
Dr. Odufalu:
Hi, David, so how are you doing today?
David:
I've been feeling great. And I'm back to riding long distances, but I'm just not sure about staying on this medication, especially now that I have to switch to Medicare, which may not even cover it.
Plus, what are the long-term data? What does that show about safety? I mean, is it really worth the risk when I'm doing so well? I just don't want to feel that all of this could cause a recurrence of the pheochromocytoma.
Dr. Odufalu:
So David, I hear you, and this is a very common and very reasonable question. A lot of patients feel this way when they're doing well.
What I usually like to share is that even when you're in deep remission, meaning that you feel well, your labs are normal, and your colon looks healed, the disease itself has not gone away. It's still there, and it's just controlled by the medication.
We have really good data from the STORI trial, which looked at de-escalation of patients with Crohn's disease who were in remission on infliximab, and about 1/2 of those patients relapsed. Most of those patients were able to recapture their disease control by starting their same therapy or switching to a new therapy, but the other 1/2 were not able to.
Even when in remission, your disease can flare again. We don't know what can cause that flare, but sometimes it can be an infection, sometimes it can be life stressors and things outside of our control, or some things that we just don't even know, and oftentimes we're not able to get back into remission like you once were. The challenge is that we don't have great predictors to tell us who will do well off therapy and who won't.
Also, we know that these medications are safe, and we know that they're efficacious long term. So from an evidence-based standpoint, we generally recommend continuing treatment to maintain remission.
David:
Yeah, I think I'd like todiscontinue this medication for now, because I'm just not sure about the data. And being on this therapy, what is it going to mean for my health long term?
Dr. Odufalu:
I understand your hesitation, and this is a shared decision. If you're strongly considering de-escalation, what I'd want to do is make sure we have a plan in place with close monitoring with labs and symptoms and endoscopic monitoring, as well as intestinal ultrasound to give us a clear understanding if there is any signs of inflammation that may be returning, even if symptoms haven't returned. We would like to act quickly and potentially restart or adjust your therapy.
There's no guarantee that if you have a flare and restart a medication we'll be able to recapture control of your inflammation. My goals are exactly the same as yours, keeping you feeling well and living your life, but also to minimize the risk of a flare that could set you back.
Dr Odufalu:
So as you can see in this clinical scenario, this highlighted the challenges with discussing continuing and de-escalating therapy in patients who've achieved remission.
This patient example highlights those challenges that were examined in the STORI trial. The STORI trial was a prospective study that looked at patients who were in deep remission with infliximab plus an anti-metabolite therapy for over 1 year. They were also in a 6-month steroid-free remission. And we looked at patients for follow-up over 1 year after infliximab withdrawal. What they cited was that there was a relapse rate of close to 44%.
Risk factors that were highlighted in the data for relapse included patients of male sex, no prior surgical history or resection, and they had elevated inflammatory markers and fecal calprotectin.
Dr. Iroku, how do you approach de-escalation in your practice?
Dr. Iroku:
Dr. Odufalu, I agree with your approach. And to add to it, I always start with empathy. I let the patient know that their treatment goal is my treatment goal. We know that patients do better, have better outcomes when the provider and the patient are on the same page.
And then secondly, I educate. I tell them about the STORI trial and other similar trials that show that this is an important question that we have been thinking about for years, and the data so far shows that de-escalation and discontinuing medication often leads to relapse.
But lastly, I always give space to the autonomy of the patient, and so if the patient has made the decision that they plan on de-escalating and stopping therapy, I want to be in on it. I want to be a co-conspirator. I want us to agree how we're going to approach that plan, and also to agree that over the next 3, 6, 12 months, how we're going to assess how they're doing or what our next step should be.
Dr. Odufalu:
So going back to our patient, 6 months later after he stopped his therapy, he presented with diarrhea and pain. His labs were notable for an elevated fecal calprotectin, and he was C. diff positive. He was admitted to the hospital and started on IV steroids and infliximab. His colonoscopy during this admission revealed severe colitis. He was started on vancomycin in addition to prednisone, without much of a response. His clinical course was complicated by a DVT requiring anticoagulation. He failed to respond to infliximab, and ultimately he underwent a total colectomy with end ileostomy.
David:
I have no idea whether I would have relapsed if I had stayed on the vedolizumab, but all the complications I had were really tough. Despite this, I've recovered, and I'm now doing well. With my ostomy, I'm still able to live my life and do the things I enjoy. I'm still an avid long-distance biker, and I just completed a half marathon.
I'm back on the vedolizumab, and I am in remission, and I continue to follow up and work closely with patient advocacy groups in my area to share my experience. I never thought I would end up on the operating table and now have an ostomy bag. I just hope that I'll be in remission for a long time.
Dr. Iroku:
So Dr. Odufalu, in this case, we have what it seems to be a scenario where the patient’s discontinued his chosen therapy of vedolizumab. But let's assume for for a second that he hadn't discontinued it. He's having a flare of symptoms. If this patient wasn't so sick that they needed a hospital admission, what would be your treatment approach in that scenario?
Dr. Odufalu:
So in a patient that is flaring but not too sick, requiring admission, I would try to get him started on vedolizumab as soon as possible and then rule out infection. I would check and trend fecal calprotectin, as well as rule out C. diff. If C. diff is present, we'd begin antibiotics, either vancomycin or fidaxomicin, and I'd likely start prednisone early to initiate a clinical response to bring down his symptoms.
I would also try to bring this patient to the office frequently. I have intestinal ultrasound in my office, so I would do serial intestinal ultrasound to assess clinical response to our therapy. If there was no response, I'd make changes early with escalation or switching mechanism if there's no response.
Dr. Iroku:
And assuming vedolizumab is a no-go, how do you decide what's next for the patient?
Dr. Odufalu:
If this happens to the patient, I'd like to first assess his comorbidities and his history of therapeutics that we use for his inflammatory bowel disease. In this case, vedolizumab was his first biologic, and I would likely start an anti-TNF in combination with an immunomodulator, given his severity. If it's not so severe and if time permits, I would consider switching to an anti-IL-23 agent.
Dr. Iroku:
And how do we know if our new approach is working? What's our follow-up strategy?
Dr. Odufalu:
This is where the STRIDE-II and treat-to-target guide our clinical approach. We look for short-term targets, so there's symptomatic response. And if these short-term targets are met, next we assess the intermediate targets with trending labs, intestinal ultrasound, imaging, and colonoscopy.
Dr. Iroku:
Are there any characteristics of the case that might make you choose one option versus the other as you're approaching this patient?
Dr. Odufalu:
Yes, absolutely. In the era that we have with a lot of therapeutics in our toolkit, I do patient-based considerations. So I consider their disease severity at the time of presentation. I take into account the route of administration, as well as their comorbidities. If there's concurrent other autoimmune diseases, I'd like to treat a medication that can treat both conditions. This really helps with guiding our next steps.
That was very insightful and an amazing review. Now, let's look at another case.
Dr. Iroku:
Ms. Cooper is a 27-year-old female with poorly controlled ankylosing spondylitis who was diagnosed with ulcerative colitis 2 years ago by her long-term local gastroenterologist after presenting with five bowel movements a day and obvious blood in her stool most of the time. Initially, her colonoscopy revealed left-sided colitis with severe disease characterized by diffuse ulcerations and spontaneous bleeding. She was induced with adalimumab and azathioprine dual therapy and successfully achieved clinical remission.
Six months ago, however, she started experiencing recurrent symptoms identical to her initial presentation. Her laboratory assessment showed anemia with a hemoglobin of 10.5, CRP level of 5, and a fecal calprotectin level of 1350. Her gastroenterologist kept her current advanced therapy but started her on oral steroids. And since then, she's been largely symptom free but is still steroid dependent.
She came to me as a transfer of care and wanted to continue her current line of therapy. Her therapeutic drug monitoring shows high levels of adalimumab drug and no detected anti-drug antibodies. Her ankylosing spondylitis remains poorly controlled with her experiencing chronic back pain and prolonged morning stiffness.
Dr. Iroku:
Good afternoon, Ms. Cooper, how are you feeling today?
Ms. Cooper:
Hi, I'm doing well. Initially, I had some complaints, but since adding the oral prednisone, my symptoms are well controlled. I'm here for a refill of my prescriptions.
Dr. Iroku:
I'm glad you're feeling better. Before we discuss refills, I want to step back and look at the bigger picture. What are your goals for therapy? What do you hope we can achieve with treatment?
Ms. Cooper:
I guess I just want to feel well enough to thrive while taking care of my everyday responsibilities.
Dr. Iroku:
I have the same goal for you as well. But one of my goals for you is that we do that with a treatment plan that is steroid-free. While prednisone has controlled your symptoms, long-term steroid use is not a safe maintenance strategy. Chronic steroids can cause weight gain, diabetes, bone thinning, infections, mood changes, and other complications. Our goal is to control your ulcerative colitis without keeping you dependent on steroids. Do you agree with that goal?
Ms. Cooper:
Most definitely. That sounds crucial to my long-term health.
Dr. Iroku:
Excellent. To determine if staying on adalimumab is still an option, we did what we call therapeutic drug monitoring. These blood tests reveal that the adalimumab levels are at an adequate level in your body, and you do not have antibodies against them. That tells us, while the drug is in your system at an adequate concentration, it's still not controlling inflammation. We call that mechanistic failure. It means your disease is now being driven by inflammatory pathways that adalimumab does not effectively suppress anymore.
In scenarios like this, it's best to consider switching to a different treatment class that works differently from the anti-TNF class that adalimumab is a part of.
Ms. Cooper:
I have a busy life. Any treatment that requires any infusions at this time is not going to work for me. I cannot afford to miss work, and I would really prefer something I can take for myself.
Ms. Cooper:
My aunt has rheumatoid arthritis and takes oral methotrexate pills and is very happy with it. Is that an option for me?
Dr. Iroku:
Methotrexate is not an effective therapy for ulcerative colitis. It is used for rheumatoid arthritis, but in ulcerative colitis, it has not been shown to have a reliable benefit.
Let's explore what our options are. You're 27 and of childbearing age, as we say. Do you have any plans for pregnancy in the near future?
Ms. Cooper:
Not right now, but I want to plan one in about 2 years.
Dr. Iroku:
Understood, I ask because some medications are contraindicated in pregnancy, we just can't use them. It's important we align your treatment with your long-term plans.
I will say many patients find infusions easy to work into their schedules, and there are excellent treatment options that start as infusions but then can switch over to self-administered home subcutaneous treatment after as little as 2 weeks, as in the case of vedolizumab. However, since you're strongly stating that it doesn't work for you, there are more appropriate options for you, which include the oral JAK inhibitors, such as upadacitinib, a subcutaneous induction and maintenance IL-23 inhibitor such as guselkumab, or an oral S1P receptor modulator such as etrasimod.
Given that you've already been exposed to advanced therapy and experienced mechanistic failure with an anti-TNF inhibitor, the American Gastroenterological Association recommends switching to medications with proven moderate to high efficacy in this patient population. That leaves us with the oral JAK inhibitor and with the IL-23 inhibitor guselkumab, since it can be entirely administered as subcutaneous.
Considering your ankylosing spondylitis, a JAK inhibitor is particularly attractive because it treats both the ulcerative colitis and the ankylosing spondylitis. This gives us one medication addressing two inflammatory conditions.
Ms. Cooper:
So that would not require infusions, right?
Dr. Iroku:
Correct. JAK inhibitors are oral medications. They provide rapid symptom control, and they are efficacious in patients who failed anti-TNF therapy. We would monitor labs periodically, but it avoids infusion scheduling and steroid dependence. Our priority is to transition you off prednisone safely and to move to a durable, steroid-free remission strategy that controls both your colitis and your ankylosing spondylitis.
Ms. Cooper:
Wow, that sounds like that perfectly meets my goals and preferences, sign me up.
Dr Iroku:
Excellent. Let's review the risks and benefits in detail and develop a transition plan.
Ms. Cooper:
Honestly, coming into this appointment, I was relieved that my symptoms were finally under control with prednisone, but I didn't fully realize the long-term risk I was taking on. Hearing Dr. Iroku explain the bigger picture changed my mindset, because I'm not just trying to feel okay right now; I want something sustainable that supports my future, especially for when I start planning for a family.
I also really appreciated being heard when I said infusions wouldn't fit my lifestyle. Finding balance in my life is already difficult, so having a treatment option that I can manage on my own makes a huge difference.
When I learned that my current medication isn't working the way it should, I was a bit concerned, but it actually gave me so much clarity on why I still needed steroids.
One medication helping my ulcerative colitis and ankylosing spondylitis feels like a huge win. At the end of the day, I feel more informed, in control, and hopeful that I can move forward with my life in a way that supports my health and lifestyle.
Dr. Iroku:
So this is a classic example of when the patient feels fine, but the objective markers are not showing a resolution of the inflammation. Patient-perceived improvement is not always endoscopic or histologic improvement, and we know steroids are not a long-term solution, even if the symptoms improve.
And so in a scenario like this, we have to do what's called therapeutic drug monitoring. We're checking our patients' drug levels, and if they're at goal but they're still not able to achieve inflammatory control, we call that mechanistic failure. And once that's confirmed, we switch to another class of medication.
We have a number to consider in ulcerative colitis, between anti-TNFs, IL-23 inhibitors, our JAK-STAT inhibitors, our S1P modulators, or our anti-integrins. And so we switch to a different type.
And then ultimately, this is all within the guidelines that we get from the AGA, which assure us that in ulcerative colitis, if a patient has failed or been exposed to advanced therapy but needs to be on another medication, there are some medications that just are not strong enough to get that exposed population under great control. We wouldn't go back to an S1P modulator. We wouldn't go back to an anti-integrin. And so we can consider another option for this patient's care.
Dr. Odufalu, this is also a case that shows the existence of extraintestinal manifestations in our IBD patient. What are extraintestinal manifestations, and how do they influence IBD management?
Dr. Odufalu:
So great question. Extraintestinal manifestations, or EIMs, are indicative of inflammation outside of the GI tract that may or may not correlate with GI tract inflammation. Most commonly in IBD, we have joint pain and inflammation. That is the most commonly reported extraintestinal manifestation, and that often correlates with inflammation from inflammatory bowel disease. There are several cutaneous forms of extraintestinal manifestations, including psoriasis, plaque psoriasis, and erythema nodosum.
I like to take into account extraintestinal manifestations when selecting a therapy, because since there is a common mechanism of inflammation, several of our therapies can work to treat both inflammatory bowel disease and extraintestinal manifestations.
Dr. Iroku:
I agree. In choosing advanced therapy for our ulcerative colitis patient, we can start with understanding what are concomitant immune conditions and extraintestinal manifestations that our patient has and see how that lines up with our therapy approach for treating their ulcerative colitis.
If a patient has plaque psoriasis, it makes IL-23 and anti-TNF inhibitors a likely option, because that can treat both issues. If a patient has psoriatic arthritis, we can use those and could also consider a JAK inhibitor. If a patient has spondyloarthropathy, we can consider our anti-TNFs and our JAK inhibitors. For our atopic dermatitis patients, we can consider JAK inhibitors. And for our uveitis patients, we can consider our anti-TNF inhibitors.
So in this case, the patient is not planning pregnancy anytime soon, and I think that's an important part of the discussion.
Being of childbearing potential does not automatically place medications such as JAK inhibitors or S1P modulators off the table, provided effective contraception is in place. In cases like this, we can focus on getting the patient healthy first with our best choice of medication, and then we can adjust to any future goals as they come along.
Let's assume that this patient does want to become pregnant in the near future. How would you approach optimizing her treatment in light of her ongoing active inflammation and yet the need to align therapy goals with her childbearing attempts?
Dr. Odufalu:
So this is an excellent question. We know that women with ongoing inflammation from inflammatory bowel disease have worse outcomes and complications of pregnancy. And so in my practice, I like to address patients of childbearing potential early on in their diagnosis, as well as at several points during their maintenance. I like to stress to patients to get their disease under control prior to getting pregnant to provide the best environment for a smooth pregnancy. JAK inhibitors and S1Ps are contraindicated in pregnancy and in lactation. Some patients immediately trying to conceive, we will avoid or have a plan for de-escalation early on prior to conception.
Dr. Iroku:
Excellent. Another important feature in this case is the route of treatment administration. We know that for our five or so classes of therapy for our ulcerative colitis patients, some of them can be self-administered. These, of course, include our oral medications, our JAK-STAT inhibitors and our S1P inhibitors. This includes subcutaneous administration for induction and maintenance for guselkumab, but also for maintenance for our other IL-23 inhibitors.
And of course, when it comes to our anti-integrins, like vedolizumab, these have to start off by being infusions in the office, but then subsequently it can switch to being subcutaneously administered if necessary. And then, of course, there are some anti-TNFs that can always be given for induction and maintenance as well, such as adalimumab.
Question for you, immunomodulators featured in this case, in your practice, do you use these? When, if ever, are you using it as monotherapy? What do you say to this?
Dr. Odufalu:
I definitely use immunomodulators in my practice; however, I don't use immunomodulators as a monotherapy. I mostly use them as an adjunct to biologics. We have data from the SONIC trial emphasizing its efficacy. This was one of our first studies showing efficacy in combination therapies. And so I will generally start an immunomodulator when we start an anti-TNF, and I'll use this for a period of 6 to 12 months. And then once patients have established remission, then we withdraw, and I don't use immunomodulators as a monotherapy anymore.
Dr. Iroku:
Excellent point.
I completely agree with you. Thank you for helping me think through a very complicated ulcerative colitis patient case.
As you saw, IBD care goes beyond just starting therapy. It's also about recognizing when therapy isn't truly working, counseling our patients through complex decisions, and using a thoughtful treat-to-target strategy to achieve durable remission and prevent long-term complications.
Well, with that, our time is up. Thank you for joining.
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