Ruxolitinib Cream Shows Promise in Prurigo Nodularis at EADV 2025

At the 2025 European Academy of Dermatology and Venereology (EADV) Congress, Sonja Ständer, MD, presented late-breaking results from the TRuE-PN program evaluating topical ruxolitinib (Opzelura; Incyte) 1.5% cream in adults with prurigo nodularis (PN).¹ PN is a chronic inflammatory skin disorder marked by severely pruritic nodules and a profound impact on patients’ quality of life. Despite its burden, therapeutic options remain limited, underscoring the importance of novel interventions.²

Ständer began by highlighting the evolving understanding of PN pathophysiology. “It becomes more and more evident that JAK-mediating signaling pathways are involved via Th1, Th2, Th17, and Th22 cytokines and chemokines, especially Th2, with the dominant figures of IL-4, IL-13, and IL-31,” she explained. This mechanistic rationale supports the investigation of ruxolitinib, a selective JAK1/2 inhibitor, as a potential topical therapy.

TRuE-PN Clinical Trial Program

The TRuE-PN program includes 2 pivotal phase 3 studies, TRuE-PN1 and TRuE-PN2, each consisting of a 12-week double-blind, vehicle-controlled period followed by a 40-week open-label extension. Patients enrolled were adults with moderate to severe PN, defined by ≥6 lesions across multiple body areas, an Investigator’s Global Assessment (IGA-CPG-S) score of ≥2, and severe pruritus with a baseline Worst-Itch Numeric Rating Scale (WI-NRS) score of ≥7.

In TRuE-PN1, Ständer stated ruxolitinib cream met its primary endpoint. At week 12, 44.6% of patients achieved a ≥4-point improvement in WI-NRS compared to 20.6% in the vehicle group (P=0.0003). Benefits emerged as early as day 3 in some patients. Ständer noted, “We see that after 3 days, there is a significant separation of the 2 arms, and that also really produces a significant difference versus the vehicle."

Secondary endpoints also favored ruxolitinib cream. By week 4, 29.7% of patients achieved WI-NRS4 versus 12.7% with vehicle (P=0.0034). Improvements in lesion clearance were documented through IGA-CPG-S Treatment Success, with separation between treatment and vehicle arms evident by week 4.

TRuE-PN2, however, did not meet its primary endpoint due to an unusually high vehicle response. “The second phase 3 trial didn’t make the primary endpoint because of a very high vehicle rate. It’s not a placebo, but a vehicle effect, but multiple secondary endpoints have been reached,” Ständer clarified.

This divergence highlights the challenges of dermatologic trial design, particularly in pruritic conditions where vehicle formulations can confer meaningful symptomatic relief.

Open-Label Extension and Safety

In the open-label extension, patients initially randomized to vehicle who later switched to ruxolitinib cream demonstrated “catch-up” responses, with itch and lesion outcomes aligning with those who received active treatment from baseline. By Week 24, researchers found improvements were sustained across cohorts.

Safety findings were consistent with prior experience. “The safety is very easy to report. The application site reactions are very low, 1.1% in both arms,” Ständer stated. No new safety signals were observed, and serious adverse events deemed treatment-related were absent.

Clinical Implications

Ruxolitinib cream’s rapid and durable reduction in itch, coupled with improvement in nodular lesions, positions it as a potential first-in-class topical therapy for PN. As Ständer summarized, “I hope we could demonstrate today that ruxolitinib demonstrated significant improvement versus the vehicle treatment in signs and symptoms, and that those patients who received ruxolitinib after the vehicle showed a similar trend and improvement until week 24."

The TRuE-PN data will inform regulatory discussions, with the goal of expanding ruxolitinib cream’s indications beyond its current approvals in atopic dermatitis and vitiligo. If approved, it could offer PN patients a targeted topical therapy—an unmet need in clinical practice.

References

1. Ständer S. Efficacy and safety of ruxolitinib cream in patients with prurigo nodularis: pooled results from the phase 3 TRuE-PN1 and TRuE-PN2 randomized, vehicle-controlled studies. Presented at: 2025 European Academy of Dermatology and Venerology Congress; September 17-20; Paris, France.
2. Mullins TB, Sharma P, Riley CA, Syed HA, Sonthalia S. Prurigo Nodularis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; March 1, 2024.