Florian Rieder, MD, on Monitoring Strategies in IBD

Dr Rieder details the use of a treat to target approach in monitoring treatment of patient with IBD, including the use of biomarkers and imaging to assess progress in healing or detect early signs of potential relapse.

Florian Rieder, MD, is the vice department chair and cosection head for Inflammatory Bowel Diseases at the Cleveland Clinic in Cleveland, Ohio.

TRANSCRIPT

My name is Florian Rieder. I'm the vice department chair and cosection head for Inflammatory Bowel Diseases at the Cleveland Clinic for gastroenterology, hepatology and nutrition. And it's my pleasure to recap my recent presentation at the Advances in IBD conference.

I was speaking on monitoring considerations in IBD therapy, specifically about how and when to determine response to therapy in IBD. I discussed the monitoring strategies and then discussed the treat to target approach that we use in 2025.

But it's important before you monitor response to therapies to first determine what is actually your goal in inflammatory bowel diseases that you want to then follow with your patient. And this goal may be distinct from what your patient feels versus what the physicians feels. We tend to be fixated on mucosal healing, histologic healing, reducing the amount of steroids, whereas your patient may be focused on lower costs of care, avoiding hospitalizations, having more days at work, and being able to socialize.

But once you determine the goal together before you even get started to monitor, when you start treating the patient with, for instance, a biologic, you want to get the lay of the land and understand which markers are actually elevated in association with active disease that you then can monitor to assess improvement of it. And this includes as a baseline assessment, complete blood count, C-reactive protein, albumin, fecal calprotectin, and then the objective standard modalities-- colonoscopy, in Crohn's disease, cross-sectional imaging. And if in Crohn's disease you have symptoms in the upper GI tract, you may also get an upper endoscopy. And then you start treatment. You correct anemia, optimize nutritional status, and encourage physical activity.

And then once you start the journey with your patient of treatment of active disease, you want to have an idea of how long it will take for the patient's symptoms to respond. And this varies greatly between different treatment modalities and this has been summarized by the International Organization for Inflammatory Bowel Diseases, but ranges from a 2-weeks response time, for instance, for anti-TNF and JAK inhibitors, to a response starting to be seen at around 6 weeks for anti-integrins or anti-interleukins. Then when you have the patient come back 3 months after initiation of biologic therapy, you repeat the panel of lab tests and stool tests that I just introduced to you, and after 6 months, then you repeat the colonoscopy. If you had cross-section imaging before starting therapy, you may repeat that as well as an upper endoscopy.

What is critical is you repeat the lab chemical tests that have been elevated in conjunction with your initial positive colonoscopy. And the reason for that is that C-reactive protein can first be falsely elevated in patients for other systemic inflammatory problems, even for instance, a viral infection. But in 20% of patients with IBD, CRP does not increase despite active disease. And this is owed to a genetic variant has been linked with inflammatory bowel diseases. It renders these patients incapable of mounting a CRP response. But if CRP is elevated in conjunction with active disease, it is a good short term and midterm predictor for flares. And the higher the CRP value, the higher the likelihood for early flares in our patients on therapy.

Fecal calprotectin works very well in colonic disease and may or may not work in small bowel disease, which is why particularly in small bowel Crohn's disease, again, you want to link the fecal calprotectin with active disease on endoscopy. So when you monitor these patients, then every 3e months when they are hopefully in a clinical and endoscopic remission, you will see fecal calprotectin or C-reactive protein creep up even when the patients are not yet symptomatic because it's a disconnect between symptoms and endoscopic severity of disease. But then you can respond early and assess and change therapy.

Two modalities I want to bring up in addition is capsule endoscopy, which is largely underutilized in small bowel monitoring in Crohn's disease, largely due to the exaggerated fear of capsule retention. But if the patient does not have a stricture on cross-section imaging and the patency capsule passes, their risk for retention of a small bowel capsule video capsule is actually quite low. And this is a good long-term predictor, is actually better than CRP and fecal calprotectin to predict if a patient will have a flare within the coming 2 years in a possible future. A treatment goal is transmural healing or transmural assessment with cross-sectional imaging, MRE, CTE, and/or intestinal ultrasound. And this is in the process of being established as a formal treatment target, but there is an association if you heal the entire bowel wall in Crohn's disease and onset of colitis, you may have better outcome.

Can we determine who to monitor more closely versus others so we can let loose a bit and perhaps monitor we had one point every 6 months instead of every 3 months. And there are factors particularly for anti-TNF therapy that make us monitor more and there are certain risk factors for higher clearance of anti-TNF. For instance, if you do not use immunosuppressants, if you have anti-drug antibodies present, if your serum albumin is low, we have a high inflammatory burden. There's also a recently discovered genotype HLA DQA 105 that pertains a higher risk for formation of anti-drug antibodies in anti-TNF patients.

Then there's the big question about proactive versus reactive drug monitoring with anti-TNF therapy and that this is still to be determined, but prospective studies in adult populations have not shown a benefit of proactive versus reactive drug monitoring. And the levels you would want to aim for in maintenance that are commonly accepted for infliximab, for instance, 5 to 10 and for adalimumab 8 to 12 for maintenance.

I want to put this all together. So in 2025 we practice a treat to target paradigm. And the treat to target is exactly what I mentioned to you throughout this presentation. You first set a treatment goal with your patient, then you put the patient on therapy and you modify the therapy until you reach the treatment goal with repeated assessments. Once you reach the treatment goal, you then monitor, initially lab chemicals every 3 months once you achieve the goal, and you do endoscopy, then usually every year unless otherwise indicated. And then you frequently monitor that you maintain the target and if you don't, you adjust therapy again.

But this is successful, has been shown prospectively where symptom-based management was inferior to symptom and biomarker-based adjustment of therapy. And if you did a tight control with biomarkers with fewer hospitalization, longer periods of remissions, that increased quality adjusted life-years.

So in summary, treat to target is the paradigm in 2025. You set the goal, you set a therapy to achieve the goal until the patient is in remission. You adjust the therapeutic approach when the patient is in remission. We initially monitor every 3 months lab chemically and then every year with endoscopy, cross-section imaging or upper endoscopy in case of upper GI Crohn's disease. And this has already shown and in my opinion, will show even more in the future benefit for our patient outcomes. This concludes my summary from my presentation at advances in IBD 2025 and I'm looking forward to discussing with you more. Thank you for your attention.