David P. Hudesman, MD

But maybe we could finish up this discussion. And Dr Seminerio, you could start us off. Maybe a piece of advice or one take home message from the discussion today and we could go around.

: The take home is that there is a lot that's coming and that it is going to be very, very important for us to have discussions with our patients, come up with a plan together, and just be very cognizant that that plan may need some adjustments. If we put that out there that it's not a failure if we have to make an adjustment or one treatment doesn't work but that we're on top of it as quickly as possible. That is the best thing we can do for our patients is to show that we're never going to give up on them.

I'd say a couple of things, one listen to your patient. Obviously, the shared decision, set the goals with the patient. And then number 2, like we've talked about is if you know that Crohn's disease, 80% of Crohn's disease, from the start will require an advanced therapy. Starting that earlier, Jen said that several times, but also then, even within that group, what are the ones with the highest risk factors? Fistula and deep ulcers, multiple segments involved versus which are the ones that are moderate to severe single segments. I know we have great options for both.

: Not much more to add other than we are not exactly at precision medicine and practice of precision medicine in IBD but we are certainly getting there. And again, identifying- initiate early appropriate therapy and recognize that we could still practice individualized care.

: I would echo everyone's comments here. But the key takeaway I would say is start our patients early. Don't delay their care. We can limit all the complications and poor outcomes if you start that patient early. Then personalize it based on all their risk, their severity, comorbidities. Choose appropriately. And then once you have done that, follow them closely over time. This is not a disease that ends after one year. This is a chronic lifetime disease. You cannot go wrong by starting early, choosing a therapy that you think may be the best for that patient. It may or may not work but if it doesn't then you know that you're following them closely and then follow them throughout their time. And of course, you can adjust how frequently you follow them once you get them into complete remission.

I agree. And just one last thing to add is personalizing the target. We've been hearing about treat to target so much. But the target for each patient is different. And as we started the discussion, it's different for each patient. Starting early and personalizing that target. But I want to thank everyone for this rich and informative discussion and thank you for watching this 

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Experts in gastroenterology share advice for the treatment of patients of Crohn’s disease.

Take-Home Messages for the Management of Crohn’s Disease

Dr Afzali, we've talked about many different options and in the next 1, 2, 5 years there's going to be newer options as well. Some similar mechanisms, some a little bit different. Could you just briefly comment on what you're most excited about?

: I'm excited about a lot of stuff. As the pipeline and the medicine cabinet is expanding it gives me additional hope and certainly for our patients it helps them as well. I appreciate that again going back to how studies are now being designed where it's more of the type of patients we see in clinic in a sense of different therapies being ineffective for them as an example. But then also additional trials are looking at combination of therapies, combination of biologics as an example. Because, again, this is perhaps where we're headed and to have clinical trials where we are looking at a P19 antibody and a TNF together, oh goodness, what's going to happen? Well, let's try it out. These trials are going to be very informative. Oral small molecules, the JAK inhibitors, that's in the pipeline to come for Crohn's disease as well. And I think again that's also exciting to see. And then also, there's newer therapies certainly in Phase 1, Phase 2 but antifibrotic therapies. Finally. And hopefully that will get to that next level as well.

And Dr Regueiro, with all these new therapies, what are still some of the unmet needs for our IBD patients?

I think some of them we talked about earlier is that kind of precision medicine biomarker, and the biggest unmet need is seeing remission rates that are consistently above 80%. We've continued to move the bar and we need to move it even more. Imagine a day when we're not talking about a 40% remission rate. We're talking about an 80% and we're getting smart about which treatment we're using first because we understand the biomarker, the makeup of that patient on a molecular basis. We're in the realm of looking at that. I think, again, thinking back 20 years to when anti-TNF started where we are today. I would say in the next 10 to 20 years that's possible and certainly before that we're going to see higher remission rates. We're already seeing that with our therapies. And then the other biggest unmet need and barrier, which we've talked about is just making sure the payers can also keep up with what is happening and making sure the education is there as well.

Yes, I agree, and I think what we've been seeing in our conference as well is access to care. So, access to care for all our IBD patients and all of our GI patients. It's been really nice going to these meetings now and seeing- showing some data about these access issues and how we address it.

Dr Anita Afzali and Miguel Regueiro discuss emerging therapies and combinations in the pipeline for Crohn’s disease as well as unmet needs in the field for disease management.

Emerging Therapies and Challenges for Crohn’s Disease

We just had a great discussion on our current therapeutic options. But we have 3 biosimilars now in the US, for infliximab and coming next year, we're going to have multiple. I don't even want to know how many for adalimumab. Dr Abraham, if you could comment on the biosimilars, is this a concern, is this something that's an easy switch for you?

: The data for biosimilars is out there now. At least right now, we can be comfortable with the evidence that biosimilars, the switching that's going to take place soon, especially with the adalimumab category, that it will be safe, it will be efficacious. We don't necessarily have to worry that when the patient switches they're going to have lower efficacy or end up having more safety concerns. The data is there that it is safe to do so. The emerging information that we're getting for these biosimilars is that initially, the FDA did not account or accept for interchangeability. But in real life practice, we're having patients who switch jobs, they end up being on the bio-originary drug, then switching to the biosimilar and then they switch to another job or move away, and they must go back to the originator or back and forth with multiple biosimilars. And that was initially concerning to me. But now the data is emerging that interchangeability might be OK. So, if the FDA actually allows for that for all of our biosimilars moving forward, now that we have the data, I feel very comfortable discussing them and choosing it, of course, for the patient. Patient's concerns are that, Oh it's biosimilar. Is it OK for me to switch? I want to make sure that I stay on the originator. But what could happen often is that if we end up trying to appeal to the patient because they want to stay on the originator and try to appeal to the insurance to keep them on the drug. Now, with the data, the insurance companies are also saying, no we're not going to do that. That ends up delaying our patients care of being able to get the medication on time. I'm highly encouraging my patients who demand that they stay on the originator biologic that we absolutely should not do that. It's going to put your health in danger. And with the anti-TNFs, we know that if you delay therapy for too long, they're going to be at increased risk of developing anti-drug antibodies. We must, as providers, to be able to educate our patients that biosimilars are OK. They are fine to switch. There's no increased risk of safety concerns or lower efficacy. And avoid that nocebo effect where the patient is concerned and will end up having an adverse effect of the medication because they are so concerned about it. It's kind of like the anti-part of the placebo effect I've encouraged my other healthcare providers, my office staff, my nurses, my infusion nurses, when a patient asks about it, that you don't discuss it. Oh, my gosh you're going to be switch to a biosimilar? Oh my gosh that's going to be scary. We don't have that discussion at all. We say, Oh that's fine. We have data. It’s the same as your originary biologic. Shouldn't be a problem. Let's go ahead and make the switch and we'll talk about how to get that ready for you.

: This is an area where we have such power as providers and how we move forward with this. From everything you said, I think from the standpoint of the way we present the drugs moving forward is not using brand names and really focusing on the generic name of it that when there are these switches, they're- you don't have to have that discussion. When you're dealing with interchangeability, it’s all about trying to minimize the anxiety that goes into that when they've had an effect. And there's so much with that. But beyond everything that we can do, we have a power in our education to the community on this. If we, as IBD-ologists, stand and say, interchangeability is OK. Do not delay treatment. I think then the community providers are going to feel more comfortable with it, they're going to fight it less, and ultimately, it's going to be beneficial for our patients down the line. I think it's all about being calm with this. The data is out there, and this is something that we're now going to see a lot in the coming year.

It's a great point and education is key and I think when the ifliximab biosimilars first came to market in our practice, we were struggling, the insurances, the- our back end team was trying to get authorization, things were getting switched in how to communicate. And now, I think what's extremely important is we have a system in place is when this coming up. We all know it's not a big deal but how do you communicate that to the patient that they feel the same way ahead of when they get a letter from the insurance, or they hear from somebody else? And that's key and once we figure that out it'll be just fine with adalimumab as well. It's the messaging.

Bincy P. Abraham, MD, MS, AGAF, FACG, and Jennifer Seminerio, MD, comment on emerging data for interchangeability of biosimilars and biologics when treating Crohn’s disease.

Role of Biosimilars for the Management of Crohn’s Disease

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?

: 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.

: 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.

: 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.

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.

: 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.

Experts in gastroenterology review the use of IL-23 inhibitors such as guselkumab and risankizumab-rzaa for the management of Crohn’s disease.

David P. Hudesman, MD

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