PARIS – A cream formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, outperformed triamcinolone cream 0.1% and vehicle control in a large, phase 2, dose-ranging, randomized trial in patients with atopic dermatitis (AD), Brian S. Kim, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This novel topical JAK inhibitor not only modulates inflammatory cytokines involved in the pathogenesis of AD, including interleukin-4, -5, -13, and -31, but Dr. Kim and his coinvestigators also demonstrated that ruxolitinib has antipruritic effects achieved by acting directly on sensory nerve fibers.
“Ultimately,said , a dermatologist and codirector of the at Washington University, St. Louis.
The trial included 307 adults, mean age 35 years, with a median 21-year disease history and a mean of 7.3 flares within the past 12 months. Dr. Kim characterized the study population as having AD of “high-moderate” severity, with a mean involved body surface area of 9.7%, half of patients having a baseline Eczema Area and Severity Index (EASI) score greater than 7, and having a mean itch numeric rating scale of 7. Two-thirds of patients had an Investigator’s Global Assessment (IGA) score of 3 and the rest had scores of 2.
Patients were randomized to one of six study arms entailing 8 weeks of double-blind therapy: ruxolitinib cream 1.5% once daily, 1.5% twice daily; 0.5% once daily; 0.15% once daily; twice-daily vehicle; or triamcinolone cream 0.1% twice a day for 4 weeks followed by 4 weeks of vehicle.
All the ruxolitinib regimens provided dose- and time-dependent efficacy, compared with vehicle. The best results were seen with ruxolitinib 1.5% twice daily, which outperformed triamcinolone cream.
The primary study endpoint was change in EASI score from baseline to week 4, but the week 2 and week 8 data were also informative. Key secondary endpoints included the proportion of subjects achieving an EASI-75 response and/or an IGA response, which required improvement to an IGA score of 0 or 1 with at least a 2-point reduction from baseline.
As for itch, ruxolitinib cream provided rapid and sustained improvement, said Dr. Kim. Indeed, within the first 2 days of the study, the ruxolitinib 1.5% twice-daily group had a mean 1.8-point reduction on the numeric rating scale, compared with a 0.2-point drop with vehicle and a 1-point drop with triamcinolone cream twice a day. By week 4, the twice-daily ruxolitinib 1.5% group had about a 4-point drop from baseline, the once-daily ruxolitinib 1.5% group had a 3.5-point drop, and the triamcinolone-treated patients had a 2.5-point drop.
Topical ruxolitinib was not associated with any significant safety or tolerability issues, and there were no clinically significant application site reactions, according to the dermatologist.
Session cochair, a Swiss dermatologist, commented that she could easily imagine this topical JAK inhibitor also being useful in other diseases with itch.
Dr. Kim reported serving as a consultant to and recipient of research funding from Incyte, which sponsored the study.