IBD Drive Time: The Best of ECCO With Dr Frank Farraye

Dr Frank Farraye joins IBD Drive Time hosts Millie Long, MD, and Raymond Cross, MD, to review the best of presentations on the natural history of IBD at the European Crohn's & Colitis Organization meeting held earlier this year.

Francis A. Farraye, MD, MS, is a professor of Medicine at the Mayo Clinic in Jacksonville, Florida, where he directs the Inflammatory Bowel Disease Center.

TRANSCRIPT:

Hi, this is Millie Long, cohost of IBD Drive Time. I'm here with Ray Cross from University of Maryland, my cohost, and we have a fantastic guest today on our podcast, Dr. Frank Farraye, who is director of the IBD Center at Mayo Jacksonville.

So Frank, we are thrilled to have you today to talk to us a little bit about lessons learned at ECCO, and in particular, focusing on the natural history and epidemiology studies that were there. So welcome to the program.

Dr Farraye: Thank you so much, Millie, thank you, Ray. I did have the opportunity to go to Stockholm and attend the ECCO meeting. And I was specifically interested in looking at natural history and epidemiology. So I've got a potpourri of key abstracts that were presented.

The first one was digital oral presentation 29. It was titled "Cure CD: Endoscopy-Guided Versus Standard Treatment in Quiescent Crohn's Disease." So we all are quite familiar with the importance of mucosal healing and changing the natural history of Crohn's disease. This was unique. It was a study from Israel that looked at capsule endoscopy to guide proactive treatment optimization in patients with Crohn's disease.

It was a prospective randomized controlled trial that enrolled patients with Crohn's disease. who were in clinical remission with small bowel involvement. There were 60 patients in the study. Patients who had a high degree of active small bowel disease using the capsule endoscopy Lewis score were randomized to either proactive treatment optimization or standard care, and this was for 24 months. And what they did was repeat the capsule endoscopy every 6 months in those individuals and they intensified therapy. So if the patient was feeling well, but had ongoing active endoscopy changes by capsule, they either started new biologic therapy, optimized or switched therapy. And there were 20 patients in the standard care arm and 20 patients in the proactive arm and remember these were followed for a period of 24 months.

Now, first question you might ask is, well, they're doing capsules in patients with Crohn's disease. Were there any complications? There was only one transiently retained capsule in the study. So all the other patients did perfectly well. And the primary outcome was clinical exacerbation assessed by an increase in CDAI activity or by hospitalization in those patients or surgery.

And so ultimately what they found at 24 months is that the clinical exacerbation rate was significantly lower in the proactive treatment group. So only 25% of the patients, of the 20 patients, had clinical exacerbation versus 70% of those individuals who basically got standard care.

So I thought there was a pretty interesting abstract. The individuals doing the study did not report on imaging, did not report on calprotectin. But this would suggest that we should be thinking about capsule endoscopy in patients who have isolated small bowel disease and use that as a mechanism to basically escalate a therapy. So I thought it was kind of interesting. Any thoughts about this abstract?

Dr Long: You know, Frank, I think that's interesting, too, in that the field is now moving towards this idea of kind of optimization and being proactive and the potential for improving outcomes.

I guess one question, were these folks that the disease wasn't within reach of another modality because obviously we all have trouble dealing with people with only isolated proximal small bowel disease that may not be within reach, or is this something that, you know, maybe have been more predominantly terminal ileal? I guess mostly just to help us to operationalize it. And my other question to you is, do you know if they had some sort of cross-sectional imaging before? I'm always a little leery doing a capsule in a patient with Crohn's disease if I haven't done another assessment, if I'm concerned about the possibility of a stricture and capsule retention. And I'm just wondering if they had a protocol for that.

Dr Farraye: So baseline patients had clinical biomarker, imaging, and a patency capsule. So they all had a patency capsule that passed. And again, only 1 patient over time had transient retention. They didn't specifically go over what they saw on colonoscopy or upper endoscopy, but they specifically said these were patients with isolated small bowel Crohn's disease.

Dr Cross: And Frank, when you go to the video capsule, you often see some aphthae even if a patient is doing well and our biomarkers look good. So I can't remember, did they specify how deep the remission they were shooting for? Were they just trying to get rid of large ulcers? Were they using a Lewis score or any other score as a target, do you remember?

Dr Farraye: No, they didn't specifically talk about that. They just basically said if there was residual or ongoing active disease, that group of patients, even though they were both clinically at the beginning asymptomatic in clinical remission, they then went ahead and tried to either start a new therapy, optimize the present therapy, or switch.

Dr Cross: So we'll learn that in the full manuscript.

Dr Long: Right. I think, you know, for our listeners, something practical out of this may very well be that kind of symptoms aren't everything and Crohn's, we've known this for a while, but that adding some sort of objective marker to help you with dose optimization may be helpful. In some instances, that's calpro, but obviously it's not fantastic in the small bowel in some instances. Another modality that could be thought about that's noninvasive is intestinal ultrasound, but that really is only appropriate kind of in the terminal ilium. It also doesn't look well at the proximal ilium. But the idea of using an objective biomarker, is that kind of your take home message as well, Frank? I don’t know that here in the US we'd be able to do Q6 month capsules, but the idea of using something objective to guide dose intensification.

Dr Farraye: Yeah, I think this just basically fits with our treat-to-target algorithm in a disease location that typically is not amenable to endoscopic evaluation. And just as you said is not…fecal calprotectin that may not perform as well. And similarly, you know, 6 months is expensive, although it's safe. And I don't think I've been this aggressive in managing small bowel Crohn's disease. I'm not sure I'm going to start doing more capsules, but this is certainly food for thought.

Dr Long: No, it's great. I think it helps us to see where the future's going and hopefully we'll improve the care of our patients. You also mentioned a second abstract that you wanted to discuss, Frank, more surrounding the association with IBD and spondyloarthropathy.

Dr Farraye: Yeah, for sure. So this was another interesting study that was performed. It's a digital oral presentation 60, “Prevalence of inflammatory bowel disease and spondyloarthropathy patients.” So this was a cross-sectional observational study conducted in 13 Spanish hospitals including 559 patients. They were all 18 or older, and they either have an axial spondyloarthopathy or psoriatic arthritis. And none of these patients at the beginning were on biologic or systemic steroids.

Of the group, 37% has spondyloarthopathy, these are the most frequent, 37 % spondyloarthopathy, 36% peripheral psoriatic arthropathy. So not surprising is you know many of these patients are on nonsteroidals. And if you look at the data between 35 and 65 % of the patients were on nonsteroidals, and they basically obtained the fecal calprotectin on everybody.

And 40%, so a large number, 40% of 560 patients had a fecal calprotectin that was greater than 80. And what they did then, was evaluate these patients for Crohn's disease or ulcerative colitis using colonoscopy. And 28% of the patients were diagnosed with IBD. This is 28% of the 40%. So that gives you a prevalence of 5.7%. So 5.7% of asymptomatic patients with spondyloarthropathy or psoriatic arthritis on no biologics or systemic steroids had IBD. And if you broke it down, it was more common in patients with the axial spondyloarthropathy. It was almost 9% in axial spondyloarthropathy and 2.4% in patients with psoriatic arthritis. Now, when they did the analysis, the majority, 24 of the patients had Crohn’s disease, 3 or 4 had unclassified IBD, and of those patients, only 1 in 4 had symptoms. So the bottom line in this very large, well done, prospective observational study was that 5.7% of patients with spondyloarthropathy had IBD, basically. It was more common in the axial than the psoriatic and it was predominately manifesting as Crohn's disease. So they basically felt that fecal calprotectin would be a valuable test in detecting IBD in patients with spondyloarthropathy. The question however really is, is how is this going to change your practice? So if you knew someone with ankylosing spondylitis, for example, had asymptomatic or minimally symptomatic Crohn's disease, would you choose a drug, for example, that would treat both of those as opposed to using Enbrel or something that doesn't really work for patients with inflammatory bowel disease?

So, like the previous abstract, places like Europe can do these large, observational studies where they can basically follow a large number of patients and again I chose this one again as food for thought to let us think about a low threshold for looking for IBD in patients who have spondyloarthropathy and again I think in I think rheumatologists are certainly aware of this and they have a low threshold to refer patients who have any GI symptoms for colonoscopy and GI evaluation.

Dr Long: That's really interesting, Frank. Those are relatively high numbers and I think one key point is you mentioned that these are patients that weren't already on biologics. You know one of my first thoughts as you started presenting was, oh, I wonder if these patients were on an IL-17 you know like secukinumab, which is known to be associated with development of IBD. But no, they weren't on that. This is just like inherent background rate.

One question, and then I'll know if they were able to tease this out. You know, it's not necessarily that uncommon to have some degree of inflammation in the GI tract associated with regular NSAID use that may not be IBD. Do they really think all these cases were IBD or how did they differentiate this from, you know, just high-dose NSAIDs? Because sometimes you'll even find some chronic changes on biopsy with NSAIDs.

Dr Farraye: Right, so the way they did this was they were kind of creative in that if the fecal calprotectin was greater than 80 and they were not on NSAIDs, then they got a colonoscopy. But the fecal calprotectin, the only patients on nonsteroidals who got a colonoscopy had to have a significantly higher fecal calprotectin greater than 160. So I think what they were trying to do was eliminate patients who might have nonsteroidal damage to the bowel.

We don't have the data on the number of patients who had fecal calprotectin greater than 160 on nonsteroidals who were still given a diagnosis of Crohn's disease. And you're absolutely right. We all see these patients where the pathologists will say that there's chronic injury, maybe pyloric gland metaplasia, something that would make us think that this is more IBD, but you can see it in patients who are on nonsteroidals.

Dr Long: Well, I think it gives us food for thought and that this could certainly help our, you know, multidisciplinary colleagues kind of select treatment options, as you mentioned, potentially avoid treatment options like an IL -17 or, you know, ways to minimize, in particular ways to minimize NSAIDs. This would be an indication to start a biologic, you know, along those lines as well. So great work.

Well, I'm going to pause briefly and just make an announcement about an upcoming Advances in IBD regional that will take place June 21st to 22nd in Houston, Texas. We'd encourage all of our listeners to try to attend this regional with great IBD education. We'd also like to thank our sponsor, the Gastroenterology Learning Network, and remind our listeners —they've probably found us somewhere—but that we are is on Apple Podcast, as well as Spotify, as well as a link on the Gastroenterology Learning Network. So now I'm going to turn it over to Ray to discuss further studies with Dr. Farraye.

Dr Cross: And Millie, I just want to clarify for the regional in Houston, registration is free, correct?

Dr Long: Correct, no charge.

Dr Cross: And you and I will both be speaking there. So if that's an added draw, then it's an added draw. to come to Houston and see.

Dr Long: It's either an added draw Ray, or it's a reason not to come, right? We hope it's the added draw.

Dr Cross: For me, it's a reason not to come, but for you, it's an added draw.  Okay, Frank, I think you have 2 more studies. One is on dysplasia surveillance, and I think the other is on pregnancy. So why don't you tell us about this one?

Dr Farraye: Let's do the pregnancy one. This was digital oral presentation 72, “Pregnancy for IBD patients with an enterostomy is feasible but associated with complications.” This was a study between 2016 and 2023 at 3 Dutch hospitals and they collected data on 37 women who had 48 pregnancies; 65% of the women had Crohn's disease and 33% had ulcerative colitis. And I think we all know that women with ostomies can have an increased risk of complications related to their ostomy.

And the data that they presented showed that 68.2 % of the women who had full-term pregnancies had complications. Now, some of them are easy to manage, like decreased stoma output, but others are more severe, like small bowel obstructions. Another, more easier to manage, presumably, with a good stoma nurse, is leakage as the enlarging gravid uterus increases.

Now, 1 in 4 of these women required surgical revision because of bowel obstruction, prolapse, or herniation. So again, I do think—and then C -section rates were high, and now, surprisingly, 41 % of the women had C -sections, 17 % of the infants were born prematurely, and another 17 % had low birth weight or small for gestational age.

So what this tells me is that in women who have ostomies, I think it obviously, by definition, all our patients with IBD, whether it's active or not, need to see a high-risk OB. But I would have a very low threshold if there's any suggestion of ostomy dysfunction to have a colorectal surgeon involved with their care so that they're ready to move on it. So I was aware of ostomy issues, mostly stoma output and leakage.

I was not aware that there was such a high rate in this population. And again, not surprising, some of these infants were low for gestational age or small for gestational age and were born prematurely.

Dr Cross: That's pretty sobering, Frank. I mean, 17% preterm birth and 17% low birth weight, I'm sure some of those overlap. But Millie, that's higher than what we saw in PIANO in general, wasn't it? And I don't know if you should understand that.

Dr Long:  Well, it's unfortunately not that much higher. I mean, the issue is active inflammation, right? And so I don't know that it's actually the issue of having the stoma, but there's the issue of if there is active inflammation contributing, we do see much higher rates of preterm birth, small for gestational age, and all of these complications. And so I don't know, Frank, did they have a measure of kind of disease activity in these individuals? Do we know kind of how well their inflammation was controlled?

Dr Farraye: No. Remember a third of the patients had ulcerative colitis and presumably had a permanent end stoma and so they would not have active disease and then two-thirds of the patients had Crohn's disease but in their presentation they did not tell us if there was active disease in those patients who had a total proctocolectomy and end ileostomy.

Dr Cross: So Millie, for the listeners, can you just —because I obviously don't know this — just generally what was the low birth weight, pre-term birth in PIANO overall and then did you guys look at stoma patients yet as a subgroup to see how they did?

Dr Long: I'll start with the second part first. We've actually wanted to look at stoma patients but unfortunately kind of the way we have collected the data we don't have the exact timing of the stoma and whether it occurred during pregnancy. And so we actually modified how we've asked those questions and now we'll actually have access to that specifically.

As you know, with ulcerative colitis, there can be staged procedures. And so sometimes, you know, with one pregnancy or someone may have a stoma with another, they may not. So we actually really do need to have access to those data to help us.

And so I think these are important. This happens not infrequently. I have patients with stomas who want to get pregnant. And generally, we provide reassurance. And as Frank mentioned, one of the things that you can see is particularly in the third trimester with pouching issues, just because of the change of the contour of the abdominal wall associated with the rapidly emerging gravid uterus during the third trimester. But often working with an ostomy nurse can really help with that to avoid some of the leaks and other issues.

But outside of that, prior to this study we haven’t noticed that the ostomy itself is necessarily associated with adverse outcomes. That’s what makes me very suspicious that there was some active inflammation, particularly among the Crohn’s disease patients. And don't forget that in ulcerative colitis, if for some reason the Hartman pouch is still in place and they haven't had a proctectomy, that can be kind of like a sink for inflammation where you can still have active inflammation there in the rectum that could be driving some processes.

I would encourage our listeners, if you haven't looked, the website for the PIANO Study is actually incredibly helpful. This is a study led by Uma Mahadevan out of UCSF that really looks prospectively at pregnant women with inflammatory bowel disease on all sorts of different mechanisms that has really provided the robust data we have that is incredibly reassuring to our patients on all biologics about the safety of these medications during pregnancy. If you go to www.pianostudy .org, you can actually see kind of graphs linked to real-time data. You can see numbers of patients treated with various medications that we have outcomes on. So it's really pretty impressive and something that you can completely discuss with your patients.

I think it can be helpful for them. Sometimes some of my patients are very leery. I don't know how many patients have actually been treated with this drug that I'm on and it can really be quite nice data.

And so the PIANO study—the main results which we published back in 2021—actually followed almost 1500 women with inflammatory bowel disease. And we really showed that biologic medications and thiopurines, it really showed no increase in congenital malformations, spontaneous abortions, preterm birth, or low birth weight. But interestingly enough, active disease was associated with increased preterm birth. And then importantly, increased preterm birth was also associated with infections in the first year of life for the children.

So kind of the root cause here is the active inflammation and by controlling the active inflammation, we actually may be able to kind of prevent some of these outcomes. And so the rates of preterm birth were highly different based on that baseline disease activity.

Dr Cross: And for the listeners that haven't been to ECCO, it really is, I think, a phenomenal conference. And these digital oral posters are only 5 minutes in length. So they're ultra-high, like right to the point, this is it. So I think for the listeners here is, you know, be aware that pouching issues are fairly common, be aware that there is a possibility for obstruction and getting your colorectal surgeons involved early, seeing these patients regularly, communicating with them that there can be issues with pouch function or with ileostomy function and obstructions, that they're aware and continue to follow them to pregnancy. Frank, how about the last abstract?

Dr Farraye: Sure. The last one is digital oral presentation 28, the name of the study was “Yield of surveillance colonoscopy in patients with primary sclerosing cholangitis.” It was another Dutch study of 1203 patients.

Now the study began in 2008. So again, endoscopic techniques and the quality of the colonoscopes that we have clearly changed from 2008 to the present. But of the 1203 patients, 82% had large duct PSC. There were 4099 colonoscopies performed on 759 patients with a median follow-up of 11 years. I should point out, however, that only 12% of these colonoscopies were performed with chromoendoscopy.

Now, the sobering fact was that dysplasia was detected in 11.4% of patients, so 341 of the 1203, and 6% of patients developed colorectal cancer under surveillance. Now the interesting part—and again what didn't go into this all that much—is that 26% of the patients had their dysplasia detected through random biopsies.

Now if the majority of those patients had chromoendoscopy, whether it be dye spray chromoendoscopy or virtual chromoendoscopy, I expect that the number of patients who had dysplasia identified through random biopsies would be lower, but this group of patients continued to worry me. I unfortunately have seen some interval cancers in patients with PSE, and I continue, I do both narrow-band enhanced chromoendoscopy as well as dye based chromoendoscopy. But the PSC patients, I continue to do random biopsies in for fear that these patients are at such high risk. So I don't know about you, Ray and Millie, whether you continue to do random colon biopsies in your PSC patients, or if you're doing chromoendoscopy, just do targeted biopsies.

Dr Cross: Well, I do narrow band. With the pandemic, we had to have an extra person in the room for the chromo and so we just learned a narrow band technique and just never went back to chromo. And so that's acceptable. But I don't really do the 4 biopsies every 10 centimeters, even in PFC. I do some sampling, I'll usually do a couple biopsies on the right, a couple transverse, about 4 on the left and 2 in the rectum, just to look for histologic activity. And of course, you're going to get a look for dysplasia as well.

I'm just concerned when you're doing that many biopsies and you're just sort of mindlessly passing the forceps that you're just not paying attention, you're just not looking and you get distracted. And so that's my bias. I don't really do extra biopsies in PSC unless they've had known dysplasia in a segment, and then I'm going to try to oversample a little bit.

But Millie, I don't know if you do that.

Dr Long: So PSC worries me. So I don't do chromo for all of my patients with UC. I really reserve it to those with PSC, those with prior low-grade dysplasia, as Ray mentioned, or really those with like, you know, those burnt-out colons of 30-plus years that look like tubes that you're just really concerned. And in those individuals, I do chromo. Otherwise, I do high definition white light, but the one group—Frank, I don't know if you practice similarly and I think it's just because I've seen this prevalence in my own practice—that I do random biopsies in particularly PSC patients and I try to really focus on the right colon as well because I've when I have seen dysplasia and unfortunately It's not infrequent, and with PSC It's tends to be right-sided lesion.

So, Ray, to your point I'm trying to do a really careful exam but I do definitively do some oversampling with PSC just because of some of what you've described in terms of the prevalence. I think these are unfortunately high-risk patients that we just have to keep a super close eye on and obviously here in the US we're doing the scopes annually. So we are doing that but it's definitely a group that I worry about.

Is that the same for you? Frank? Do you worry about these folks?

Dr Farraye: Yeah, I just want to clarify. I don't do random biopsies in patients who are undergoing colonoscopy with narrow band or dye-spray chromoendoscopy. I do the kind of samples that Ray talks about just for disease activity, histologically. But in the PSC patients, I don't know. I continue to do random biopsies. I'll do five bottles. I do do right colon, transverse colon, descending sigmoid, and rectum with 3 passes or 6 biopsies in each. I just am so worried about this group of patients developing interval cancer, especially if they have active disease.

Now, if the colon is pristine and glistening and I'm doing a PSC surveillance, then I may not do that, but in anyone who has active inflammation, I continue to do it. And certainly would want the audience to think about doing random biopsies in PSC patients who are referred to you because they've had a previous random biopsy, you know, an untargeted biopsy showing dysplasia.

Dr Cross: Yes, I think that Jim Lewis has an NIH-funded study called the URBI trial that is going to get underway here soon. I think that's really going to definitively answer this question in the modern era of endoscopy with HD and so forth. And it's going to really answer the question about the yield of random biopsies compared to the staging ones that I'm talking about. And it will include patients with PSC.

So I think in the next few years, we'll have an answer and you can see that there's a little bit of variability in how we do things.

So Frank, real quick question. Where were you fishing most recently? All the listeners know that you're a big fisherman. So what was your most recent fishing trip?

Dr Farraye: Well, my most exciting fishing trip was I managed to sneak away in Vancouver last October for the ACG meeting and did some salmon fishing and managed to hook 8 salmon and land 4 so that was pretty exciting but I live in Florida so I'm fishing just about every weekend in fact we're going to be having some fish tacos this evening when I get home from the flounder that I caught the other day so that's what I've been doing.

Dr Cross: Awesome. Frank, this has been great. Thanks for doing this and hopefully you and I will get to go to ECCO again next year in Berlin and do this again next spring.