Role of IL 12/23 Inhibitors for the Management of Crohn’s Disease

David P. Hudesman, MD: Dr Seminerio, the most recent biologics for Crohn's have been approved, or there are IL-23 - selective IL-23 inhibitors or IL-12/23 inhibitors. Can you talk a little bit more about how you're incorporating them now?

Jennifer Seminerio, MD: It's been really exciting. Obviously, the IL-12/23 ustekinumab has been out on the market. And we've got nice long-term data on it as we look into those original clinical trials. You know, its incorporation into the field is easy to see. You've heard us talk about the fact that it can be a good first line therapy, that it also serves a great purpose as a second line therapy. Now, at the selective IL-23, having not only a new mechanism of action, but a new mode of administration is amazingly exciting for patients because we've talked a lot about the Crohn's disease space being infusion, and or self-injectable. And sometimes that's hard on both ends for patients to have something where they don't have to see the needle, and they can put it onto their body and go about their day through the on-body injector, also serves such a great purpose. And, of course, the long-term data will come. But you know, based on what we know, and since we're very lucky or not lucky that a lot of our drugs come from other spaces, we can know a little bit more about safety data than the exact moment it hits the market. Both serve a great purpose as first line, they're also good second line agents. They are great in the space where we talk about comorbidities, such as psoriasis and patients who have developed either a drug-induced psoriasis or have a standalone secondary autoimmune process. It's very helpful there. And we've also seen some benefit in other dermatologic skin conditions and psoriatic arthritis. It's very good there. I think you must know though, what the underlying secondary autoimmune diseases. And understanding that sometimes these have a better potential at hitting some of the posterior spondyloarthropathy is not necessarily some of the anterior spondyloarthropathy. Having that knowledge base can also help gauge where all selected in my treatment paradigm for a patient. But ultimately, the greatest things about it are the mode of administration, the frequency, which patients really like, and of course, the safety.

David P. Hudesman, MD: Great. And maybe Dr Abraham, you can talk more about the efficacy and safety of these agents.

Bincy P. Abraham, MD, MS, AGAF, FACG: I completely agree. It’s reassuring when we talk about these medications with the patients, of the safety. Of course, efficacy is there, we know that. Patients often ask, you're going to put me on this medication, is it going to work for me? You can of course, provide the data. Often patients want to also know how quickly is it going to work for me? Of course, if a patient has had long standing Crohn's disease, had multiple surgeries, we know. And I also educate the patients, we're on the same goal set here, that you're not going to improve overnight, this is going to take longer, than someone who's in newly diagnosed and we're starting them as biologic naive, initiating therapy upon the early onset of disease. We must set expectations to patient when we talk about efficacy of this medication. We look at overall efficacy from a clinical trial, we have a group of patients coming from across the spectrum - some newly diagnosed, some had disease for many years, some had been on prior biologic therapy. Setting expectation is very important when discussing the medication to them to talk about that efficacy. Because what we don't want is a patient to walk out thinking, oh, my doctor said, there's a great medication, I'm going to start in and feel better the next day, and they're calling and complaining, oh, I'm still having these symptoms. But if you set the expectation that it may take few days, sometimes a few weeks, or in some cases, several months if they had severe disease for them to feel better. Of course, it's always nice to have a pleasant surprise of, oh, the patients feel better within a week, and we didn't expect them to feel well that quickly. But it's better than setting the expectation that they're going to feel better the next day and they don't. From the safety standpoint, the more specific we're getting and more targeted we're getting were seen in even better safety, that's even a possibility. We have data from the psoriasis registries with these medications that it's not just one year data, or just 3 months data from the approval of a new medication for us, that we have a decade worth of data of its safety. And we're seeing with these new biologics is that we don't have to discuss the concerns that we used to have in the past with anti-TNF, so immune modulators. We're not discussing forever the concern for lymphoma, we're not discussing forever, the risk of infections. Sure, you know, cancers can occur, infections can occur. But it's very important to talk to your patients that having active disease can lead to complications, can lead to infections, can lead to colon cancer. And they need to understand that risk of therapy can be there, but the risk of active untreated disease is significantly worse than the safety issues with a new medication. It is very important. Sometimes patients forget that, or they have a disease that can deal with it, and they may be worried about starting a new agent. But we need to educate them that they need to be worried about having continued disease that leads to not just colon or small bowel involvement and their symptoms, but it can lead to systemic effects, including increased cardiovascular risk or increased risk of thrombosis from active inflammation, cancer risk, and infections. So they get complications from Crohn's as well.

Anita Afzali, MD, MPH, MHCM, FACG, AGAF: And I will add that, when I'm now discussing safety especially with the newer p19 antibodies - I remind myself in a sense of as we're having this discussion, this is a good way to highlight that the results of the safety results from our trials showed that uncontrolled disease certainly was an example of increased risk. Meaning that the placebo arm, those who did not get early appropriate therapy had more complications, they had more infections and more bad outcomes, because they had uncontrolled disease.

David P. Hudesman, MD: I agree. We have a lot of data now showing how safe this class is going back to ustekinumab in the PSOLAR registry, the psoriasis registry really showing no increased risk of serious infection, cardiac events, malignancy.

Transcript Edited for Clarity