Late-Breaking Data at AAD on Topical Ruxolitinib Show Itch Relief in Atopic Dermatitis, Prurigo Nodularis

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At the American Academy of Dermatology 2025 annual conference, Shawn Kwatra, MD, FAAD, physician scientist at the University of Maryland Medical System, presented late-breaking research on topical ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, highlighting its rapid and effective relief of itch and inflammation in atopic dermatitis and prurigo nodularis.

Additionally, Kwatra addressed the broader landscape of JAK inhibitors, both topical and oral, and their role in treating various chronic pruritic conditions, emphasizing the importance of individualized treatment selection based on factors like itch severity, comorbidities, and dosing frequency, while also discussing "The Dermatologist's Playbook for Chronic Itch" approach to patient workup and therapy selection.

This transcript was lightly edited for clarity; captions were auto-generated.

Transcript

Given the late-breaking data on topical ruxolitinib's effectiveness in prurigo nodularis and its rapid itch relief, how do you foresee this impacting treatment paradigms for chronic pruritic conditions?

There's been a lot of discussion at this conference about both topical and oral JAK inhibitors. In our JAK inhibitors session at the AAD, I discussed the role of JAK inhibitors in atopic dermatitis, prurigo nodularis, and also pruritus, or itch in general.

For topical agents, we focused on topical ruxolitinib, a JAK1/JAK2 inhibitor. We talked about this data in atopic dermatitis. This drug has been approved for a few years now, and from subsequent studies, we know that the activity on itch in these patients is very quick, as quick as even a few minutes: significant, very fast. The topical ruxolitinib is actually more potent with the itch and the inflammation as compared with one of our mainstays, medium-potency topical steroids like triamcinolone, but without the side effects of hypopigmentation, atrophy, or many of those other features.

I also shared some cases and difficult patients that did not respond to topical steroids or many other agents but responded well and quickly to topical ruxolitinib. I also had the honor of presenting late breaker data for topical ruxolitinib in the treatment of prurigo nodularis. This is a first, because there's never been a topical agent that's been studied in prurigo nodularis. This was a global phase 3 study, the TRuE-PN1 study [NCT05755438].

In that study, at week 12, the primary end point was the percentage of patients who had a 4-point or greater improvement of itch. This was over 44% [in the ruxolitinib group] compared with around 20% for the placebo group, and also significant improvement in all the secondary end points, so skin lesions, also people who met both the itch and the skin lesion improvement. Actually, improvement in itch was as early as day 4 in this study.

We also presented some data from the TRuE-PN2 study [NCT05764161], which met its secondary end points and also for the primary [end point] 40% of patients had an improvement in itch. There was a 36% rate for the placebo, so that's being looked into further as well.

These are exciting developments for topical ruxolitinib in general. Also, we talked about in our session oral agents, so oral abrocitinib and upadacitinib, JAK1 inhibitors, and when to give them to patients. We discussed the safety of these agents and other features about how they target a broader array of cytokines, not just IL-4, IL-13 or IL-31 but also IL-22 IFN-γ, IL-6, and other cytokines that can be involved with tissue fibrosis or acanthosis. Also, we discussed the itch response and switching between agents for a diverse population of patients.

How do you prioritize and select the most appropriate therapy for an individual patient, especially when considering factors like rapidity of itch relief, comorbidity coverage, and dosing frequency?

Today, I also spoke about our “itch playbook” [The Dermatologist's Playbook for Chronic Itch]. Itch can be a really difficult concept in terms of how to manage. I went through several cases of itch patients that come in and talked about the appropriate workup and treatment options for these patients. For an undifferentiated itch patient, you want to think about a systemic workup, you want to get a blood count, you want to look at the liver and the kidneys, think about thyroid disease, and get that basic workup.

Then you want to see if the itch is localized or generalized. If it's localized, you can also think about neuropathic itch syndromes. Then I also focused on chronic pruritus of unknown origin, which is actually an entity where you have itching all throughout your body, and in many cases, this is the immune system that's slightly upregulated. We know that many of these patients have responded to therapies like dupilumab off-label, intramuscular steroids, methotrexate, and then there's also other populations of more generalized, neuropathic itch options.

We also went through a new form of erythroderma that our group discovered, characterized by IL-13 and IL-17 expression from the peripheral blood mononuclear cells. Then also I went through different treatment options for neuropathic itch and the emerging landscape and atopic dermatitis. We have dupilumab, tralokinumab, the new IL-13 inhibitor, lebrikizumab, nemolizumab, an IL-31 inhibitor. We discussed all of these different options, like Q2 week [once every 2 weeks] dosing or Q4 week [once every 4 weeks] dosing.

We talked about rapidity of itch, the effects on inflammation or skin rash, safety, comorbidity coverage. We know agents like dupilumab have been approved for several years and now are also approved for asthma and can actually modulate the atopic march. We know agents like nemolizumab work fast for itch. We know drugs like lebrikizumab have a nice balance of itch and inflammation in the option for Q4 week dosing. We're trying to give "docs pearls" on those agents, in addition to JAK inhibitors, and when you might switch between these agents.