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Treatment Challenges in IBD

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Miguel Regueiro, MD: Marla, this is a nice segue into unmet needs and how the field is evolving. You heard from Bill about some of the different agents, but what do you still see are some of the unmet needs that we have in IBD [inflammatory bowel disease]?

Marla C. Dubinsky, MD: I'm going to bring it back almost to the beginning when we talked about personalization or individualized care for patients, for which we will establish certain biomarkers and risk models to talk about how this patient needs this drug, at this time, at this dose, and start to customize the approach because we're going to have all of these amazing advances in our field and therapeutic choices. I don't know which one to choose first, and as I noted before, the first one's the most important. We all, in parallel, need to be ready to answer this question as to whether there is a biomarker in the blood or in the tissue itself that's going to help us derive what the first therapeutic algorithm is going to look like. That's also very interesting to think about after you've stratified your patients to know if they have these factors or not. If so, do they merit this therapy?

One of the other things to think about in the future is this idea, are we going to be able to use combination therapy or use small molecules as a bridge to a maintenance biologic, for example, combining some of these JAK [Janus kinase] inhibitors? The question is do we need chronic JAK inhibition when we could use JAK as a way to induce quickly, as we talked about speed, or an anti-TNF [tumor necrosis factor]? Then, maybe use an integrin or an IL-23 [interleukin-23] blocker as a maintenance therapy based on our safety profiles that we have, starting to figure out what is the ideal combination.

Interestingly, Bill's group did publish in AP&T [Alimentary Pharmacology and Therapeutics] using 2 biologics. We just submitted in The Journal of Pediatrics where, when we can't operate, these patients have growth failure. They already have ostomies, and we looked at adding a JAK inhibitor. Right now, it's only tofacitinib available, plus integrin or even ustekinumab or vedolizumab versus ustekinumab, showing that deep remission was possible when you added a second agent. Then, you were able to withdraw once you'd been able to get them into remission. For these concepts of combination and personalization based on if they have skin manifestations or arthropathies, like everyone had been saying, we would sell each other short in terms of what the future is. It gets back to what we're experiencing in the pandemic, how are we going to tight control our patients? And what is going to be the role of using real-time communication, with our patients being pinged when they're flaring and being able to get on a call or being able to communicate in real time?

Another unmet need is going to be the integration of small bowel ultrasound into the practice in real time. Being able to, with the patient in front of you, look at how the patient is doing, both from small bowel, and now there are data on UC [ulcerative colitis]. I'd be remiss in not saying, given both of our areas of interest on the idea of mental health, and being able to approach the impact of IBD; 40% of our patients have mental health comorbidity, and we know that cost of care is up to 3 times higher when we have young patients with comorbid mental health conditions. That's where the combination therapy is going after the mental health comorbidities, behavioral health, and the role of resilience, as we all know that that's an important topic, while we're also approaching the actual disease biology, which are often linked. We're missing the idea that we need to go after both aspects of care. Those are the key highlights moving forward of where we need to start to explore further and implement it into real time in our practice.

Miguel Regueiro, MD: Great, this individualized approach, looking at new radiographic means, remote monitoring, and then what combination means. Not only biologics, but with the whole-person care, as you mentioned, the mental health aspect.

Transcript Edited for Clarity


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