396 Rapid, substantial and sustained reduction of itch in adults with atopic dermatitis applying ruxolitinib cream 1.5% (SCRATCH-AD)

Abstract

Abstract Atopic dermatitis (AD) is a chronic, recurring, highly pruritic inflammatory skin disease. The mechanical injury from scratching contributes to skin inflammation and barrier disruption, exacerbating the itch–scratch cycle, which perpetuates the disease. Ruxolitinib cream is a topical formulation of ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, approved in the USA for the short-term and noncontinuous chronic treatment of mild to moderate AD in patients ≥12 years old whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In two pivotal phase 3 trials (TRuE-AD1 and TRuE-AD2) in adolescents and adults with AD, ruxolitinib cream 1.5% demonstrated significant improvement in itch vs. vehicle cream, as early as 12 h after initial application. A phase 2, open-label, single-site study (SCRATCH-AD; NCT04839380) was undertaken to further understand the short-term clinical benefits of ruxolitinib cream to control pruritus and reduce disease severity in participants with AD. Participants enrolled in the study were aged 18–65 years with AD for ≥6 months, with chronic itch related to AD for ≥3 months, 1–20% affected body surface area (BSA), Investigator’s Global Assessment (IGA) of ≥2 and a peak pruritus numerical rating scale (PP-NRS) score ≥4 at baseline. Participants applied ruxolitinib cream 1.5% twice daily to all lesions identified at baseline and any new lesions for 28 days. The primary endpoint was change from baseline in PP-NRS at Day 2 (24 h after the first application of ruxolitinib cream). Secondary endpoints included change from baseline in modified PP-NRS (mPP-NRS; current itch intensity) at 15 and 30 min and at 1, 2, 4, 6 and 12 h post-treatment on Day 1, as well as change from baseline in PP-NRS from Days 3 through 29, change from baseline in IGA at Days 8, 15 and 29, and safety. The primary analysis included 46 participants in the modified intent-to-treat population. Median age (range) was 30 (18–64) years; 69.6% were female, and 89.1% were White. At baseline, mean (SD) affected BSA was 9.5% (4.94%), mean (SD) 7-day average PP-NRS score was 6.7 (1.36), mean (SD) pretreatment mPP-NRS score was 6.4 (1.72) and 89.1% had an IGA score of 3. The mean (SD) change from baseline in PP-NRS on Day 2 was –3.4 (1.85). The mean (SD) change from baseline in mPP-NRS at 15 min post-treatment was –2.3 (2.34), peaking at –4.2 (2.12) at 4 h post-treatment and was –3.1 (2.00) at 12 h post-treatment. The mean (SD) change from baseline PP-NRS continued to increase through Day 29 [–5.7 (1.60)]. The mean (SD) changes from baseline in IGA score on Days 8, 15 and 29 were –1.4 (0.73), –2.0 (0.87) and –2.2 (0.90), respectively. Treatment-emergent adverse events (TEAEs) were reported in 15/49 (30.6%) participants (none were serious); one participant had a treatment-related TEAE [grade 1 application site reaction (acne)]. No participant discontinued treatment due to TEAE. Lesional skin treated with ruxolitinib cream 1.5% twice daily showed substantial decrease in transepidermal water loss from a baseline mean (SD) score of 35.0 (17.47) to 13.1 (4.42) over 4 weeks, thus reaching similar levels to the nonlesional skin score of 12.7 (4.56) at Day 29. Participants with AD applying ruxolitinib cream 1.5% experienced rapid, substantial improvement in itch, which was sustained and further improved through 28 days of treatment. Itch reduction was observed as early as 15 min, and peak reduction was observed at 4 h after first cream application. These results further demonstrate the clinical benefits and are consistent with the established data on ruxolitinib cream as an effective, well-tolerated topical treatment for AD.