IBD Drive Time: Sara Horst, MD, on the Best of ACG

Drs Ray Cross and Millie Long discuss with guest Dr Sara Horst the best presentations and abstracts on inflammatory bowel disease from the American College of Gastroenterology scientific meeting held in October. 

Raymond Cross, MD, is director of the IBD Center at Mercy Medical Center in Baltimore, Maryland, and professor of medicine at the University of Maryland. Millie Long, MD, is a professor of medicine, vice chief of education, and director of the fellowship program in the Division of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill. Sara N Horst, MD, MPH, is an associate professor of medicine and assistant chief for clinical informatics in the Division of Gastroenterology, Hepatology, and Nutrition at Vanderbilt University in Nashville, Tennessee.

TRANSCRIPT

Hello everyone, I'm Raymond Cross from Mercy Medical Center and I'm here with my good friend Sara Horst from Vanderbilt University. We're going to do the best of ACG 2024 for this IBD Drive Time episode. Sara, welcome back to IBD Drive Time.

Dr Horst:

Thank you. I'm really happy to be here

Dr Cross:

And I just wanted to announce to everyone that Sara as agreed to be a guest cohost for IBD Drive Time in 2025 and we hope that Sara will be joining Millie and I for at least 4 episodes of IBD Drive Time next year. So Sara, thank you for doing that.

Dr Horst:

I'm also very excited about that, so thank you.

Dr Cross:

So just a reminder to the listeners that we are sponsored by the AIBD network and we are on Spotify and Apple Podcasts. What Sara and I thought we would do is just go over what we thought were the foremost interesting abstracts from ACG. This was not a scientific process. We decided what we wanted to talk about. I think Sara is going to present 2 abstracts and then I'm going to present 2. And Sara, if you want to go first, ladies first. Go ahead.

Dr Horst:

Awesome. Well I think the first one I wanted to talk about is actually one that was led by one of my partners at Vanderbilt. Her name is Dr. Audrey Bennett and she is an awesome doctor who takes care of patients with IBD and has also been really interested in an area that we really have little data on. So she was able to present her study on patients who are transgender with inflammatory bowel disease and who are starting gender-affirming hormone therapy. This is a really untapped area. We have really little understanding of what happens when patients start gender-affirming hormone therapy and they have inflammatory bowel disease. In reality, we don't know all that much about patients who are on hormone therapy in general, even cisgender patients, but this is a really important study. So she spearheaded a multicenter retrospective look at patients who were transgender, starting gender-affirming hormone therapy, and looked at the risk of flare.

And the risk of IBD flare was defined as new prednisone start, emergency department visit that was associated with inflammatory bowel disease, or a need for an IBD medication change. And there were 5 centers included; they were able to look at 85 patients who received gender-affirming hormone therapy, about half were trans women and half were trans men. And really tried to understand if starting this gender-affirming hormone therapy would increase the risk of flare. In looking at the year prior the risk of flare to the year after risk of flare.

In general, the overall population did not have an increased risk, which was really good to see when the group looked at univariate and multivariate analysis. Interestingly, a few things did come out. So things that didn't matter were age, whether the patient had Crohn's disease or ulcerative colitis and what type of advanced therapy they were on.

But what did matter was if the patients had inflammatory bowel disease symptoms at the start of their gender-affirming hormone therapy initiation, they were more likely to flare. And also transgender men who were initiating testosterone therapy were actually more likely to flare after this initiation. So this is really fascinating. We've never really seen this before.

This is obviously retrospective data, so we really need to look at this in a prospective manner, but I think it's really important for us to be looking at populations like this and to try to understand what happens. And I think for my practice, this is really important. I think when I talk to patients in this space, I think we would need to educate them that the best thing we can do is get their inflammatory bowel disease in the best remission or response that we can prior to hormone start and watch them really closely. This is a group that we may need to watch a little bit more closely than we would typically after they start hormone therapy. So I thought this was a great study and I'm really excited for this multicenter team to continue thinking about this population.

Dr Cross:

I think it's really timely and I have a fairly sick patient who's undergoing therapy and it crossed my mind is the therapy they're being treated with, is it contributing? And we really don't know. And I think here, thinking similar to women who are trying to conceive, is that you want your patient to be in the deepest remission possible before starting this. How deep is that? I don't think you and I would suggest that they need to heal every aphthous ulcer, but at least clinical, biologic, be in the best place possible. And then maybe if you do 2 times a year monitoring if they're stable, maybe you increase that a little bit, do the biomarker assessment a little more closely. Very practical things that we can implement in clinical practice.

Dr Horst:

Absolutely. This has also brought up some really interesting data about testosterone in general. Actually there's very small studies that show that testosterone, and this isn't in patients with inflammatory bowel disease, but if people who are starting gender-affirming hormone therapy, they actually have increased risk of pelvic pain. So again, this really is important, right? We also need to pay attention to these patients and say, Hey, you may get some more pain and because of that we need to have baseline parameters like however we're following you, fecal calprotectin or CRP, we need to know that baseline. So if you do start to get symptoms, we need to understand if this is your inflammatory bowel disease or not. So just really interesting work and I think it's helped me in my clinical practice as we continue to take care of these patients.

Dr Cross:

I was thinking as you were presenting about how we could get a definitive answer and clearly the best way to do this would be to do a prospective observational study, which is going to take years and years and years to do and many, many centers and at considerable costs. I was thinking with some of our pharma colleagues whether some of their health outcomes groups could potentially look at this. And I would think that if you have access to gender and you see a prescription for an estrogen-based therapy in a man or a testosterone in a woman, that you could then look at some kind of composite of disease relapse in those patients. And I don't know if our pharma colleagues are listening, if they have an appetite to do that, but I would imagine you could get numbers probably in the thousands perhaps doing that.

Dr Horst:

It's a great idea and I think that that's another option is to even think beyond the 5 centers that looked at this. I think the nice thing about the 5 centers when we did this is we really had detailed data. We weren't relying on just a hospitalization or something like that. We could get more data. The group tried to look at some subset analysis around fecal calprotectin and endoscopy, but we didn't have that quite uniformly enough to make a lot of conclusions. So I think that's a great idea as well.

Dr Cross:

Great. And before I have you do the second abstract, I missed a mention that my cohost, Millie Long, is joining us as well today. So Millie will say hi, and Sara, you can present your next abstract.

Dr Long:

Hi everyone, such a great topic and thanks for being here, Sara.

Dr Horst:

Yeah, absolutely. Thanks and welcome. All right, well I think this is, I'm so glad you joined because the second abstract that I thought was really interesting was an oral presentation around the RSV vaccine, which I think is really important and I think understanding and just really focusing on preventative care for our patients with inflammatory bowel disease, I'm always pushing that. So I was really excited to see this abstract. So this was an oral presentation and it was looking at a retrospective cohort study and they used the TriNet database to look at patients who were adults over the age of 60 who were diagnosed with inflammatory bowel disease. And then they looked at 2 groups, they looked at the patients who had received the RSV vaccine compared to the patients who had not received the RSV vaccine. And I thought they did a really nice job in this study because they really tried to get matching as best they could in a database.

They did a one-to-one propensity score matching for demographics, comorbidities, risk factors for pneumonia, lots of things, malignancy and IBD medications. And then looked at the risk of RSV pneumonia, acute respiratory failure, hospital inpatient admission, critical care services, all occurring 30 more or days after the vaccine was administered. So they ended up with a pretty good number. They had about 440 patients in each group and they found that the vaccinated group had a lower risk of all of these things. Lower risk of pneumonia, lower risk of acute respiratory failure, hospital admission, ICU services compared to the unvaccinated group. So I think this is super important. I use this every day in clinical practice when I'm talking to patients about how important the RSV vaccine is for them. And so I was just really pleased to see that this abstract was presented.

Dr Long:

I was going to say it's really important and I think that one of the things we need to remember is that we also need to make sure we are applying this vaccine currently in the ages that are studied and emphasized. So really it's age 60 and up that the RSV vaccine is recommended. And that's the group that I am highlighting. Remember that it's kind of the older individuals and then newborns that are at the highest risk for RSV. So that's the best group to intervene on. And we now know that those with IBD have increased complications. So I'm really targeting that group and recommending vaccination. There are no data that this will somehow exacerbate inflammatory bowel disease. That's not a concern. But I think that one thing that will be interesting is to determine over time perhaps as we study things and try to understand this better, it may be eventually that patients with IBD might need this at a younger age, but we don't know that yet. Is that correct?

Dr Horst:

As far as I know, we don't know that answer, but I think just targeting this group is so important. I mean in my clinic when I feel like sometimes I'm the first person that's asked them about it, even though they've seen their primary care, I mean primary care doctors have so much on their plate, but I think this is a real opportunity for me because I have time there in front of me, we can talk about preventative care and they've never heard of it. So it's just so important to try to remember to do this as much as you can and really getting that education out there.

Dr Cross:

And as I've gotten older and sorry, I guess maybe a little more nuanced in my discussions with patients about risk, I always emphasize when I'm talking about the risks of therapy, I emphasize there are risks of poorly controlled disease activity and there are of course tremendous risks of being on steroids. And anything we do that controls your disease activity and gets you off of steroids is going to actually probably be most certainly be a net decrease in your risk. But then I also remind them that there are common infections and we have pretty good vaccines for, and if we can give them these vaccines, we can reduce that risk even further. And this is just one more infection in our older population where that's very relevant. So I think it's super important as well, Sara. It's already changed my practice.

Dr Horst:

Absolutely. I think this is, all of these kind of data is really important because it informs the patients and this is the kind of stuff we can use to really emphasize why you need your vaccine.

Dr Cross:

All right, so that's a good segue. So we were talking about safety. And so one of the abstracts I picked is entitled Major Adverse Cardiovascular Events in patients with IBD patients taking anti TNF versus JAK inhibitors in propensity match cohort analysis. And the senior author on this was Freddy Caldera, who would be very happy, we're talking about vaccines. This was a retrospective cohort study using the TriNetX database and it was looking at adults with IBD that initiated therapy with an anti-TNF or one of the 2 approved JAK inhibitors. And as Sara mentioned for the first study that she presented, propensity score matching was used to try to make these patients as even, as similar as possible; they excluded patients who had a previous history of cardiovascular disease and their primary outcome was a major cardiovascular event that's going to be stroke MI or an episode, an ischemic limb or venous thromboembolism within a year of starting treatment.

So these observations are only for the first year after starting treatment. They had a robust sample size, 3740 patients initiating a JAK and the same number initiating an anti-TNF; patients were about 43 years old and almost 50/50 split of men and women. So very similar to what a typical IBD practice looks like.

And the main results were that 1.8% of patients treated with a JAK inhibitor had a major cardiovascular event and 1.9% of those treated with anti-TNF. And you don't have to be a statistician to know that that has ratio is going to be almost identical as almost 1. They didn't give the absolute percentages for venous thromboembolism, but my guess is that it was lower than that. But there was, again, no difference with the adjusted hazard ratio between the 2 groups. They did a subanalysis in patients that were 65 years of age or over and the rates there were 5.3% with the JAK inhibitors and 6.4% in the anti-TNF treated group. And again, that has ratio was not different. And likewise the VTE risk was not different.

They did look at some clinical outcomes and the only thing that was negative for the JAK inhibitor-treated group is they had a slightly higher risk of intestinal resection and the hazard ratio was 1.32; there was no difference in prescription of steroids between the groups. They also did subgroup analyses looking at Crohn's versus UC and the results were the same. They looked at UPA versus TOFA and again, highlighting what I said before is I don't think selectivity matters for safety and they did not see a difference between the 2. And they also looked at JAKs overall compared to just infliximab and there was no difference.

So I know that there was something similar at DDW in May that should actually, there was a reduction in risk with anti-TNFs and VEDO and so maybe not an increased risk with JAKs. And this is a slightly different analysis, but I think this is what biologists have been saying is that our patients are not like those in the ORAL surveillance study, that was a different population and this reinforces what we've been screaming and I doubt that it's going to change the FDA label and allow us to use these important drugs sooner. But I think it's important data that we can use to counsel our patients.

Dr Long:

Absolutely. I think the more studies we have of patients with IBD that don't have RA that are in this age group for the most part was who we see, the younger middle-aged folks, they really don't have significant increased cardiovascular risk. And I think Ray, you and I practice similarly and that I really don't think there's a contraindication to a JAK unless there's a woman who's saying, I want to start trying to get pregnant within the next 6 months. And so the main issue is we learned from ORAL surveillance that if you're over the age of 65, you have a history of prior cardiac disease, you had a stent or some sort of atherosclerotic disease, and you smoke, then we’ve got to think twice about a JAK, potentially. But as long as you don't have those characteristics, just like in this study, I think it shows that these are safe drugs to use and that controlling the inflammation is what's most important.

I mean there are caveats in observational data. I think one thing is we all kind of know this and so maybe we are self-selecting those patients without those cardiac risk factors to go onto the JAK. You don't know. I mean there could be some degree of selection bias. They do try to propensity score match and other things. But then again, also the most severe IBD patients to go on the JAKs. And so that would go in the other direction. So I think that overall these data are really reassuring. I mean I think that in my mind, just me, I'm going to keep practicing the way I am, but perhaps for others out there you might feel more comfortable starting a JAK, which is great. These are very effective drugs. I mean really.

Dr Horst:

Yeah, I completely agree. This is so important. Also, I completely agree with you, Millie. I sort of thought about it the same way. I thought, well, this is real-world data. So even in these older patients, we are finding the patients who are appropriate for this JAK inhibitor therapy and they aren't having increased risk of these events. So we're doing a good job. I think finding the right thing.

Dr Long:

I think so too. And I totally agree with Ray too. I don't think selectivity matters when you're pushing UPA up to 45 milligrams for induction. It has some pan-JAK effects when you look at the zoster risk, it's the same for UPA and TOFA. So I'm not sure that from a safety perspective the selectivity matters. I think from an efficacy perspective, I think UPA got the dose right and it's probably a little bit more effective in that sense. It may actually reduce some complications just by being more effective, but I don't think there's a safety difference. Is that your impression as well, Sara?

Dr Horst:

I completely agree and we need more and more of this data because I do think there is hesitancy, understandably, when you're a busy gastroenterologist and you're trying to know everything about everything and you're here about a JAK inhibitor and you've heard about the risks, you could be hesitant to use it. But this is so reassuring that a medium- or low-risk younger patient, for sure, and probably even in that older patient with minimal risk factors, that you're doing right by starting the drug the patient needs. And I was talking to someone a month ago and they were still a little bit hesitant to use these, and so I really think these are the kind of data and we need to keep talking about this and help clinicians understand how important these are because of their efficacy. It's just been amazing I think as a gastroenterologist over the past few years to be able to use JAK inhibitors, especially in ulcerative colitis. I mean it's just been a game changer. So we just want to make sure this is getting to the patients that need it.

Dr Cross:

I want to throw in 2 points. Millie brought up a patient with perhaps known cardiovascular disease who's actively smoking and people's reticence to use a JAK. And I'm not suggesting that's a perfect JAK patient, but let's say you did try a novel biologic and maybe an anti-TNF as well in that patient. And I would challenge a community provider or any provider to say, well, giving that patient prednisone is not helping any of those doctors.

They're poorly controlled Crohn's or colitis. It's driving up their inflammatory cytokines and maybe contributing to plaque rupture. So even in that setting a JAK can be very, very appropriate if surgery is not an easy option for that. And by the way, it's not a great surgical patient either that Millie was describing. So that's my caveat.

And the other thing I feel like I can hear Adam Faye and Bharati Kochar in my ear, particularly, as I'll be 54 in January, is that age is not chronologic anymore, age is physiologic. So there are 68-year-old pickle ballers that are making me run all over the court and then there are 56-year-olds that are incredibly frail and brittle. So that chronologic age as much as we can until we have a frailty index that's easy to use. I suspect that we'll eventually just not look at the number and look at some other indices index.

Dr Long:

I completely agree with you, Ray, and yes, I have patients who've had a history of coronary disease who are older who are on JAKs. You just have to have an informed discussion with them, think about their individual risk scenarios. They're not good surgical candidates and they're perfect on the jak. So I have a 90-year-old on a JAK, so you just have to understand the scenario and discuss the risks and the benefits, but I think they're very effective drugs.

Dr Cross:

Alright, so I'm going to take us out of orbit here for the last study. So this is the GRAVITI study, which is looking at the efficacy and safety of guselkumab induction therapy in patients with moderate to severe Crohn's. This was presented by Remo Panaccione as the first author and I mentioned it's looking at guselkumab subcutaneous induction. So to be clear, with the anti-p40s and P19 inhibitors, they're getting IV induction, either 1 or 3 doses. This whole class is IV induction, subq maintenance. I'm sure that Sara and Millie, we could commiserate over a cocktail about how frustrating that dual authorization process is and what a burden it puts on our office. So if we could actually give a drug subq straight through, it would be very, very nice for us and our office staff. So that's what they evaluated in this study. There were 347 patients randomized one-to-one to either guselkumab induction, which was 400 milligrams monthly times 3, or placebo.

This was a treat-straight-through design. So the first 2 randomization groups, they all got the same guselkumab induction, but then they were randomized to either 200 subq Q4 or 100 subq Q8 or placebo maintenance. They had a rescue at timeframe was week 16 so the placebo patients could go on to guselkumab. Whereas the guselkumab patients received a sham rescue. The coprimary endpoint was clinical remission and endoscopic response at week 12. At baseline, these patients were a little younger than the first I presented— about 38 years old. They had Crohn's for about 8 years and about half of the patients were bioexposed and about a quarter had been on 2 or more therapies before. So fairly a mix of a sick and less sick population. And these are the primary endpoint numbers. So the clinical remission rate at week 12 for the guselkumab groups, remember they all got the same induction dose, was 56% versus 21% for placebo.

And now this is what's really interesting, so pay attention to this, the bioexposed group, it was 60%, the bionaive group, it was 50%. That's unheard of, that the exposed population actually did better than naive population. I think the deltas were similar, but that's very impressive. And for the endoscopic numbers it was endoscopic response is going to be a 50% or more improvement in the SES-CD. That was in 41% for the guselkumab group, 21% of placebo. Now here it was flipped where the naive population, it was nearly 50% and it was only about a third for the bioexposed. And I don't think we're surprised by that, that maybe endoscopically and it would lag behind. Looking at a couple other endpoints, clinical response, 74% versus 33%, and again, it was actually it was almost 80% in the exposed population. Now looking at 6 months, the remission rates ranged from 58% to 61% versus 21% in placebo.

Week 48, this is in treat straight through, it was about two-thirds of patients versus 17% of placebo; endoscopic responses were a little lower, around 50% versus only 70%. And again, the bioexposed group for endoscopic response was actually, I'm sorry, here for the guselkumab maintenance, it looked like actually the Q4 group did a little better in the bioexposed group than the every 8 week. It was about 55% versus 36%. Looking at safety, no real safety signal here. The Q4 week group was 1.7% risk of serious infection versus almost 1% in the 8-week dose. There was 1 basal cell cancer, there were 2 opportunistic infections, esophageal candidiasis, one of those was a placebo-treated patient and there were no episodes of drug induced hepatitis in this study. So I had like to get your thoughts, but I was really blown away by this data and a treat straight through design. I think this has the potential to be a game changer in our IBD treatment.

Dr Horst:

I completely agree. I'm so excited to be able to get to something where hopefully the initiation is we're not having to do an approval for a medical insurance and an approval for a pharmacy benefits, be able to do this one time and have the patient be able to have an induction with subq. I think it's a game changer. Frankly, I am really excited to be able to get access to this for our patients. I mean obviously also the efficacy is extremely impressive. And I mean this class, this anti-IL 23 class, I've been able to use quite a bit in my patients with Crohn's disease who frequently have failed one anti-TNF or multiple biologics. And in the real-world setting, I've been really impressed with this efficacy as well with risankizumab. So the ability to do this is just, I'm really excited for our patients.

Dr Long:

No, I agree. I think in someone who practices, I mean our referral population is about a 5-state radius and so this really makes things a lot easier. It's always very hard to, when you have patients in rural areas, to operationalize IV and here we see data that, I mean granted you don't have necessarily head to head, but the numbers are the same if not better than the IV. So I think we can feel pretty comfortable with the subq load and continued subq maintenance. And so this does make you wonder who's the patient that gets IV. I mean it might be that we pretty much just use the subq. Hopefully there'll be some subgroup analyses that'll tell us that maybe in a patient with a higher BMI or maybe there'll be some groups, maybe if they've previously failed a JAK inhibitor as well as a biologic, we need to try to understand who really does need the IV. But otherwise I think most of my practice will be this subq just for all those reasons, ease of access, patient accessibility, efficacy, and really just the fact that it seems to work quite well and work just as well as the IV if you look at the numbers.

Dr Cross:

Alright, so we usually finish with a fun question, but Millie and Sara—obviously Millie's on all the time and Sara's been on before. So instead of the fun question I'm going to ask Millie first, do you have anything fun planned for this holiday season? I'll go to Sara and then I'll finish.

Dr Long:

I don't have anything fun for the holiday season, but we are doing a trip to New Zealand this spring that I'm very excited about. I've never been to Australia or New Zealand area, so that'll be fun.

Dr Cross:

Millie expanded it beyond the holiday season

Dr Long:

Because I have nothing. I'm working, I'm going to be here at the hospital so that's not so fun. So hopefully you guys are doing something fun.

Dr Horst:

Well that sounds extremely amazing. I'm actually really excited. I have 2 younger sisters and they have collectively 5 children ages 6 and under and they're all coming to my house and staying with me right around the New Year's holiday. So I get to have a lot of little children and fun people in my house.

Dr Cross:

How long will that be, Sara?

Dr Horst:

It's about 4 days.

Dr Long:

So Sara, it's either going to be really fun or really not fun.

Dr Cross:

It may be one day too long, but that sounds really fun.

Dr Horst:

It's going to be amazing. And then they all get to leave after 4 days.

Dr Cross:

Millie and Sara, now I'm 50% Italian and so I'm excited to go home and see my mom and sister and do our traditional Italian 7 fishes dinner, which will be either the first or the second full weekend in January. So that's my fun trip for January.

Dr Long:

That sounds amazing.

Dr Cross:

I'll gain 6 pounds but it'll be good. Alright Sara, thanks for doing this; Millie, thanks for joining. And Sara, we're going to have you back at least 4times in 2025. So looking forward.

Dr Long:

Toast 2025! Thanks all.

Dr Cross:

Bye guys.

Dr Long:

Bye.