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At the recent Digestive Disease Week (DDW) conference, a study was presented that assessed the predictive role of biomarkers and intestinal ultrasound parameters after infliximab (Remicade) induction therapy to predict endoscopic healing 1 year after treatment.

In this last of four exclusive roundtable episodes, 乌鸦传媒 brought together three expert leaders in the field -- moderator , of Baylor College of Medicine in Houston, is joined by , of Michigan Medicine in Ann Arbor, and , of Yale School of Medicine in New Haven, Connecticut -- for a virtual roundtable discussion on this study.

Following is a transcript of their remarks:

Hou: For our last discussion, we'll be going over the abstract, "Early intestinal ultrasound remission is associated with endoscopic healing after one year of infliximab therapy in Crohn's disease: a multicenter prospective study" by Dr. Revés. Jill, can you lead us through this one?

Gaidos: Yes, absolutely. So I selected this abstract to talk about just because if we're not including something on intestinal ultrasound training or use of intestinal ultrasound in IBD [inflammatory bowel disease] management, I think we're behind the eight ball at least in the discussion. As both of you know, intestinal ultrasound has been used for many, many years in Australia, Europe, and Canada. And now a lot of U.S. academic centers have been implementing it and sort of getting it up and running. With the implementation and sort of the uptake in the U.S., we've seen an influx of abstracts, publications, a lot of data. And so this was a nice study that really just highlighted how we can use early intestinal ultrasound to assess our response to therapy.

So this was a prospective multicenter cohort study. The inclusion criteria were active Crohn's disease without previous surgeries, and all patients were started on infliximab therapy and followed for 54 weeks. They assessed disease activity at weeks 0, 14, 30, and 54, using disease activity scores, CRP [C-reactive protein], fecal calprotectin, and then also intestinal ultrasound. And then at week 0 and week 54, all patients underwent ileocolonoscopy.

Their endpoints were clinical remission, which was a disease activity score of Harvey-Bradshaw less than 5; laboratory remission, which was a CRP less than 0.5 and fecal calprotectin less than 150. Endoscopic healing was an SES-CD [Simple Endoscopic Score for Crohn Disease] score of less than 3. And then they looked at transmural healing, which was assessed by the intestinal ultrasound machine.

And they found that intestinal ultrasound findings at week 14, so the transmural healing, which was assessed at week 14 by intestinal ultrasound was an independent factor for endoscopic healing after 1 year of therapy. So as early as 14 weeks they were able to determine who was going to have the highest chance of endoscopic healing with infliximab therapy.

So as we talk about targeted treatments, or targeting endoscopic healing, thinking about transmural healing kind of going along with histologic healing, which we talk about as potentially a future target of therapies, being able to use intestinal ultrasound ideally at the bedside in clinic early on in the course to either say yes, this is working versus let's change your therapy now with dose escalation or switching therapy, early interventions to try and get inflammation under control, particularly in our Crohn's patients who have a risk of strictures and fistulas and adverse outcomes.

So I think the study just sort of highlights how we can use it early and really the benefits of being able to provide point-of-care testing.

Cohen-Mekelburg: Definitely. And I think this work really gives us a better understanding of how to interpret intestinal ultrasound findings as it's becoming more commonplace, like you were saying, including intestinal ultrasound findings in their predictive model. It did quite well. I think the area under the curve was 0.82. And just thinking about this kind of in the wider context, a lot of the data they show kind of is consistent with what we know. For example, the fecal calprotectin and transmural healing at week 14, that was predictive of endoscopic healing at week 52. Like, to me, that's consistent with principles of treat to target. We know that if patients make it into remission early, they're more likely to stay in a remission.

I do think, though, there are things to consider with this study, and I know this is kind of early in thinking about intestinal ultrasound and prediction, but the P value, while they are statistically significant, the 95% confidence intervals for these different findings were really quite wide, which I think just speaks to the small number of patients that were included.

And so I think generally the small number of patients really limits the power of how many characteristics can you really include in one model. And so to me, this is really a good proof-of-concept study, but it really should be replicated in a larger and kind of more heterogeneous population. And I think it will be interesting to see, how do people respond to infliximab kind of in a real-world population, and what role does intestinal ultrasound play?

Gaidos: The study design is very clean, which I think is probably hard to do in a non-pharma-sponsored study. I mean, really, let's be real. But so they did have very well-defined endpoints, and very clear objective data that they were monitoring. But like you said, Shirley, it was a smaller, kinda on the smaller end, I'm sure they had probably hoped to include more study subjects.

But I think we'll continue to see this. It's already in the ECCO [European Crohn's and Colitis Organisation] guidelines, as far as disease monitoring, there are sub-analyses within some of the clinical trials that are already ongoing where they're looking at intestinal ultrasound endpoints for some of the newer agents that are coming to the market. So I think it's coming. It's probably here to stay.

There are obviously some challenges with implementing intestinal ultrasound training or the use of intestinal ultrasound at everybody's center. Obviously the machines are really expensive and the training requires you to take at least a month off to go to an expert center to get your hands on the machine. So those are absolutely barriers, but I think some of the workarounds are to train your advanced IBD fellow to do it, and then have them come back and stay at your institution -- ideally. But I think it's kind of the wave of the future that is happening now.

Cohen-Mekelburg: Interesting. So that's the way you do it, you have one of those folks go out there and get trained. Yeah, I think one question that this kind of leaves me with, just thinking about the predictive capacity of these intestinal ultrasound findings, is should we be including fecal calprotectin and CRP in labs in these models together with intestinal ultrasound findings? In the sense of, is intestinal ultrasound an adjunct to what current standard-of-care evaluation tools are? Or is it really an alternative? And so I think that's something that needs to be further examined.

Gaidos: Yeah, I think it depends on who's doing your intestinal ultrasound. I mean, I think in the expert centers the places where they're teaching others to do this, they have been able to implement this as an alternative. I think as new sites get up and running, they tend to do it in conjunction until they feel more comfortable with their own interpretation and what they've been able to do.

But I think colonoscopy's not going anywhere. We still have to do colon cancer surveillance, which intestinal ultrasound does not take the place of. So that's still on the list for our patients. And, unfortunately, we can't get rid of it completely for them. But it may be one less stool test for our patient. It may be one less CT scan or MRI that we can spare the patient for. And also just have a conversation, show them while they're awake what the inflammation looks like and be able to make treatment changes if needed, right there in that same clinic visit.

Cohen-Mekelburg: I guess one other comment, just kind of thinking about this study that I thought was interesting -- their rates of clinical remission at week 14 were really quite remarkable for infliximab, 89%, I believe, at 14 weeks and 90% at 52 weeks. And that kind of just made me wonder like, what is this patient population? Is it generalizable to mine, for example? I wish I had as high of rates.

But you wonder if this is like a subgroup and kind of what's going on with different groups. And I think that's part of what's interesting as intestinal ultrasound becomes more commonly used, is really understanding its use not kind of in the ideal population, but in different subgroups. Older versus younger patients, overweight versus underweight patients, Crohn's versus UC [ulcerative colitis], and kind of going from there.

Gaidos: Right. And then you get the patients who've had multiple surgeries and you don't know what's attached to what when you're looking at the machine, that's another limitation.

Hou: Do either of you guys have access to intestinal ultrasound at your centers right now?

Gaidos: Not right now. I am going to do the second part of the training, so 2 weeks actually in Houston in August.

Cohen-Mekelburg: Yeah, we haven't really initiated it yet either. I think one of the bigger barriers is really the training and the time burden of that. And so I'm interested to see what will happen as it becomes more common in the United States and kind of opportunities for access to training. Because a lot of folks aren't going to be able to take that much time off to get the training done. And so it'll be interesting to see how that educational piece evolves.

Hou: Yeah, there's obviously a big push. It's nice that there are at least U.S.-based training sites now, which is a big difference than just a couple years ago. But yeah, this is obviously exciting. I think the question about how we incorporate this into the decision making is the key thing. I don't think it's replacing colonoscopy. I think if it replaces CT scan, that's a huge win, I think, for both patients and payers and everybody. I don't know if it's going to replace calprotectin, but just something as simple as replacing some cross-sectional imaging could be a huge win for patients, probably faster, things like that.

I think that getting to this abstract, some of the details, again they found that the transmural healing at week 14 was the best predictor. But looking at the numbers, only 20% of patients were at transmural healing. So if you're trying to think of how this goes into your management algorithm, it's not like, just because they don't have transmural healing, you're going to escalate these patients, right? And these are patients who were, as Shirley noted, 90% were in clinical remission already.

So still some big unknowns on how we're going to fit that in. It's interesting that it can predict it relatively early and perhaps better than the lab markers, at least that we have available now. But it doesn't quite, I think we really need to see how you use that to change your management on these patients. I think it'd be hard to say you're not going to change treatment, obviously, at week 14 just because they don't have transmural healing at that point. Again, 90% were in remission. So I think more to see on where that fits into the paradigm to come.

Gaidos: Right, yeah. Week 14 seems a little early for transmural healing anyway.

Hou: Yeah.

Gaidos: It's a little off.

Cohen-Mekelburg: I mean, when you're describing those, there's so many opportunities for this. If you alone looked at its role in shared decision making, and how that would impact quality of life and kind of patient decision making and satisfaction, let alone just access, it'll be interesting to see in the long run. Part of this access question is education and educating the staff. But if we are able to disseminate this widely, does this improve access, let's say to diagnostic testing for folks who, let's say, live in more rural areas. So that'll be interesting.

Gaidos: Yeah.

Hou: And I like the point you actually mentioned, Shirley. I've heard some of the early adopters for intestinal ultrasound saying the shared decision-making piece is actually a tremendous reason they do this, is they're showing the patient what it looks like at the bedside. The patient's watching the screen and they're like, oh, what's that? And they see that impact live. Because CT scans, they're not seeing it live and it's hard to understand, but they'll look at that and they're like, oh, that looks bad. And they've said, I've heard some of these providers saying that it really has helped push, encourage patients to be more proactive about their management. Because they want to see it next time. They go on a treatment, they actually want to look at their ultrasounds to see, does it look better now?

So that's an interesting piece that's a little harder to quantify in something like this. But it'd be interesting to look at from the shared decision-making standpoint, patient acceptance, and how patients accept changes in therapy based on their intestinal ultrasound findings.

Well, that's a great discussion. To wrap up this abstract, again, looking at using intestinal ultrasound transmural healing findings after infliximab induction was associated with and predictive of endoscopic healing in this relatively small population. Very helpful, very interesting abstract to tell us, to show us the power of and potential of intestinal ultrasound. Again, will need to be reproduced, so we have a better understanding both with infliximab, as well as other disease states and with larger, more diverse populations. But I think at this point we have all accepted intestinal ultrasound is not going away. And we'll have to figure out how we embrace that in our centers even here in the U.S.

Thanks for the discussion, both of our presenters today, Dr. Cohen-Mekelburg and Dr. Gaidos. Thank you all for participating, and thank you for listening.

Watch episode one: Reaction to FDA's Approval of Upadacitinib for Crohn's Diseaseopens in a new tab or window

Watch episode two: Risankizumab Safe in Older Crohn's Disease Patients

Watch episode three: High-Dose Upadacitinib Appears Safe, Effective in Acute Severe IBD

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