Durability of IL-12/23 Inhibitors in Crohn’s Disease

Jennifer Seminerio, MD, discusses long-term outcomes and clinical remission rates for patients on an IL/23 inhibitor for Crohn’s disease.

David P. Hudesman, MD: Let's follow this discussion in we're talking about onset of action, but a big thing we heard about is loss of response and the concept of durability. Maybe you could comment on the durability of long-term outcomes on patients on ustekinumab or IL-12/23 inhibitor.

Jennifer Seminerio, MD: The long-term extension data is out there. We know, you know, some of the 5 year and we're able to look at clinical remission scores. And, you know, amongst the patients who can get into clinical remission, we're able to see that they're able to maintain it in the long term over the subsequent four years of data. And that that matches with the real world, we always show it. In a clinical trial, it is an idealistic setting, you must be qualified for the trial, you're maintaining a dose. In the real world, we can adjust, and we're all aware of this. And we're all aware of off-label uses. And if we see something happening, and this is where we talk about Stride-2 guidelines and using the tools that we've now created for ourselves to make changes. If we're following fecal calprotectin, and we're seeing that rising, we can make an early aggressive intervention, potentially, change the frequency on second induction dose, and keep these therapies around even longer. I take the clinical data with a grain of salt and tell myself that we can - in real world - be even better than that. We already had great data in a clinical trial environment. And we know we can do better than that.

David P. Hudesman, MD: That's a great point. With our anti-TNF, you know, I always tell my patients about 70% will respond. But if you're just following the standard dosing, at least a third of them are going to lose response. And a big part of that immunogenicity - and as you brought up Dr Regueiro - with the low immunogenicity of an IL-1223 inhibitors and assuming we'll see the same in a selective IL-23. That's part of why the durability data for these agents are so strong.

Miguel Regueiro, MD, AGAF, FACG, FACP: And it's also getting it right in induction, I also tell that to my patients. If we get it right in induction, well more likely, you're going to have a sustained response. What we're seeing - especially with the Select of IL-23 - we're getting it right in induction. And then to Jen's point, that durability of remission, it grabs hold and it keeps the patient in remission.

David P. Hudesman, MD: And just to be clear, getting the right dose are more appropriate you say?

Miguel Regueiro, MD, AGAF, FACG, FACP: Getting the right induction, meaning, having a high induction rate of remission, which means higher doses, maybe selectivity and getting the right induction. Because before we were seeing these induction rates that were quite low, and then the durability also was quite low. Part of its immunogenicity and maybe pharma could kinetic switches in biologics. But getting right induction, putting the patient in a full remission calprotectin sound endoscopic healing, and keeping them on that dose with low immunogenicity, which again, the IL-12/23, IL-23 class size.

Transcript Edited for Clarity

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