00:00:00: Hello, everyone.

00:00:00: Welcome to this episode of the UG podcast.

00:00:04: I'm Pradeep Munderi.

00:00:05: I'm a Gastronautologist from the UK and I'm one of the co-hosts for the UG podcast.

00:00:10: This is not the usual episode.

00:00:12: Here we are covering the highlights and the very best of IBD.

00:00:17: during the recently concluded UEG week in Berlin, which is definitely my favorite international conference.

00:00:25: I'm sure it is for all of you.

00:00:27: Those of you who are there and some of you who are not there, IBD once again seem to dominate.

00:00:32: this year's UEG, not just with the scientific program, but also with massive industry stands by the mere physical presence.

00:00:41: As we move further away from the world of thiopurines and anti-TNFs, which seem to be certainly my favorite drugs in IBD, to a totally new world of IBD therapy, we seem to be flooded with limitless choice.

00:00:58: Now, whilst choice is important and one would think that more choices will make decisions easier, But having a choice overload is making us much harder for either healthcare professionals to make decisions on treatment.

00:01:13: And more importantly, it's even more confusing if we allow our patients to make choice on these drugs.

00:01:19: I think this is more important as most of the advanced IBD therapy sits similar in terms of efficacy.

00:01:25: In the last couple of podcasts that I did on this topic, Best of IBD with Tim Rain and Aris Totan, Couple of drugs seems to stand out in the last two years.

00:01:35: I guess what we want now is probably not new drugs, but we want drugs that stand out from the rest of the lot, or maybe some sort of advancement in the targeted treatment with either a molecular or genetic or phenotypic markers that would aid in targeted treatment to improve efficacy.

00:01:56: During the four days at Berlin, there was some exciting new science was presented, and I was gutted that I couldn't attend many of those, but we have our very special guest today to debrief us on the very best of IBD from the GUEG Week.

00:02:11: I'd like to welcome Dr.

00:02:12: Claude de Belkog, who is a gastroenterologist.

00:02:17: and IBD specialist at arts and the Royal London Hospital.

00:02:20: Bell was also the UEG Education Committee e-learning team and is a faculty at the UEG Summer School and is one of the authors of

00:02:30: the

00:02:31: recently published British Society guidelines on IBD.

00:02:35: Welcome to UEG Podcast, Bell.

00:02:37: Thank you very much, Fredy.

00:02:39: It's really great, as always, to be a part of anything UEG related.

00:02:43: It's very nice to be here today to talk about some of the IBD highlights from what was indeed another strong UAG week.

00:02:51: I'm not sure how much easier I will make it for you or other listeners with regards to treatment choice or other decisions, but certainly lots of interesting data to discuss.

00:03:01: Lovely.

00:03:01: So, well, let's start with the obvious, probably the most groundbreaking science that was published.

00:03:08: And why do you think that's important?

00:03:11: Yeah, I think one of the most groundbreaking studies presented in the plenary opening session was presented by Meta Julesgaard.

00:03:18: It looked at pregnancy and infant outcomes following the use of Jack inhibitors in pregnant women with IBD.

00:03:25: And this really stood out because Jack inhibitors are considered unsafe in pregnancy.

00:03:31: That's due to their ability to cross the placenta from early pregnancy and that raises any concern.

00:03:38: But that's based mainly on animal... There are no data in humans.

00:03:42: And this was a real-world study from twenty-two centers contributing patients across fifteen countries.

00:03:49: So they had fifty-five pregnancies.

00:03:51: Women exposed to all three Jack inhibitors with TOVA, UPA and Phil Gottenhipp.

00:03:56: And importantly, this was not only early in pregnancy.

00:03:59: Thirty-nine women were treated with Jack inhibitors throughout the whole pregnancy.

00:04:05: And the results were surprisingly reassuring in that maternal complications were low.

00:04:09: There were no genital abnormalities.

00:04:12: Very development was normal.

00:04:14: Vaccine responses among the neonatals normal.

00:04:18: And so an important conclusion from the authors was that, okay, of course, it should not be used regularly.

00:04:24: It should very much be reserved for situations where there are no other viable treatment options.

00:04:29: And if it is used, it should definitely be with caution through very shared cautious decision making.

00:04:36: But it does finally give us some real world insights to inform those very difficult decisions that some women with IBD face.

00:04:44: So Bill, how would this knowledge help you with your current practice?

00:04:47: Or how would you change what you do currently?

00:04:51: Yeah, so I don't think it changes our standard guidance that we say it's not a drug for pregnancy.

00:04:56: We will stop the jack inhibitors four weeks before a woman tries to conceive.

00:05:01: We inform women that this is not a drug for in pregnancy.

00:05:05: However, there will be a small, very small subset of women that are very sick and for whom a jack inhibitors is the only drug and they may choose to use it and continue it.

00:05:16: And if they ask me what is the data, I now have something to discuss with them.

00:05:21: Okay, that's great.

00:05:22: Thanks, Bell.

00:05:23: Now,

00:05:24: was there something in Berlin that sort of surprised you during the UG Week, which kind of goes against the popular belief so far that we have on IBD?

00:05:33: I guess this is probably one of them, but maybe there's something else.

00:05:36: This was one of them.

00:05:37: Yeah.

00:05:38: Yeah.

00:05:38: So I think another study to highlight would be the Cure Study, which was presented by the JetAid group.

00:05:44: Maybe it's not entirely unexpected, but we certainly probably had hoped for different results.

00:05:51: So we recently had a profile study that showed that the top-down approach in early Crohn's can really dramatically improve outcomes.

00:06:00: And this study then took it a step further and asked, could we actually cure Crohn's disease?

00:06:04: Meaning they studied patients with very early Crohn's disease.

00:06:08: They were treated with Adelimumab.

00:06:10: And then when they reached deep remission, Adelimumab was stopped to see if the patients then remained flair-free.

00:06:17: So, i.e.

00:06:18: if they could manage their Crohn's after that without Adelimab.

00:06:22: And

00:06:23: unfortunately, the answer was no.

00:06:25: So stopping therapy was not successful for these patients.

00:06:29: So we are not yet at a point where we can have durable remission of treatment for patients with Crohn's disease.

00:06:37: Okay, so let me summarize that.

00:06:38: These are Crohn's patients, new diagnosis.

00:06:42: They were treated with deep remission and the drug was stopped and that didn't lead on to sustained remission.

00:06:51: Is that correct?

00:06:52: Yeah, exactly.

00:06:52: Well, there were a couple of surprising things.

00:06:54: So after one year, only twenty-two percent of patients achieved deep remission, and this was endoscopic remission.

00:07:02: But if then Adelima was stopped, only a quarter of patients were still in remission.

00:07:08: So a second year on, only four percent of the total cohort were in deep remission.

00:07:13: OK, that's great.

00:07:14: And was there any new science that was presented?

00:07:19: and that would change our current clinical practice straight away.

00:07:22: Maybe give us confidence to help us with our current practice.

00:07:27: I think something that is quite achievable, it requires some learning maybe, but it's very achievable for everyone, is monitoring our patients with IBD differently.

00:07:36: In general, we're now slowly moving away from solely relying on endoscopy for the routine monitoring of disease activity.

00:07:44: I'm sure you know there's been a huge growing interest in intestinal ultrasound for this purpose.

00:07:49: Andoscopy, it's invasive, expensive, not very user-friendly or end-user-friendly.

00:07:55: In contrast, ultrasound is non-invasive, cheap, and patients love it.

00:08:00: And there's now a good evidence base for using ultrasound for IBD disease monitoring.

00:08:06: There was a whole session at UEG that included several studies on this.

00:08:10: So there were two studies that looked at ways that we could also assess rectal inflammation.

00:08:15: It's very easy with ultrasound to see inflammation in the whole column.

00:08:20: The rectum is not well visualized.

00:08:22: It's behind the bladder.

00:08:24: One study showed that you can use a transpirineal ultrasound technique to quite accurately assess rectal inflammation.

00:08:31: Another study showed that also just transabdominal ultrasound can do it quite well.

00:08:36: So we're probably able to do this better and better.

00:08:39: And other studies showed that you can predict with ultrasound quite early on if a patient is going to respond to filgotinib.

00:08:45: and a final study showed that in Vettelizumap, you can get in Crohn's disease, you can achieve transmural healing.

00:08:53: So it highlights an increasing role for ultrasound for us in Ayurveda monitoring.

00:08:58: I've got a question for you, though.

00:09:00: We will never stop entirely doing endoscopy.

00:09:02: You're an endoscopist.

00:09:04: And I think it was more and more therapeutic.

00:09:06: There was a study also on endoscopic stricture treatment.

00:09:10: I don't know if you saw the study.

00:09:12: So this was the best CD trial.

00:09:13: So what they did, they compared endoscopic techniques for treatment of short strictures in Crohn's disease, either using endoscopic balloon dilatation or an endoscopic stricturotomy.

00:09:25: And it showed that the endoscopic stricturotomy had less clinical recurrence of strictures.

00:09:31: So I'm just trying to think how strictotomy is done, probably using a knife and cutting the little strict choke.

00:09:36: It seems to work better for even the upper GI tract.

00:09:39: For whatever reason, I guess the balloon is a bit blind and crude, whereas strictotomy is more precise.

00:09:46: So I can imagine that it would work better compared to balloon.

00:09:51: I need to look at the study and what they did, what the technical details of that.

00:09:55: So that's a good one to highlight.

00:09:56: Thanks, Bill.

00:09:57: Yeah,

00:09:58: so this was some interim data, so I think in upcoming conferences we'll hear more about that.

00:10:03: Yeah, good.

00:10:04: Now, a lot of our centres don't have interstellar ultrasound.

00:10:07: How do we go about, I guess we need training, I'm assuming gastroenterology is the best place.

00:10:13: in taking this on rather than our radiologists for intestinal ultrasound.

00:10:17: How did it go about getting training?

00:10:19: Are you aware of anywhere where people can get trained?

00:10:23: Yeah, so IBS is an international organisation for intestinal ultrasounds.

00:10:28: They provide a framework on how to do this.

00:10:31: So they've got some teaching modules and they have some guidance on how you should be trained and competencies that people should achieve.

00:10:39: I guess they can more or less compare them with Jack.

00:10:43: offers for endoscopy.

00:10:44: So that would be a good starting point to have a look.

00:10:46: Yes, certainly it's the IBD physicians that should be doing the ultrasound.

00:10:50: Yeah, yeah.

00:10:51: As long as they're not biased, as long as their assessment is objective.

00:10:54: Of course, of course.

00:10:55: Yeah, yeah, yeah.

00:10:56: And this is again what IBIS does.

00:10:58: It offers a real structured framework for recording the findings.

00:10:59: Yeah.

00:11:03: Lovely.

00:11:03: That's great.

00:11:04: So that's the way to go.

00:11:05: I think more and more, certainly up.

00:11:07: not, at least in my centre, we don't do.

00:11:10: And I'm not too sure.

00:11:11: In the neighbouring hospitals, I'm not aware.

00:11:13: At least the centres we train.

00:11:15: So that's the way to go and more and more people vouch on this as we go along.

00:11:20: Thanks for that.

00:11:21: Is there any new knowledge that would change how we use our current existing treatments, either in the realms of safety or any long-term data that was highlighted at the meeting?

00:11:33: And

00:11:33: yeah, I think it's nice to see more data about the IL-IIIII inhibitors.

00:11:38: We now have three drugs available, recent Kizumap, myric Kizumap, and also gazelcomap.

00:11:44: And we show some data about the durability of Risenkismap in Crohn's disease from longer, open-label extension.

00:11:52: We see that Risenkip remains very effective and also remains very safe.

00:11:57: This was studied, patients having been treated with Risenkismap up to four years.

00:12:02: And then there were also extra data on Guzelcomap.

00:12:05: What do we do when patients have been on Östekinemap in order to this targets both IL-II and IL-III?

00:12:11: And they presented us the Galaxy long-term extension, and it showed that if patients had either non-responsive or loss of response to Ustic Kinamap, they could still have a good response to Guzelkamap.

00:12:23: Those are the new drugs, which I'm just starting to be aware of.

00:12:26: I'm surprised there's four-year data for these things.

00:12:28: Yeah, I know.

00:12:29: Today it takes a while, but for a nice approves it.

00:12:31: But it should be on your form very soon, I hope.

00:12:34: OK.

00:12:34: And these drugs, I know reason is the map, Guzelkamap, that's available everywhere, generally in Europe.

00:12:40: Yeah, so it's licensed for the use both in ulcerative colitis and in Crohn's disease and NICE has also approved it.

00:12:46: Okay.

00:12:46: So it should know everywhere be implemented.

00:12:49: I don't know if the home care companies in England can deliver it yet, but should be very close.

00:12:53: Excellent.

00:12:53: Okay.

00:12:54: The next one is close to me.

00:12:55: Not that I see a lot of IBD patients, but the ones I diagnosed always ask me about the etiology and deep within somehow I feel IBD is almost like a symptom of the primary disease, which is lifestyle or something or the other.

00:13:11: We don't know whether it's genetic or the environmental factors, but lifestyle, I feel it's a lifestyle disease.

00:13:18: But maybe what are your thoughts on this?

00:13:19: And was there anything that was presented?

00:13:22: Because that's so important, I think, because we seem to be coming up with so many new drugs, but we never seem to go anywhere close to finding out an etiology.

00:13:33: Yeah, you're absolutely right.

00:13:34: It's really important.

00:13:35: Environmental factors, including lifestyle and diet, play a huge role.

00:13:39: Last year, some data were presented from the... There are more and more studies that are presented that show that with diet modifications, Crohn's disease in particular can be modified.

00:13:49: There was not that much on that in this conference.

00:13:52: We do not know the single cause for IBD because there isn't one.

00:13:56: IBD is a spectrum of diseases and it's not only those environmental factors, they only then push IBD.

00:14:02: in someone that's genetically predisposed.

00:14:05: And I think the more and more we understand genetics, it allows us to understand the disease biology and maybe have further therapeutic targets.

00:14:13: So there was one study that looks at very early onset IBD because it gives you a real window for understanding IBD disease because those very young people often have a single gene defect.

00:14:25: This was a study in a family that had an epithelial barrier.

00:14:29: gene defects highlighting the role of the epithelial barrier in developing inflammatory bowel disease.

00:14:35: There was a finished study that showed that if a certain gene variant is predictive of greater need for aggressive advanced therapy, so providing potentially precision medicines or a tool of identifying patients that need more aggressive treatment.

00:14:52: And then people are also starting to do now single cell RNA sequencing studies to sort of map on the single cell RNA analysis data and then linking it with response to specific medications.

00:15:05: Because this is of course a big question for us is which drug will work and which patient.

00:15:10: They did not really have that answer yet, but it was a really elegant study.

00:15:14: It was presented by Brita Siegmund, a collaboration that is starting to build in Atlas.

00:15:18: that then provides a resource for researchers to move again towards personalized treatment plans.

00:15:24: Thanks, Bell.

00:15:25: Thanks for highlighting that.

00:15:26: The next discussion point, which I really wanted to avoid, something about highlighting any new drugs.

00:15:33: I was wondering if there are any new drugs.

00:15:36: We really didn't want to discuss this.

00:15:38: As long as they have names, we can discuss.

00:15:40: We don't want letters and numbers.

00:15:43: Was there anything exciting for the specialists like you?

00:15:48: Yeah, I can give you real

00:15:49: names.

00:15:50: OK, good.

00:15:50: And I can be very brief.

00:15:52: They've been on the horizon now for a little while, and more data on them, promising data on these drugs have been presented.

00:15:59: One is called Oberfalsimod.

00:16:00: It's a tablet that enhances the expression of a little micro RNA that then in turn reduces inflammation.

00:16:08: new mechanism of action.

00:16:10: That's obovacimod and further efficacy and safety data on this drug were presented.

00:16:15: And the second new target is TL-Ia.

00:16:19: So this is a protein that's involved in both inflammation and fibrosis.

00:16:24: And there's a new monoclonal antibody that's called Jullisokibart.

00:16:28: that shows promising data for the use of ulcerative colitis was presented on this study.

00:16:34: Yes, Oberfassimod and Julius Okibard.

00:16:37: And do they stand out at all?

00:16:39: or are they similar?

00:16:40: or are we very early to say that?

00:16:42: I think that Oberfassimod shows promising data and Julius in particular.

00:16:48: Okay, that's great.

00:16:49: Is there anything else that you wanted to highlight?

00:16:52: No, it's just as I was thinking back about the conference in preparation for talking to you today, it was just so nice to see so many European and global collaborations.

00:17:04: I think the IBD world and I think in general is very collaborative.

00:17:08: And that's really nice to see in the current climate with lots of diverse presenters.

00:17:13: So I think, yeah, this is lots of hope for the IBD community and for our patients.

00:17:18: That's great.

00:17:18: First of all, really like to thank you for taking time today on Friday afternoon to come on the podcast.

00:17:26: And thanks for attending all the talks and giving us a brief summary.

00:17:30: Thanks, everyone.

00:17:30: Hope it was fun and exciting.

00:17:34: Once again, see you next time.

00:17:35: Thank you very much.

00:17:36: It was lovely seeing you today.

00:17:37: Thank you.

00:17:38: Bye.