Transcript
021631 TIIJC v01_v1
Dr. Mesinkovska: Hi, my name is Dr. Natasha Myshinkowska, and I'm here with Dr. Christopher Bunick for an episode of Practical Dermatology Journal Club. Today we're going to discuss a very, very cool article that was published recently, and it's all about atopic dermatitis in children, dupilumab, and linear growth. So this article was very sensational.
In which sense? Because it showed that maybe when you put kids on dupilumab, what happens to them, Dr. Bunick?
Dr. Bunick: Well, it shows that dupilumab can help restore kids on their growth curve. So what do we know about that? When we think about atopic dermatitis in children, it's a little bit different in that we don't have as much data on what atopic dermatitis does to children as we do in adults.
What that data does show in children, however, is that atopic dermatitis children tend to fall off the growth curve at young ages. And why might that happen? It's been attributed to a couple things. It's been attributed to lack of sleep. So why might that be important? Well, it's during REM sleep that growth hormone is most produced.
If you don't sleep as much, then you're not going to grow as much. It also turns out that growth hormone receptors are on the ends of bone plates, and we often use a lot of corticosteroids to treat atopic dermatitis. We know that in our patients 18 and over, we have now six FDA-approved therapies, and in fact 12 to 17 we also have a number of FDA-approved therapies.
But for that age group of 6 months to 11 years, we only have one FDA-approved therapy. And what that means is that for a long time we have been using a lot of corticosteroids in these younger children. What's the consequence of the corticosteroids? Corticosteroids can actually impair bone formation.
They impair osteoblasts, so you get less bone formation. They also can impair growth hormone receptor expression at the end of growth plates, so you can end up with less growth due to the steroids. You also can end up having, when you put all of that together, you have inflammation with atopic dermatitis, and there have been concerns that this unchecked, untreated ... the consequence of untreated systemic inflammation from atopic dermatitis can also impair the growth of kids.
For example, you're also very itchy. If these children are itchy and they're not sleeping, then it compounds the sleep, the use of steroids, the impact on growth hormone, growth hormone receptors, and all of that together may cause these children to fall off their growth curve.
Dr. Mesinkovska: Well, wait, so, like, I remember 2023 telling my students, I'm like, "We need to collect our data because we will start kids on dupilumab,” and in a month or two when they come back, they're like five pounds better."
And you're totally right, they catch up with the growth curve. But one thing that I found we don't do in our offices is we weigh the kids, but we don't measure their height. So when I saw this article come out, I was like, "Oh my God, this is it." What do you think about the role of inflammation on the gut?
Because that's the first thing that the parents will say, "Well, I think maybe now..." What if they're not as allergic to foods? Is there any thought about dupilumab maybe affecting some of their food sensitivities or anything else?
Dr. Bunick: Well, nutrition, poor nutrition or undernutrition, has also thought to be a driver for impaired growth or impaired height in atopic dermatitis patients.
So there are a number of factors beyond sleep, beyond steroids, nutrition being one of them, asthma being another. When you think of Th2 or Type 2 inflammation, all of the different ways in which you can get Type 2 inflammation could be affecting these children. Ever more, there's that connection between the gut, the microbiome of the gut, the gut-brain-skin axis, that entire axis.
And undoubtedly, food allergy and inflammation in the gut can impair, likely, many processes in the body, including growth. What was really fascinating about the treatment of children with dupilumab is it did restore their, their growth. This was the height, the weight. But also, another measure that was looked at was bone alkaline phosphatase.
And it actually turns out that the children on dupilumab get restoration of the bone alkaline phosphatase, phosphatase. It actually goes down in these children that are impaired with their growth.
Dr. Mesinkovska: That's really cool to learn. But why was there a little pushback against the article? Not pushback, but there was like, is it really all the dupilumab, or is it the fact that these kids are not on something else, like methotrexate, cyclosporine, other immunosuppressive thing? What's your thought on that?
Dr. Bunick: Yeah, I have a few thoughts on that. So first, I'm glad you brought up methotrexate and cyclosporine. There's a trial called PEDISTAD, and it's very clear in that trial that dupilumab had superior effect compared to methotrexate and cyclosporine in terms of just treating the underlying atopic dermatitis in the children. It really is the first line therapy in children six months to 11 years. It's the only FDA approved therapy at the moment. I think that the issue comes down to data collection. We have spent so much time on the 12 and over age group, and less collecting data on the younger age group.
We've had it ... in history with atopic dermatitis, it's only in the last few years that we've had this really transformation in emphasis on patient reported outcomes. Now, not all of what we're talking about in children is patient reported outcomes, but documentation of not just the weight, but as you said, the height, the sleep patterns, all these other variables that may impact the height, weight, growth of children, we haven't been focused in dermatology on collecting that data.
Dr. Meseinkovska: We didn't even have anything to, like, measure height in the office, so I'm like, "Oh, well this study's not going to go anywhere," so I was happy that it was done. But I think it's not that we don't want to take care of the kiddos.
Do you think most of them just go to pediatricians first for, like, the mild cases? Which also brings me to another point, the importance of treating early with systemic medications, and what's your thought on that?
Dr. Bunick: I'm a big believer, treat early, and the reason is there's a consequence to not treating that systemic inflammation.
You want to treat early, and you want to treat early with approved therapies, and that right now in the 6 month to 11 year age group is dupilumab. There are still unanswered questions as we were talking about when it comes to is it the dupilumab itself that is promoting the growth of the children, or is it the control of the inflammation that then allows the children to resume the growth?
Is it the fact that you don't need the corticosteroids and that's the major driver? Really dissecting out what is driving the restoration of the growth, height, weight, and bone mineralization still needs to be figured out. My personal hypothesis is that it's multifactorial. My guess is it's all the positive changes that occur with treating that Type 2 inflammation, decreasing that inflammation throughout the body, improving the sleep, decreasing the itch, and reducing the corticosteroids. It's probably a combination of all of that.
Dr. Mesinkovska: OK, so you heard it, folks, straight from the expert's mouth. So one takeaway foreverybody. Anything for, like, a future study or just, like, something so we can all learn from you from today.
Dr. Bunick: Well, I think that in order for us to continue to understand what's actually happening in the young children in the growth restoration, we need to collect more data.
We also need to see, is this a phenomenon that's unique to dupilumab, or are we going to see with our other Type 2 inflammation biologics? You know, we have tralokinumab, we have lebrikizumab, and nemolizumab just had data at the AAD in children. All of these other biologics, how are they impacting the growth and bone mineralization of children, and the oral JAK inhibitors as well?
We are going to learn so much about early intervention of atopic dermatitis in this younger age group over the coming years as these pediatric studies come forth, and I think that's going to be a great thing for the field. And we have to understand that children are not just little adults.
Dr. Mesinkovska: Everybody keeps saying that. I don't even know what that means. I have to say it. Just kidding, don't kill me pediatricians.
Dr. Bunick: What it means is that the children have different metabolic and physiologic needs than us as adults, and I'll give a great underlying example. There's a huge difference in the consequences, in my opinion of the systemic inflammation in children and adults. And the main reason is, in adults, we have underlying atherosclerosis from years and years of either poor nutrition, poor exercise, or genetic factors, or many other factors. The children aren't dealing with atherosclerosis. The adults are. The nature of the inflammation and the consequences of the inflammation are different.
And I think that as we further investigate atopic dermatitis as a systemic inflammatory disease, I think some of the answers as to how children respond to therapy and early therapy versus how adults respond to therapy, we're going to start to tease out those differences.
Dr. Mesinkovska: OK, good. So the best way to end this Type 2 Inflammatory Journal Club, that is that we have a lot of options for kids and adults.
Future's bright. Thank you.
Dr. Bunick: Thank you, Natasha.
