Topical JAK Inhibitor Shows Improvement for PN

ORLANDO, Fla. — The topical Janus tyrosine kinase (JAK) 1/2 inhibitor ruxolitinib improved itching and nodules in patients with prurigo nodularis (PN) significantly better than a vehicle within a week after starting therapy, with improvements continuing out to 3 months, in a global phase 3 clinical trial.

“There’s statistical significance at week 12 in the primary and secondary endpoints,” Shawn Kwatra, MD, professor and chair of dermatology at the University of Maryland School of Medicine, Baltimore, said at a late-breaker session at the American Academy of Dermatology 2025 Annual Meeting, where he reported results from the TRuE-PN1 trial.

“Ruxolitinib cream may be a novel approach for the treatment of PN,” Kwatra said.

The primary endpoint was at least a four-point improvement from baseline in the Worst Itch Numeric Rating Scale (WI-NRS4) at week 12. Secondary endpoints were WI-NRS4 response after a week and 4 weeks on therapy, and overall treatment success and response was based on an Investigator’s Global Assessment for Stage of Chronic Prurigo (IGA-CPG-S) Treatment Success ( IGA-CPG-S-TS) at week 12.

Study Results

“We had significant itch improvements early at week 4, and the overall safety profile was very similar to what’s known about ruxolitinib from other clinical studies,” Kwatra said. “You can see at week 4 you have some separation between the ruxolitinib and vehicle groups, and at day 7 also. With skin lesions, you have still significant improvement at week 12 from baseline as well.”

The TRuE-PN1 trial enrolled 204 patients randomly assigned to 1.5% ruxolitinib cream twice daily or a vehicle cream for 12 weeks. After 12 weeks, all patients were crossed over to as-needed ruxolitinib twice daily for 40 weeks. Participants were adults diagnosed with PN at least 3 months earlier. To be eligible, they had to have six or more pruriginous lesions on at least two different body areas, an IGA-CGP-S score of ≥ 7, and a treatment area of ≤ 20% of their body surface, excluding the scalp. The average age was 63 years in both groups, and about two thirds of participants were female.

In the ruxolitinib group, 44.6% had a ≥ 4-point improvement in WI-NRS at week 12 vs 20.6% of the vehicle group (P = .0003). At all intervals, the ruxolitinib group had a significantly more robust response than those on a vehicle, although the disparity narrowed from 19.8% vs 4.9% at 2 weeks — a fourfold difference — to about a twofold difference at week 12.

The results for IGA-CPG-S-TS were more modest: 15.8% of the ruxolitinib group and 3.9% of the vehicle group met that endpoint at 12 weeks (P = .0048), Kwatra said. And 11.9% and 2.9%, respectively, had an overall treatment success (P = .0164), which was defined as the patients who achieved WI-NRS4 response and an IGA-CPG-S-TS.

Safety outcomes were similar in both groups: 31% of the ruxolitinib group and 36% of the vehicle group had a treatment-emergent adverse event, although 9% of patients on ruxolitinib had nasopharyngitis vs 1.9% of the vehicle group, he noted.

Early Data From Second Trial

Kwatra also presented preliminary data from an identical second phase 3 trial (TRuE-PN2). The response to ruxolitinib wasn’t as robust, with 40% of those patients having a > 4-point improvement in WI-NRSA at week 12 vs 36.2% of those on a vehicle, “which is common throughout the itch studies,” he added.

Asked to comment on the results, Kristina Callis Duffin, MD, MS, chair of Dermatology at the University of Utah, Salt Lake City, said the disparity in the results between the two trials needs to be evaluated before drawing definitive conclusions about the effectiveness of ruxolitinib for treating PN.

“There seemed to be itch reduction that was significant in the first study, but then in the second study the itch NRS score was not statistically significant,” she told Medscape Medical News. “I think that’s important to note. They’re going to have to review that data very closely to explain the different results.”

Duffin, who was not involved in the trials, added that PN “is still not that well understood. There could be variations presenting with this end-stage disease.”

“It’s a very new area of therapeutics,” she said of PN, “so we’re still learning about that disease state and the therapeutic agents and how they work with itch and the structural lesions.”

The study was funded by Incyte Corporation. Kwatra disclosed financial relationships with Incyte Corporation, along with AbbVie, Amgen, Arcutis Biotherapeutics, ASLAN Pharmaceuticals, Cara Therapeutics, Castle Biosciences, Celldex Therapeutics, Inc., Galderma, Johnson & Johnson, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi.

Duffin disclosed financial relationships with AbbVie, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, FIDE, Janssen Pharmaceuticals, Novartis, and Pfizer.

Richard Mark Kirkner is a medical journalist based in Philadelphia.