Ruxolitinib Cream Shows Strong AD Efficacy and Rapid Itch Relief in TRuE-AD4 Trial

Incyte has announced positive results from the phase 3b TRuE-AD4 trial evaluating ruxolitinib cream, 1.5% (Opzelura) in adults with moderate atopic dermatitis (AD) who demonstrated an inadequate response, intolerance, or contraindication to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs).¹ The data, presented at the 15th Georg Rajka International Symposium on Atopic Dermatitis (ISAD) in Melbourne, Australia, reinforce the efficacy and tolerability of topical ruxolitinib as a nonsteroidal treatment option for moderate AD.

Study Design and Population

TRuE-AD4 (NCT06238817) was a randomized, double-blind, vehicle-controlled phase 3b trial enrolling 241 adult patients with moderate AD, defined by an Investigator’s Global Assessment (IGA) score of 3 and Eczema Area and Severity Index (EASI) >7 at baseline.

Participants had AD affecting 10 to 20% of body surface area (BSA) (excluding the scalp) and a documented history of inadequate response, intolerance, or contraindication to TCS or TCI therapy within the past 12 months. Patients were randomized 2:1 to receive ruxolitinib cream 1.5% twice daily or vehicle cream for 8 weeks.

The study’s co-primary endpoints were achievement of EASI-75 (≥75% improvement from baseline) and IGA Treatment Success (IGA-TS)—an IGA score of 0 or 1 with ≥2-point improvement—at week 8. Key secondary endpoints included ≥4-point improvement on the Itch Numeric Rating Scale (NRS4) and changes in Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI) scores.

Efficacy Results

After 8 weeks of treatment, ruxolitinib cream achieved both primary endpoints with high statistical significance. EASI-75 was reached by 70.0% of patients treated with ruxolitinib compared with 18.5% in the vehicle group (p < 0.0001). IGA-TS was achieved by 61.3% versus 13.6%, respectively (p < 0.0001).

Early improvements were observed by week 2, when 43.8% of patients on ruxolitinib cream achieved EASI-75 compared with 3.7% on vehicle, and 29.4% versus 2.5% achieved IGA-TS (nominal p < 0.0001 for both). By week 8, 59.4% of patients in the active arm achieved both EASI-75 and IGA-TS simultaneously, compared with 13.6% on vehicle.

Notably, pruritus relief occurred rapidly. As early as the second day, 29.1% of ruxolitinib-treated patients achieved Itch NRS4 versus 14.3% with vehicle (p = 0.0072). By the end of the trial, 62.5% of treated patients met the NRS4 threshold compared with 19.8% receiving vehicle (p < 0.0001). Improvements in current itch scores were also detected as early as 15 minutes after application (16.4% vs. 7.7%).

Patient-Reported Outcomes & Safety Profile

Ruxolitinib cream yielded substantial improvements in patient-reported outcomes. At week 8, 39.7% of patients achieved POEM scores of 0–2 (“clear” or “almost clear”), compared with 8.6% for vehicle. Mean DLQI scores improved from 19.3 to 4.3 with ruxolitinib, indicating a shift from “very large” to “small” effect on quality of life, versus an improvement from 19.1 to 10.7 with vehicle. Ruxolitinib was well tolerated throughout the 8-week period. No serious infections, major adverse cardiovascular events, malignancies, or thrombotic events were reported. The most common treatment-related adverse effect was application-site acne, occurring in 4.4% of patients in the ruxolitinib arm and none in the vehicle group. Discontinuations due to adverse events were rare.

“TRuE-AD4 offers compelling support for the utility of Opzelura for patients with moderate AD who have limited treatment options due to inadequate responses or intolerances to TCS and TCI-based topical therapies, who may otherwise be recommended for systemic therapy,” said Andreas Wollenberg, MD, PhD, Professor of Dermatology and Allergy at Augsburg University Hospital in Germany. “AD is a challenging, chronic condition and I believe that these data reinforce Opzelura as an important therapeutic option.”¹

Next Steps

Based on these results, Incyte plans to submit a Type-II variation application to the European Medicines Agency by the end of 2025, seeking approval for ruxolitinib cream 1.5% in adults with moderate AD. The company aims to continuously expand access to this nonsteroidal, topical JAK1/JAK2 inhibitor that addresses both inflammatory pathways and pruritus in patients with AD.

“The TRuE-AD4 data further reinforce the safety and efficacy profile of Opzelura and its ability to control key signs and symptoms of moderate AD, including improvement in bothersome symptoms like itch,” said Jim Lee, MD, Group Vice President, Inflammation & Autoimmunity at Incyte. “These data will support the filing of a Type-II variation application for ruxolitinib cream 1.5% (Opzelura) in Europe, as we seek to meet the needs of more patients around the world who require nonsteroidal topical treatments for moderate AD.”¹

Reference

1. Incyte Announces New Data from Phase 3b TRuE-AD4 Trial of Opzelura® (Ruxolitinib Cream) in Adults with Moderate Atopic Dermatitis. News release. Incyte. Published October 25, 2025. Accessed October 28, 2025. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-new-data-phase-3b-true-ad4-trial-opzelurar