Optimal Management of Biologics in Crohn’s Disease - Episode 8

IL-23 Inhibitors and IL-12/23 Inhibitors for Crohn’s Disease Management

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Dr Miguel Regueiro comments on the safety and efficacy of approved IL-23 inhibitors and IL-12/23 inhibitors for the treatment of Crohn’s disease.

David P. Hudesman, MD: Regarding efficacy where we don't have as much data, we don't have head-to-head trials. Dr Regueiro, how about a selective IL-23 inhibitor versus an IL-12/23? Is there a difference? Do we have any evidence we could pull from the trials where you're starting to lean one way or the other?

Miguel Regueiro, MD, AGAF, FACG, FACP: You're right, we don't have a head-to-head yet between the 2. Some of the signals we're seeing, if again, try not to cross compare too much. But some of the signals we're seeing with endoscopic improvement, which was a novel endpoint for risankizumab at a 12-week endpoint. That took a big risk because we look at endoscopic improvement at a year in Crohn's trials. This is the first, this is a selective IL-23. And there was significant improvement endoscopically. With that going forward, my sense is the selective IL-23s may be different in terms of endoscopic rapidity of onset. Safety in general looks good, but the more selective you become, the better. From looking at selectivity, the New England Journal of Medicine looked at kind of a broad swath of immune-mediated diseases. And one of the things that was interesting in that article was looking at the IL-23 mechanism, and the IL-23 may be the mechanism and TNF to some degree in Crohn's disease. When you ask about selectivity, that's going to be important. The safety is outstanding, probably the dosing is now going to be higher, we're going to see higher doses of what might be better efficacy at the 23 and grade-safety as well.

David P. Hudesman, MD: I agree, we need these head-to-head trials, and they are ongoing. But there's the singles as you mentioned, endoscopy and Crohn's with risankizumab with UC. We went in our other selective IL-23 inhibitors, guselkumab shown improvement compared to IL-12/23. As you mentioned, more refractory patients that are entering these trials. These refractory patients in these selective IL-23 trials, we're still seeing good response and remission rates that we haven't seen and maybe some of our other therapies. And it's interesting, obviously, we're not talking about IBD. But in psoriasis, the selective IL-23 inhibitors significantly outperformed the IL-12/23. There's the singles there. I don't think we're ready to incorporate that necessarily. But right now, these are both very good options. And hopefully in the next year or 2, we'll have some, just ahead.

Miguel Regueiro, MD, AGAF, FACG, FACP: One thing was safety just briefly mentioned with IL-12/23 and IL-23, these are very low immunogenicity. We started some of our conversations with the anti-TNF for TNF inhibitors were probably it works better with combination approach. That doesn't seem to be needed for either IL-23, or IL-12/23. So that doesn't distinguish 23, but at the same time, the immunogenicity is low. And I'm not using combination with these therapies.

Jennifer Seminerio, MD: We talked about the rapidity of response. One thing that we're seeing with the selective IL-23 is that we've put it, we were seeing this emphasis now on rapid induction. And we're seeing stronger induction regimens, which is unique. And that the induction regimen that exists is part of the reason that we're going to see such great efficacy is because when we're very aggressive early on, which has been the comments that have been made over and over and over again, then we can get them into a maintenance feed and go into every eight weeks in a majority of the patient population, but you have to get them there first. And that the other thing that sort of separates us from our colleagues in rheumatology, and dermatology, and neurology, the GI tract is difficult to penetrate. We all understand this. We require higher doses of medications. And putting that emphasis on trying to get there giving the GI tract a chance to slow down, stopping that massive cytokine response that's been attacking, and then maintaining it, and really putting our focus on maintenance. What we'll see is our ability to have conversations about keeping them there in the long term and talking about lasting remission, because we were able to get them there in the first place.

Miguel Regueiro, MD, AGAF, FACG, FACP: Jen, something you mentioned is so important. And I know we've This is not 23-specific, but we do have the Seavue study, which looked at adalimumab compared to ustekinumab. These higher rates, almost two thirds of the patients achieving this remission and your point about earlier treatment. Although the study didn't show that there was a difference was not inferiority difference, they're both about the same. We saw some of the highest remission rates we've seen in any studies because of the earlier treatment. That just drives home that point.

Jennifer Seminerio, MD: Look at any clinical trial, and when we're looking at the median duration of disease, we're looking at 6 years in the intolerant or failure, whatever term you want to use, you're looking at 10 plus years. These are areas that we can improve on in our field.

Transcript Edited for Clarity