IBD in the elderly

Här kan du se fimen från webbinariet IBD in the elderly

Dokumentet innehåller en transkription av ett webinar om inflammatorisk tarmsjukdom (IBD) hos äldre. Webinaret fokuserar på utmaningarna och behandlingsmetoderna för äldre med IBD, särskilt Crohns sjukdom och ulcerös kolit. Experten Adam Faye diskuterar hur IBD-patientpopulationen åldras och betonar att biologisk ålder inte alltid motsvarar kronologisk ålder. Han påpekar att äldre ofta behandlas mindre aggressivt trots liknande sjukdomssvårighetsgrad som yngre patienter, vilket kan leda till underbehandling och sämre utfall. Faye argumenterar för vikten av tidig och adekvat behandling för att förhindra skörhet och andra negativa konsekvenser av obehandlad inflammation. Diskussionen inkluderar också strategiska kirurgiska ingrepp för att förbättra utfallen hos äldre.

(denna sammanfattning är AI-genererad och inte korrekturläst, scrolla ner för en fullständig utskrift av webbinariet)

Moderator: Pontus Karling

Föreläsare: Adam Faye, assistant professor, New York University Langone

Fullständig utskift:

[00:00:00] Jesper Lundblad: Good afternoon and a warm welcome to today's webinar, which is arranged in cooperation between SKF, the Swedish Medical Society and Mediehuset.

[00:00:21] Today we will focus on the topic IBD with the elderly. Before I hand over the floor to today's moderator, Pontus Carling, we would like to say a big to our main sponsors, Abbvi, Pfizer, Takeda and Tillots, for making this series of meetings possible and making it free of charge for all participants. We will now start with a short greeting from our sponsors.

[00:00:42] There still is high unmet need in IBD. The road to durable clinical and endoscopic remission is long and complicated, and only part of the patients reach it. At AbbVie, we are proud of the recent developments of our IBD portfolio. With RINVOC, first in ulcerative colitis and Crohn's disease, and now lately with SKYRISI, first in Crohn's disease and ulcerative colitis, receiving marketing authorization in July this year.

[00:01:16] We hope that more treatment options lead to better outcomes for more people. Hi, my name is

[00:01:23] Sofia Beite and I work at Takeda. Advanced training, especially in IBD, is something that is close to our hearts. We provide both physical and web based training. And if you want to know more about them, go to our web portal, GastroKoll.

[00:01:59] Do you miss anything or have any questions, feel free to contact any of us in the gastro team. Sanna, Seva, Per Fredrik. We also want to point out that parts

[00:02:09] of the lecture awards for today's meeting have been donated to the MAG TARM fund. We

[00:02:14] also encourage you as viewers to contribute if you want, either by scanning the QR

[00:02:28] code shown here, Or by swishing a contribution to 123 947 55. Finally, a reminder that you can also ask questions to the lecturers via the chat during the entire meeting. With that said, I now hand over to Moderator Pontus Carling. Please go ahead, Pontus.

[00:02:46] Pontus Karling: Good afternoon! We are today at

[00:02:52] this webinar very pleased to welcome an international guest. It's Adam Fabe from New York City, United States. Uh, Adam Fie is an assistant professor of medicine and popular health and director of clinical research in New York University IBD center. Adam has published in the recent years several articles on the theme IBD in the elderly and, and the, the fragile or.

[00:03:27] Patients and Adam will give us a talk. And as Jesper just told us, we are very pleased and encourage you to, um, write questions in the chat so we can have a discussion after the talk. But now, Adam, I leave the stage to you.

[00:03:49] Adam Faye: Thank you so much Pontus and thank you to the organizers. I'm absolutely delighted to be here.

[00:03:54] Let me share my screen and make sure that, uh, this is coming through to everyone. Does that look good to you on your end? Looks good. Okay, perfect. Alright, so I'm going to start and talk about IBD in the older adult, which is a topic I'm quite passionate about. So, to just get started, these are my consulting fees and grants from the NIA, the American College of Gastroenterology, and the Crohn's and Colitis Foundation.

[00:04:23] To support our work. So first, let me talk to you a little bit about an aging IBD patient population. So this is what it looks like in the United States. These are projections from 2016 to 2060 for individuals 65 years And older. And what you can see here is that not only numerically do the number of millions of older adults continue to increase up to 2060, but you can actually see the percentage of individuals are increasing.

[00:04:53] So fast forward to 2030, more than 20 percent of the entire United States population is going to be 65 years and older. And an IBD, when we think about the bimodal peak, Mhm. Meaning that older adults may develop new IBD at around 60. When you look at 60 or older, it actually is more like 25 to 30%. Well, does this actually mirror in Sweden?

[00:05:17] Well, it does. If you look in today's day and age in Sweden in 2023, regardless of IBD or other medical conditions, as healthcare practitioners, we're going to be seeing more and more of these older adults. So as of today, In Sweden, 26, so one out of every four individuals are 60 years or older. So this is widely prevalent.

[00:05:39] These are going to be the patients that we're seeing very often in our clinics. And yet, there happens to be a dearth or a shortage of data in this incredibly vulnerable patient population. So that's the entire population. How does that translate into the IBD patient population? Well, if you look at this Danish based study, you can see That the incidence is increasing over time, and that's that third box over here.

[00:06:03] And you can see the incidence is increasing for older adults with Crohn's disease. Less so for ulcerative colitis, but if you look at the graphs all the way at the right and you look at the prevalence, what you can see in 1995 at the area of the dark blue, you can see that those individuals who are 60 years and older, there was a bit of a plateau or a peak there.

[00:06:25] Fast forward to 2016, so as you move down the graph, you can see this entire curve has really shifted to the right. So you can see that the entire IBD patient population, both for Crohn's disease and ulcerative colitis, is aging. And what does that look like? Well, it's the median age is actually increasing by six to seven years.

[00:06:46] And again, this was back in 2016. The graph is continuing to shift. So we're seeing an incredible rise in the number of older adults with inflammatory bowel disease. This was a recent study published in gastroenterology, uh, by Jim Lewis and some others, and it looked at Medicaid, Medicare, and commercial insurance, and staggering, if you look at the individuals 50 and 60 and over, the prevalence of IBD in the United States is And this has also been shown in Canada as well, more than 1 percent of older adults.

[00:07:18] So if you see a 60 year old or 65 year old, 1 percent of that patient age demographic actually has inflammatory bowel disease. So think about that for a second. That is an incredibly high number of people. Okay, so there are a large number of older adults. It's rapidly increasing with inflammatory bowel disease.

[00:07:38] How are we doing in terms of our data? Well, if you look at the 222 phase 3 studies, age, chronological age, which actually used an exclusion criteria, in about 60%. So this demographic, which is now comprising maybe 20 to 30 percent of all individuals with IBD, We're excluding as part of our clinical trials, and of the small number of trials that did include older adults, 65 and older, only 5 percent of patients were actually 65 years and older.

[00:08:09] So, again, really doing a woeful job trying to capture how to best treat this patient population, given it's representing 25, 30 percent of the demographic, we have very little data here. Okay, so when we talk about older adults with inflammatory bowel disease, it's really comprised of of two different populations.

[00:08:29] One is the younger adult who developed IBD early in life and has now aged, so maybe they've had disease for 20, 30, 40 years. The second is that bimodal peak, so someone who newly develops inflammatory bowel disease later in life. Now, when we have individuals who newly develop IBD later in life, it can be a diagnostic challenge, right?

[00:08:52] As we age, there are some conditions that may mimic IBD or may overlap. Um, in some of our symptoms and findings, and it can be difficult to tease out. I'm not going to go through these in depth, but here are a couple of them. So we can think about NSAID, right? Aspirin, ibuprofen, medications like that induce dental colitis, ischemic colitis.

[00:09:13] radiation colitis or proctitis. Uh, I just had a patient who was 83 and got sent to me for a second opinion of Crohn's disease and it turned out to be segmental colitis associated with diverticula. These can be very difficult to disentangle. There are some clinical characteristics and distinguishing findings, but again, it can be difficult and this can lead to diagnostic delays and we'll talk about the impact that that can have.

[00:09:39] But when you look at younger adults, we're much quicker to make a diagnosis, to evaluate, and really the delays are maybe two years at max. In older adults it can be, data shows it can be up to six years. When we think about new onset IBD in the older adult, there may be some phenotypic differences and there may also be some clinical presentation differences to think about.

[00:10:04] So you actually may see more older adults with Crohn's disease. Present with rectal bleeding. If we look at the disease locations, this was a study I believe in Spain that looked at I think 20 or 25 different centers. Over 1, 400 patients, again, a single region, so maybe it, it varies based on geography, but at least this has been corroborated in some other studies.

[00:10:27] For ulcerative colitis, older adults may actually be more likely to have just left sided colitis. So if you see an isolated proctitis or a pancolitis, that may be more common in your younger adults. What about Crohn's disease? Well, they may be more likely to have ileal. or colonic disease, but they actually may be less likely to have both ileal and colonic disease.

[00:10:51] And when you look at the phenotype, they're actually more likely to have stricturing disease and a bit less likely to have penetrating disease. So this is important because as you're evaluating these older adults, you have to think about these differences a little bit. So if you're seeing someone with Ileo or just colonic disease.

[00:11:08] Um, that may be what's to be expected in an older adult. So we don't classically go to ileocolonic as we may, may think about with our younger adults. What's driving the development of IBD later in life? Uh, we don't know is the simple answer, but we know that IBD is some complex interplay between our genes.

[00:11:30] So genetics, And the environment. We think based on genetic studies and based on looking at family history that IBD developing later in life may be more driven by environmental factors and less by genetics. And why is that? When you look at family history, you can see younger adults have a much stronger family history.

[00:11:52] 10%, 15 percent have a family history of IBD that number 5 percent or so is much smaller. In, uh, individuals who develop inflammatory bowel disease later in life. So to look at some of those environmental factors, we actually did two studies. So one, uh, I did with Jonas Ludvigsen, um, at Karolinska Institute, and we looked at atherosclerosis.

[00:12:14] So plaques in arteries. It's actually thought to be a very inflammatory process with a lot of overlap in the inflammatory cascade with IBD. TNF and so forth. We actually found that in patients who develop IBD later in life, that they have a higher proportion of cardiovascular disease beforehand, and that includes heart attacks or myocardial infarction, whether they had a diagnosis of atherosclerosis or a prior stroke.

[00:12:42] There's also been some other work, um, that Jonas has done and that we've recently done looking at antibiotics. And so we looked at antibiotics as an environmental risk factor. And what you can see here. Is that the 60 plus year olds are in red and the 40 to 60 year olds are in purple. And what you can see, if you just go to the bottom 1, the number of courses of antibiotics, the more courses of antibiotics.

[00:13:04] The higher the risk to develop inflammatory bowel disease, particularly in individuals who are older, right? So it seems to be driving it less so in younger adults, which again goes to the hypothesis that maybe environment is playing somewhat of a larger impact on our older adults who develop IBD. When you look at the time course of the risk, so that's in the top graph.

[00:13:26] You can see that the closer to, um, the development of IBD, the higher the risk. So if antibiotic use was 3 or 4 or 5 years prior, it may contribute less so, but still, even 5 years prior, there does seem to be an increased risk for the development of inflammatory bowel disease 5 years later. When you look at the antibiotic classes, interestingly, the nitroimidazoles and fluoroquinolones, which we often use to target gastrointestinal infections, and may modulate the intestinal microbiome more, actually carry the greatest risk.

[00:14:01] Most of the other antibiotics, which do modulate the microbiome somewhat, carry a bit of an attenuated or mitigated but still present risk. And nitrofurantoin, which really doesn't seem to impact the intestinal microbiome so much, actually seems to not increase the risk. So perhaps giving a plausible idea to the might be driving changes in the microbiome that can increase the likelihood of developing IBD, particularly in older adults.

[00:14:32] So these are just things to think about as you're seeing new patients who are older, who maybe have new onset of gastrointestinal symptoms and expedited workup, thinking about those other diagnoses, thinking about the differences in the disease location. And also perhaps taking a good family history, medical history about cardiovascular disease, and also about any potential recent antibiotic use.

[00:14:57] Okay, so the question then becomes, For older adults who develop IBD later in life, There used to be, or there is this thinking that perhaps the conception is it's less severe than, uh, individuals who develop IBD earlier on. So let's take a look. This was a study that essentially pooled a lot of population level data, and they looked at individuals who developed Crohn's and ulcerative colitis early in life, and individuals who developed Crohn's and ulcerative colitis later in life.

[00:15:28] And what they did was they said, okay, between those two cohorts, What is the risk of surgery, hospitalization, or need for steroids at 10 years? And if you just quickly take a look across the board, the older onset ones are colored in, so the colored in circle and the colored in square, versus the open circle and the open square.

[00:15:48] What you can see here is that pretty similar across the board, for both surgery, Hospitalization and corticosteroid use. Now this may be somewhat driven by differences in treatment, which we'll talk a little bit about, but at the very fundamental level, our outcomes at 1, 5, and 10 years, surgery hospitalization and steroid use, are pretty similar.

[00:16:06] So this, at least to me, suggests that IBD developing in a 60, 70, even 80 year old may not be less severe than IBD developing in a 20 or 30 year old. What about this idea? Does disease burn out over time? Right? This comes up often. We do not have great data for this, although we are working on it. But for now, if we look at this interesting study back in 1978, which was based on survey data, and I think in some ways that's actually quite nice that it dates so far back, because our treatment options were limited.

[00:16:39] So we really get to see the natural history of disease over time. And it asked the question, well, among individuals who had 3 years of Crohn's disease versus 25 years of Crohn's disease, who was still on some medication, and who had a relapse within the past year? So if you look, 3 years after diagnosis, 34%, so about a third had a relapse in the prior year.

[00:17:03] 25 years later, did it burn out? Well, about a quarter had a relapse. But if you look, how many still required therapy to be managing their disease? Well, three years after was about 40 percent and 25 years later was about 50%. So if you add these cohorts up, Those that flared in the past year, or those that need therapy to maintain in quiescent disease at that time, it's about the same number.

[00:17:27] So again, gives credence to this idea that disease may not burn out over time, at least in the majority of individuals. Okay, so now let's talk a little bit about the medical treatment of older adults. So, if we think about Disease does not burn out over time if we think that the severity between older and younger onset is pretty similar, are we treating them in the same way?

[00:17:51] And the answer is, it appears not. So this was recent data, although there's been older data corroborating this. And if you look, steroids at 1 in 5 years between older and younger onset IBD, Pretty similar. But if you look at diopurines and biologics, so any of our immunosuppressive therapies besides steroids, we are using them much less often in our older adults who develop IBD than in our younger adults who develop IBD.

[00:18:21] Even when we are using biologics, we are underdosing or we are differentially dosing them between older adults and younger adults. So we did a study looking at about 30, 000 samples at Prometheus Laboratories. And what we found is that older adults were less likely to receive dose escalation of their infliximab.

[00:18:41] So this only occurred in about 38 percent of older adults versus about 50 percent of younger adults. Additionally, when you look at the development of antibodies to anti TNF therapy, right, this is something that we really try to avoid if possible. You can actually see that older adults, despite what we might think about immunosenescence, were actually more likely to make antibodies to the drug than older adults.

[00:19:05] As compared to younger adults, and this was even independent of our dose. So really need to be, if we're using anti TNF therapy or other drugs, we need to be cognizant about how we're dosing it. There's been no studies to show, at least to my knowledge, that a higher level leads to a increased risk of adverse events.

[00:19:22] So if we're using it for ileal disease, if we're using it for perianal disease, we really need to be adequately dosing it. Okay, so there's an over reliance on steroids. This was a much older study, but it basically showed that over 40, uh, 30 percent or so of older adults 65 years and older were actually using steroids for more than six months.

[00:19:45] Now this was an older study, so probably has improved a little bit by now with, uh, some of our newer biologics. But if you actually look at 1991 to 2000 versus 2001 to 2010, You might think, Oh, well, maybe we improved over time. Actually, steroid use doubled in that latter half. So we actually were prescribing more steroids later on.

[00:20:08] And when you look at the doses, we're actually giving more or higher doses to our older adults than our younger adults. So we need to be quite cognizant about this. So this really, to me, begs the question, why are we not using immunomodulators or advanced therapies, biologics, small molecules? And I think the key is we are often concerned about malignancy and infectious risk.

[00:20:29] Um, and this comes from a lot of the prior data. It's not without, um, you know, real world evidence. When you look at some of this data, efficacy and safety of anti TNF in elderly patients. You go to the conclusions, elderly patients treated with anti TNF have a lower rate of clinical response, higher rate of adverse effects.

[00:20:48] Same thing here. If you look at the conclusion, advanced age associated with an increased risk of infection. Here, increased discontinuation rates of anti TNF in older adults. So, this idea that older adults are at higher risk for infections and adverse outcomes as compared to our younger adults. What this has done though, in my mind, to our older adults is now we have shifted to think less about efficacy in the adult and more about safety in the older adult.

[00:21:16] And this is solely based upon chronological age. Now, I put these medications here not to suggest that some are more efficacious than others, but I think we often think about the anti IL 12 23s or 23s or betalizumab, which is the anti integrins, as our safer options, and this is what we should be ideally using in our older adults.

[00:21:36] And while I do agree with that on many principles, there are times, particularly with efficacy, you have a patient with acute severe ulcerative colitis or a hospitalized Crohn's disease patient with deep ulcers, these are patients I'm using anti TNF, potentially jack inhibitor or surgery, but even in those cases, we tend to be favoring safety over efficacy.

[00:21:58] And I'll quickly just mention this, I don't know how many of you know this, um, uh, this is an ethical dilemma that often comes up in psychology courses and so forth, but it's called the trolley problem. And what happens is that the trolley is about to run over five people, and if you do nothing, it will run over five people.

[00:22:17] You have the option and you can push one person off the track. And if you push that one person off the track, you are doing that one person harm, but you are stopping the trolley and you are saving five people. So the, the, in psychology, the ethical question is what would you do? I think about this often in IBD.

[00:22:34] As physicians and practitioners, our first kind of credo is do no harm. So we never want to enact harm. But what happens is by maybe under treating the ongoing inflammation. We allow the disease activity to go on and run over those five people. Now, we think maybe that's not our doing or active, right?

[00:22:54] We're not making that push or deciding to use a therapy that leads to an adverse outcome. But by under treating and letting that inflammation go, you actually may be contributing to more harm. Now, on the flip side, when we do start that anti TNF or surgery or a JAK inhibitor, and we do have that one patient who develops a thrombosis or a bad outcome, we feel very, uh, we internalize that in, in a sense that we made an active decision that may be led to harm in that patient.

[00:23:20] But we really need to be balancing these and think about the active harm that's actually going on from untreated or ongoing disease activity. Okay, so getting back to those other studies, again, valid real world data showing that older adults are at higher risk of adverse outcomes from our therapies.

[00:23:38] But the question in my mind is really, what about when you take older adults, Who are untreated and older adults who receive the treatment, right? We're not comparing older to younger adults. What we want to know is, in an older adult who has maybe moderate to severe disease, what is the attributable risk, if any, to the medication?

[00:23:58] Well, this was one of the first studies that really looked at it. And it pooled RCT data from our ulcerative colitis TNF trials and it took our older adults and asked this question. Now, if you look, the older adults are in the blues, younger are in red and yellow. If you look across the board, older adults are at higher risk than younger adults for everything, right?

[00:24:17] Serious adverse events, hospitalization, infection. This is true no matter what. Older adults are at higher risk for any clinical outcome, pretty much, that you can think of across all disease states, um, even in the absence of disease states. They have a higher incidence of mortality and so forth. That's not the question at hand.

[00:24:34] The question at hand is now the patient in front of you who's 70. Am I going to make them worse if I prescribe anti TNF for their disease, or am I going to make them better? And that's really the question at hand. That's the, what is the attributable risk to adding the drug? And what you can see, again, this was pooled retrospective data, so underpowered.

[00:24:54] What you can at least see is that there's no difference between the two cohorts. But if anything, although not statistically significant, you can see there's actually a clinical decrease or a decrement, a benefit, To the TNF therapy. So the older adults who got TNF actually had lower rates of serious adverse events, lower rates of hospitalization, and lower rates of severe infection.

[00:25:16] So now, in our patients who have severe disease and warrant these therapies, not only are we not increasing that risk that we're worried about, but actually we may be decreasing that risk. This was another, um, cohort study that was done, I believe, in Denmark, and it propensity matched Vitalizumab versus TNF, and there was actually no difference in infectious risk over one year.

[00:25:39] And again, when you look at the composite outcome, not to suggest TNF is more efficacious than Vitalizumab by any means, but probably, uh, over time, the patients who were not frail were getting TNF antagonists, and you can see that That IBD related major abdominal surgery, hospitalization and steroids are actually lower in the TNF.

[00:25:58] So just the idea that if you're adequately targeting the inflammation and what my suspicion here is, even though it was propensity match, is that despite inflammation, um, patients were receiving probably vitilizumab who maybe were more frail or they were worried about adverse outcomes and maybe they were being undertreated.

[00:26:16] So again, treatment of disease adequately can actually improve outcomes. Okay, so when we think about safety of biologics, we're, what are we concerned about? Are we concerned about a urinary tract infection? Of course, but what we're really concerned about are pneumonias, septicemia, things that can land our patients in the intensive care unit and have lasting comorbid mortality effects, right?

[00:26:38] And so this was a study that looked at, um, claims data within the U. S. and it looked at TNFs, 1223s. From what you can appreciate, just to quickly take away, is that very few percent had sepsis Or pneumonia, right? So even when we're using these therapies, they are unlikely to cause these serious adverse events that we are thinking about.

[00:26:59] And when you look, it's pretty similar across the cohorts between anti TNF, integrin, IL 1223. Not going to spend too long on this. This was a nice post hoc analysis of the REACT trial. What was the REACT trial? Well, it said, what if we do anti TNF and immunomodulator for Crohn's disease versus just usual therapy?

[00:27:18] And what you can see is that there is no difference in outcomes between older and younger. What you can see is that the mortality was higher for older adults, but again, That makes sense. Mortality is always going to be higher for older adults than younger adults. But what about the older adults who got conventional management versus the older adults who got early combined immunosuppression?

[00:27:37] Well, in fact, the older adults who got early combined immunosuppression actually had a lower mortality. Again, reinforcing this idea that maybe early control of ongoing inflammation can actually improve clinical outcomes down the road. Okay, in the interest of time, I'm going to move quickly through frailty and IBD, um, and I may skip over a little bit.

[00:27:58] But we've talked a lot about chronological age, and one of the biggest take home points of today is chronological age and biological age are not the same thing. So here we have two individuals who are the same chronological age. One on the left you may recognize was a recent speaker of the United House of Representatives and one on the right is requiring two people to help assist them across the room.

[00:28:23] So this idea, they're the same chronological age, but biologically very different. And so this really introduces this paradigm shift. So we need to be thinking not just in chronological age, but how can we incorporate that biology into our treatment paradigms? So there's frailty, which is a loss of physiologic reserve.

[00:28:43] There's sarcopenia, which is a loss of muscle, mass, strength, and function. And I'll talk a little bit more about this. But what this can do is using these concepts can help risk stratify our patients and allow for more timely interventions. And what this is what I see often as I get referrals for patients.

[00:29:01] Um, an older adult, they have ongoing inflammation. What is that doing over time? These patients are much more vulnerable than our younger adults to physiologic decline, malnutrition, and cognitive decline. We're adding maybe short courses of steroids on trying to help maybe with symptoms or whatnot. And then what happens is they come to us, and they have quite severe disease, and now they're requiring either anti TNF, surgery, and so forth, we use that therapy, and then they have an adverse outcome after that, what that does is it actually deters the use of that anti TNF or surgery, because it reinforces this idea Well, if I use that therapy, they have an adverse outcome.

[00:29:40] What in fact it should be reinforcing is perhaps if we are controlling inflammation in a more timely manner, if we're able to risk stratify and intervene earlier, we can actually shift that trajectory. Okay. So we'll talk very quickly about frailty. So frailty are 4, 000 patients with IBD of all ages.

[00:29:58] They looked at ICD codes to define cumulative deficit model of frailty. And what you can see is if you were frail or fit in the year prior. Then you were treated with an immunomodulator or anti TNF. If you were frail, you actually had a higher risk of infections after immunosuppression. So not surprising, if you're frail in that prior year, when you start a medical therapy, perhaps you're at a higher risk for adverse outcomes.

[00:30:22] We did a study looking at about a million and a half hospitalizations in US database and having frailty independent of age, comorbidities, and other clinical co variables. Um, was that Re admission was higher if you were frail, and we'll talk a little bit about the mortality as well. Also, when you look at hospitalization, frail patients had a three day increased length of stay.

[00:30:47] So not only does that increase healthcare related costs, but in older adults, there's a, there's a geriatric kind of saying that one day, For an older adult in the hospital, requires about a week of recovery at home. So if you think about every day that the older adult is staying there a bit more, that requires an extra week each day at home on the backside to help physically, cognitively, nutritionally recover.

[00:31:11] So these days, while we think about in our 20 or 30 year olds, six days, nine days may not make such a big difference in our older adults. This can translate into enormous clinical outcome differences. Not all studies have shown that frailty was associated with an increased risk of serious infections.

[00:31:28] Although in this study, it did show that this was the case for vitilizumab. And that I think is interesting. Probably in more frail individuals were preferentially Thinking about Vitalyzumab, um, as opposed to anti TNF, which probably we're using, you know, in our more robust individuals. And I'll get a little bit more into that.

[00:31:46] Um, I've already kind of gone through this, and I'll just, for sake of moving along, but frailty also has shown independent of other clinically important, um, variables to be associated with mortality. I will pause on this slide for one second, because I think this is a key take home point. So ongoing inflammation may drive frailty, so that should really be embedded in our brains by the end of this, hopefully.

[00:32:10] So this was a study of 1, 200 patients of all ages. When they looked, who responded to therapy at the one year, for those individuals who did not respond to therapy, 27 percent were frail. For those who did respond to therapy, 7 percent were frail. There's been more recent data prospectively looking at about 60 patients who were frail to begin with, and then they followed them over time.

[00:32:34] And those that actually, uh, went into clinical remission reversed their frailty. And those that didn't go into clinical remission were less likely to reverse their frailty. So really emphasizes, emphasizes this idea that treating the underlying inflammation, that the inflammation itself may be driving progression towards frailty, and early treatment of this can actually change outcomes.

[00:33:00] This was one of the cross sectional or prospective. It just looked at geriatric patients and looked at different assessments, geriatric assessments, so activities of daily living, social domains, mental domains. All it showed, um, and re emphasized is that more disease activity, more geriatric deficits.

[00:33:17] Again, just reinforcing this idea that inflammation may translate into progression towards frailty. And so what does that look like? As we go along and have ongoing stressors and have ongoing inflammation, as we get older, it gets harder and harder to return to our baseline. And so, if we have ongoing inflammation, what that does is the ball continues to roll down and can actually progress us closer to frailty, hospitalization, adverse events, and death.

[00:33:46] But with treatment of the underlying inflammation, we can actually mitigate progression towards frailty, and that's that green line. This is not unique to IBD or gastroenterology. So in heart failure, they're starting to add frailty into their clinical trials. And this was kind of a brilliant study that looked at, uh, one of their medications, and looked at, well, what about frailty status?

[00:34:08] Does it matter? Do we make patients worse if they're more frail and we use this medication? Well, if you look At the frailty index, no frailty was 0. 2 or lower, medium frailty was 0. 2 to 0. 3, and high frailty is 0. 3 or greater. And what you can see across the board is that the hazard ratio pretty steadily stays below 1.

[00:34:29] So this means that regardless of your frailty, the medication actually benefits you, right? And what does that mean? It means less heart failure or cardiovascular death. Now, when you look at the event rates, If you were lower on the frailty scale, it helped prevent 3. 5 events per 100 person years. What if you look at the high frailty?

[00:34:50] 7. 9 events per 100 person years. So you can imagine, if we think heart failure is driving frailty, treating the underlying condition may actually have the greatest benefit. And I think this concept in many ways applies to IBD. If we think in this individual that frailty is driving, or IBD is driving frailty, then treating the underlying IBD, you'll actually have the greatest benefit in, and we should be, um, properly or adequately controlling inflammation and not really moving away from using therapies at this patient.

[00:35:23] I'm not going to go through this. There's multiple different ways you can measure and assess frailty. There's a deficit model, physical functioning. We're doing a multi center study where we're following over 300 patients right now. And we should hopefully have some data to present soon at one of the conferences, hopefully ECHO or DDW or ECG.

[00:35:42] Okay. So let's talk a little bit about surgery in the last couple of minutes, because I want to leave some time for questions. Think with surgery, we need to be careful about cycling biologics to avoid surgery in older adults. And what does that mean? I see this often. So an older adult comes in, they have ongoing inflammation.

[00:36:01] No one wants to send them for surgery, they're 72 years old. So what happens? We put them on drug A, whatever that may be. Maybe they need a little bit of corticosteroids. This goes on for six months. It's not working quite so well, so they go to drug B and we need another course of corticosteroids. Another six months.

[00:36:16] Drug C, another course of corticosteroids. What's happening over this year and a half? Well, this patient is now developing physiologic cognitive decline, malnutrition, and eventually, when they then come in with a perforated colon or, uh, small bowel obstructions that they then need surgery, what happens is when we do the surgery, they have a bad outcome.

[00:36:37] And what does this tell us? Don't operate on older adults. That is the wrong take home message, at least in my view. What I think we should be thinking about is if we operated on this person earlier, six months, 12 months, 18 months earlier in their cycle, they would have not progressed towards frailty.

[00:36:53] That decline that they went down would have not occurred. And so they probably would have had a much improved clinical outcome, better quality of life, and so forth. So it's really about, um, adequate surgical timing and not just delaying due to chronological, um, age alone. Why are we avoiding it? Well, we're worried about adverse surgical outcomes.

[00:37:14] So we published a recent study looking at surgical outcomes in older adults, and it was about 37%. 30 day risk of, uh, major adverse, uh, surgical outcomes compared to about 25 percent in younger adults. When you look at what are the risk factors, well, it's the things we talked about. Physical, dependent functional status.

[00:37:34] If you need emergent surgery, right, so delaying too long and now the person needs emergent surgery. Developing preoperative sepsis because now they have an abscess there for untreated disease for the last 18 months. Developing malnutrition. And when you look the odds ratio, so the how each of these variables is impacting the surgical outcome is pretty similar between the older and younger adults.

[00:37:55] But what you can see. Is that a much higher proportion of older adults need emergency surgery, much higher proportion develop sepsis, malnutrition, functional status. So these are patients who are very vulnerable and we're letting them potentially go too long and then when they need surgery they have a bad outcome.

[00:38:14] I'm sure many of you are familiar with this. This is the Lyric Study. Again, I'm not going to go in detail just because I want to leave some time for questions, but emphasizing that maybe in certain individuals. earlier surgery may actually have improved outcomes, so about 20 to 40 percent in the resection group of those with terminal iliitis didn't actually need any therapy by five years or just a prophylactic dose, and in the infliximab group, 50 percent needed surgery anyway.

[00:38:42] In a real world study of this, which I was, um, part of in part, uh, we looked at TNF versus surgery in Crohn's disease patients, and again, showing that maybe there's a benefit to surgery. In the stratified analysis, who is the, uh, who is the individual most likely to benefit? It's the older adult. So when you look, it's those who developed IBD later in life, had the lowest hazard ratio.

[00:39:04] So showing that surgery up front might be a better option. Anti TNF therapy. This has also been shown in ulcerative colitis. When you look at data showing mortality risk versus therapy versus elective colectomy, what can you see? Well, at five years elective colectomy actually had improved outcomes, and you might say, well, in everyone, or who, well, it's actually in those patients who had severe disease who are 50 years and older.

[00:39:32] So again, emphasizing this idea that perhaps in our older adults. surgery to get rid of ongoing disease activity early may actually have improved outcomes. This is unpublished, but Jonas and I have been looking, and this kind of confirms it. Of the patients who need or get surgery, who's likely to not need any future medications, IBD hospitalizations, surgeries within the next five or so years.

[00:39:58] And you can see it's really those older adults. So not only may earlier surgery actually lead to better clinical outcomes, you may actually obviate the need or eliminate the need for future therapy in this cohort later on. Um, we also looked at sarcopenia, which I mentioned briefly before, which is muscle mass.

[00:40:17] How can we better risk stratify, right? So if right now we're using chronological age to risk stratify and say, I don't want to operate on a 75 year old. Can we move away from chronological age and can we move more towards biology? So we looked at muscle mass and we asked two questions. One of the questions was, can we just use the psoas muscle in green?

[00:40:38] Or can, or should we be using all skeletal muscle? And what we found is that Using all skeletal muscle was actually a better predictor. So you can see here at a higher AUC as compared to the psoas muscle in predicting 30 day outcomes among older adults who are undergoing surgery with IBD. We also looked at other variables, and we can see that skeletal muscle mass Seems to drive clinical outcomes.

[00:41:03] So maybe we can start to think about integrating this marker. We often have preoperative imaging. We can now pretty quickly segment these muscle mass indices. So imagine you can get a very quick readout and have a better sense. Someone who's low risk for surgery in 75, you send them to surgery pretty early on.

[00:41:21] Someone who's maybe higher risk, maybe we start to think about prehabilitation, physical therapy, nutrition, to optimize them beforehand. And we're studying that as well. Okay, I will end in the next three minutes. Um, I just want to go through one quick case. So this is someone I saw maybe about a year ago now.

[00:41:39] So she was 74, she had moderate ulcerative colitis, and she was initially given a couple weeks of corticosteroids. Okay. Have to think about it. Our older adults are particularly vulnerable to steroids. Again, not only over the whole years, right, 30s, 40s, 50s, when they got it, it can increase their risk for diabetes and bone loss.

[00:41:59] But now as a 60, 70 year old, corticosteroids can have an increased risk for cognitive issues. It can affect their sleep, which can increase cognition that can be more likely to make them fatigued. So they decided to start them on mezalamine with some improvement, but not quite there. So they increased the mezalamine dose and added enemas.

[00:42:20] Okay, so we know that oral and rectal therapy may be better, um, but the question is in someone who's 60, 65, 70, can they actually administer an enema, right? What about giving them now four pills per day plus an enema therapy? What about polypharmacy? So we just published a study looking at this and independent of comorbidities and other variables, severe polypharmacy and moderate increases the risk of a hospitalization at one year.

[00:42:48] You can imagine if you're lining up eight to ten pill bottles, it can be difficult to remember which one I'm supposed to take four of today. And maybe you take four of your antihypertensive and that lands you in the emergency department. So when we're making these judgments. safety and efficacy. We need to also be thinking about how are these medications affecting some of these what we call the five M's of geriatric care.

[00:43:12] Okay, so they start on amazalamines, colonoscopy a year later. So this person is now an ongoing disease for a year, shows more severe disease, starts on ustekinumab. So now with some of our newer agents, we have to think, can the person inject it? If not, do they have someone at home who can? Also, we need to think about what matters to them, right?

[00:43:32] We think about this in all patients, but particularly in older adults, they're very vulnerable. So if the person is not leaving the house, Because of urgency or incontinence, a 25 year old may be able to do that for a month and rebound. A 65, 70 year old who's not leaving the house, not socially engaging with the world, may have cognitive decline.

[00:43:55] They may have physical decline because they're no longer going out and walking. And a month, six weeks, six months of this, a year of this can have long lasting impacts on that frailty curve that can be incredibly hard if at all possible to reverse. So we need to be thinking about that. So the patient has a reaction to the first infusion, more rectal bleeding, loss of appetite, and now comes to see, oh, this is before she saw me, sorry, and had a 50 pound weight loss.

[00:44:22] And they were started on Vitalizumab, worsening symptoms. And then now I meet this person in the hospital two months later. With acute severe UC, now with a CRPR of 106, an albumin of 1. 9, and a hemoglobin of 8. And now, what happens if we choose surgery or anti TNF? This person has gone through that frailty curve.

[00:44:42] We have pushed them to a physical, probably cognitive decline, malnourished state, and they're at a much higher risk of an adverse outcome. So when we do surgery or an anti TNF or a JAK inhibitor and we see an adverse outcome, The issue is not, don't choose those treatment modalities. The issue is, had we intervened a year, year and a half earlier, and adequately controlled that disease inflammation at that time, we could have prevented that fall down that frailty line.

[00:45:10] So, I'll leave you with a few take home points. So, one, the IBD patient population, I hope I've convinced you, is rapidly aging. So, this is something we're all going to be seeing. Chronological age does not equal biological age. Despite what I think to be similar courses or disease severity as compared to our younger adults, our older adults are less often treated with advanced therapies.

[00:45:35] Remember, corticosteroids are associated with the highest risk of adverse events. And when we think about treatment, think about their comorbidities, those five M's I just discussed, but also think about the risk of undertreatment, like on that trolley problem. So, you know, we often, again, think about TNF or JAX and worry about side effects or adverse outcomes with surgery.

[00:45:56] But think about if we're leaving this person with ongoing inflammation or under treatment for the next 1, 3, 5 years, what is that going to do in the next 5 or 10 years later on down the road, right? We could be contributing to significant clinical decline. Remember, ongoing inflammation is a major driver of clinical outcomes in all adults, but particularly older adults.

[00:46:18] And frailty can develop as a result of ongoing inflammation. So, really, earlier treatment, adequately targeting that inflammation, can improve outcomes in older adults with IBD. And it's incredibly important that we kind of focus on this. So, first, I'd just like to thank everyone at NYU on the GI and IBD team, all my mentors, collaborators, particularly Jonas Ludvigsen and all of his team.

[00:46:41] And, um, this is a picture of my daughter. We were in Echo last year. We all came to Sweden and we went up to Karuna, um, to the Arctic and went to the Ice Hotel, which was absolutely stunning. So if you haven't been up there, um, absolutely do it. But it was the best. So again, thanks so much. And I really appreciate, um, the invitation to come speak today.

[00:47:04] Pontus Karling: Thank you, Adam. Excellent speak on this jealous and difficult topic. Um, um, um, I, uh, I will see this lecture one more time. I think it was very, uh, included. I have for some questions. You know, we have a tradition in Sweden that we use the appearance. Right. Right. What is your opinion on that, on the thiopurines treatment in the elderly?

[00:47:35] Adam Faye: I think two things. Um, one, if it's adequately treating the inflammation, I think it's fine. The second question, which I'm actually, um, looking at a study right now, um, but we have a lot of older adults, I think in the U. S. and, uh, Canada, we, we bias away from the thiopurines. You know, costs and all things contribute to that more towards the biologics, but the question is, we know thiopurines increase the risk of malignancy and other things in older adults more so.

[00:48:05] So the question I have, particularly in the patients who have maybe, we have some of them who have Crohn's disease on thiopurines for 20, 30 years, should I leave them now that they're 70 or should I switch them to betalizumab or something else? That's a question that still remains unknown that we're looking at right now, but.

[00:48:22] The question of if we switch them, do we still capture, keep them in remission and decrease the risk of what lymphoma, skin cancers, or do we increase the risk of flare? And really, even though the absolute risk is still not very high, maybe we should just be keeping them on the thiopurines. I think it's a very interesting question that remains to be seen.

[00:48:45] But I have no problem using thiopurines if they adequately control the inflammation. If they don't, then you have to move on.

[00:48:53] Pontus Karling: Okay, that's good. If you have an example on the elderly that you said, drug A, corticosteroids, drug B, but to summarize a little bit more opinions, what do you choose as a drug A and a drug B and a drug C?

[00:49:11] I

[00:49:13] Adam Faye: think, um, that's kind of the nuance and, and, uh, part of what I love about inflammatory bowel disease. It's very, it's hard to. Uh, give you a cookie cutter and say, you know, always try this drug first. It depends. So what do I think about? I do think about comorbidities, right? If they have severe heart failure, I'm not running for a TNF, but in my patients who have a severe disease, so maybe an ulcerative colitis flare that's about to land them in the hospital, or they were just in the hospital, or this is a Crohn's disease patient with severe ileal disease, deep ulcers.

[00:49:47] Or this is someone with perianal disease. I'm starting with a TNF therapy. These are not patients that I'm, you know, trying maybe thiopurines or vitilizumab on. These are patients that I'm going right towards a TNF. Now patients who have more colonic disease, but it's more of the mild to moderate, you could think about the vitilizumab, S1Ps, more moderate, uh, ileal disease, you could think about the IL 23s, but it depends on the patient.

[00:50:13] Also look at the extra intestinal manifestation. So if they have, if they have some spondyloarthropathy, I'm using anti TNF. If they have psoriasis and IL 12, 23 or 23. So it's kind of like a dance. And then surgery is also part of that conversation. So if you have someone with acute severe, you see, or limited, but deep ulcers, and maybe they've been not diagnosed for 2 or 3 years and already starting to have a stricture, I've had this conversation with a couple of my older adults.

[00:50:40] Maybe we just take it out earlier, right? If you're going to need it five, ten years down the road, we're not getting younger. We're only accumulating more comorbidities. And in fact, if I take that out, you may not need therapies for the rest of your life, because their time horizon, Is also shorter. Someone who's 20 may have 60, 70 years to think about someone who's 75 may only have 15, 20 years to think about, and they may not need therapy anymore once we take their disease out.

[00:51:07] So these are, it's kind of a moving target, depending on the clinical characteristics and also how the symptoms are driving, um, you know, the patient. Again, I mentioned staying at home exercise in the geriatric world, right? First, second, and third, the thing that helps prevent aging is exercise. So if your patient is sitting at home because they have incontinence or urgency and they can't get out, that to me is probably the worst thing that can happen.

[00:51:35] So if I try betalizumab and after six, eight weeks, 12 weeks, they're not getting any better, this is not the time to continue. Maybe think about switching to an anti TNF or something that can have a bit of a quicker onset and really get them on that proper trajectory. Great.

[00:51:53] Pontus Karling: Okay. Do you ever use a Jack inhibitors in the elderly?

[00:51:57] Adam Faye: I do. So we're presenting an oral ACG where we're looking at thrombosis risk. That's a little side passion of mine is thrombosis. Um, and. You know, the data with oral surveillance shows at least with TOFA there was, maybe with OOPA there's less so, but I do. If it's the right patient, I absolutely do. I do talk about risks.

[00:52:16] Um, there's a lot of unknowns there, right? So we worry about cardiovascular and thromboses. Someone who had a cardiovascular disease and was stented and maybe they're on dual anti platelet, they actually may be well covered and you can safely use this medication. Um, patients who have maybe a higher risk or less mobile, maybe I'll, I'll think about using an aspirin with it to decrease platelet aggregation because there is some data that the JAK inhibitors work through that.

[00:52:44] But the, the simple answer is yes, I do use it. The second caveat is if it's someone with acute severe UC and they're 80 or so, I also have a conversation about colectomy, right? Because this is someone now, if they respond to Jack, they're going to stay on for the next 15, 20 years, or do we think about just taking the colon out and obviating the need for any therapy?

[00:53:06] And that comes into their preference. Um, what other comorbidities and medications and all those things.

[00:53:14] Pontus Karling: Yeah, I also have the question of this biologic, biologic aging. Yeah, in the clinical practice in the non academic hospital. Uh, what? How should you try to judge the patient's biologic, biologic age?

[00:53:35] Adam Faye: Yeah, it's a great question.

[00:53:37] Um, the upshot is, um, We should hopefully have more data soon. There's some good data even in other fields to suggest maybe grip strength on can be enough alone, right? Because you can't in a clinical in a busy clinic. You can't be doing 30 different measures to figure out someone's biological age. Um, there's some, uh, vulnerable, uh, there's like the V.

[00:54:01] E. S. scores where you can visualize. And check. They may not correlate well with with some of those other markers, so we're studying it. There's really going to be probably two ways. One is maybe a deficit model where you can imagine in your electronic health record or whatnot, it can put all the deficits together and give you a score.

[00:54:20] They're in a low frailty, moderate or high, and then second will probably have to boil down from this cohort that we're studying. Is there one or maybe two quick metrics, right? You can imagine. Nurse comes in and does vital signs and grip strength for someone 65 years and older and does a three question malnutrition screen and you can basically risk stratify their frailty.

[00:54:40] So it's coming. We don't have it quite yet. What is like the single tool you could quickly use, but that's probably what it'll look like in the next few years. It's a great question.

[00:54:52] Pontus Karling: Yeah, I have a I have a last question here from. For myself, it's a couple of months ago, and I read two articles on and on patients with diabetics.

[00:55:04] They are usually older and it was an epidemiology study that show that persons with diabetic. treating with metformin had a lower risk of getting inflammatory bowel disease. And I also saw an article from a little small study from Egypt that used metformin in combination with mesalazine to treat the bowel disease.

[00:55:30] inpatient ulcerative colitis with promising results. Have you heard anything about this, or is this something you should start studying? No,

[00:55:40] Adam Faye: it's a good question. Definitely needs more data. Metformin, I think, has gained a lot of excitement, even outside of, I think, There was a thought that maybe metformin can, uh, mitigate the effects of aging over time.

[00:55:53] It's interesting. I don't quite know, is it that the diabetes or what we've shown with the cardiovascular disease underlying inflammatory component is being mitigated by the medication and that's what's driving maybe a change in the development of IBD, is metformin working on a certain pathway? Um, this is what I think the fun of A lot of the data being done in Sweden and other of the Nordic countries is we get the epidemiologic data and then we can dive into some of the biology behind it.

[00:56:22] Um, I don't know. It's an interesting thought, but there's certainly metformin has gained kind of. Interest in in in other areas as well as potentially helping out aging and so forth. So, yeah, it's exciting.

[00:56:37] Pontus Karling: Thank you. Adam. This is very good and great. I, I, I William hope this lecture will be seen by money people here in Sweden and, um, I leave the word to yes for them.

[00:56:52] Jesper Lundblad: Alright. Uh, thank you very much Adam and Ponto. I will, I will now switch over to, to Swedish.

[00:56:58] And it will also be available as on demand on SKF's website and at medevents. se, so feel free to give tips to your colleagues who may have missed it now. Finally, I would also like to give a tip about the two upcoming physical meetings that Mediuset is arranging after UEG Week this fall. Post UEGV in Stockholm and the Western Swedish UEGV meeting in Gothenburg.

[00:57:19] These meetings will summarize the most important insights from the UEG congress in Vienna, and even these are free of charge for participants. So please visit medvends. se to read more and sign up. Det för att ni har tittat.