Using Selective IL-23 Inhibitors for the Treatment of Crohn’s Disease

David P. Hudesman, MD: We have one selective IL-23 inhibitor, as we discussed, on the market now for Crohn's but there's more coming. Dr Seminerio, do you want to comment on one of the other selective IL-23 inhibitors guselkumab and your thoughts in that agent and then maybe if everybody could join in the discussion on do we think there's going to be a difference between one IL-23 versus another?

Jennifer Seminerio, MD: It's exciting. And we saw this with the anti-TNF class, is that you can have different drugs in the same class that serve different purposes. The guselkumab early data looks fantastic and there's a lot of people that are excited about this drug entering into that IBD space. I've seen a few patients on it through, again, comorbidities, that then also come in with IBD and have had good response. From the very low end of clinical patients that I've had on it, it's been beneficially for them. We're going to see differences in these. Not all drugs are created equal. And the best analogy that I ever heard, and I wish I could take credit for it, but I can't, I live in Florida it's comparing these drugs to cruise ships. It's as if you're on Royal Caribbean and you're in the Oasis class. There are different ships in the Oasis, there's different ships in the Oasis. They're all a little bit different. They all serve a little bit of a different purpose. We're going to find little modalities that are different. From a generalizable standpoint, safety, long term efficacy and we're going to be able to see very similar effects. The same way we do with the anti-TNF's but I do think that we have to be cognizant of including everything as the same. We don't do it in the anti-TNF class and we shouldn't do it as we get into these selective IL-23s.

David P. Hudesman, MD: Any other thoughts on this?

Bincy P. Abraham, MD, MS, AGAF, FACG: The differences may be there. But my take on it, looking at the data that's coming from the Phase 2 trials and now the Phase 3, that there may be some subtle differences. We don't have head-to-head of them right now. But is the difference a 2% or 5%? Is it clinically meaningful? I'm not sure yet because again, safety, efficacy is quite good. But it comes down to individual patients and we may not know it until we start practicing using these medications over time. Our clinical experience will help guide us. Perhaps we'll find out that certain patients go to one IL-23, maybe it works for them. But for example, their psoriasis isn't working as well or it's not getting treated as well and perhaps decide to switch to another and still works great for their Crohn's, their psoriasis gets better or vice versa. That's a possibility. I'm suspecting we'll probably see some subtle differences but I'm not sure if we're ready to say based on my interpretation of the separate data that we're going to see over 20% difference between these categories of medications.

Anita Afzali, MD, MPH, MHCM, FACG, AGAF: I will add and obviously we published this as far as our early results. But I will say with guselkumab what we are seeing and what is nice is the design is so unique in the sense of that active comparator with ustekinumab. And we may not and more to come and we're presenting more here soon as well. But I think having that active comparator and determining the dose based off not just comparative placebo but on active comparator in determining if there's any impact because of that exposure potentially will help us identify with positioning, sequencing of therapies, et cetera a little bit better. And then also, with some of our additional analyses where we are looking at, again, real world practice of the individual where they have been exposed to TNF specifically, we are seeing a bigger delta, if you will, specifically and again, evaluated with guselkumab among the patients who have been exposed to a TNF versus not. And this was also very reassuring in a sense of saying it's not necessarily it's agnostic to TNF exposure and efficacy and response but certainly we are seeing a beautiful number that is more to come, of course, with time.

David P. Hudesman, MD: This was a great discussion going over our therapeutic classes. And just to summarize, for our moderate to severe Crohn's patients, the patients we're concerned about the deep ulcers, the fistulizing, we're going with our anti-TNF. But now for the rest, which is probably the majority, these more moderate patients, we have great options, and our newer classes of agents give us not only good induction dosing but there's some good durability data. The future is bright and again, it all comes back down to the patient and having that discussion with the patients and what's the drug that's going to work for them.

Anita Afzali, MD, MPH, MHCM, FACG, AGAF: And I'd like to add that it's also- the future is bright because with the- excuse me with the efficacy and the dosing and the selectivity and all of this, we are not having to exchange great efficacy for safety. Oftentimes, we feel when we're presenting our therapies for our patients, we almost must weigh what additional risks are we willing to take with treatment. And it's nice to be able to offer therapies now where efficacy is high, high rates of remission, and durability but it's not at the expense of how safe it is.

David P. Hudesman, MD: Great point.

Transcript Edited for Clarity