Episode Transcript
[00:00:09] Speaker A: Welcome to this podcast spotlight on the management of perianal Crohn's disease, where we will discuss the key highlights of the BSG guidelines.
My name is Naila Ribi. I am a gastroenterologist at St. Mark's National Bowel Hospital.
It's a pleasure to be here with my colleague, Mr. Janendra Varisavitarne, who is a colorectal surgeon.
[00:00:32] Speaker B: Thank you very much for your kind introduction, Naila. Actually very delighted to contribute to this podcast, since perianal Crohn's disease is a condition best managed holistically and within a multidisciplinary team, where a seamless interaction between surgeons and gastroenterologists are critical to to optimize their outcomes. And it's also really important to include the patient in that decision making. So the intention of this podcast is to draw out a few important aspects of the Perianal Crohn's Disease section of the IBD BSD guidelines in the form of a clinically meaningful dialogue. To start off, I'm going to ask you, Naila, why do we need to have a dedicated team to perianal Crohn's disease in the Crohn's Disease Guidelines section?
[00:01:22] Speaker A: Thanks, Janendra. Well, there are three main reasons in my eyes. Well, firstly, perianal Crohn's disease is a common phenotype of Crohn's disease.
The reported prevalence rates range between 20 and 40% of cases, with a significant impact on quality of life.
It also carries a unique management considerations.
Secondly, there are prognostic implications of having a diagnosis of perianic Crohn's disease. Perinaal Crohn's disease is a poor prognostic factor that's associated with a high risk of progressive disease and this manifests as more complications and poorer outcomes, such as a higher rate of hospitalisation and higher surgical rates, and so optimal management may modify the disease course.
And then lastly, it can be quite a diagnostic challenge, particularly when it presents as isolated perinecron's disease in 5% of cases.
And in such a situation it's notoriously difficult to diagnose, particularly when the rest of the bowel looks normal and biopsies from the plastic tract come back as negative.
And I suppose on this last point on the subject of diagnosis, I was going to ask you, Dalindra, do you have any tips for our listeners about reaching a robust diagnosis in Perin or Crohn's disease, particularly in those cases, maybe isolated perinecronal disease, or even sometimes these patients present as an emergency, what do you do then?
[00:02:54] Speaker B: Actually, Naila, this is a really very hard. But it's a good question and it's a question we get asked quite frequently.
We often see patients with fistulas that don't heal and despite some of the recognized surgical treatments, they still won't heal. And it is at that point that we have to start thinking, does this patient actually have a diagnosis of Crohn's disease? And it's the most important thing in these circumstances is to have an open mind that this possibly could be Crohn's disease. Going from there is not easy. We did actually look at the calprotectin levels in a lot of those patients who originally presented in the emergency setting, but it didn't really give us a clear guidance as to who has Crohn's and who doesn't. And wasn't really the most effective way of diagnosing Crohn's disease in your initial presentation.
I think we have to have a very high index of suspicion. And when people are not healing properly, that's the time to biopsy these patients and look in a more comprehensive way.
But this is also when we have to start doing MRIs to actually look at what the complexity of the fistulas, and if there are multiple tracks are looking more complex, then I think we are starting to look at a more Crohn's type of picture.
I think the key here is to ensure that there's adequate drainage in these fistulas and that this has to be achieved by making sure that the MRI is viewed appropriately and we look at them at the time of doing the examination and anesthetic and make sure that all those tracks are dealt with.
After that, I'll take a step back, hand over to. You can bring out all the magic potions and with all the available treatments, how do you choose the best for perianal Crohn's disease?
[00:04:44] Speaker A: That's a very fair point, actually.
Thanks for that question.
Well, you know, it's important to recognize at this stage that the other sections of the BSG guidelines have specific grade supported treatment recommendations because the quality of evidence for the interventions, the medications is high and there's a certainty about the outcomes.
But when we came to look at the evidence for our perianal Crohn's disease, although there were a few randomised controlled studies, these were downgraded because of the uncertainty about the outcomes from that evidence.
And the management, therefore, for perianal Crohn's disease, because of this, is presented as Good practice statements.
There is a systematic review of 19 randomised control studies where the outcomes for fistulising Crohn's disease were reported.
And across these studies, there's an indication of a superiority for anti TNF therapies.
And then a sensitivity analysis of the pooled data for anti TNFs showed fistula induction of remission and maintenance of remission was superior for the anti TNFs compared to placebo.
But then when it comes to the individual anti TNFs, I would say the Accent 2 study is the only one where there was a population limited to fistulizing Crohn's disease.
And in the study, patients were randomized to two doses of fliximab versus placebo.
And the primary endpoint here, because it is quite important, because we need to discuss this, what we're trying to achieve with patients in this particular study, it was the reduction of 50% of more from baseline and the number of draining fistulas observed at two or more consecutive study visits. And then the secondary endpoint was the closure of all the fistulas. And if we look at the 5 milligram per kilogram dose, which is the better outcome compared to 10 milligram dose for the primary endpoint, 68% achieved the primary endpoint with infliximab compared to 26% of placebo, and then the secondary endpoint for fistula closure, 55% compared to 13% placebo. So they're not chubby numbers at all. But what's often overlooked in this study is that 10% had abdominal fistulas, not perennial fistulas.
Yet it remains a valuable study because no other study uniquely investigated this perianal Crohn's disease population.
There are other drugs that we can use supported by subgroup analysis of data.
And since the publication of this infliximab study in 1999, we've also changed the way we use anti TNF therapies. The management pathway has evolved. We can see higher response and higher remission rates to be achieved. And if we use combination therapy, if we escalate therapy, and if we aim towards achieving higher drug levels for both infliximab and adalimumab.
So the question that sometimes arises is, when anticnfs fail, which drug do you choose? There is data for post hoc analysis, from post hoc analysis, suggestive superiority for ustekinumab and upodacitumab. And that's what the good practice statement in the BOHG guidelines supports.
But speaking of outcomes, I think fistula closure is an important outcome. For patients. But obviously for this to occur, many patients tend to have a seaton and that seaton needs to come out. And in some cases additional surgery may be needed. So I'll hand this back to you now and ask you when is the best time to remove a seaton and when would you consider additional surgical interventions in this group? Once I've actually started the treatment.
[00:08:34] Speaker B: Thank you, Naila. I think there's no set time to remove a seton and I think if we set a time, that sort of sets a very bad precedent. But we've got to actually look at when is the right indication to remove a seaton rather than the right time.
So I usually like to see what's on an mri and if we've got a single tract and the multiple other tracts have been gone and the tract is fairly visible and in a good place, we can then think about removing the seton. And I always tell the patient if you remove a setone to let us know if there's increased pain or discomfort, because the important thing is we don't want them to end up with an abscess and go back to square one just because we've removed the seaton. And then if that happens, we of course have to do an urgent examination and anesthetic in relation to surgery. If there's no proctitis, then we can look at dealing with a single track fistula. And there are many sphincter's preserving operations that we can do, like the lift procedure or an advancement flap, which are the commonly demonstrated ones. But there's also laser procedures which can be done and on average those have a healing rate of about 70%. But it's very, very important to select the right patients.
And probably the best way of working that out is to use the most recently published top classification on perianal Crohn's disease, which is a really good way of categorizing patients into where we think their fistulas fit and then coming up with the best way to deal with them. So if you've got a class 2A patient, those are the patients that usually are suitable for some sort of surgical procedure to cure their fistula. But some of those Class 2B patients which are not necessarily suitable for here a ring type surgery can be pushed into two way, if we deal with it in the right way, in a very joint way.
But we also have to say that a lot of these patients with complex fistulas will live with their seatons because that's where the class 2C comes into being, where they're just going to not move into the right position to where they might be able to have curative surgery.
[00:10:58] Speaker A: So that's the seton and the curative surgery. But what about when things are very bad and you are considering defunctioning a patient, creating a stoma to give time for the perianal disease to heal? Are there any criteria that you might use to guide you when the correct time to defunction? I know it's a difficult question, but maybe you can share some insights and, you know, what about the reversal? Is there a time window that you have to try to achieve the reversal or the patient has to remain a stoma with a stoma for the rest of their life? Do you have that particular time window?
[00:11:33] Speaker B: So I think I usually say that the decision to go for a stoma or defunctioning is really up to the patient because different people will have a threshold where they say, I've had enough and I really need a better quality of life.
Because we find that if you look at the patient reported outcome measures, the most common ones which really upset the people are the discharge and the pain.
And when it gets to that point where both of those things are at a level where they can't handle it, that's when they usually will come to wanting to have some sort of defunctioning. And whether we do an ileostomy and see how things go or come to doing a proctectomy will very much depend on the degree of disease that's present at the time.
But I would say that if you were to really talk to a patient, we have to be very careful to say that if you do defunction them, it's highly likely that they're going to stay defunctioned. Because the evidence suggests that it's only about 10 or 15% of patients who have some sort of temporary, for want of a better word, defunctioning will ever be reversed back to their original state.
But in all of this, it's also really, really important that we don't miss a cancer. Because in the presence of cancer, quite significant inflammation where the tissue is very hard and you can't differentiate one from the other, it is important to actually make sure that we biopsy those patients at the right time to not miss a cancer as well. And the MRIs are also helpful in pulling that out.
[00:13:16] Speaker A: Yeah, good point. We often forget about that.
I'm sure you'll agree with me there's much more we could talk about, but within our limited time constraints, I think we've covered some of the more all important aspects And I wondered whether we could leave our listeners with a few take home messages and I hope you'll agree with me. I think for me it is deciding the treatment goals with patients and also working with them to optimize outcomes. And to do this you need a good mdt, you need a good radiologist, good surgeon, good physician, good pharmacists, good ibd. So all the members of the team are important.
I think the second point is to do a full assessment early on and make sure that you drain any sepsis and you may need repetitive drainages throughout the treatment course.
Ensure early therapy. We hear about early therapy in all aspects of Crohn's disease. But also important here to avoid the destructive nature of this disease. It can be quite aggressive.
First line is anti TNFs as combination therapy. Also would regular blood monitoring, also closely monitoring the patients and draining sepsis as it occurs. It may be needed in some patients. Is there anything else you would add to this list? You know, we kind of really have to focus here for this podcast.
[00:14:34] Speaker B: I think all those are the most important things and I think the MDT and working together.
But also it's important for patients to have some form of access so they're not lost in the system.
And I think otherwise it's about doing the best by them. Thank you very much.
[00:14:51] Speaker A: Fantastic. So that concludes our podcast. I hope you found it useful and feel free to reach out to Janendra or myself if you have any additional questions about Perina Crohn's disease. Thank you for your attention.
