Optimal Management of Biologics in Crohn’s Disease - Episode 5
Drs Miguel Regueiro, Jennifer Seminerio, Anita Afzali, and David Hudesman review currently available biologic therapies for moderate-to-severe Crohn’s disease and the evolution of the disease treatment landscape.
David P. Hudesman, MD: I'd like to get into our biologic options. There are therapeutic options for our patients. Dr Regueiro, if you could walk us through our different biologics for moderate to severe Crohn's patients.
Miguel Regueiro, MD, AGAF, FACG, FACP: Today we really have several classes of what we would consider biologic therapies. The TNF inhibitors are obviously the oldest class that we have. And then we have the alpha 4 and beta 7 integrin, the integrin class. And then more recently, we have the interleukin 12/23, and now more recently a selective IL-23. Those really comprise the class of medications for Crohn's. I know we're not going to talk about ulcerative colitis because we would add more to that but on the horizon maybe we'll talk about that. And those are different biologic therapies that are largely cytokine based monoclonal antibodies the target therapy and you've heard from the panel. Largely, they're either given intravenously, subcutaneously, or a mix of intravenous subcutaneous.
David P. Hudesman, MD: And Dr Seminerio, how has this changed over the years and why is it important that we have all of these different options?
Jennifer Seminerio, MD: As you look at the history of Inflammatory Bowel Disease as we spoke about, the ant-TNFs are the most historical in the group but even with that you're talking 20 plus years. And within that we've found such great efficacy and they still play such an important role. But you needed to go beyond that because in and of themselves, they do not get 100% of the disease state under control. There was always that hope, that goal for better, more effective therapies. Beyond that, we all understand that there's a risk of loss of response, antibody formation with that class. And in those patients you needed another mechanism of action and I think that that's what we've seen. We've seen more specificity, more research directed at safety, long term outcomes, lasting remission. The other factors that are important, we talked about symptoms being very important to patients early on. But then as we talk about this being a marathon, there's what happens 5 years, 10 years in a disease state that they're going to live with for the rest of their life. As we've gotten these better therapeutic options, as we talk about what is on the horizon for the future, there is so much that these patients have to look forward to. And think beyond all of that, the biggest thing that it gives to patients is hope that they're not going to run out of options. Because that fear, that if I've gone through 2 biologics already that I'm almost at the end, lives with them day in and day out. And it can make them afraid to switch therapies because they feel like they're getting closer to the end. What we've set ourselves up for is a future where the options are limitless. And even as Dr Afzali said, we want to be cognizant of early, aggressive intervention. But we also want to be prepared that as thought leaders in this field that if we didn't get there, there is still options and hope for the future.
David P. Hudesman, MD: I guess just to follow up on that Dr Afzali, with our biologics now that we're using more and more frequently, when's the appropriate time to start?
Anita Afzali, MD, MPH, MHCM, FACG, AGAF: Great question and it would be look at each individual patient. If we know our patient has an aggressive disease phenotype based off prognostic factors, young age at the time of diagnosis, extensive involvement, small bowel disease involvement regarded to that, penetrating disease. If these individuals have or present with those factors, we absolutely know that these individuals, without appropriate therapy will have a progression of their disease. They'll develop perianal more fistulas, they will have complications, require more and more surgeries, et cetera. So, you must look at each individual patient and based off of those prognostic factors what we label as disease severity not disease activity, how are they at the time of your clinic, at the time of your colonoscopy, or even at the time of the ultrasound, but more so, what happens over time? It's a marathon over time? 10, 15, 20 years from now. What is the likelihood that they will require surgery or have other complications? Based off that, if my patient has those prognostic factors then I'm initiating early appropriate therapy and that will be early appropriate biologic treatment as well.
David P. Hudesman, MD: That's the key point. We want to start early and if we look at our clinical trials post-op which Dr Regueiro led. If you're starting before we even have endoscopic disease, we see some of the highest rates, pediatrics we see some of the highest rates.
Anita Afzali, MD, MPH, MHCM, FACG, AGAF: Absolutely.
David P. Hudesman, MD: In some more recent studies, the earlier that you treat, especially in Crohn's disease, lessens negative long-term outcomes like hospitalizations and surgeries.
Anita Afzali, MD, MPH, MHCM, FACG, AGAF: More likely that the treatment will work because you have active inflammation you're trying to target. Unfortunately, our therapies, as of right now, they're not antifibrotic and antistrictures and antifistulas at present. And it's that window that you need to initiate appropriate therapy so you could be able to have effective therapy during that time period.
Transcript Edited for Clarity