New data announced from Phase IIIb TRuE-AD4 trial of Opzelura (ruxolitinib cream) in adults with moderate atopic dermatitis – Incyte

Incyte announced new data from the Phase IIIb TRuE-AD4 study evaluating the efficacy and safety of Opzelura (ruxolitinib cream) in adults with moderate atopic dermatitis (AD) who had an inadequate response, intolerance or contraindication to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). These data will be presented during the Systemic and New Therapies for Atopic Dermatitis session on Sunday, October 26  at the 15th Georg Rajka International Symposium on Atopic Dermatitis (ISAD), held from October 24 – 26, 2025, in Melbourne.

TRuE-AD4 (NCT06238817) is a randomized, double-blind, vehicle-controlled Phase IIIb study designed to evaluate the efficacy and safety of Opzelura (ruxolitinib cream) in adults with moderate atopic dermatitis (AD). The study enrolled 241 patients (≥18 years old) who meet the specific inclusion criteria, including an Investigator’s Global Assessment (IGA) score of 3 and an Eczema Area and Severity Index (EASI) score greater than 7 at both screening and Day 1 and who have AD on 10% to 20% of their Body Surface Area (BSA; excluding scalp). Patients also had to have a documented history of inadequate response, intolerance or contraindication to topical corticosteroid (TCS)s and topical calcineurin inhibitor (TCI)s within the 12 months prior to the screening visit. Patients were randomized 2:1 to receive Opzelura administered twice daily (BID) or vehicle (non-medicated cream) BID.

The co-primary endpoints of TRuE-AD4 are the proportion of patients achieving IGA Treatment Success (IGA-TS), defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a two-point improvement from baseline, and EASI-75, defined as ≥75% improvement in EASI score, at Week 8. Key secondary endpoints include the proportion of patients with a ≥4-point improvement in Itch Numeric Rating Scale (NRS4) score at various time points. Other exploratory endpoints include the proportion of patients who achieved IGA-TS, NRS4, EASI-75, a decrease from baseline in the affected body surface area (%BSA), change from baseline in the skin pain NRS score, EASI90 and more, measured at various time points. The study also tracked the frequency, duration and severity of adverse events associated with the use of ruxolitinib cream.

Data from TRuE-AD4, which build on previously announced topline results, show the study met its co-primary endpoints at Week 8, with a statistically significant proportion of patients achieving both a ≥75% improvement in Eczema Area and Severity Index (EASI75) score from baseline (70.0% with Opzelura vs. 18.5% with vehicle, P<0.0001) and Investigator’s Global Assessment Treatment Success (IGA-TS; 61.3% vs. 13.6%; P<0.0001). Patients treated with Opzelura demonstrated improvement in EASI75 (43.8% vs. 3.7%, nominal P<0.0001) and IGA-TS (29.4% vs. 2.5%, nominal P<0.0001) at Week 2. More patients treated with Opzelura achieved both EASI75 and IGA-TS at Week 8 than vehicle (59.4% vs. 13.6%; nominal P<0.0001).

Additional key findings from the TRuE-AD4 study include:

• • Improvement in itch as measured by a ≥4-point improvement in Itch Numeric Rating Scale (NRS4) score.
  • •Nearly two-thirds (62.5%) of patients treated with Opzelura achieved Itch NRS4 by Week 8 (vs. 19.8% with vehicle, P<0.0001).
  • •There was significant improvement in worst daily itch at Day 2 with 29.1% of patients treated with Opzelura achieving Itch NRS4 vs. 14.3% with vehicle (P=0.0072; by multiple imputation).
  • •Current Itch NRS4 was also measured at 15 minutes (16.4% with Opzelura vs. 7.7% with vehicle).
• • Improved Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI) scores:
  • •More patients treated with Opzelura vs. vehicle achieved a POEM score 0–2 (clear or almost clear) at Week 8 (39.7% vs. 8.6%).
  • •Patients treated with Opzelura showed a mean DLQI score improvement at Week 8 (from 19.3 to 4.3 with Opzelura vs. 19.1 to 10.7 with vehicle).
• • Opzelura was well tolerated with no serious infections, major adverse cardiovascular events (MACE), malignancies or thromboses reported during the 8-week vehicle-controlled period. The most common treatment-related adverse event observed in the Opzelura arm was application site acne (4.4% vs 0% in vehicle arm).
• “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 Dr. Jim Lee,  Group Vice President, Inflammation & Autoimmunity, 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.”
• “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 Dr. Andreas Wollenberg, Professor of Dermatology and Allergy, Augsburg University Hospital, Germany. “AD is a challenging, chronic condition and I believe that these data reinforce Opzelura as an important therapeutic option.”