Exploring Long-Term Data and Combination Therapies

In this Dermatology Times Expert Perspectives series, 5 experts delve into the multifaceted aspects of pediatric atopic dermatitis care including demographic variances to long-term safety and efficacy, comparative analyses, key takeaways from recent research, personalized approaches, and future research directions. Discover clinical insights into the role of ruxolitinib (Opzelura) in addressing critical challenges and enhancing patient outcomes.

Brian Kim, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York, New York, explores long-term ruxolitinib data and combination therapies in the treatment of pediatric AD.

Episode Transcript

Kim: I'm a physician scientist. So I spend 90% of my time doing science, running a laboratory to make basic discoveries. Ten percent of my time is in the clinic, and we also design clinical trials to bring new treatments to patients as well based on our science.
I think for any drug, for long-term observation, you want to look at, not just efficacy, but also safety. Is there anything weird that's showing up that you didn't expect? Or any kind of even small effect, [such as] irritation or something like that? And I think that's true at topical ruxolitinib. It's a great drug. We have a lot of experience with it in adults now. So we know it has a very good profile, and I don't anticipate anything in postmarket long-term in children or anything like that, but you do need to make sure there isn't any kind of excessive absorption or infection or something that maybe you didn't anticipate.
We do see a lot of potential for topical ruxolitinib to be combined with other treatments. In fact, that is something that I already do in the clinic. So one thing I think we often don't appreciate is that with the advent of many systemic therapies, biologic therapies, that are highly effective for AD, we're actually increasing the population of patients who have more localized rashes or itch in particular. And that's where actually topical ruxolitinib can come in and really be effective and mop up residual disease and that population is actually growing. So I think we're going to see a lot more combination of topical ruxolitinib, especially since it is topical. It allows you to kind of mop up hot spots and such. I think you'll see it also expand into other conditions in the future.
There are a number of things that are exciting in the AD space. There's a lot at this meeting [AAD]. There's new mechanisms of action. There are new targets. A number of them, people are hearing about literally as I speak, such as nemolizumab, which targets IL-31 receptor. There's also OX40 as a target. There's a number of agents that are coming for AD, but even earlier, there are new agents that are trying to target multiple pathways at once, barrier pathways that actually come with a very different kind of mechanism of action.
And I think what we'll see a lot more in the coming years is what we call bispecific antibodies that target 2 pathways to treat AD, not an additive fashion, but actually synergistically. So the the 2 pathways by knocking them out, you'll see actually much, much more amplified effects in terms of efficacy. Unfortunately, a lot of these pathways are already proven to be quite safe in terms of blocking. So what I predict is a lot more efficacy with even improved safety, something that a lot of people ask me is, "You know, what do you think about topical JAK inhibitors?"
I actually have a very strong opinion on this. I think topical JAK inhibitors are gonna put topical steroids out of business. And what I've realized, actually from my experience with topical JAK inhibitors like ruxolitinib, which I'm very biased about because I did design the pivotal phase 2 clinical trial, so I'm very academically biased for its success in many ways. But also it is a very effective treatment. One of the things that I've learned from using topical ruxolitinib is that actually topical steroids have a lot of drawbacks that I either didn't see or didn't perhaps want to see because it was the only thing I had topically to use for eczema and other dermatosis. It does damage the barrier. It thins the skin. It makes the blood vessels pop out, and these are things that actually long-term are not good for inflammation, but topical steroids work. So what we were doing is we were actually using topical steroids to treat say eczema for 2 weeks short-term game, but then after that we weren't really sure what to do with the steroids. Are we risking overusing them and long-term actually paying because we're actually damaged in a barrier and causing all these effects on the skin that actually make the eczema long-term actually much worse? We're completely avoiding that now, with topical JAK inhibitors is what I found.
It's much easier if you just say, "Just use it twice a day. Don't worry about it. Just use it. And we'll see you in a month." Topical steroids...we've been playing this game of how much is underuse, how much is overuse? I don't think anyone could really answer that question. And that is something that's always plagued dermatology. How do we actually really use topical steroids? Long-term, not short-term. Short-term gain, but there's a bit of long-term pain associated with them.

Transcript edited for clarity