The American College of Gastroenterology published an update to the clinical guideline on ulcerative colitis in adults (Am J Gastroenterol 2025;120[6]:1187-1224). GEN’s Katie Prince sat down with lead author David Rubin, MD, the chief of the Section of Gastroenterology, Hepatology, and Nutrition and the director of the Inflammatory Bowel Disease Center at The University of Chicago Medicine, to discuss the update and its implications for clinical practice.
GEN: What prompted the guideline?
Dr. Rubin: The ACG practice guidelines for adults with ulcerative colitis had not been updated since 2019, and between 2019 and 2025, there were nine new therapies approved by the FDA for the treatment of moderate to severe ulcerative colitis. In addition, there were other advances in the space, including deeper end points for remission. And we felt strongly, especially because this is primarily for a U.S. audience, that there were pressures and forces at play that were limiting choice among doctors and nurse practitioners and their patients that we wanted to call out and provide guidance on.
GEN: What’s new in the guideline that clinicians need to know?
Dr. Rubin: A few things. The first one I want to highlight is that although we don’t know the cause of ulcerative colitis, we understand better how to manage it. The goal of treatment is to eliminate symptoms of stool frequency, rectal bleeding, and, importantly, urgency of the bowel but also to pair that with evidence of disease modification, which means that we heal the bowel by endoscopic appearance and normalize lab markers of inflammation or other abnormalities. When we do those two things, we improve quality of life and gain more sustained control. People feel better, and it lasts.
So, what we’ve learned from our new treatments and our evolving treatment strategies is that therapies that work often make people feel better, but better therapies are the ones that enable the bowel to be healed and for people to stay well over time. That’s the first major message for people to understand.
The second major message is that we have new treatments for them to learn about. There are distinctions and important considerations based on the mechanisms of these drugs, but they all work fairly similarly in the sense that they’re targeting the immune system, trying to turn down an overactive or dysregulated inflammatory response to enable the body to catch up and restore homeostasis.
We also now have two different classes of oral small-molecule therapies. Because they’re oral small molecules and not large molecule proteins, they avoid one of the challenges we have with monoclonal antibodies, which is that they can leak through an inflamed colon. Small molecules are absorbed in the small intestine, which is not involved in ulcerative colitis, and, therefore, there is a much more predictable pharmacokinetic profile and faster onset of action.
GEN: How do you think the new guideline will change practice?
Dr. Rubin: Guidelines are not meant to represent the standard of practice, but they are meant to provide guidance for how people think about managing patients. There are a couple of major messages that I think should resonate with our colleagues and, I hope, will influence practice.
The first one is recognizing the goals of treatment.
The second one is the recognition that choice of therapy should be based on how sick the patient is when you meet them and their prognosis. The reason this is relevant is because too often people present with moderate to severe colitis and they’re treated with mesalamine, which is a treatment for mild to moderate colitis. They’re undertreated, which has a consequence. Also, too often people who are feeling somewhat better but are not yet in stable remission are shifted to a maintenance therapy or taken off medicine, and they end up having relapse or living with active inflammation when they shouldn’t.
We went out of our way to be very specific, to say that patients who have a prognosis consistent with moderate to severe colitis—which means a higher risk for hospitalization or surgery or cancer—should be maintained with therapies that are known to control moderate to severe colitis. Clinicians should not undertreat with mesalamine or rely too much on steroids.
GEN: What were some of the hottest points of debate among the guideline panel, and how did you resolve them?
Dr. Rubin: That’s an interesting question. I would start by saying we added intestinal ultrasound to the ACG Ulcerative Colitis Disease Activity Index as another marker of disease activity. We did this without prospective trials demonstrating that it’s an effective strategy for managing the disease, but we know that it correlates well with bowel inflammation, and we wanted people who were starting to adopt it to know how to incorporate it into practice. I wouldn’t necessarily say it was a big debate, but it was something very new that required conscientious and intentional thinking.
There also was careful discussion about use of Janus kinase inhibitors for severe colitis. When this guideline was published, the available data reflected open-label off-label dosing, higher doses, and there had been insufficient long-term follow-up to clarify whether these are effective options for patients. We ultimately said that this is an evolving space of great interest but that the data were not strong enough yet for us to make a graded recommendation.
This is an important point because a lot of clinicians want to know more about these agents. I would encourage them to read that part of the guideline for some clarity.
Third, distinct from the American Gastroenterological Association guideline, we intentionally avoided using network meta-analyses to position therapies. Network meta-analyses are hypothesis-generating and an important exercise, but we didn’t use them for our guideline. We didn’t want to provide no guidance, but we wanted to base what we were recommending to our colleagues on available strong evidence and then provide them with guidance about the goals of management, rather than “start with this particular antibody” or “use this small molecule over this one,” because the data do not support that yet.
GEN: What are the biggest remaining gaps in evidence and areas for future development?
Dr. Rubin: One important area for further development is that we still do not have predictive therapeutic biomarkers to tell us which treatment to use or which treatment not to use, and, obviously, that would be a game changer for us. There are a number of therapies in development that have companion diagnostics tied to them that may provide that in the near future. This is a major area of interest in a crowded landscape, and with all the confusion about how to use our treatments, having that as an additional tool in our tool belt would be really helpful.
The second area we highlighted is that we think there should be more of a phased management strategy going forward. What I mean by that is, for example, combination therapies to induce remission, with the acknowledgment that we can move to monotherapies in maintenance. The idea is more intensive therapy to gain control and a less intense strategy for maintenance of remission. There is a lot of evidence indicating that is possible and there are many ways people do it in practice, but we need some more pragmatic evidence of this.
The third area for development is that there is obvious interest in histologic remission, treating to the level of biopsy remission, but I want to highlight that we aren’t there yet. A prospective randomized trial is exploring that end point in further detail to tell us whether it is, in fact, a better end point. I think it might be. But how we get there, whether it’s worth the extra squeeze to get to that level, is not known yet. So, that’s another major area in which we’re waiting for more research.
Finally, more active monitoring strategies, whether it’s using intestinal ultrasound or fecal calprotectin or a variety of different wearables that are being developed, are areas that we expect are likely to be further incorporated in the next guideline update..
To this point, we are recognizing how fast the field is moving. We’ve been commissioned to submit regular updates in the space. So, even though these guidelines were just published earlier this year, we already have multiple things that have been published and changed in our space.
I think we’ve moved toward being a little bit nimbler, and we recognize there are a lot of different audiences for guidelines like these. One, of course, is our colleagues in clinical practice, but also very important are the other people who read this, like industry, which is trying to develop better therapies and think about where the landscape is taking us. And payors look at these guidelines; maybe they don’t look as often as we want, but we do recognize that they should, so we rely on these guidelines to nudge the field forward.
For those who are interested in reading the guideline, or at least becoming more familiar with the things we discussed, I refer them to Tables 2 and 3 in the guideline. Table 2 has the 54 graded recommendations that we made and Table 3 has the 57 key concept statements, where there isn’t graded evidence, but the recommendations are considered best practice and consensus-based. If someone doesn’t want to (or have time to) read the whole 40-page guideline, they can look at those two tables and feel very up to date.
This transcript has been edited for length and clarity.
This article is from the December 2025 print issue.