IBD Drive Time: David Schwartz, MD, on Managing Perianal Crohn Disease

In this episode of IBD Drive Time, host Raymond Cross, MD, discusses treatment options, positioning of therapies, and surgical approaches to perianal Crohn disease with Dr David Schwartz.

Raymond Cross, MD, is a professor of medicine and director of the IBD Program at the University of Maryland School of Medicine. David Schwartz, MD, is the director of the McClain Family Directorship in Gastroenterology and of the Inflammatory Bowel Disease Center at Vanderbilt University Medical Center in Nashville, Tennessee, where he also serves as professor of medicine.

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TRABSCRIPT:

Raymond:

Welcome, everyone, to IBD Drive Time. I'm Raymond Cross from the University of Maryland School of Medicine, and I'm delighted to have one of my good friends, David Schwartz, here to talk about perianal Crohn's. David, welcome to IBD Drive Time.

David:

Thanks, Ray, it's really an honor to be here. Thanks for inviting me.

Raymond:

So let's jump right in, and I mean, I think that most of us would agree, patients with perianal Crohn's are probably our most difficult subgroup of patients to manage, and I think you're probably one of the world experts in managing perianal. So tell our listeners, what's your approach when you see a patient with an active fistula?

David:

So I think the very first thing, the foundation of everything after that is really to get an accurate assessment of what's going on. If you think about your worst perianal patient, you can imagine how inaccurate even the really skilled rectal exam's going to be. So I usually will start by setting them up for some imaging study. Here, we do it with rectal US, but most places are probably going to do it with pelvic MRI, and that helps figure out what type of fistula it is. And about 20 years ago, the AGA recommended we divide the fistulas into simple and complex, and that really helps sort of me think about how to approach the fistula tract.

So we'll get the imaging study, we want to get some colonoscopy or flexible sigmoidoscopy to assess the activity in the rectum. And then, once we have that sort of baseline information, we send the patient to a colorectal surgeon, who hopefully will use that information to clean up all that purulence that's there, and get setons in fistulas, if it's a complex fistulizing process. The simple fistulas can probably just be treated medically, primarily. Once we have the setons in place, then we start an antibiotic, so either Cipro or Flagyl. And then, if they haven't been on a biologic, most likely, we're going to be starting them on an anti-TNF and concomitant immunomodulator at the same time.

Raymond:

And you've taught me this, David, but for the listeners, what's the role of setons? So why setons? Other than getting some drainage initially, what's the rationale for longer-term seton use?

David:

Sure, so just to ... Because a lot of people don't even know what a seton is. So a seton is a string or vessel loop that traverses the fistula track, and the purpose of the seton in an IBD patient is to allow for drainage. So it makes sure that all the purulence has somewhere to go, and the inflammatory secretions can come out so you don't get an abscess. And that's really important for a complex disease, because some of the fistula tracts can be quite long, centimeter, two centimeters, or more. And so, you have this long area of inflammation and infection, and if the body closes off the internal and external opening prematurely, which it tends to want to do, and that process is really, rapidly accelerated by biologic therapy, then you just get another abscess and more destruction of the anal sphincter. So a seton essentially allows you to control the rate of fistula healing so the medications can work more effectively.

Raymond:

And we've all seen ... I mean, patients with perianal disease are often going to have significant scarring in the perineum, but the ones that seem to have the worst, or the old school ones from years ago that have multiple, multiple INDs, and they're almost completely disfigured, so you don't want them going back for an IND, for sure. When you use combination therapy, are you trying to maximize both for a dual mechanism, or is the immunomodulator just on board to increase drug levels of the anti-TNF, or to prevent antibodies? Do you maximize both drugs?

David:

So my practice has changed a little bit over the years. So initially, definitely, I was maximizing ... I tend to use Imuran, so I was maximizing Imuran at two and a half milligrams per kilogram, and trying to maximize the biologic. Now, because of some of the information that's come out that you probably don't need maximum immunomodulator dosing to get kind of that combination therapy benefit, I'm shooting more for the lower end of normal, so maybe around two milligrams per kilogram, initially. And then, I'm becoming more and more a believer in monotherapy and checking drug levels, so I do try to get them off the immunomodulator as things heal, about six months, and continue monotherapy afterwards.

Raymond:

Thank goodness that Millie's not here, she'd be upset to say you're more of a monotherapy person. So we'll see what she says after she listens to this. So you do a good diagnostic study, you have an excellent colorectal surgeon who establishes drainage, you've got antibiotics on board, then you start combination therapy. So what's the best time to evaluate for a clinical response? And then, the follow-up to that would be, when do you pull the setons, when do you stop the antibiotics? Sorry, that's a triple question.

David:

That's okay. So what we have found and others have found is that you can kind of predict the winners, the people who are going to do the best very early on. So with anti-TNF therapy, let's say with infliximab, really, shortly after that third infusion, if someone hasn't had a rapid improvement, they're probably not going to get better after that. Most of the people who are going to heal will have at least had significant improvement after their induction. So I tend to bring them back to the office right around that time to do an exam. I believe that imaging is really sort of the equivalent of mucosal healing with endoscopy and biologic use, so I tend to re-image patients when they tell me that the drainage has slowed down, and it's become more serosanguinous and not purulent, and I look for sort of internal healing of the fistula tract.

If things look better at that point on imaging, and they're feeling better, then I tend to pull the seton at that point. And I do continue antibiotics for a week or two afterwards just to help ensure the fistula will close without an abscess forming. So a lot of the time, most of the time, actually, it's about three to six months in before I'm even thinking about pulling a seton, which is a little bit of heresy if you're talking to a colorectal surgeon, because they worry about epithelialization of the tract. But I've just found that if you pull the setons too early and there's still a lot of inflammation, that fistula tends to come back, or they get an abscess, and so, extending the time with the seton in place seems to result in better durable fistula healing.

Raymond:

So to summarize, it's fair to say that you're going to use diagnostic imaging to guide removal of the seton, and you're flexible on when that occurs based on the type of drainage they're reporting?

David:

That's exactly right. I will have the patient tell me when they start to feel things have converted over to the less purulent type of drainage that slows down, and then that's kind of where we pull the trigger on imaging. A lot of times, you can do it just by asking the patient how many pads a day they're wearing at baseline, and then you sort of track that over time, and when it starts to dramatically decrease, that's kind of the time to re-image them.

Raymond:

So for those of us that re-image, I think probably 95% or more of the US is using pelvic MRIs, serial pelvic MRIs to monitor this. And if I remember, what you taught me is that if you still see significant hyper enhancement of the tract, or if you still see branching of the tract, that it's unlikely that they're going to do well if you pull the seton. Is that right, or did I misunderstand that?

David:

No, that's exactly right. On MRI, that's exactly what we're looking for, is a dramatic reduction in that T2 signaling that tells me that inflammatory component of this has really decreased significantly.

Raymond:

So what do you do in the patient that has a partial response? So let's say they're reporting that they're still having purulent drainage, they're using a pad four times a day, and they're not having sex because they're embarrassed, and you have them on combo therapy. So let's say you're three months in, what do you do then? Are you checking drug levels? If you are checking drug levels, is there a certain target that you're looking for with infliximab or adalimumab, and I guess, when do you cut bait and go to something else?

David:

Right, and then, I would have to say, unfortunately, that's the most common scenario. We have very good medications, but most patients are not going to have a really perfect response to therapy. So what I normally will do is look at the different factors like you mentioned that we could potentially modify. So we'll check a drug level and make sure that we've really maximized the anti-TNF, if that's what they're on at the time. And we're shooting for levels above 15, ideally, so if they're not there, we'll adjust the anti-TNF. I also will re-image the patient, because sometimes what happens is that even though you send the patient to a surgeon and you hope that they are actually looking at your report or looking at the MRI, they may have missed something. And so, sometimes it's that they have setons in two of the fistula tracts, but there's a third branch or third tract that wasn't addressed and needs to be addressed to really make sure that you have good controlled fistula healing.

If you do all that, and the drug levels are good, and there really isn't anything missed, the first thing I might do would be to change antibiotics, because sometimes you'll get resistant to, let's say, ciprofloxacin, so we'll switch to metronidazole, or vice versa. If after all that, they still have a lot of inflammation, and they're not doing well, then that's where we talk about switching to a different biologic. Or, right now, thankfully we have a couple of stem cell studies that they might be candidates for, so we might consider even enrolling them in one of those trials if they were a candidate.

Raymond:

So David, if you do have to switch therapies, I mean, do we know which therapy ... I'm putting you on the spot, but do we know what alternate therapy is the best therapy for perianal disease?

David:

We have data with both ustekinumab and vedolizumab. They both look pretty good, maybe not as good as the anti-TNFs, but I would be comfortable with either of those. It really just sort of depends on where their disease is located, how well their luminal disease is under control, and all those kind of things. But either one of those would be, I think, a reasonable next step for that patient.

Raymond:

And we generally know you don't need to carry on the immune suppression with the immune suppressant with a novel biologic, but in perianal disease, do you keep the immune suppressant on board in case you have to go back to an anti-TNF later?

David:

I don't, and I think some of this has changed over time, just as I have had a few patients develop lymphoma over the years, and so I've become a lot more cautious with continuing immunomodulators when someone's on a biologic. So I usually will try to stop the immunomodulator after six months, if I can, and so, by the time we're thinking about switching to a different agent, they're likely off of the immunomodulator at that point.

Raymond:

Got you. And before I go onto the next question, I just wanted to remind the listeners that this podcast is sponsored by Advances in IBD and the Gastroenterology Learning Network. And speaking of Advances in IBD, there is a regional virtual course coming up on August 27th, so by the time this posts, you'll have plenty of time to sign up for that excellent virtual course. David, I find that I get patients a lot better, but I can't get them perfect. Who do you refer to the surgeon to try to close the fistula? Let's say you've got good drainage, you don't need to put another seton in, you're thinking about a lift procedure or advancement flap. Have you had success with that, and which patients do you send?

David:

It depends on the symptom the patient's having, and how much it's affecting their quality of life. So right now, we're in a period of time where we have, as I mentioned earlier, a couple of stem cell trials. So a lot of those patients were preferentially referring them for the trial, because I am really optimistic with some of the response rates I've seen from the data in Europe, and patients being referred in the trial. Before the trial, it would be the patient where I feel like I've really maximized the medicines, and the inflammatory component is largely gone, so I feel like the medicines work fully, but they still have a tract, and those are the people I think that do the best with some of those procedures that you mentioned.

Raymond:

And you brought up stem cells twice, so let's talk about that a little bit. So I guess what was so remarkable in that trial, the phase two trial, was the closure rate and the group that got [inaudible 00:13:23]. And I guess I've interpreted that two ways. One is, it's a highly select group of patients with perianal disease, it's probably not the DEFCON 1 perianal Crohn's that we see. And secondly, it just shows the value of a good colorectal surgeon and getting good drainage of the tract and getting the seton, in this case, even if it's just temporary. What was your take on that high closure rate in the [inaudible 00:13:49] group?

David:

That's right, I think the setons have some success rate, and even before we had biologics, that was the treatment of choice for perianal disease, and it did work. And so, I think that just reflects a good UA, a good seton placement, and the benefit of that, even in the absence of stem cells. And remember, these patients were allowed to continue on their therapy, so a lot of them were on TNFs and other medications, as well.

Raymond:

And do you think that stem cells, the role there is going to be add-on therapy in a patient at six months, who still has some drainage, or using it in more simple fistulas early on? Where do you think that's going to fit in to the algorithm?

David:

Well, initially, I think it's going to be ... Where it's being studied, really, is in biologic failures right now, but what I anticipate is that you can probably get really ... Kind of the idea of combination biologic therapy with UC or Crohn's, I think you can get a really synergistic effect from the very beginning if you were to give stem cells with a biologic right from the beginning. And I imagine that, as we get more comfortable with stem cells, hopefully it gets approved in this country, that'll be something we'll explore and see if we can even do better for our perianal patients.

Raymond:

And then, do you think you'd maintain, just with a single agent, with an anti-TNF, or do you think if you get them super deep, that you could withdraw everything?

David:

If they had just isolated perianal disease, potentially, you could withdraw everything. I think the issue is that having perianal disease is one of the markers for really, more aggressive Crohn's disease, in general, and so, I think most patients, we're going to probably err on the side of leaving them on therapy even after the fistula closes. It's really just to treat the luminal disease and kind of prevent progression.

Raymond:

And I want to follow-up on the isolated perianal Crohn's. I think that troubles us when we don't see Crohn's anywhere else, and we see complex fistula. I mean, that's Crohn's, right? I mean, what else could that be? I mean, we talk about malignancy and infection, but it's pretty unusual that we find those things.

David:

Exactly, but it's a very difficult diagnostic dilemma, because you have this patient, you do everything you can to try to prove they have Crohn's or not, including colonoscopies, obviously, serologies would kind of be the second line of things I would check. And when all those are negative, you kind of have to go back to the patient and say to them, I really strongly believe you have perianal Crohn's. I can't prove it, but I want to take a little bit of a leap of faith and start anti-TNF therapy, almost like a diagnostic challenge. I've kind of found that if they do have perianal Crohn's, you generally will see some improvement after induction. If they don't have any improvement, then a lot of times, I'll stop and sort of reevaluate. But if patients are willing to go on that journey with you, it's a nice diagnostic challenge for patients, where they have just isolated disease, and you're pretty sure they have Crohn's.

Raymond:

And last question before the fun question I was just thinking about as you were talking, what's the role for diversion, and I guess, what's the chances that you're going to be able to reverse that if you go to a diverting lube colostomy or ileostomy?

David:

Yeah, unfortunately, diversion, when it's been looked at, most of those patients never really get to the point where you can restore intestinal continuity. And if you do, a lot of those patients will have recurrent perianal disease. So really, diversion is for quality of life, someone is just miserable, and you're diverting them to reduce the pain, and also, to hopefully get them used to the idea of living with an ostomy. Now, some of those people, you can reverse, and the patient I think that's ideal for that is someone who's really not been on therapy, comes to you with really bad perianal disease, just miserable, sometimes diverting them, optimizing medications, allowing them some time for things to heal, will give you an opportunity to put things back together, but that's really in the minority of patients.

Raymond:

Yeah, I agree, I think the successes I've had in reversal have been the ones that had an acute issue, and the surgeon diverted them, and then they were [inaudible 00:18:03] to treatment, and we put them on treatment, and we were able to reverse it. But those that we were trying to manage the steps as you described, it's very unlikely you're going to be able to reverse them if you go to a stoma, and you can't give patients false hope that everything's going to heal and you're going to be able to reverse them, just as you said.

David:

And I have even had almost like the opposite, where I've diverted someone because they had really bad perianal disease, and they've gotten so much better. I went to them and said, hey, let's think about taking down your stoma, and they just felt so much better, they didn't want to do it. They didn't want to go back to that type of quality of life, and they diverted, and we just left them diverted, and they've done fine.

Raymond:

Completely agree, I've had the same experience, that people don't realize how miserable they were until they're not miserable anymore. All right, fun question, David. I may know this about you, but tell the listeners something about yourself that they wouldn't know, or they might not know.

David:

I think probably the most significant thing that most people don't know is that medicine was sort of a second choice for me. I was a history major in college, and was all set to be a history professor. I was accepted to a grad program, and then sort of had a curveball thrown at me. I broke my ankle playing soccer, and had to work as a research assistant for an orthopedic surgeon, and just absolutely loved that. Sort of fell in love with medicine, and [inaudible 00:19:30] my acceptance to grad school, and did my pre-med requirements, and then went to med school. So I think that's probably the biggest thing.

Raymond:

I did not know that. And although history professors are very valuable, I'm glad you decided to do IBD.

David:

Oh, thank you, I appreciate that. I'm curious, what you were thinking I would say?

Raymond:

Developing the program at Vanderbilt from scratch is ... I don't know if people know that, because the program is so big now. And I'm sort of fascinated by your fasting during endoscopy, so I thought it might be something like that. What you told the listeners, I didn't know, so I learned something about you today that I didn't know, or I forgot, perhaps.

David:

Oh, fantastic. Well, I'm glad I was able to surprise you.

Raymond:

All right, David, this is wonderful. I'm sure our listeners learned a lot. I always learn something about perianal disease when we talk. I hope we can have you back soon.

David:

Love to anytime, just let me know.

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