"Management of Pediatric IBD" presented by Elizabeth Spencer, MD, MSc
A virtual course series created by Dr. Jean-Frederic Colombel and his team to provide medical education on IBD management to IBD physicians practicing in Ukraine, addressing the lack of educational opportunities available as a result of the war.
Chapters (Click to go to chapter start)
Challenges in Pediatric IBD Unique Features Addressing Unique Features Precision Therapy in Pediatric IBD Highlight of Therapeutics & Monitoring
Hi, I'm Lizzy Spencer. I'm an assistant professor of pediatric gastro neurology um here at Mount Sinai and I was gonna talk to you about the management of pediatric IBD. Um I've sort of I have a few different things to talk about it in this talk. I tried not to focus too much on medications um that we use, although I do talk about it a little bit because I know um there are some limitations to what's available. Um Alright, so first, why does it matter? Um and about a quarter of patients are pediatric inflammatory bowel disease patients. You can see here the age of onset of IBD. Um and a quarter of those occur before the age of 20 from by the age of 20. So in the pediatric age range, so very common. And then there was a recent meta analysis just from this year um looking at the epidemiology of pediatric inflammatory bowel disease. Um and there was consensus that the prevalence of pediatric IBD is rising amongst all studies that looked at it. Um And and 84% of the studies um said, not only is the problems rising, but the incident is rising. Um you can see here is a breakdown by sort of location. I've circled here for you Eastern europe, which is a pretty broad range of 2 to 14 incidents per 100,000 person years, which is actually not so far off from the U. S. Which had a 2 to 8 per 100,000 person years. Um There's a thought that this is all due to industrialization. If you look at sort of the historical timeline. Um and then of course, always a call out to dr Cronin here from the from Mount Sinai um and his publication back in 1932 which identified um regional um ili Itis. So, um, just an overview of the talk, I'm gonna first talk about um just challenges generally in pediatric IBD, um, unique features and then addressing those unique features. Um and then precision therapy and pediatric IBD, which encompasses a few different topics. And then I'm just gonna do a few highlights on therapeutics, um, sort of some novel ideas and therapeutics uh and monitoring strategies. So, first of all, the challenges um in pediatric IBD are just the fact that um we sometimes get folks coming to us um, even before really we can make a firm diagnosis. Um, so we'll get sort of these soft findings and it's a little bit of a challenge to know how to deal with with someone who you think is going to be disease, but doesn't actually meet yet the criteria. Um, and that usually then just leads to too close monitoring and can be a really great scenario to catch someone early. But we do struggle with this sort of early patient and then um, just inherent to being a pediatric diagnosis is you're gonna have the disease for longer. So you're going to be exposed to the disease for longer and the risks that that brings you're going to be exposed to the medications for the disease for longer. Um and the potential adverse events that that brings. Um and that's just inherently a major problem in pediatrics. Beyond that, pediatric patients just tend to have a presentation that's more severe um than adults in extent, not necessarily in complication, but in an extent. Um and so that can impact how we manage the patients. And then in listening to Asher really another kind of common one That we have is that dozing is really poorly understood um sort of, I think generally for pediatrics, uh and what we find is actually that Children need higher doses than adults. He was talking to you about how five and 10, there isn't much of a difference in his acute severe, you see, there is in pediatrics, they do tend to go through the drug faster and and we tend to use higher doses than our adult colleagues comparably per weight. Um and then finally you have a developing brain and developing sort of psyche and your pediatric patients. And this can have real impacts on that that really impact their their full life. Um So another important consideration. So what are some of the unique features for Children for people who are diagnosed in a pediatric age range? First of all, they can have really subtle symptoms. I feel like the refrain in my clinic is always, but they seem fine. Like I don't under like, they don't know why they can be diagnosed with IBD, they seem fine. Um And the more kind of common thing that brings kids to us is actually delays in growth and puberty, which obviously isn't necessarily seen in adults outside of maybe weight loss. Um Although you are going to get a nutrition talk just after me which will go into that in more depth. Um And then of course the psychological issues that I talked about before. The main one unique to pediatrics is this sort of evolving self esteem. Um And a lot of our medications have side effects like like steroids that can really impact self esteem with moon face. And there was a recent um paper that just came out and was presented at U. E. G. World um where they showed that actually up to 5% of people who have suicidal ideation um when they're on steroids. So it's really something to consider. Um And then of course, as I was saying before, the extent is greater in pediatric patients. So you see more commonly presents with a pan colitis than in adults. Um Crohn's disease more commonly involves the colon. Um pretty consistently in studies, 80% of pediatric patients will have some sort of colonic involvement which is distinctly different from adults. Um although Crohn's patients, pediatric patients are more likely to be uncomplicated at presentation compared to adults. Um and then of course the impacts on nutrition and development. And then finally upper tract disease is much more common in pediatrics which changes a little bit our way we diagnose it. So first of all let's just dive into growth and puberty. I feel like that's the one people realize is the most the biggest difference between pediatrics and adults. Um And it's very very common to have growth impacts in impedes IBD. So we see about a third of patients are having some sort of issue with either growth or puberty delays. Um much more common in Crohn's disease than in all sort of colitis. Although it is present in all sort of colitis. I think they get this sort of thought that you see patients don't experience it at all. They do as well. Um up to 12%. Uh and we can commonly look back at the growth charts because we always request growth charts on our patients and we can predict when I. B. D. Probably started when we started to get that pre clinical disease because you'll see them start to fall off of their growth chart. Um And that's a kind of a common interesting thing to do in IBD and the pedes side. Um And then uh there have been um sort of estimates that up to a quarter of patients might not achieve their full adult height potential because of the myriad sort of impacts on on growth. Which of course corticosteroids uh kind of exacerbate and then um The it's not just corticosteroids, there's actually a pretty complex kind of a number of risk factors that lead into growth issues. And I. B. D. Um Which I assume you might actually get a little bit in the nutrition because some of them are from uh poor nutrition. Um And then the impacts on growth hormone um where you get growth hormone resistance, it's very common to see in our pediatric IBD patients even post treatment will see it. Um And then of course the side declines where TNF will actually go to the joints. Um And there's a pretty clear data showing that when you give anti TNF, that's really one of the best ways to um allow a child to grow. Um And it's probably because of that because it can clear that TNF out of the joints. And then there are further susceptibility genes um tied to it that are actually linked to IBD um as well. So you can see short stature um a little bit more commonly because of those shared risk alleles. Um Then of course the journal disease which upper tract disease is more common in pedes um digital diseases linked to growth issues. Um So it can also have really large impacts. Um And then something else just for the adult doctors on the call is after the age of 18 height velocity may be non zero and pediatric patients, former pediatric IBD patients because they have some ketchup growth and actually their growth when you compare them to non IBD controls. Um they grow afterwards, so they can grow into their twenties. Um And you should really Make sure that you're cognizant of that and you're sort of peeking out every potential inch that they might have because they can actually have significant height velocity after the age of 18. Um so if you make sure you manage their IBD that can help them to achieve their full height potential. And this is particularly important in male disease patients is where they have seen the biggest sort of delta here. Um so how do we manage all these unique clinical features and I'm sorry, this is a bit of a busy slide. Um but first of all we monitor growth and puberty very closely. Uh so I always get a mid parental height when I first meet a patient. So I know sort of what the expectation is for their growth and then I think really strongly in my, when I'm choosing therapy about where this child is in growth. Like is this a 15 year old where I'm sort of I have only a short amount of time to achieve their growth potential. Or is this a nine year old where I have much longer to get them well to then allow them to grow? Um So I'm thinking of that when I'm choosing therapy and thinking about my speed of therapy. Um There's also growth and psychological impacts are tied very closely. One of the most common sort of self esteem issues in our boys with diseases that they're shorter than their peers. Um This can actually lead to a lot of bullying and problems. Um So I just want to make sure that you're hearing them about their their goals because I did have um some boys recently decided they would rather to have surgery up front to remove the disease so that they could have a speedier sort of improvement and hopefully speedier growth to catch up with their peers. Um So you kind of have to keep that in mind when you're deciding on your patient's treatment plan. Um There are a couple of things I like to highlight on nutrition and diet for pediatric patients and that's just um in with restrictive diets which tend to be used more in pediatrics. Parents are very happy to um put their Children, I suppose under restrictive diets, it can actually lead to a lot of problems. And we're seeing a rise of specific eating disorder called avoidant restrictive eating. Um where they really only are eating a very limited amount of food. Um And that can be quite problematic. Uh and require therapy for that eating disorder. Um So you want to make sure you're not pressing restrictive diets and you're giving them some education about sort of the limits of what certain restrictive diets can accomplish. Um And then in the US we see a lot of times obese patients. Um And we need to be cognizant of the fact that they still may be experiencing malnutrition which is sort of a common entity that we need to keep in mind. Um Other psychosocial impacts that I haven't already touched upon our school attendance and making sure that you're supporting them. I'm not certain what you all have there but we have accommodation plans that we can do with the school called five or four plans. Um And I provide one to every patient to make sure the school can sort of accommodate them for any missed classes. Um And allow them to go to the bathroom if they need to go. Um And then um always think about if you're patient has any sort of food insecurity that may be impacting your sort of treatment plan or any financial impacts getting the therapies have on the families. They did they looked in the U. S. And food insecurity was actually extremely common. And inflammatory bowel disease patients a little bit more so than I thought it was present. But um I could approach a third and I imagine this might be a real problem with some of your patients. Um And then finally just because of the upper tract disease um With pediatric IBD we do an E. G. D. And upper endoscopy for everyone. Um And this is a distinct difference between the pediatric and the adult guidelines. You can see the A. C. G. Guidelines they say only if they have symptoms should you do it. Um And they quote um and upper track disease. Um 5% in adults with IBD. In pediatrics it can really approach half the patients having upper tract disease. Um Including you see patients will have upper tract disease. So we always do an E. G. D. In some sort of formal small bowel assessment whether that be an M. R. I. Or a capsule endoscopy um depending on sort of what are our patients um sort of need. Uh And then finally in pediatrics we really try to use an uh an approach where we have a bunch of different subspecialty providers um supporting the patient from endocrinology for growth. Um Two psychologists that we have a nutritionist to help make sure that we're addressing these special components of their care. Next I'm gonna switch gears and talk a little bit about precision medicine and um how to practically approach precision medicine today. Um precision medicine. All that means is that you're choosing the right patient to comparing them to the right therapy, choosing that right dose pediatrics. I was telling you could be higher um picking the right time to give the therapy which we already had a question about today is when when she do position biologics. Um And then also how to monitor the patient it's a lifelong disease. We have to make sure that therapy continues to work. Um And then I'm gonna start with the right time because I think that's sort of the most. Um, the question that we struggle with a lot. Um, so you can see this is a slide I took from David Rubin. Um and the IBD armamentarium that we have available to us is quite large. I know that there are some sort of limitations, but I will say in pediatrics you can see there's only one approval for anti TNF. There's inflicts a mob and mob here in the US. Nothing else is approved. Um, so we we too don't have many meds that are formally approved. We we have to often go through a lot of different hoops to get some of these other medications. Um, but it it is making a bit harder to choose when you have so many choices. Um, which is, you know, not necessarily a problem. It's a good thing that there are a lot of choices for us. Um, but it it can make it more difficult. So when do you start therapy? Um, I don't know if you've gotten this talk before about early effective therapy, it sounds like maybe you did on the last set of talks, but this is the pediatric evidence for it. So in um, in Crohn's disease in the risk trial, which is a big inception Cohort where they had 1800 patients newly diagnosed with Crohn's disease before they started therapy. And they followed them very closely with a lot of different multi atomic kind of uh collections that they did and what they found was that those who received TNF early compared to those who got an immuno modulator had improved remission at a year 85% versus 60%. So really a distinct difference between the two and not only that as I was telling you, TNF is quite good for growth. Um And they found this the same that linear growth was improved only in that group that got early. TNF. A smaller study from South Korea showed the same thing. Um Those who got inflicts met just after diagnosis did better than those who had to fail um by appearing and salome first. Um And then the duration of um like their durability on the medication was also better. They they had a short window between their diagnosis and inflicts and start they did a lot better and they had fewer relapses over three years. Um So it's it's good in the short term, it's good in the long term. And then finally um there is a multi center trial that just came out from europe. Um That was really quite nice and showed that first line inflicts a mob if you gave it before an immuno modulator. Um You also had improved short term long term remission and growth. So sort of book ending all of these showing the same, very similar thing for Crohn's disease. Well, sort of colitis just as the story is um not very supportive of the same early treatment and all sort of clerestory adults. Um There just isn't really data in pediatric patients. There's one study of thigh appearing early versus late which is before six months or after a year. And what they found was that there weren't any differences in hospitalization or long term outcomes depending on if you gave it earlier late. So you see as a little bit of a different entity but in this disease there's clear evidence and why that is this is Jean fred's kind of famous. Um I figured that he had used which is showing that the relapsing remitting course, which is this black line of inflammation kind of coming and going and then you're accruing damage over time. If you institute that therapy early, you sort of stop the damage in its path and you're able to then control the patient over the lifetime. And that could be quite a long time in pediatrics. Um so how do we choose then? Um First line therapy and there are some head to head trials now which I'm not going to present because I didn't think they were so pertinent for a minute. But there are network meta analyses that say, you know, inflicts mob is actually pretty good um in the biologic naive for both. You see and then also here for Crohn's disease in these network meta analyses, which suggests that those are the kind of to to use first after inflicting exposure for you see suggesting um and then it's suggesting risen, risen or an adult with a thigh appearing for Crohn's disease. Um So in positioning is definitely not a bad choice, which it sounds like you can give your patients. Um How do we choose who needs some sort of early therapy? Most pediatric, as I was telling you, is more extensive, more severe from the start. Um So in most of our cases we early therapy may be warranted but we do use um some clinical features um to help us decide upon that. Um A lot of those have to do just with how extensive and how complicated um the diseases. And is there um Concomitant c diff like, gosh I was talking about. Sorry. Um but we do need some more precise markers to help us better break down this like heterogeneous population of IBD patients. Um So right now we still sort of use this one size fits all approach. But hopefully in the future we will have those markers that can break people down based on their pathway and let us choose the drug to pair to the patient. Um with the obvious caveats that a lot of these drugs are very expensive. Um and that may be a limiting factor in being able to do something as sort of pie in the sky is this. Um And then finally, in pediatrics, one of the really important things is aligning on treatment goals using shared decision making. Um So we really do have a discussion with the patients about. Are they traveling a lot um Are are they going off to college and it might be easier to be on an inch. Um And we do incorporate that into our medication choice and Corey Siegel has done a lot of work on this showing that if you do have this discussion and make the patient a part of the discussion it leads to improved adherence um and just better outcomes in general for your patients. Um Some of my work has been on using pharmacogenomics um to also pick therapies um to know what kind of adverse events. I'm sure you guys are aware of the thigh appearing. The T. P. M. T. T. 15 2 risk alleles genetic risk alleles tied to leukemia. Um So we check those before we would start appearing and you can adjust the dose or in the presence of both potentially not start the medication. Um There's also an H. L. A. Um uh risk variant tied to pancreatitis. Um that's not clinically used yet but may be used in the future. Um Where up to 20% of patients who have this could experience pancreatitis with my appearance and then to go back to the pants study um uh showed the H. L. A. D. Q. A. 105 a variant was tied to the development of anti drug antibodies particularly within flicks a mob um where they had 90% of the patients who had this risk variant having um anti drug antibodies um at one year So they had recommended checking it. Um or uh and if the patient has it considering combination therapy to sort of stave off of these antibodies. Um We um don't tend to actually use combination therapy on the pediatric side here. Um We use just hire dozing um with really tight control with therapeutic drug monitoring. Marla Dubinsky has um talked about this extensively but this is her data showing that those who were on this accelerated dosing schedule um were less likely to have anti drug antibodies. Um And I actually took the data from this study to look back at that age chile and say in our method where we just use accelerated dosage and we have high levels on our patients because we are really aggressive with our dozing Does H. L. A. Even matter in the face of high levels. Um And what I found was it didn't really matter if you're using proactiv sort of aggressive monitoring. Which I think either one to be honest is fair like if you're gonna not use progressive aggressive monitoring or you're gonna want to decide between combination therapy or stopping combination therapy. Um checking the H. L. A. Is a fair thing to do. Um But if you are using um proactive monitoring you may not need to to know the H. L. A. Status. Um And then finally some of our work here is really focusing on trying to figure out how different cytokines signatures. And someone could make us choose a therapy yes or no. Like is tina right therapy from the start even though those network analysis say you you should um do it um Or should we actually be using something like um Stelara or Skyrim or something that's in aisle 12 or 23 Blocker. And currently, even though we don't have um like a test yet to do that, I actually do often start with an aisle 12 or 23 um blocker in people who have concomitant psoriasis which is a little bit more common in pediatrics um than than in adults but in that concomitant psoriasis um will start that instead of using anti TNF. Um And it seems to work nicely but you can think of that for a lot of the other uh coexisting immune conditions where you're going to pair something um That can treat both conditions a little bit better because we know that some of our therapies are a little bit better for extra intestinal manifestations that are a little better for other immune conditions. Um And it can help in your treatment selection. Um This is just combo. I think I'm gonna skip this. I'm sorry. Um But and go to the treat to target strategy. So stride to added pediatrics and just added growth as one of the kind of goals um of monitoring. Um So this is where you're treating not to just symptom response. You're treating to deeper markers like protect and crp growth in pediatrics and then ultimately endoscopy and maybe trans mural healing. Um We are using more intestinal ultrasound here which I think dr Dollinger, my colleague mike um probably gave you a nice talk about it um just where he showed that it can be feasibly done. Um And he presented some probably. Sorry, I didn't realize it was all animated. Um He presented some really nice data I think about how in pediatrics the bowel wall thicknesses thinner. Um So we probably have slightly different goals but we can in pediatrics really nicely achieved trans mural healing probably cause we are catching that disease a little bit earlier. Um So it should be a goal um In pediatrics we should be able to decrease that bowel wall thickness over time as you're on therapy. Use it as a nice easy kind of cheap monitoring strategy. Um And then once you achieve treat trans neural healing people have much better long term outcomes. Um So it is a goal that we can achieve and we should try to achieve it. Um And that's it. I'm sorry it's sort of meandered through a bunch of different things. Um But thank you so much lizzie. I must say it's so precious to have lizzie. She's an amazing radio attrition doctor and amazing researcher. Thank you so much lizzie. uh lexi Alex. Sorry, any questions? Thank you. Doctor sponsor? Yeah, I got a couple of questions. And the first one is the about this thing you mentioned about the growth chart and how you see that there is like the growth the way before the clinical manifestation. How long is this period actually before we actually see a clinical manifestation and IBD and the moment when we see the growth. Um The way Yeah, you know what I was actually looking cause I I think it's a good research question to ask is are we any better at identifying folks early and seeing where this drop off of the chart occurred to see if 10 years ago it was longer than than it is now. But the answer is no one really knows. I'll tell you from just my clinic that usually it's like a year or two. Um is the drop off that I see um is the most kind of common. Um So it is a while and it's just because kids are subtle, parents will always be kicking themselves that they missed it but it's very subtle. Um and really their pediatrician is the one who missed it because of that fall off the curve. Thank you. And the second question about the small bowel imaging. Uh I know you mentioned that the recommendations are mentioning that but uh there is a lot of technical difficulties and I'm sure in States still regarding the M. R. I. And capsule. Uh how many patients actually having this image in uh done and what is the value of the small bowel imaging? If there is no concern about small bowel in movement? That's a good question. Sometimes I do take it on a case by case basis because in the little ones you write it can be very difficult to get these things accomplished. Um We we do try to do it mainly because we're wanting to know where we should position surgery because the little kids tend to present more with colonic disease. But then they can you know change oh over to more of a like phenotype. So we want to know from the outset to know are they candidate potentially for collecting me or where should I position this patient? It's I agree I have even a two year old now who I haven't gotten small battle imaging on yet because it's just been not feasible. Um And so you kind of have to take it in stride and what you're actually wanting to know. But I would do it before doing surgery. I would I would really get imaging to know if um sort of the risk of having problems with the pouch if you're gonna consider um ilia pouch anastomosis. Um But I hear you and then there's small bowel follow through which you could do instead which we don't commonly do. But that's a definitely a viable technique or C. T. Um Can also be good. We just try not to irradiate. Um Kids thank you. And there's another question in the chat from Dr Klimenko and I think that's one of the favorite question for Professor Colin bell to the steroids. Uh How you approach like using steroids if you have to. Yeah I so I know I'm in sort of a rarefied position but I I try not never to use steroids. Um So I will go straight to the biologic. I know that was I think a question for action. We we try pretty extensively to go straight to biologic um knowing that they're going to be on it eventually. And we'd rather than never see steroids. Um If they do then I use a lower dose than what Asher was describing. Usually we actually cap out at 40 mg of predniSONE or the equivalent I. V. Dose. Um And that's again taken from the same sort of study showing that the high doses were not any more effective. So 40 mg pregnant zone or the equivalent sometimes I'll go up to 60 rarely. Um um But it usually doesn't do much of a difference. And then for the anti TNF um I often see kids with alba mons two or lower that we can salvage with inflicts a map. So I think it's a little bit different than the adults because it's just a common presentation again because of that upper track disease where they're losing albumin through their small bowel um where we see very commonly this type of album anemia that we have to overcome, which pushes that dose. Um There is some data though that steroids plus inflict does lead to better outcomes. Um So sometimes if I have a very sick child, I will use steroids um hoping to sort of salvage them. Um But for us um in the hospital, are you talking your easy? Uh Those are the doses I use, but I'll probably give up around the 5 to 7 day mark. Um If I'm not salvaging someone. Thank you. Thank you so much lizzie as always. Uh maybe as a transition question with a talk by staff, Are you? Because I know that in France and I don't know how it is in Ukraine were using a lot of uh literal nutrition in kids instead of using steroids, Are you still using it? But with with feeding tube not to go home? Yeah, us it's less popular. I don't I still don't know why. Well, I can tell you why. So it's not a maintenance strategy. So I just I think it's very silly to put a child through the social impacts of going on exclusive ventral nutrition when I'm just going to put them on a biologic therapy anyway. Ultimately for me, so it makes no sense to me from that standpoint. And I also am bothered by the fact that people think that it's okay for kids to be an entry nutrition. But this is not a recommendation for adults. Why? Because it's socially difficult and people are okay to put this on their Children but they're not okay to do this for themselves. You can do it during the night and then they can go to school without the tube and this is what and they can't eat with their friends. What's the most social thing that we do as humans, we eat with each other, destroying their like social skills. I'm eating you. I'm hearing you I'm I'm I'm mentioning that because in the context of countries where maybe there is difficult access to biologics and especially you can maybe this is an alternative. Yeah. It's just so I guess what I'm saying is it's not a great maintenance strategy. It's never been shown to be effective in maintenance because people cannot adhere they lose adherence over time because it's it's very difficult. Um But it is really great for I guess there's two kind of context. It is good for induction if you don't have anything else that you're um that you can use. It's great for induction. It really does work in lieu of steroids in lieu of inflexible it can work. The other thing that's really great at is pre op so to get someone into like sort of the best state pre op it really is quite good. And there was a nice study that was presented at d D. W last year showing that if you gave a few weeks of central nutrition pre op, you had much better outcomes afterwards. And so I do use it in that case. Um Not necessarily exclusive but I will give supplemental lentil nutrition to my my kids to enhance sort of their outcomes post op. Okay. Thank you so much.
