'Exciting' Future for Topical Ruxolitinib in Atopic Dermatitis

At the American Academy of Dermatology Virtual Meeting Experience (VMX), multiple post-hoc analyses were presented regarding the efficacy and safety of ruxolitinib (Jakafi) cream, a topical selective inhibitor of JAK1 and JAK2 being developed to treat atopic dermatitis.

In this exclusive MedPage Today video, Jonathan Silverberg, MD, PhD, of George Washington University School of Medicine and Health Sciences in Washington, discusses the studies and the potential future of topical ruxolitinib cream.

Following is a transcript of his remarks:

Topical ruxolitinib cream is under investigation now for mild to moderate atopic dermatitis. And we've already seen now results for two phase III studies that were done in atopic dermatitis that this is a subset of patients with mild to moderate disease with a limit of body surface area of up to 20%.

And what we've seen previously disclosed was that ruxolitinib resulted in significant improvements in a proportion of patients achieving clear skin, significant improvements in terms of the eczema area and severity index, which looks at both lesional severity and body surface area or extent of lesions, and several other endpoints.

More recently as just presented at the American Academy of Dermatology meeting, the VMX virtual meeting, were multiple post-hoc analyses that examined various domains of improvement with topical ruxolitinib cream.

One study found considerable improvements with respect to multiple patient-reported outcomes with respect to itch, quality of life, the patient-oriented excellence measure, which looks at the patient-reported symptoms of atopic dermatitis. And we know that patient-reported outcomes are very important in this disease just given how highly symptomatic it is.

There was a post-hoc analysis looking at work productivity. Clinically we recognize that particularly for our more severe patients, but even in that mild to moderate subset, that there is a substantial amount of impact in terms of both absenteeism and presenteeism at both school and work. And so there was a post-hoc analysis presented that examined the benefit for the efficacy of topical ruxolitinib cream on the work productivity and activity impairment, or WPAI index, and found significant improvements compared to placebo on multiple domains in terms of absenteeism and presenteeism and daily productivity.

So that's something that of course is very exciting, especially for patients really suffering in that way. We've seen post-hoc analysis showing that regardless of patient past exposure, past treatment, that topical ruxolitinib cream works quite well. This is important, right? Because we may not be using ruxolitinib cream as a first-line topical agent in all patients. And if we're using it in someone who's maybe already a topical steroid failure, well we want to know how well they do in those cases.

And so we've seen here that regardless of them being treatment-naive previously, or using only topical steroids previously, or even using systemic agents previously, that ruxolitinib really was quite effective and achieved good results across all of those patient subsets. So those are just a few of them.

There were actually other analyses as well that have shown even improvements in terms of sleep, rapid improvements with respect to itch. I think that's one of the very intriguing parts about this. As a non-steroidal you know, we sometimes have settled on them being a little bit slower in their onset of effect in general, but with topical ruxolitinib cream, there were significant improvements of itch and skin pain already, but by day 1, by even 12 hours.

And that is something that rapidly continues to grow over time. So we've really seen now quite a bit of data to suggest that ruxolitinib is really working holistically on all aspects of the disease with a rapid onset of effect.

And of course, maybe this is obvious, but ruxolitinib is a topical JAK inhibitor -- it's not a steroid, it doesn't have those steroid side effects. We don't have those concerns about long-term use causing atrophy and things like that. So I think many promising aspects to this agent in atopic dermatitis.

Currently, topical ruxolitinib cream is under review by the U.S. Food and Drug Administration. We hope that it will be approved imminently. Once it is approved, there's obviously some things we'll await to see the language in the label and if there are any restrictions or precautions or things like that.

But you know, we've seen from the trials a clear dose response where that highest dose of ruxolitinib has really achieved the best efficacy. And that would be the 1.5% cream. So my assumption is that will be the dose to aim for whether or not there will be two doses available to us, or just the one dose -- I think we'll see all of that in the labeling.

But once that is approved and on the market, I think that we'll start learning more and more about where the real world value is and who are those ideal subsets of patients. I think we think about certain subsets that logically, patients who've already failed or had an inadequate response previously to topical steroids or patients where they may have had adverse events or are prone to adverse events.

But with a medication that seems to work this potently and this rapidly, potentially this doesn't have to be used as a second-line agent. Potentially this could be used as a first-line agent, assuming that of course the payer access is there. And that's another thing that, of course, we'll have to see in the real world how that plays out.

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