The Shifting Treatment Paradigm in AD Management

Transcript:

Lawrence Eichenfield, MD: We talk about our IL [interleukin]-4/13 blocker; what mechanisms are being investigated in pediatric AD [atopic dermatitis], and what's the rationale for these other potential treatments? I think there are 2 big avenues. There are other biologics and then there are JAK inhibitors. The other biologics, 2 IL-13s are being studied, and IL-31. IL-31 is directed more toward itch. We'll see how well it does in pediatric atopic dermatitis because there haven't been a lot of kids studied with that particular drug.

Regarding IL-13, one of the questions is how important is IL-4 as a contributor in the blockade? In pediatrics we don't know yet, but there have been some of the IL-13 drugs that are well on their way in phase 3 trials right now that have included studies and others haven't.

Remember there's the JAK-STAT pathway, and different JAKs are hit by different drugs. JAK inhibitors are different medicines in that they’re oral, potentially an advantage in kids, but they also require blood monitoring it seems, and there’s a degree of historic concerns in certain medical issues. Several of the JAK inhibitors have been approved in other diseases, and therefore have a history of use and an adverse effect profile associated from those other diseases. And there are others that are being developed specifically for atopic dermatitis that don't have that history, and we have to figure out the adverse effect profile. Some have included kids in their trials already, age 12 and older, and will be marching down as well. Then there are several other oral agents that will be developed and other potential biologics.

I think since they're not ready to be handed off to clinical use, that may be enough of a comment, but I think that the JAK inhibitors for pediatrics, we're going to be a little bit more concerned about immunosuppression with them. We may be reserving them for more severe patients who haven't responded to the biologic agents, or who are so needle phobic that even though we tell them that they can't be needle phobic, they still are. Or other particular reasons why the overlap of their conditions may argue more for those particular agents compared to biologics.

Elaine Siegfried, MD: The pipeline is incredibly robust, and I think one of the things that's going to help us, right now we have a dull instrument. We've got an IL-4/13 blocker. But with the phenotype that is atopic dermatitis being able to help identify which patients are going to be better responders to which treatments, and then having a giant variety of targets.

Lawrence Eichenfield, MD: It's really interesting because psoriasis was ahead on that, right? They already started to collect huge amounts of phenotyping data to go along with their genotyping data so they could pick out which very expensive drug to use based on that psoriasis. But what happened with psoriasis is that the next 2 stages of biologic agents blew away the disease at such high rates across the population that it took away the incentive to figure out the selectivity for which drug, for which individual.

I think the heterogeneity of atopic dermatitis—that approach is going to be more important for us because there's such variations in the disease. And I bet you we’ll see patients who respond to certain types of drugs much more than others. It will be a really interesting 10 years, 15 years as we figure it out.

Future paradigms: let's cross the whole spectrum from good skin care, avoidance of irritants, allergens, our topicals and systemics. Peter, how do you think the future treatment paradigm is going to look for pediatric AD?

Peter Lio, MD: First, I think it's going to look very bright. For my 15-year clinical practice career, this is the first time I really feel like we are on the verge of some awesome things coming. But I also think what Elaine said is right on, that we are getting more precise. We're heading towards precision medicine, and we're learning what these levers do. What things can we pull to affect different subtypes? I'm really excited to see what's going to happen with our understanding of the role of Staphylococcus aureus, where maybe there will be some products where we can target Staph and break this early on. I can't wait to see where moisturizer science goes. I know Elaine's a little skeptical of the Cosmo complex, but I still think it's fascinating to think we could do active moisturization and barrier repair and maybe not even have to tinker as much with the immune system in some situations.

Then on the immune side we're getting more and more targeted, safer, and more effective treatments, but we're also looking in other areas like itch. IL-31 is so interesting to me because that's really more of an itch cytokine, and of course there are other products that are in the pipeline that will have other effects on itch and other inflammatory modulators.

I'm so excited to see how we're going to be able to put all these together and start rebuilding our entire therapeutic ladder. At the same time, I think we're also making the bar higher and higher. Our treat-to-target goal is now going to be to the point like psoriasis, where it's like, the only thing acceptable is basically being clear. Well, OK, maybe 1%.

Lawrence Eichenfield, MD: Fred, anything to add, end result—how do you think we're doing in the field and how we’ll be doing in the future?

Fred Ghali, MD:I think it's an exciting, promising pipeline. I think that we were dependent upon using systemic immunosuppressants as our first line after failing topical therapies, and now instead of broad immunosuppression, we have more targeted immunomodulators. I'd be interested to see if some of these medicines you're talking about, JAK inhibitors, how they're going to perform in topical formulations. Is it going to be something that can be used by other specialists as well? It'll be really interesting to see if not only do we have oral or injectable, but are there going to be other topical therapies available for not only us, but our primary care colleagues?

Lawrence Eichenfield, MD: In summary, it's a very exciting time. We bring our knowledge and detail work taking care of these patients and families, but we also want to bring the promise of better long-term disease control and minimal impact of the disease to our patients and families and our primary care doctors in between to send out the word that we can do better. I think we're going to continue to do better as time goes on.

Well, I thank the great faculty for the rich and informative discussion. I hope you found this a worthwhile exchange of information, and I thank you very much. I hope you get as excited as we are about our ability to take care of our patients with atopic dermatitis better. Thank you.

Transcript Edited for Clarity