Optimizing Treatment Strategies to Manage Inflammatory Bowel Disease - Episode 5

Treatment Goals and Guidelines for Ulcerative Colitis and Crohn’s Disease

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A panel of experts discuss the latest guidelines and how they make a treatment decision for patients with ulcerative colitis and Crohn’s disease.

Remo Panaccione, MD, FRCPC: Jessica, over the last—I would say the last decade—we have had several guidelines from different professional societies or different consensus guidelines, even, from IOIBD [The International Organization for the Study of Inflammatory Bowel Diseases]. As we sit here in 2021, what are our goals of our treatment for Crohn’s disease and ulcerative colitis (UC)?

Jessica Allegretti, MD, MPH: I think, really, the treatment paradigm has evolved in that you want to be aggressive upfront. You want to get patients on the right therapy early on to prevent long-term consequences of disease, right? That is really the goal here: to get the patients well quickly, to prevent a lot of the stuff that we have been talking about already today, some of those downstream sequelae that come with having uncontrolled disease for long periods of time. There have been many guidelines, as you pointed out, and consensus statements that have come out fairly recently and the trend is, as you are seeing, biologic use early on. We are not waiting around; get patients on the right therapies early. I think the question around which biologic to start with is still one that is being discussed and how you make that decision. I will say that, with the most recent AGA [American Gastroenterological Association] guidelines—especially for moderate to severe UC—that came out, we see we have even more options. This was after the approval of tofacitinib [Xeljanz] and also the approval of ustekinumab [Stelara] for ulcerative colitis, so we have more therapies in our armamentarium. There have been some attempts using, say, network meta-analyses from Siddharth Singh, MD, to really help us try to understand how to start positioning these therapies. We can certainly discuss the pros and cons of those types of studies, but I think those are really the debates we are having now, not about early aggressive therapy, which I think, really, is the consensus. We should be getting patients on appropriate therapy upfront to prevent downstream sequela.

Remo Panaccione, MD, FRCPC: Ed, back to treatment targets for a second—what are your thoughts on STRIDE-II? It is now, I think, fully published, updating treatment target guidelines. How much value do you put into that type of consensus, and do you adhere to those treatment targets in clinical practice?

Edward Loftus Jr., MD: I think they are useful, they are often aspirational, and I think they highlight the importance of an endoscopy as a target. It recognizes the disconnect between symptoms and objective inflammation. I would say they are aspirational. I think we all have many patients in our practice in whom we see a clinical response or even a clinical remission and yet, there is some endoscopic inflammation. Maybe they are maxed out on their particular medicine and we are not willing to switch because of that and so I do think—I have said this for a long time; this whole idea of mucosal healing or, I should say, endoscopic remission makes it a binary thing. It is probably a continuous variable. There is probably some degree of endoscopic improvement that is good enough and so it is that dynamic between cycling through too many therapies and trying to get as good as we can. I do think the endoscopic targets are important and, in the case of patients with small bowel disease, radiologic targets are probably just as important. There is probably more work that needs to be done in radiologic targets to define what the actual final end point is.

Remo Panaccione, MD, FRCPC: Bill, what are your thoughts on targets and how far we push to try to get there? I think, in my opinion, that these were, as Ed suggested, [are] aspirational. I think we wanted to believe that if we achieved certain targets, we would change long-term outcomes. There is probably a degree below; you do not reach the target, but you change the natural history, and I always struggle with seeing patients who—because we have been beating the endoscopic remission drum—go through 6 drugs in 18 months. I don’t know if we are doing a service to those patients. Bill, you have published on this. Where are we? Do we need to be perfect or is this good enough?

William Sandborn, MD: Well, it is somewhere in the middle. You never get to check your brain at the door, right? You always have to think. It cannot be reflexive, so all of the association data that I am aware of suggests—our group just published a meta-analysis on ulcerative colitis, even looking at histologic permission. It looked like there was incremental value and histologic remission with as much as a 20% relative improvement in big-ticket, long-term outcomes relative to endoscopic remission. There was certainly more than clinical remission. We saw the same thing in patients with Crohn’s disease. There was a big interventional trial. Now, the VERDICT trial is randomizing patients, treating them through an algorithm which includes changing drugs and intensifying therapy to the histologic remission versus endoscopic permission with the goal of prospectively evaluating the results. There is also a trial that is about to come out; It took patients with Crohn’s and randomized them, essentially. They had a colonoscopy every 4 months until they got mutual healing using an iterative treatment algorithm versus treating clinical symptoms. We will see what that shows.

On the other hand, my colleague at UCSD (University of California, San Diego) Parambir S. Dulai, MBBS, and I did some Markov modeling where we were looking at treating the clinical symptoms versus fecal calprotectin versus endoscopy. We found that, actually, endoscopy had the best cost utility for patients with Crohn’s disease and fecal calprotectin was better for patients with ulcerative colitis. Part of the issue with it is that there is the lack of efficacy of the second-, third-, fourth- and fifth-line drugs. Anything that minimizes switching in a sense is more cost-effective because the incremental utility of the switch is not that high, so I think it would all turn on its head if you had highly effective strategies. For instance, some of the next-generation products we see, with JAK1 [Janus kinase] inhibition, that it may be possible to get as much as a 20% increase in the absolute remission rates over treatment with the placebo. Well, at best we had 10%, previously, so that is doubling the relative efficacy, and then if you look at p19 inhibition in biologic refractory Crohn’s disease, it is same thing. You can have a 20% ramp up and absolute remission rates, so that might totally change the calculus of treating to target—switching to a highly effective therapy. Then, imagine if you had precision medicine—the right drug, the right patient—and you could get a 30% or 40% delta. Well then, absolutely you want to treat the mucosal healing. It is complex.

Remo Panaccione, MD, FRCPC: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our eNewsletters to receive upcoming Peer Exchanges and other great content right to your inbox. I am sure you will see the folks in front of you on future programs. With that, thank you very much.

Transcript edited for clarity.