IBD Drive Time: Best of DDW, Part 1

In the first episode of this two-part series, Dr Raymond Cross of Mercy Medical Center reviews his top picks for the best abstracts on inflammatory bowel disease presented at this year's Digestive Disease Week. Be sure to watch for part 2, coming soon, when cohost Dr Millie Long from the University of North Carolina discusses her choices.

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.

TRANSCRIPT: 

Hi, this is Millie Long from University of North Carolina as one of your cohosts for IBD Drive Time. I am thrilled to do a collaborative interview with my cohost Ray Cross from Mercy in Maryland.

And Ray and I thought what we would do is just give a highlight of some interesting abstracts that were presented recently at Digestive Disease Week in May of 2024. Just as a reminder, this podcast is brought to you by the AIBD Network. And with that, let's get going.

So, Ray, we had some great IBD research presented at DDW. And I know you've selected a few kind of real-world studies that will help us in terms of how we take care of our patients. The first had to do with acute severe ulcerative colitis.

Dr Cross: Great. Thanks, Millie. This is my first IBD Drive Time as a member of the Faculty of Mercy Medical Center. So this is my inaugural drive time for my new job. So maybe we'll do one and then talk about that and then do 2 in tandem and talk about that. Is that okay?

Dr Long: That sounds good.

Dr Cross: So I found this study very interesting. It's number 662, Outcome of Acute Severe Ulcerative Colitis in Elderly Patients, a Multicenter Experience. And this is from Mayo Jacksonville and Mayo Rochester. It was a retrospective study, but as you said, real world. They included 120 patients that were 65 years of age or older that had acute severe ulcerative colitis. This is a pretty sick cohort.

So 84% of them had a Mayo endoscopic score of 3. Their median comorbidity score was 4, so lots of comorbid conditions in these patients as well. Just over 20% had C. diff during the index admission and about 6% had CMV infection, which I think that number is a little higher than what we would see normally. They didn't specify whether this was PCR or this was immunohistochemistry, but 6% had CMV.

Of the outcomes that are important here about a third of the cohort had a colectomy either during the admission or within 30 days post discharge and about 10% of patients were readmitted. Prior steroid use, prior anti-TNF use, and infliximab salvage therapy during that admission which was used in about 20% of the patients, were predictors of colectomy, which is not surprising, I don't think.

But what really struck me about this abstract was that 15% of these patients died.mAnd I know that with mortality, we normally think that it's in the low single digits, so 15% was just striking to me, and that's why I wanted to discuss this with you.

Dr Long: Yeah, absolutely. Well, you know, with that high CMV rate, it makes me think there were a lot of steroids. When I see CMV, it's because someone's been on steroids, and it's like this terrible reactivation. Maybe with elderly patients, sometimes we wait too long for the definitive therapy, whether that's medical or surgical. Did they have any data surrounding that? They were really sick when they came in with the Mayo endoscopy score of 3, but I'm wondering, you know, if they had data on how long they'd have been on steroids, you know, and some of these other factors.

Dr Cross: Not in the abstract and the abstract reported the percentage of patients that had been on prior treatments. I think it was around. I think it was under 50% were on steroids at the time of admission. Of course, everyone got steroids, 99% got steroids during the admission. But I suspect that you're obviously delays in initiating advanced therapy. We know that happens in older patients. And so that could be part of this.

Maybe the comorbidities is a big factor. This was just a really group of patients that had lots of other medical problems as well. For me, I'm trying to think how this would change my practice. I already recognize that these patients are our sickest patients that we treat— one of the sickest subgroups of patients we treat. I don't use steroids very long for these patients. Three days typically is my cap. And then I move on to something else, whether that some be infliximab, a JAK inhibitor or surgery. I do think it highlights the need to not delay moving from steroids to an advanced therapy and then surgery is rescue.

It also brings up this whole idea of prehabilitation. If you can, if you have time, right? And, you know, enteral nutrition and, you know, potentially physical therapy, et cetera, et cetera. But in these patients that are so sick, you don't have a lot of time to do that. Certainly you can start enteral supplements the minute they're admitted. You can treat their severe anemia with intravenous iron, obviously DVT prophylaxis.

That also brings up a point of, is this a group of patients that are after discharge, should they be offered extended DVT prophylaxis because if I remember right from the presentation a number of these deaths were due to thromboembolic phenomena and they weren't all in the hospital. So is this a group that should get extended DVT prophylaxis? Now how you would get that practically and get it paid for, I don't know, so we'll need to see this full paper and dissect it a little more.

Dr Long: No, but I think your take on points are exactly right. This is not the group where you kind of keep them on the IV steroids longer and hope they're going to turn around. No, you need to make a decision, whether that's surgical or medical. And the risks of that advanced therapy are less than the risks of extending the duration of the disease, obviously extending the corticosteroids and the risks therein. A lot of this clotting, these are deconditioned patients, if they've sat in the hospital a long time, they're already elderlt, I mean, really we've got to act.

So I think that's a great take-home point. And I agree with your thoughts on, you know, kind of even thinking about post-discharge anticoagulation, especially in individuals with, you know, low mobility, that it's a huge, huge risk for some of these older individuals. So great points and I think some teaching points for our listeners.

Dr Cross: And you mentioned steroids, Millie. And I just wanted to, with JAK inhibitors and anti-TNFs with the fast onset of action, I've really changed my practice now where I think if I'm thinking about steroids, I just go to infliximab or I go to a JAK and try to prevent the tapering course of steroids. And we're just speculating that steroids are part of the issue here with the frailty and thromboembolic potential linked to mortality, but is that how you're thinking about the things?

Dr Long: That is exactly how I'm practicing. Interestingly, when you look, even some work that we've done in terms of looking at risks associated with medications for the infectious risks, steroids are the worst. And unfortunately, what happens is, is in many instances, people think of them as benign, and they're just on and off of steroids, which are actually the worst thing we could do in these scenarios. So, like you, I think about our faster onset of action drugs, the anti-TNF, and the JAK inhibitor, and I try to use those to be steroid-sparing.

I think that, you know, certainly in older individuals who have cardiovascular disease, there are some considerations for JAKs if they have underlying cardiovascular disease than our smokers, but otherwise, the JAKs are actually, you know, something that I do use in this population. I want to emphasize that in people without significant cardiovascular risk factors like that, you know, the JAK would be a preferable option to the, you know, extended corticosteroid course. So just make sure we're offering our patients the options that may actually be more effective for them.

Dr Cross: That's a perfect segue to the next 2 abstracts because we're going to talk about JAK inhibitors. So oral presentation 718 was entitled, Biologics and JAK Inhibitors Decreased Major Cardiovascular Events and IBD Patients, Data from a Large National Cohort. Is it the mechanism of the drug or control of the disease? And the lead authors here were from Medical College of Wisconsin. And for full disclosure, I was one of the authors of this abstract.

This was a retrospective study using the Chinetics database from 2015 to 2023. And they looked at the outcomes of myocardial infarction, ischemic stroke, stenting or cabg, so revascularization, and then all 3 of those as a composite.

And they compared groups that were on conventional therapies, so steroids, 5-ASAs, immunomodulators, anti-TNFs, anti-integrins, anti-IL-12/23s, and JAKs. They had too few S1P receptor modulator patients to really do any meaningful analysis.

They had nearly 114,000 patients in this database, and what they found is that basically all classes of advanced therapy were associated with decreased rates of those events, including JAK inhibitors. But when you adjusted for confounding factors, they found that anti-TNFs decreased the composite outcome of major cardiovascular events by 22% and revascularization by 44%, and anti-integrins decreased the risk of major cardiovascular events to composite by 24%. So the others weren't statistically significant, meaning JAK inhibitors weren't associated with increased risk. So it really makes you wonder if the ORAL surveillance study, what we were seeing there was not an increased risk associated with JAKs, but a decreased risk associated with anti-TNF use that artificially made it looked like the JAKs were potentially leading the cardiovascular outcomes.

So I thought that was this to me was really reassuring. They also looked at another abstract was 720 which was done from Cleveland Clinic and it was entitled “Oral small molecules are not associated with increased cancer rates in IBD patients,” also using Chinetics.

What they did, they created a propensity score-matched cohort to look at oral small molecules versus other therapies and looking at the outcome of cancer. What they found is there was no increased risk of cancer 1 year, 2 years, 3 years or 4 years after a JAK inhibitor was started. They did a subgroup analysis and those who were 50 years of age or older also saw no increased risk. And then they compared oral small molecules with biologics as a comparator, and there was no increased risk. And they also did another analysis just looking at JAKs without the S1Ps. And again, there was no increased risk. So I thought these two were very reassuring, really for listeners to get, to feel reassured about the safety of JAK inhibitors.

Dr Long; No, I think these are great data. And that's frankly what I've been seeing in my practice too. I have not been seeing, you know, increased risks associated with these therapies and they're highly effective and we often need to use them. And in that scenario, we should feel comfortable using them. I'd be interested to hear in your practice, Ray. In my practice, I am using JAKs across the age spectrum. The caveat is, is that if someone is over the age of 65, have a history of atherosclerotic cardiovascular disease and they've had stents before, and they're a smoker, those are the things that they're all there, then that is someone who I would probably not put on a JAK based on some of the post hoc data from ORAL surveillance.

But unless you meet those criteria—and you've just showed us more broadly that the safety is comparable to our other advanced therapies and biologic therapies—I think we should feel more comfortable of counseling patients and using these therapies because if we can control the inflammation, we're actually going to reduce many risks over the long term.

Dr Cross: Yeah, I think that patient you described, Millie, clearly if infliximab was available and that patient had not seen it, I think that would be ideal or another anti-TNF, particularly for talking about Crohn's disease, right? But for UC almost exclusively, I think you and I used infliximab, but for Crohn's, it's more broad with anti-TNFs.

Now, what I would say is, if that patient had severe inflammation, severe symptoms, and had seen an anti-TNF before, I still think you could consider a JAK because the reality is you're going to have to use a steroid bridge to something else and the steroids are going to be worse than the JAK. Now, the question there would be, if you did use a JAK in that hypothetical patient…

Dr Long: …would you put them on anticoagulation?

Dr Cross: Well, right, would you do that? The other question is, would you use JAK inhibitor pulse therapy to induce remission and bridge to another advanced therapy with a slower onset of action or would you keep them on a JAK but would this be the patient you try to do the lower dose maintenance with a JAK instead of the high dose?

Dr Long: Yeah I think all of those would be options, frankly, in my practice. Using it plus anticoagulation, using it as a bridge to a different agent or using it and then trying to drop the dose. I think the intricacies of which one of those I would do would be with shared decision-making with the patient and understanding where their risk thresholds lie and understanding in many instances that the option is often surgery, which can also have significant cardiovascular risks in someone who has underlying cardiovascular disease.

So I don't think any of those are off the table.

Dr Cross: I agree. And clearly the surgeons—although I do think our colorectal surgeons are really, I think they're heroes because they tackle these really difficult IBD cases—but even they aren't going to be excited to operate on an older person with cardiovascular disease who's actively smoking, right? If they have to, they will, but they're probably not going to be excited about that either.

And postoperative morbidity is going to be significant. I just showed you data from Mayo on the severe UC population, and that's a pretty high mortality. So I would think that if you had to use a JAK, the outcomes are going to probably be better.

Dr Long: I know I would agree, and especially if you can get them to quit smoking, too. There's more than one reason for that, right?

Dr Cross: Right. So those are my three, Millie.