Episode Transcript
[00:00:09] Speaker A: Hello and welcome to this BSG podcast which is largely based around the first line treatment of Crohn's disease with advanced therapy. And we're going to be really focused on the IBD guidelines and how these are hopefully going to help us deliver better care for our patients moving forward. Forward. We're joined today by Polychronis Pavlides, who was the joint lead for the Crohn's Disease treatment section on the guidelines and is also a consultant gastroenterologist at King's College Hospital in London. My name is Fraser Cummings. I'm a consultant gastroenterologist in Southampton and lead the adult IBD service there. So nice to join you for this meeting, Cronus. I think it's a great opportunity to talk about some really important.
[00:01:03] Speaker A: Guidelines in terms of helping us and supporting us in providing better care for our patients.
To begin with, do you have any reflections on the process of drawing up the guidelines? I know that they were a massive amount of work and commitment.
How did you find the process of drawing up the guidelines?
[00:01:26] Speaker B: Thank you, Fraser. It's great to join you today and really working on a topic that I feel very strongly on about early effective treatment in mortally active Crohn's disease. And thanks for the question. Yes, being part of this guideline writing group was a long journey, fulfilling journey with a lot of hard work, not just by me, but the group that I led with Matthew Sale, who's my colleague on this particular section of the guidance, but also are the people who are members of this team and worked very hard, having meetings, often training as well, and participating obviously in the voting that we had for the recommendations back in November 2023. It has been a long journey and from the recommendations that were voted for in that time, you know, we saw the guidelines coming out the summer past in Glasgow in the BSG 2025 and I think it's a great opportunity to talk about some of those recommendations and perhaps some of the changes that we see now in comparison, particularly to the 2019 iteration of the BSG guidelines, the management of IBD in adults.
[00:02:42] Speaker A: I'd like to maybe drill down a little bit more on those. What's changed between 2019 and the 2025 guidelines in terms of our approach to the management of moderately severe Crohn's disease.
What's new?
[00:03:00] Speaker B: Yeah, I think the 2019 guidelines were really forward thinking guidelines, really putting a lot of weight on an accelerated step up approach at a time when, you know, as a fibrin monotherapy, perhaps steroid after steroid course was perhaps a routine practice in the field. So if you remember, there was a recommendation there about considering escalating treatment beyond two courses of steroids, talking about.
[00:03:31] Speaker B: Starting the thiopurine on the photrexate sort of early on and then by monitoring people closely, accelerating sort of into that next phase of moving to an advanced therapy. And typically in any tnf, I think what we see here, particularly with the data and the way we approached sort of the body of evidence that we went through for the guideline development, it felt that we had, you know, the evidence that support a recommendation where we would suggest that early effective treatment. So a top down approach should be sort of first line for this group of patients with moderately severe Crohn's disease and focusing on reducing perhaps the number of courses of steroids. So on this guideline we talk about one course of steroids, you know, eight weeks on, already thinking about starting an advanced therapy and really building on them. Sort of the fantastic data that Profile brought in and supporting that practice.
[00:04:33] Speaker A: Although Profile wasn't part of the guidelines, was it? It came out a little bit later, didn't it?
[00:04:38] Speaker B: That's right. So I think we didn't even have access to the abstract. Obviously many of the members of the GDG were participating in the study and they had a feel about the message coming through there.
We already had the data from sort of the phase three terms that really showed that patients who are on advanced therapy do better than people who are on placebo. And by placebo I mean either on steroids or an immunomodulator. And that's one of the beauties of the analysis that was performed with the meta analysis that Maurice and his team with Vasiliki Sinopoulou managed to sort of put into the way they analyze the data and showing the difference again between sort of the immunomodulator group or steroid group and those within advanced therapy. On top of that, obviously we had the studies looking at a top down versus step up approach that really gave us that confidence to make that recommendation.
And obviously seeing how Profile came through and the data then, you know, while we were writing, after having voted on the recommendations, it was easier even for us to have, you know, that support and explain how Profile supports that recommendation. I don't be surprised if in the future actually that recommendation becomes even stronger because at the moment it is suggested, right? And we typically with these recommendations we use the language provided by grade and then we give sort of those measures of confidence, but also efficacy as well, as we've agreed on the map priori.
[00:06:20] Speaker A: Okay. So I guess one of the key messages is early effective treatment with advanced therapies.
So you've got a new patient in front of you, you've just scoped them, you're seeing moderately active Crohn's disease, they've got good going symptoms that correspond to that. How do the guidelines support the treatment choice that you make in with that patient sitting in front of you in the real world?
[00:06:50] Speaker B: Yeah, that's a great question. And I think it's important to remember that it's about discussing with the patient about the options that they have.
Again, through the thread of the guideline is around multidisciplinary team decision making and having the patient with a condition at the center of the decision making. But I think it's quite clear that whilst we accept that steroids can be used to help the person get into remission, perhaps we already need to think about advanced therapy. So perhaps in the prose, that is introduction to the Crohn's sort of section of the guideline, we are highlighting that. And obviously, you know, the guideline now suggests against using, for example, immunomodulators like as A5 and type purins as an option for induction and maintenance of Crohn's disease. On the other hand, we have that recommendation about an advanced therapy in managing disease. And also then we have the recommendation for using an anti TNF with a thiopurine, ideally in combination.
[00:08:06] Speaker A: I guess it's making the point that why we're using the thiopurine in those circumstances, we're not. We're using it to support the advanced therapy, the infliximab or adlimumab rather than as a treatment by itself. Is that a fair, a fair statement?
[00:08:21] Speaker B: Yeah. No, I think so. And you know, we know that that early period of time after diagnosis is really key for us to try to get on top of the inflammation. Right. Profile really speaks on that. If you think about this. In the profile trial, we have patients who really have an accelerate step up approach and still they don't manage to reach the same kind of outcomes that the other group got the people who started on the combination therapy early on. And we can see that in 12, at the 12 month sort of time point.
I think we have data also about sort of time points further down the line. So I think this is a very, very important message. And I think the other thing that was important to sort of highlight through the guidelines and the profile has been mentioned was the Main reference for that is around the safety of the approach. Right. So those concerns perhaps that have been a bit more sort of common early on, sort of the journey of the advanced therapies and how they were introduced and the worries about sort of immunosuppression, perhaps risk of infections and other complications. I think certainly Profile, a study that was a pan UK study really, you know, looking at our practice, showed that actually is a group that is not treated effectively that have that really face the problem. So we don't that and we don't want that. So really the safe treatment is the efficacious treatment. I think this is what Profile teaches us and I think this is what the guidelines suggest.
[00:09:51] Speaker A: Okay. There were a few other interesting parts of the guidelines.
First of all was the vedelizumab story. It's a drug that many of us have used for many years to treat Crohn's disease. I suspect probably in the older patient groups who perhaps you're worried about the risks of azathioprine more. And also looking at pants data, patients who really ran into trouble on anti TNS tended to be the older patients as well. So we've used veto for a long time. Yet the guidelines perhaps are not supportive of that. Particularly, is there.
[00:10:32] Speaker A: Anything that we can take away from that, anything that we can apply to our clinical practice?
[00:10:36] Speaker B: No, I think that's a very fair point. And you know, all of us have had good experiences with using vidolizumab in Crohn's disease. We've also seen people who haven't responded as well, perhaps the vedolismab or other treatments. I think the selection of the right drug for the right person really, at the end of the day is in the hands of the person who is to apply this, you know, body of evidence for that particular person they see in front of them. And you're right, we should take everything into consideration. Now, it's important on this topic of adolesum lab to think about what were the questions that we were trying to answer. So the pico questions that they sort of, they were set up a priori so we don't have a separation between perhaps treatment naive patients and patients who have had experience before to maybe anti TNF or other advanced therapists. Although edelizumab was the drug after, I guess.
[00:11:34] Speaker B: But the other thing we need to think about is that a priori there were some effect thresholds that were set and based on those.
[00:11:45] Speaker B: I guess, instruction we had about how we'll make those decisions and how we would vote in that mythic November 2023.
We had to make a decision that perhaps sounds. That goes against our practice. But in many ways, I don't think that the language is restrictive. I think it just helps us weigh a bit more about what treatments we would be thinking at what time for the patient in front of us. You mentioned verdolizumab as an option for those people who perhaps would feel that a more gut selective agent is more appropriate. But I would argue perhaps that, you know, Ustekinumab is a drug that is also something that we could use in that cohort, or Perhaps they're anti P19s now, for example. So I think it's important, you know, we have an open mind. We have new agents as well. And I think it's important that we weigh the benefits and the risks and the safety of each of the drugs. And of course, it's also about the experience of each unit. Right. I think what I quite appreciate in this guideline is the fact that you can go from the evidence as it's synthesized and as you can access that in supplementary figures to, you know, the recommendation. And also underneath the recommendation, there is usually a paragraph describing what is perhaps what was going through the mind of the people voting for that, and also some ideas about how we're going to implement that. So this is what we call the evidence to decision framework. And it's important to highlight that, you know, in that part we actually say that there is a group of people who will benefit with vedelizumab. And, you know, we also say clearly that we should not stop vendelizumab for those people who are already on the drug. That's not the purpose of this guideline. These guidelines are supposed to be restrictive. It's supposed to follow an agreed sort of recipe of how to make to come up with recommendations so that everybody sees transparently how that came about.
[00:13:47] Speaker A: Yeah, that's really clear. Thank you for. Thank you for taking us through that and giving us a much better understanding of the process behind arriving at that recommendation.
Another really interesting part, I think, is whenever we make any treatment decision with a patient is saying, when do we expect that.
[00:14:10] Speaker A: The drug to have an outcome? And I think we all recognize a real move towards going beyond simple clinical remission. Following the STRIDE guidelines, we're talking about looking at biochemical remission and perhaps even moving towards endoscopic healing. Now, we could go. I think you can go as deep as you want, but in the context of the guidelines, I think there is Some really interesting data in the guidelines that do support those conversations.
[00:14:41] Speaker B: Yes, no, that's a very good point and it's important to highlight that. So there is a table in the guideline that is taken from the stride recommendations on time points to assess for symptoms, you know, to look for clinical remission, to look for biochemical response or normalization from biomarkers that we can measure in the periphery like CRP or esr. And obviously looking at that key biomarker that fecal calprotectin is, as well as for endoscopic healing as you describes. And obviously I'm a very big fan of intestinal ultrasound and hopefully at some point we'll be able to talk about transmural healing time points as well. But I think that's a key point there. And perhaps it's more important about thinking about optimized monitoring of the treatment that you started, perhaps, and being prepared to accept that maybe it's time to move on rather necessarily what will be the first treatment? As long as this is an advanced therapy, perhaps.
But you know, again, it's about trying to personalize care for the person in front of us. As we know, we don't have good biomarkers for that, but we have our experience and our acumen and we have the body of evidence that we can sort of draw from to guide that decision making. But certainly also looking for that response at the different time points. And we have for the first time, specific time points there in alignment with international recommendations, I think is key for the outcomes that we're looking for.
[00:16:17] Speaker A: I think this table is really important when we start to think about the IBD standards, KPIs, things like that. When, when would you be making that first assessment of response to induction? And I think it's really important that the guidelines, I think, are a living document that actually do get translated into everyday clinical practice. And I think the guidelines are really nice in that respect and they do give us a clear pathway to then start translating them into standards, into KPIs, into quality improvement and so on. So I think they're a really nice, really, really important foundation that, that process moving, moving forward.
You said earlier very eloquently that patients are at the center of what we do, what all of us do, and their preferences and views are really important in all of this, in this process of selecting treatment, the best treatment for them at the right time.
Is there anything in the guidelines that help us with that and would guide us in terms of managing our patients and what they are expressing?
[00:17:32] Speaker B: Yes, absolutely. So I think from the beginning and from the outset, people with a lived experience were participating in the writing of this guideline from the decision making about how this would be set up with a wider group, but also voting on those recommendations and also helping with them sort of the final write up as well. And I think the ethos of the guideline is really about that entity, discussion, and again, not just with the healthcare professionals, but with the patient at the center of that decision making underneath each of those recommendations, again, when we have them, considerations for implementation. Again and again, people read, you know, discussing with the person in front of you about exploring what may be acceptable or not.
And I think that's, you know, what is key in treating people with a chronic condition like Crohn's disease, for example. We also need to build that report and that confidence in the relationship. And I think that by being open and also going through the data and explaining perhaps and what the data is and why we're making those decisions or we're making the suggestions will be key. And I feel that the guidelines are doing that.
[00:18:51] Speaker A: Yeah, that's critically important.
I mean, one of the challenges I suspect you had is your comparative effectiveness and how do we know if drug X is better than drug Y at any particular time in the patient's journey? How did you find, what was your experience of looking at that evidence base and, and trying to bring that into the guidelines?
[00:19:17] Speaker B: No, that's an excellent question. And as you, I'm sure you've noticed going through the document, perhaps we don't really have any algorithms.
[00:19:26] Speaker B: To be honest, we didn't have any algorithms before either in 2019 to sort of think about where to position and medication. And we thought about this, you know, a lot. I was quite strong proponent perhaps, that we should try to look at naive or experience separately. There was the argument that perhaps with the experience group, maybe data for drugs like Infliximab or the Limbab won't exist because obviously those were the first drugs to come out.
There was discussion about including perhaps longevity data as an outcome, but in the end, you know, the outcomes were set based on the clinical remission response, you know, the endoscopic remission and response in biochemical, and you can see all those outcomes there. It was felt that we should analyze.
[00:20:20] Speaker B: Data for both naive and experienced patients as part of the same pico question. So, you know, is, for example, infliximab better than placebo for the treatment of moderate to severe Crohn's disease? Illuminal Crohn's disease. And obviously that has its limitations, right? So the way to approach that was by sort of referencing perhaps studies that we were expecting to come out. You know, sequence. For example, the first head to head looking in this post anti TNF group comparing Rosenkizumab with esikinumab in open label design with the blinded endoscopic assessment was only an abstract at that time.
And also there are questions about how methodologically you bring that data if you were to try to synthesize it with other types of data. But maybe we don't need to do that and perhaps we just need to take each trial and its study as a unique body of evidence and then we make an informed decision based on that. So for example, when we mentioned about Ustekinumab or zelkizumab as options in this context, we reference sequence highlighting, you know, that data again in that abstract format at the time. So I think as we see more and more studies head to head trials coming through, I think, you know, the next guidelines will be perhaps a bit more informative on the part of sequence, I guess, which is what you're asking me about. At that time it was felt that we, without the data we would not be able to make a recommendation. It would be more like a good practice statement which perhaps would be helpful. But at that time the feeling was that maybe would not be.
[00:22:07] Speaker B: Best practice for our guidelines.
[00:22:09] Speaker A: Certainly some of the other guidelines have had slightly more almost best practice sections at the front, which I think have been quite useful. For example, the AGA guidelines I think do have quite a nice distillate and almost executive summary at the front, which does, does help. But I think you guys had more than enough to be getting on with with the main body of the text without adding to your, your enormous workload already.
[00:22:36] Speaker A: Thank you very much for that. I mean, I found this really illuminating in terms of how the decisions were made, how the text was generated in the guidelines. I think it's been really helpful to hear your experience of that. I think there's a few, one or two key messages that I think come from this. First of all, and you may want to come in on this, I think actually getting patients on effective treatment early in the disease course is one of the key takeaways. It's one of the major themes that comes out of this. Certainly to me, looking at the document, there's a lot more to that, as we both know, in terms of identifying patients, getting them diagnosed quickly, getting them through our pathways in our hospitals quickly. But at least this does Give us support for when we, when we make arguments for resources to, to do this. I think that is a really important key, key takeaway from, from this in terms of the management of Crohn's disease.
[00:23:44] Speaker B: No, I agree. And to be honest, that felt that was the priority at the time. Perhaps now it feels obvious, but it was not obvious back then.
And it's important to remember what was the previous state of, you know, status quo and what were the statements and recommendations before and how we have moved on. And I definitely expect the next iteration will be, you know, even more strong on those recommendations and hopefully we'll have the data to support statements on sequencing as well.
[00:24:15] Speaker A: Yeah, it's important to remember that the original Top dawn study was published in 2007, I think. So we perhaps need to get a little bit more agile about how we change our clinical practice and how we bring really important research into our everyday clinical practices is certainly a reflection that I have about some of these moves. I've been around long enough to have experienced that. I think another key thing which I'd like to highlight is when do we expect patients to respond to treatment as well, and making sure that we are doing that objectively, making sure that our pathways reflect these guidelines so that patients aren't continuing on a drug which is not meeting the targets. Patients are still having significant symptoms and we've both seen this huge growth in different treatment options for our patients. We maybe don't have the evidence to tell us which drug to use next in a particular given clinical situation. At the moment, I think is a fair thing. But as you say, hopefully the next set of guidelines, that evidence base will have grown and become much more robust to support us in those decisions. So I'd like to say thank you very much to polychronists for taking us through the journey of the guidelines.
I hope that this has been interesting for you listening to it, to the tour, and I hope that you've got things that you can take away into your everyday clinical practice to help deliver the best care for your patients.
So thank you very much.
[00:25:51] Speaker B: Thank you, Frederick.
