Drs Corey Siegel and Gil Melmed discuss results of a survey of patients with ileocolic Crohn's disease that revealed roughly equal numbers would participate in a patient preference design study in which they could choose whether to receive early surgery or IL-23 therapy. The study was presented by their colleague Simon Rader, at the ACG Scientific Conference in Nashville, Tennessee, October 12-14, 2026.

Corey A. Siegel, MD, MS, is the Constantine and Joyce Hampers Professor of Medicine  at the Geisel School of Medicine and director of the Center for Digestive Health at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. Gil Y Melmed, MD, is director of Inflammatory Bowel Disease Clinical Research and codirector of the Clinical Inflammatory Bowel Disease program at Cedars-Sinai Medical Center in Los Angeles, California.

Patients Favor Choice in Proposed Ileal Crohn’s Surgery Trial

• At ACG, investigators described a feasibility survey at academic centers in California and New Hampshire comparing patient perspectives on early ileal resection and IL-23 therapy. Respondents had Crohn’s disease for about 18 years on average.
• More than 90% said they would join a patient preference trial; about 60% would join a randomized trial. If allowed to choose, about 40% favored IL-23 therapy, one-third favored surgery, and 15% had no preference.
• Patients prioritized durable remission, treatment risks, surgical recovery, ostomy need, and quality of life. The comparative trial remains in planning.

Hi, I'm Dr. Gil Melmed, and I'm very pleased to be joined by my friend and colleague, Dr. Corey Melmed, where at ACG, we had an opportunity to share our work on patient perspectives on early ileocolic surgery versus IL-23 therapy for ileal Crohn's disease. This was a feasibility survey across urban and rural academic medical centers that was presented by Simon Rader on our team, as well as coauthors Jamie Horrigan, Nuru Noor, and Dr. Philip Fleshner, colorectal surgeon.

Dr Siegel:

Thanks. Hello everybody, and we're thrilled to have had a chance to present this. The background here is over the past five to 10 years, we've had some really interesting information about how we treat patients early soon after diagnosis. And the competing strategies are coming from the Lyric study, which were patients early in their disease course who go to short segment ileal resection, so surgery to remove the affected Crohn's segment and see how they do long-term versus the profile study, which is at the time of diagnosis being put on infliximab with an immunomodulator and seeing how they do as compared to the standard more step-up therapy where you fail other medications before you move on to infliximab and an immune modulator. In the LYR!C study, we saw some really interesting outcomes that when patients had surgery early in their course, for a large number of patients, they never needed another surgery and they never got on advanced therapy.

And just this past year, we had 10-year data that came out that says that this result persists over a long period of time, and they actually showed that this is a cost-effective strategy as well. Compared to the profile study that just came across their five-year time horizon where they also see that patients have sustained remission and do really well as compared to a more step-up strategy just by treating patients early on, soon after diagnosis. Now, the reason we did this project is we think there should be a comparison, a randomized controlled trial looking at early therapy versus surgery. And in this case, infliximab and azathioprine may not be the most modern therapy that we're using first line these days. And in particular for ileal Crohn's disease, IL-23s are becoming the preferred agent. So if you think about what trial you would want to see, it would be at diagnosis, a patient starting either an IL-23 medication versus an early ileal resection.

The trouble is if you're doing a randomized trial, would patients consider being randomized to surgery versus medical therapy? And that's what this project was about, is understanding patient preferences. Gil, tell us about the methods.

Dr Melmed:

Yeah, so we surveyed patients in California and in New Hampshire to get a sense from patients, what would their preference be around one of these modalities for treatment? We were interested to know whether patients had a preferred treatment at the time of their diagnosis, would they prefer surgery or would they prefer medical treatment? Would they be willing to participate in a clinical trial comparing one against the other? And if so, what kind of trial? Would they be willing to be randomized to one or the other or would they be preferred to be part of what we call a patient preference design where patients have an opportunity to actually choose which arm of a trial they go into? We were also interested in how patients felt the study should proceed over time with what endpoints are important to patients when studying this particular question. In order to conduct this study, we developed an educational video which included a gastroenterologist as well as a colorectal surgeon explaining the benefits of early surgery and the benefits of early treatment as Corey outlined with respect to the PROFILE trial and the LYR!C trial.

We also explained what does it mean to be randomized in a trial? What does it mean to have these different trial designs and trying to explain to patients on patient terms how to think about participation in a clinical trial of this nature. The outcomes that we found showed that the patients that we surveyed overall were rather experienced. They had overall a disease duration of about 18 years across the board. Many of them had previously been hospitalized or had surgery for their Crohn's disease. A vast majority of them were currently or previously had been on advanced therapy, although a minority had been on IL-23 therapy. What we found was that if patients had a choice, now knowing what they know of which treatment they would choose at the time of diagnosis, it was a fairly interesting split of those that would choose surgery compared to those that would choose medication with a slight advantage towards those actually choosing surgery.

If we talked to patients, about what would you prefer with respect to being part of a study? Would you agree to be randomized in a trial that actually randomized you to surgery or medical therapy? Most patients would have preferred not to actually be randomized, but would actually prefer to be part of what we call a patient preference trial with over 90% of patients being willing to participate in such a trial as compared to about 60% of patients being willing to participate in a true randomized design. And finally, we asked patients, "Well, if you did participate in this kind of study and you were allowed to choose, which arm of the study would you go into?" About 40% of patients said they would choose an IL-23. About a third of patients said that they would choose surgery, and about 15% of patients said they had no preference and would actually agree to be randomized.

And so what we learned from this study is that patients actually do seem willing to participate in this trial with the limitation and caveat that the patients that we asked for the most part really understood what does it mean to have Crohn's disease for a long time, to be on medical therapy, and in many cases to have experienced surgery. We also learned that outcomes that are important to patients were durable remission, avoiding long-term surgery, long-term medication, side effects for medication, recovery time from surgery and the need for an ostomy as well as quality of life. So let me turn it back to you, Corey, to tell us what do we think we learned from this study and how we think about this for next steps.

Dr Siegel:

Thanks, Gil, for reviewing the results there. So we started this project, as I mentioned, to understand if it was feasible to do a randomized trial comparing medical therapy versus surgical therapy. And what we see here is that it is. We don't know that it would be so feasible to do a straight up randomized control trial. It's doable, but we know that a number of patients wouldn't want to be part of that trial. I think we had just over 50% of patients. And if you've been part of clinical trial and clinical trial design, you realize that accruing patients is the most important variable that you need to think about because the study is only as good as how quickly you can recruit patients. But what we did find is that if we had a clinical trial designed as a partially randomized patient preference clinical trial, that we might get over 90% of patients who would agree.

And the reason I say that is with this trial design, what you do is you invite patients into the trial and you ask them if they want to be randomized. If they do, you randomize to one group or the other. If they say they're not comfortable being randomized, you can allow them to select which arm they would prefer to be in, either surgery versus medical therapy. We didn't make this up. This is a trial design that's been around over a couple of years. In fact, one of our co-authors, Dr. Nuru Noor from Cambridge, England, is an expert in this type of trial design. And what you see is that it actually works out about the same numbers go to both groups if you do partial randomization and then let people select one arm or the other. So based on our results, we believe that we would be able to run a clinical trial where patients are offered to join and either get IL-23 or surgery.

And if they don't feel good about randomization, we can have them select. And what we see here is that patients would select about 50% would go to surgery versus 50% getting medical therapy. So we're enthusiastic about this idea. We think this is a really critical clinical question that we need to answer and we see a pathway forward in a clinical trial such as this so that we can ultimately recruit patients and learn what the best outcome is for one patient versus another. If you're interested in this topic, particularly this idea of surgery, which is a really novel way to think about Crohn's disease, Gil and I have a podcast called Digesting and Update and IBD that you can find on Spotify and Apple Podcasts where we actually dig deep into this topic and have a conversation with our colleagues where you might learn more about how surgical therapy could be used as an early upfront treatment and which patients might benefit the most from early surgery.

Dr Siegel:

Any closing remarks, Gil?

Dr Melmed:

Thank you, Corey. I'll end with saying that I was somewhat surprised with the findings of this study in the sense that almost all patients indicated that they'd be willing to participate in a trial of this nature. Indeed, as you say and explained how a partially randomized patient preference design might work. But the fact that almost all patients, over 90% of them agreed that they would participate in this kind of trial gives me great hope that we might actually be able to pull this off in the sense of being able to find patients with relatively newly diagnosed Crohn's, giving them an opportunity to participate in a trial of this kind with an arm for surgery and an arm for medical therapy with our latest IL-23 biologic therapies, and be able to answer this critical question, which I see going forward as being a really important question that's going to have very practical and relevant implications for how we take care of patients with IBD.

And we should say that this clinical trial is currently in the planning stage and we are looking forward to telling you more about it for the future. So thank you for joining us.