IBD Drive Time: Jeremy Adler, MD, on Pediatric IBD

In this episode of IBD Drive Time, Dr Millie Long discusses the advances in care for children and transitioning pediatric patients to adult care with inflammatory bowel disease with Dr Jeremy Adler, a pediatric IBD specialist.

Millie Long, MD, is professor of medicine, vice-chief for Education and Fellowship Program director in the division of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill. Raymond Cross, MD, is professor of medicine and director of the Inflammatory Bowel Disease Program at the University of Maryland School of Medicine in Baltimore, Maryland. Jeremy Adler, MD, is clinical professor in the Department of Pediatrics, Division of Pediatric Gastroenterology, at the University of Michigan in Ann Arbor.

TRANSCRIPT:

Dr Millie Long:

Hello, this is Millie Long, one of your co-hosts of IBD Drive Time. Along with Ray Cross from University of Maryland, we would like to welcome our guest today. We are excited to welcome Dr. Jeremy Adler, Clinical Professor of Pediatrics at University of Michigan in their IBD Center. Jeremy, welcome to IBD Drive Time.

Dr Jeremy Adler:

Thank you very much. Thanks for inviting me. I'm excited to join you.

Dr Long:

Well, we're excited to really learn about the pediatrics perspective from you. A lot of our listeners, I think, are adult gastroenterologists, but there's so much to learn as we think about this continuum of care for our IBD patients. One of the first questions I had for you, which I think is actually really important, is a recent abstract that you presented at the Advances in IBD Meeting. This was entitled, Changing Use of Biologic Medications and Associated Outcomes for Pediatric IBD. Importantly, it was awarded the Best of 2022 AIBD Abstract in Pediatrics. Can you summarize this study and what you think our listeners can take from it?

Dr Adler:

Thanks for asking and our group is honored to receive the Poster Award. The history behind the abstract is, there's been a lot of changes in how we take care of patients with inflammatory bowel disease over the years and we really wanted to see how those changes relate to outcomes. We and a number of our colleagues and members of the ImproveCareNow Network—this is a big, multicenter quality improvement collaborative, and the network has a registry with data on tens of thousands of kids with inflammatory bowel disease—used the data from the registry and it included 93 centers and over 4,000 children, because we specifically focused on the kids with Crohn's disease who are enrolled in the registry soon after diagnosis. What we did is we looked at the trends in medication use and specifically the trends in when biologic drugs were used and the outcomes.

The outcomes that are easiest to measure in this registry are fistulae, strictures, perianal disease, so those were the outcomes that we looked at. We looked at data from 2010 through the end of 2019, so a full decade worth of data. In those 4,000 kids over the years what we saw is increasing use of biologics—and here we're talking primarily about the anti-TNF medications—increasing use of biologics and using them earlier. So we found that overall at the beginning of the study, about 52% of kids were started on an anti-TNF medication. By the end of the study, by the end of 2019, that was up to 76%. The time from diagnosis to the start of the anti-TNF meds went down from about 3 years at the start of this study down to about 54 days. So a little under 2 months from diagnosis to the start of the first biologic drug, which is huge change and it reflects a change across the United States at multiple practices.

What we saw in that same time period is the rate of complications went down. Overall, the rate of all of those disease complications—stricturing, penetrating, perianal complications—at the beginning of the study was 24% of patients had developed at least 1 of those complications. By the end of the study, it was down to 10%. This was across the board for all populations, including some of the populations we know have higher rates of these complications, such as African Americans, Asian patients, and adolescents.

Dr Long:

I find this to be so important because I think we can learn from this in the adult population as well, that earlier treatment to control disease and inflammation may actually help us to prevent progression of disease regardless of age, whether pediatric or adult patient. In practice— I've obviously been in practice a while too—and I remember 10, 15 years ago, of course, it's all about steroid sparing, but it was much more about using enteral nutrition to induce response and medications like methotrexate to maintain. Have these practice patterns really changed? It sounds like they have.

Dr Adler:

Yeah, it really has. So pediatrics as a field has really tried hard to avoid steroids for a long time and different groups have taken different approaches. There's some groups that use a lot more enteral nutritional therapy than others, but across the board, even the groups that use enteral nutritional therapy, even those groups are using more and more biologics over time. So we are seeing this across the entire pediatric field.

Dr Long:

That's great. And many lessons to be learned from an adult perspective. One of your other research interests that I know our listeners will be interested in is the idea of quantifying inflammatory burden seen endoscopically and radiographically. For endoscopy there are a number of validated indices, but they all have some issues associated with them. But what I'd love to hear you tell us a little bit more about the new endoscopy scoring system for Crohn's disease that you've been working on.

Dr Adler:

Thank you. So we developed an endoscopic score for Crohn's disease called the Simplified Endoscopic Mucosal Assessment of Crohn's Disease, the SEMA-CD. And this came about really because of the need for a score that clinicians can use. This was in the ImproveCareNow network. We were preparing to launch a clinical trial, a randomized comparative effectiveness study—and this was a pragmatic study that regular clinicians were going to be recruiting patients for and collecting data for it. We were looking for a way to evaluate mucosal activity that was similar for clinicians to use because the SES-CD and the CDEIS, the 2 really main validated scores for Crohn's disease were both developed as research tools and they're both really cumbersome. And a lot, or possibly most clinicians just don't use them in practice. So we developed this tool as a very simple tool.

You just score the ileum from normal to severe with one number and you score the colon from normal to severe with one number, and then count the number of segments of colon that are involved. And that's the whole score. But you can't just make up a score. We then had to study it and see if it worked. And so we studied this with videos of colonoscopy scored by blinded central readers and compared it to SES-CD in a reasonably small pediatric population and it worked, which was exciting because this was a tool that regular docs could use. The next step was to validate this in a proper larger study. And that's the study that was most recently published, where we took videos of colonoscopies from clinical trials, 1 set of videos from a pediatric trial, 1 set of videos from an adult trial—these were ustekinumab trials—and we had central readers who were blinded to all the clinical information score the videos. And these were adult gastroenterologists who are experienced central readers. And it was a wonderful study because one, the new score correlates beautifully for with the SES-CD. Two, it actually is sensitive to change. So if somebody's disease got better, the score goes down. If somebody's disease got worse, the score goes up. And I think the third feature of this, which was really nice is everyone agreed, the central readers as well, that this was just an easy score to use. So I hope that this score both makes it easier for us as clinicians to have a common language of recording how severe endoscopic findings are. But also this can now be used as a research tool.

Dr Long:

No, I think it's fantastic. And there's an added advantage that you can also use the tool retrospectively. Is that right? From reports?

Dr Adler:

Yeah, that's exactly right. We did a third study where we had central readers score the text of colonoscopy reports and then compare that to scores of the videos of the colonoscopy reports. Some of them scored with pictures and some of them scored without pictures, with just text and it worked for both of them. The pictures probably aren't even necessary. And actually it worked better than I expected. From the text of colonoscopy reports, you now can score the severity of endoscopic findings. So we're using that in a study currently, which is great for pragmatic clinical research because now we can have that gold standard of mucosal healing in clinical studies that we didn't previously.

Dr Long:

What a great advancement for the field and I look forward to having that simpler score at my fingertips in practice. You are our first pediatrics-focused podcast and we're thrilled to have you on. So I'd love to pick your brain and have you tell us what you think that, in the last several years, the top 3 advances have been in pediatrics and obviously, that impacts us as adult gastroenterologists as well.

Dr Adler:

Thank you. I'm excited to honored to be the first pediatric topic for the podcast. There's so many advances in the recent years that it's actually hard to pick my favorite. But I'd say the top few would be the availability of more advanced therapies, biologics and small molecule therapies. Because we all have patients where the first choice medicine doesn't work and it's really nice to have access to more treatment options to improve outcomes and avoid steroids. And the anti-TNF drugs, even though they're not new, they've been around for 25 years now, but the anti-TNF drugs, they're still our go-to medicines. They're the ones where we actually have data that they improve growth for children with inflammatory bowel disease. And there's some data that they can help prevent disease-related complications. So I think for long-term outcomes it's great to have these medicines that we didn't have when we first started practicing.

Along the lines with that is the therapeutic drug monitoring. I think our societies all pretty much agree that monitoring during induction is important, but where maybe we differ is proactive therapeutic drug monitoring. I understand the data is not really there to support that in the adult literature. But in pediatrics where children are growing, their metabolism is changing, they're going through puberty, their doses actually do change and should change as they're growing. So we now have a few studies that show that proactive therapeutic drug monitoring in children really does improve outcomes. So those are 2 really, I think, helpful things. Or maybe that's one thing. And I think the second thing is quality improvement. The ImproveCareNow Network is a wonderful resource to help improve care through QI methods, but through collaboration, all of us working together. And also it's a nice source of data for research.

And if I could add 1 more, I would say the very early onset IBD, the VEO-IBD. These are the children who are diagnosed under age of 6 years. They're much more likely to have monogenic disease. They're much more likely to have immune defects that, I mean, either of the source of the IBD, or mimickers of IBD, depending on your perspective. But in the last few years, that field has exploded. We know so much more now about the genetics and immunology of those conditions. And it's actually in a real way help for some of the kids to get better targeted therapies at their particular immune defect. We have a long way to go. There's still a lot we don't know. I forget the exact statistics, but maybe we find an identifiable mutation in 10 or 15% of these kids. But that's 10 or 15% that we didn't know what to do with just a few years ago. So it's really an exciting area of advancement.

Dr Long:

Great to be able to better understand and better have options for that difficult-to-treat group. No, those are wonderful components that I think really have changed and have influenced us as adult gastroenterologists as well. Well, of course, there are differences in data surrounding therapeutic drug monitoring in adults and kids. I will say that part of that may have to do with practice patterns in adults. I, for example, use a lot more combination therapy upfront with thiopurine or methotrexate to help to reduce immunogenicity. But I agree with you wholeheartedly and especially in a field where more monotherapy of TNF is utilized, such as in pediatrics, absolutely drug level checking would be imperative in that group to optimize and prevent those low levels and the increased immunogenicity.

So I think we're continuing to learn a lot about how to optimize TNFs in both the pediatric and adult populations and would completely agree with you that even in the adult world, we have the best data with TNFs in terms of really modifying disease course and preventing these complications. So they're still very relevant, even in the setting of all of these novel therapeutics.

So let me ask you one last question before I get to my favorite question. The last clinical question I'll ask you has to do with transitioning patients from pediatric to adult providers. I think probably we have a mixture of providers listening, usually more adult. And what could some simple things that both the pediatrics and the adult provider can do to help to make that transition successful?

Dr Adler:

That's such an important topic, because all of our patients grow up and become your patients, or at least they should. So from the pediatric side, I think this process of preparing people for transitioning to the adult world really begins, or at least should begin, early on. And we think of this in terms of allocation of responsibility. And I'll give credit to my colleague, pediatric psychologist Emily Fredericks for, I think she coined that term. If not, she at least taught it to me. You could think of it this way, when kids are little, the parent is running the show as far as health care goes and the kids are there going along. And over time the child grows up and needs to learn how to take care of their own health. And there should be some shifting of that allocation of responsibility so that by the time the kid/young adult moves on to the adult world, they should be in charge of their health care. And the parent maybe there maybe, but is a long for the ride.

And that takes time. There are lots of opportunities along the way for education so that the kid learns about their disease, learns about their medications, and especially learns how to be proactive with it with their own health care, learns how to refill their medications, learns how to ask questions. Because a lot of times that's something that many people struggle with is speaking up and advocating for themselves. I think that's on the pediatric side, the way we focus on preparing kids for transition. I think the next step is the handoff itself. It doesn't always work out that kids are going to transfer from the pediatric practice and they're in the same institution to the adult practice where we all have shared therapy.

Dr Long:

Right. No, often it's not. I see many of your patients and people move around the country.

Dr  Adler:

Go to college somewhere else, move somewhere else. Or even within each of our states, there are more adult practices than pediatric practices, so sometimes people just simply find an adult doc closer to home than the pediatric practice they have to travel to go to.

So I think that handoff is really important. Detailed notes summarizing the disease course. And ideally, we should talk with each other, but at the very least have some form of communication about what are the active issues, what are the issues that need to be addressed? And I should say ideally, we should do this when the patient is well and the disease is under control and stable dosing and all of that. Unfortunately, it doesn't always work that way.

Dr Long:

It doesn't always happen like that. But no, exactly. I agree. And I think from my perspective from the adult side, those kids as they transition up to the adult clinic, really trust their pediatric provider and they're meeting us for the first time and often without their parents there. And so I think it can take some time to generate that trust. And one thing I do is I emphasize to them that if we're going to make any changes, I'm going to talk to their pediatric provider as well, make sure we're all on the same page. They have some confidence there. And I think that helps as they gain some trust in the adult system.

Dr Adler:

Trust is a really important issue. And on that point, when I know somebody's going to be moving somewhere, whether they're graduating from college, or the family's moving, or whatever it is, once I know where they're going, I usually will give them some recommendations of people I know there in the adult GI world. And tell them, these are people I know, these are people I trust, and you can trust them, too. I think that also helps to build confidence that they're going to be in good hands.

Dr Long:

No, absolutely. Well, I just want to take a moment to remind our listeners that the IBD Drive Time podcast is brought to you by Advances in IBD and by the Gastroenterology Learning Network. And that actually this spring, the AIBD Regional Series will kick off in March with an in-person event in Baltimore. And there are events throughout the year so please check that schedule.

So Jeremy, my last favorite question for you, which we ask all of our guests, and we'll see if we can challenge you to tell us something about yourself that Ray and I don't know, and our listeners may not know so that we can learn something today about you.

Dr Adler:

Okay. Something new that you don't know. All right, if I can stray from the medical field?

Dr Long:

Of course.

Dr Adler:

So I played violin when I was younger in college and med school. And I had the good fortune, just randomly, of getting the opportunity to play with Ray Charles .

Dr Long:

Oh, that is cool!

Dr Adler:

I was in the university orchestra and he was invited to receive an honorary doctorate there. And he played a concert and we, the orchestra, accompanied him. So that's my little moment of fame.

Dr Long:

That is a really cool. We actually have met a number of musicians along the way with IBD Drive Time, so soon enough they'll have to be an IBD Drive Time concert at one of these meetings. We'll invite you, for sure.

Well, Jeremy, thanks so much for joining us today on IBD Drive Time. We learned a lot about pediatrics, how far the field has come, some interesting new tools that we may use and the value of quality improvement. We hope to have you back at some time in the future for our podcast. And thanks again for joining.

Dr Adler:

Well, thank you so much for the invitation. This was a lot of fun. I really appreciate it.