IBD Drive Time: Adam Faye, MD, on Managing IBD in Special Populations

Drs Adam Faye and Raymond Cross discuss the particular issues to consider when treating patients who are older, obese, or frail, as well as patients with a history of or current cancer or heart disease. 

Raymond Cross, MD, is Medical Director, The Center for Inflammatory Bowel and Colorectal Diseases​, The Melissa L. Posner Institute for Digestive Health and Liver Disease at Mercy Medical Center​, in Baltimore, Maryland​. Adam S. Faye, MD, is an assistant professor in the Departments of Medicine and Population Health at NYU Grossman School of Medicine, part of NYU Langone Health System.

IBD Management in Patients With Comorbidities and Frailty

• IBD with cardiovascular disease requires individualized prescribing. Drs Faye and Cross advise caution with JAK inhibitors and avoiding anti-TNF therapy in decompensated heart failure when alternatives exist.
• IBD with prior cancer requires consideration of cancer type, stage, and oncology input. Drs Faye and Cross favor switching from thiopurines after nonmelanoma skin cancer and advising patients to have annual dermatologic examinations.
• IBD in older adults requires assessing frailty beyond chronological age. The physicians emphasized prompt, effective, steroid-sparing treatment when inflammation drives frailty; obesity may also influence anti-TNF dosing and route selection.

Dr Cross:

Welcome, everyone, to IBD Drive Time. I'm Raymond Cross from Mercy Medical Center in Baltimore, and I'm happy to have my friend, Adam Faye from NYU here to talk about managing IBD in special populations. Adam, welcome to IBD Drive Time.

Dr Faye:

Thanks so much for having me, Ray and everyone. It's very exciting to be on.

Dr Cross:

So just as a preface, and I'm probably breaking some kind of rule here, but Adam wrote a very nice review article, which is going to be out in the red journal here very soon, about this exact topic. And as I was reviewing it, I thought this would be a great topic. So we're going to jump right in and we're going to talk about a couple different patient types.

So Adam, the first, regardless of age perhaps is going to be treating a patient with IBD that has significant cardiovascular disease or other significant comorbid condition. How does this impact your risk stratification you're prescribing for that patient?

Dr Faye:

Yeah, I mean it's a great question and we need a lot more data specifically for these subpopulations and special populations because I think we have a lot of comforting data in the field and it looks good across the entire IBD patient population. But you're right, what if we then really refine it down to those who may have a higher baseline risk? Do we start to see then that certain medications or decisions actually tend to influence outcomes in that patient population?

I think with cardiovascular disease, I mean I think we have a lot of different therapeutic options that don't really influence the cardiac comorbidities, but there are a couple that do. So with anti-TNF therapy, always something I'm thinking if they have severe heart failure, that's something I'm not considering really using or on a very special case-by-case scenario. I think the one that obviously comes up a lot is with JAK inhibitors and we talk a lot about cardiovascular disease, MACE and VTE apparently with that prior ORAL surveillance data.

The data overall, again, in the large IBD patient population has looked okay. In claims data, it's looked good. And even within some of that data, looking at these special high-risk populations where they've had cardiac comorbidities, use of medications like upadacitinib, really the absolute risk, like how often are we actually seeing these events, don't tend to happen quite often. So I think we can feel comfortable using these medications, but again, have to think about individual risk stratification. Someone who has well-controlled hypertension on a medication is probably someone very different than who had 3-vessel disease, needed a CABG, maybe had a stent or an in-stent thrombosis, and may be very different than someone who also has, yeah, they have coronary plaques and maybe even needed a stent, but now they're protected on some either dual antiplatelet or some antiplatelet and a statin and their risk of having an adverse or cardiac event is actually almost down to baseline risk.

Can we use a JAK inhibitor and feel comfortable about it in that patient population? I think we do need more data there. I do feel comfortable using it and often do there. I do think we still need to be thinking about those baseline risks, but what we're seeing is not this concern that we're worried about from that ORAL surveillance population.

And then the last one I tend to think about is S1Ps, but that's more with conduction abnormalities. But I'll pause there because I think you wanted to add something.

Dr Cross:

No, that's great. So for the listeners that maybe aren't familiar with ORAL surveillance, I think the rationale that the FDA mandated the study with tofacitinib was due to the lipid abnormalities that occur with JAK inhibitors. And actually the LDL and the HDL tend to go up at the same ratio. So most patients actually have no change in their risk. But because of that, they did a study of low-dose tofa, high-dose tofa, plus methotrexate in each group versus anti-TNF therapy, sub-q anti-TNF with methotrexate, and those that were 50 and over with risk factors for cardiovascular disease with rheumatoid arthritis. So different population. And the absolute increased risk in cardiovascular events was about 1%. And in that study, it was only those that had baseline cardiovascular disease that were really driving that risk. But even in that population, you would have to treat a hundred patients with a drug to have one more event.

So it wasn't a big risk exactly as you said.

Dr Faye:

I agree.

Dr Cross:

If active IBD is a nontraditional risk factor for cardiovascular events, is that a higher risk group that we should be starting therapies earlier in actually?

Dr Faye:

Yeah, I do think so. The flip side of the coin, which I did want to mention, is we talk a lot and I think we focus a lot about, rightfully so, safety of therapies. But we also have to understand that using a therapy that maybe has lower efficacy or keeping disease activity ongoing, inflammation at baseline, or using corticosteroids, the flip side of that coin also significantly increases your cardiovascular risk. If you look at any of the prior data from either Denmark or Sweden or others, you can see during these periods of inflammation, risk of cardiovascular events goes incredibly high. So medications that can do a good job and efficacious job of reducing that risk actually balances that out. So it's incredibly important that we should think, particularly in those with baseline cardiac comorbidities and they have a high inflammatory burden, using something that's going to work quickly and efficaciously is probably going to lower their risk of long-term outcomes from IBD, but also cardiovascular and other comorbidities much better.

And so this recent paper that we looked at was this early colectomy and ulcerative colitis. So what's the best way to get rid of inflammation, the most extreme way? Well, what if you just take it out? And if you do that early on and then you model these patients over time, you think, well, there's less ongoing inflammation. They're going to need less steroids over time. Maybe that'll reduce their cardiovascular comorbidities, diabetes, things like that that develop. And we need more data there. Obviously we need larger patient populations, but there does seem to be some separation over time. Again, giving credence to this idea that really controlling the disease early and effectively is the best way to reduce later outcomes, including the development of multimorbidity and cardiovascular disease.

Dr Cross:

So to summarize, and I totally agree, is that just remember that for any of your patients, poorly controlled disease and ongoing steroid use is usually going to be riskier than any therapy we can give them. Having said that, in a patient with known cardiovascular disease, we want to use JAK inhibitors with caution. It doesn't mean they're contraindicated. And certainly in people with decompensated heart failure, we're trying to avoid anti-TNF use unless that's really all we have and that's going to be in consultation with cardiology.

Dr Faye:

Yeah, and I completely agree. And I even think within that bucket, we need more data. There's that cardiac comorbidities, if someone's got unstable angina, yeah, that's probably not someone…maybe we can choose another agent that's more efficacious. And someone with a stent, but they're doing well on an antiplatelet and a statin, maybe that's someone with a cardiologist that their risk is actually pretty low of having a cardiovascular event and you can. So I definitely agree. We need some more stratification within there. Obviously, if there are other agents you think will be efficacious, then you don't have to do a JAK, but I wouldn't hold it if you think this is the right therapy for that patient, unless you think that they're at incredibly high risk for a heart attack or stroke.

Dr Cross:

And before I go to the next question, I just want to remind the listeners that IBD Drive Time is the official podcast of the AIBD Network and that we are available on Apple Podcasts and Spotify.

So let's shift to cancer, Adam. So you're seeing a patient regardless of age, although they tend to be middle age and older in general with a recent cancer diagnosis, so within 5 years. How does that influence your prescribing?

Dr Faye:

Yeah, I mean the good and bad is that it doesn't so much, which I think is the good. We really need to think about it in terms of what is the risk of recurrence. And from the data, again, these are all populations where we need more and more data, but the data so far really suggests that's the one thing that will tell you whether this person is at risk of recurrence is really the type of cancer they had and the stage of cancer. When you look at all the cohort studies, whether it was the UNIDA registry in Spain or the Sesame cohort or some multicenter cohorts that colleagues here have done, Dr. Axelrod and Dr. Homer, what it looks like is whether using anti-TNF or other therapies, the risk of recurrence really tends to be independent of that and more dependent on the type of cancer in the stage.

That being said, if you do think that there was particularly one therapy that may be really driving that cancer, then there maybe needs to be a discussion with an oncologist. Again, if you think that there can be another IBD-related therapy that may not be related to that cancer risk, maybe worth the switch at that time, but largely it's centered around prior stage and whatever cancer that was. And if you feel an agent is indicated, you can feel comfortable using that, assuming that the cancer's in remission over the last few years.

Dr Cross:

Let's talk a little bit about skin cancer because as you get older with your patients, that's something we see all the time. Usually basal cells are significant because cosmetically they can be significant. But when we start seeing squamous cell cancers, actually, I don't know if the listeners know this, but if you have a squamous cell cancer, it actually increases your mortality. We think it's just skin cancer, but it's not. And what's your views on thiopurines or JAK inhibitors specifically for that type of cancer?

Dr Faye:

Yeah, it's a good question. I mean, I think when you have skin cancer and when you're having multiple basals or squamous cell, and especially if you're still using a thiopurine, this is a time where I would make a switch off the thiopurine. I would not continue that therapy. If someone had a basal or squamous in the last 5 years and they're in remission, if they're on a thiopurine, I still think we have probably better and safer and more effective agents now. So I would also make that switch. Anti-TNF, I think a little bit about it with melanoma. So if someone is actively being treated for melanoma and they're on an anti-TNF, if there's another agent that's not anti-TNF related, I may switch them or I'll likely switch them off the anti-TNF to that.

And I think about JAKs in that similar vein. The data on JAKs, we need a little bit more. There's been slight increased risk of lymphoma, lung cancer, nonmelanoma skin cancer. But I think if you have someone who's starting to develop these nonmelanoma skin cancers and you have another agent that you think can be similarly or equally efficacious, then yes, I do think it'd be reasonable to make a switch at that point.

Dr Cross:

Yeah, you mentioned this, I think this was from the SOM cohort, but just for the listeners, remember that stopping the thiopurine reduces the risk of subsequent skin cancer, but it doesn't go back to baseline. Correct. Your patients can still get recurrence. And I think sometimes we worry more about melanoma than the dermatologists do. I think if it's sort of a superficial cut early, they're less stressed about it. But if it's one of these deeper, more aggressive ones, then I think I agree completely with you that let's think about another medication if we have that option as opposed to anti-TNF.

Dr Faye:

Yeah, exactly. And this is why we also counsel anyone in general with inflammatory bowel disease, but particularly on an anti-TNF, should be getting yearly dermatologic skin checks, make sure that they don't see any melanomas, squamous cells, basal cells that we need to be cautious of.

Dr Cross:

So for patients with a new diagnosis of cancer, so their ongoing treatment, the old rule of thumb was that if you were getting chemotherapy, you tend to get in remission. If you weren't in remission, you would go into remission with chemotherapy. Radiation therapy and hormonal therapy, it's not protective. But now we have all these checkpoint inhibitors and other things that are being used. So it's become way more complicated. So I presume that your approach, if they're on one of the novel biologics at 12/23, at 23, or an anti-integrin, you're probably just continuing that through.

Dr Faye:

100%.

Dr Cross:

What you going to do with an anti-TNF or JAK if they're getting, let's say it's chemo, not a checkpoint inhibitor?

Dr Faye:

Yeah, I mean if it's chemotherapy and it's a fairly, it's a potent regimen, obviously, I think it would not be unreasonable to consider. So I should say first of all, I have no problem continuing it if the disease activity warrants that we continue the TNF or JAK inhibitor for whatever reason. If they're in remission and otherwise doing well from their inflammatory bowel disease standpoint and about to start chemotherapy, you could consider a switch to an IL-23, an IL-12/23 or an anti-integrin. But I've also had it the other way around, where either you have to go back to an anti-TNF or a JAK, or this is a person who's really not done well in these other therapies and for their colitis or for their Crohn's disease, they really do need an anti-TNF or a JAK therapy. And that's when it's really a discussion with the oncologist about continuing it during the time period.

There are, again, those certain cancers, if there's an active melanoma and they're going to be getting chemotherapy, these are times when I'd really want to switch off of an anti-TNF as able. Same with lymphomas and thinking about thiopurines anti-TNF, JAK inhibitors as able.

Dr Cross:

Yeah, I agree. And I think if honestly, from the data that I'm seeing, our patients are higher risk for checkpoint inhibitor colitis. And I think to me, there's no reason you would stop their therapy no matter what it is with a checkpoint inhibitor. I think you're mandated to keep going regardless. Now, I think there's the most evidence for anti-TNFs and anti-integrins, but I would probably just keep them on whatever therapy they're on to prevent checkpoint inhibitor colitis.

Dr Faye:

100%.

Dr Cross:

Yeah.

Dr Faye:

If they're getting things like pembrolizumab and other things, I would keep them on 100%. The other thing I often think about is one, there has been some data to show that folks with inflammatory bowel disease sometimes can be undertreated for their cancer or have different regimens because of worries about their colitis. So first and foremost is whatever the oncologist thinks they need for their cancer therapy, they should get, and then we can always determine the IBD-related therapy.

And then in terms of thinking about should we switch therapy, what should we do? It also helps to think about what stage and what's the overall prognosis of the cancer, the malignancy at hand. If this is someone who can be cured and go into remission and you think that the medication may have potentially played a role, obviously a switch off of that. If this is someone who it's more metastatic and keeping the disease under control will improve their quality of life for that period of time, then maybe it doesn't make sense to be switching that around and so forth.

So it also, I think, comes down to individual characteristics of the stage presentation and overall trajectory.

Dr Cross:

And so let's stick with the middle age and older. So I don't like using the word elderly anymore because I don't know what that means. We have a patient on service who is 80 who had a small bowel and anastomotic resection. She looks fantastic.

Dr Faye:

Yeah, 100%.

Dr Cross:

So I think that there's physiologic age. So what are we doing with people that are of older age and may probably more importantly that are frail?

Dr Faye:

Yes, it's a great question. So more and more data coming out, but the more we are assessing it and studying it, you're right. There's a huge gap between what we see with chronological age and your underlying physiologic or biological age. And so we can't just look at chronological age and use that as our risk stratification tool. Particularly, I'll go even farther and say physiologic age, maybe you can't even use in some instances as a risk stratification tool, if you think their physiologic age is being driven by the inflammation.

So what I mean is if you see someone, which I had recently in the clinic who looks a bit frail, gait speed is a bit slow getting in the clinic, maybe has lost 30 pounds, has potentially some graying hair, and that we think that the inflammatory bowel disease is really driving it. Don't undertreat or avoid treatment in this, but this is the exact person you want to treat quickly and effectively because they can rebound quite nicely.

But the longer you let them go down that trajectory, the harder it can be to recover. So it depends what's driving frailty. If you think it's IBD, then getting a quick and efficacious medication on is incredibly important. As we get older, we can rebound, but it takes longer and longer and harder and harder. So the farther we let them go without giving them that effective therapy, the worse they may do in the long run.

The other complicating part is, well, what if the frailty is driven by, I have other patients with cirrhosis and COPD and underlying MAI, like a mycobacterium, how do you treat those individuals? And it can be more complicated, so it really needs to balance safety of medication, but also efficacy of the medication to tackle the underlying inflammation, which in part still drives their outcomes.

Dr Cross:

I know you agree with this, this is a historically undertreated population that gets excessively treated with steroids, which are far worse. So I think for the vast majority of the listeners that are probably not practicing where they're in a medical home, the important thing is treat their IBD as you would treat someone else's IBD, get them under control. And I think in a perfect world, this would be a multi-D approach with addressing cognition, physical therapy, nutrition, et cetera, for these patients.

But most places don't have access to those resources. So you probably do some formal measures of frailty. So one of the advantages of seeing people in person, particularly an older adult, is you can watch them get out of the chair, you can watch them climb up on a table, you can shake their hand. Now, obviously not everyone has massive grip strength. They don't try to break your hand with a handshake in general, but you can get an idea of how frail someone is by just shaking their hand, watching them get from the chair to the table.

Dr Faye:

Yes, that's exactly right. And we are studying that. Can you use grip strength? Can you use gait speed? We're studying it in individuals who are on medication therapy. We're also studying it in the preoperative state because we talked a lot about undertreatment, over utilization of steroids, and so there's also a big underutilization of surgery, this idea that, well, now we have so many therapies, maybe we'll try something else and something else and something else. And what we see is particularly in the older adults is as you push that out, that increases the risk of emergency surgery and adverse outcomes later on. And so trying to think what other metrics can we use, whether it's gait speed, whether it's grip strength, whether it's a chair stand, we're even starting to look at epigenetic markers of aging. So maybe you could do a blood sample and have a better sense of someone's actual biological age.

I think we see this a lot in the news and the media now, but someone's 70, but you take a blood sample and actually their biological age is 55 or maybe it's 80, and maybe we can use that as a better risk stratification tool as well. But from our prospective data so far, the one most important thing is disease activity and really getting that under good control. Steroid sparing, as you mentioned, early and effective therapy, and that really is what translates into the safest and best outcomes for our aging patient population.

Dr Cross:

And before we do the last two questions, just for the listeners, the national AIBD meeting in Orlando will be December 7th to December 9th. That's a Monday to Wednesday, and there are some premeetings also on December 6th.

Adam, this can be a problem with younger adults, well, it can be even adolescents and younger adults, but is your approach to overweight and obese patients any different?

Dr Faye:

It's only different in the sense that we know or we're starting to understand that having excess visceral adiposity is in self... Same with atherosclerosis, same with plaques in our arteries. It is a proinflammatory state, so it drives up anti-TNF, it can drive up IL-6. And so in particular, when you utilize anti-TNF agents, it can actually act as a little bit of a sink. So you may need higher doses or there may be a little bit of a lower efficacy. So in someone with high visceral adiposity or very high BMI, I'm a little less often using a subcutaneous anti-TNF. If I am using anti-TNF, I'm using really IV doses, and so we're talking about infliximab there.

And I think there's a lot of exciting data with the GLP-1s, both in reducing some of this visceral adiposity and BMI, but also in terms of longer-term outcomes. Will it improve outcomes in Crohn's disease? Will it actually... There's some retrospective data showing maybe it reduces risk of surgery and so forth down the road. So I think in terms of the approach is really, I tend to use less subcutaneous, particularly the anti-TNF, tend to use more IV, and then try to work with them to get that visceral adiposity down for the sake of reducing inflammation and improving overall outcomes, not just for Crohn's or ulcerative colitis, but also cardiovascular and other comorbidities. We see obviously a great benefit if we're able to reduce that.

Dr Cross:

Yeah, I think, again, as I've gotten older with my patients and you're looking at them in front of you, you realize that their Crohn's or colitis is not likely going to shorten their lifespan. It's really when you see someone who's BMI is over 30, over 35, over 40, it's really their obesity that's going to affect their long-term function and maybe not their chronologic age, but their age where they have excellent quality of life. So I've been talking to them more about GLP-1s and being supportive and referring them to our bariatric program, which is almost exclusively now medical weight loss or other people in the community, and it's very interesting. I think when you as a provider bring it up for your patient, they're way more receptive to it than I thought they would be.

Dr Faye:

100%. And I completely agree with you. A lot of our research has focused, and it's very important still, what do we do when we're older with multimorbidity and how do we manage that? Because that's not going to go away, and we need to understand that so we can best care for those individuals. But I'm also starting to think, well, what happens earlier in the life cycle, someone with Crohn's or ulcerative colitis when they're 20, 30, 40, how can we better care for them now so that they don't develop diabetes, cardiovascular disease, hypertension? So that really, you're right, it's not just lifespan anymore, not just getting to a certain age, but it's like health span. The years lived well so that when you're 60, 65, and 70, you're doing all the things you want and you don't have multimorbidity where now that's limiting what you can do.

So starting to think the decisions we make at 20 and 30 and 40 years old may actually translate into some of that multimorbidity, and we see it because there's earlier multimorbidity in IBD than in the general population. And so trying to understand what can we do when they're younger, which is reduce corticosteroids, get inflammation under better control and so forth, that can actually impact them. When I talk to my patients, say, yes, we're going to talk about now and 6 months from now, but I want to make sure you are well. I want to keep you well for the next 20, 30, 40 years from now. I want to make sure that the decisions we make now keep you well 30, 40 years from now if we can.

Dr Cross:

Adam, this has been great. What's your fun fact?

Dr Faye:

Oh, fun fact. I guess my fun fact, I don't know how fun it is anymore, but I've been to all 50 states.

Dr Cross:

I'm jealous.

Dr Faye:

Yeah, both my parents were public school teachers in New York, so we had summers off. And so my brother, I, my parents would pack our car and leave town for 7 weeks and just drive the entire country. And we did that for probably 12, 13 summers. And so we drove through and went to all 50 states, including Alaska, Hawaii, and everything. So it was amazing. I mean, now with time, we're flying and doing everything, but it was an amazing way to just really see the breadth of the countryside.

Dr Cross:

And what's your favorite state? Well, let me rephrase that. If you could go to any state other than New York, where would you take your family right now?

Dr Faye:

Hawaii is always high on the list. Alaska's a close second. Montana is close.

Dr Cross:

Second Orlando for the national AIBD.

Dr Faye:

Right. Was that the right answer? AIBD, Orlando.

Dr Cross:

Dolphin Hotel. It's the greatest place in the world.

Dr Faye:

Exactly.

Dr Cross:

All right, Adam, this has been great. Thanks.

Dr Faye:

Thanks so much, Ray. Thanks for inviting me.