Vitiligo Biomarker CXCL10 Correlation With Clinical Response

During the Revolutionizing Atopic Dermatitis (RAD) June 2024 meeting, presenters showcased how ruxolitinib cream, a topical Janus kinase (JAK) 1/JAK2 inhibitor, is the first US Food and Drug Administration and European Commission-approved repigmentation treatment for nonsegmental vitiligo in patients aged 12 years and older. A phase 2, randomized, double-blind, vehicle-controlled study (NCT04896385) aimed to evaluate changes in biomarkers, correlate these changes with treatment efficacy, and assess the safety and tolerability of ruxolitinib cream in adult patients with vitiligo.

The study involved 60 adult patients with vitiligo affecting ≤50% of their body surface area. Participants were randomized 2:1 to receive either ruxolitinib cream 1.5% or a vehicle cream twice daily for 24 weeks, followed by an extension where all patients used ruxolitinib cream up to week 52. Biomarker changes, including C-X-C motif chemokine ligand 10 (CXCL10), were monitored at weeks 4, 12, and 24 using various assays and quantitative polymerase chain reaction  on skin biopsy samples. Efficacy was measured by changes in facial and total Vitiligo Area Scoring Index (F-VASI and T-VASI), while safety was assessed through the frequency and severity of adverse events.

The study population had a mean age of 44.7 years, with 56.7% male and 53.3% having lighter skin types (Fitzpatrick I–III). The median disease duration was 12 years. Baseline F-VASI and T-VASI scores averaged 1.1 and 12.1, respectively. Significant reductions in serum CXCL10 levels were observed as early as week 12 in patients treated with ruxolitinib cream. Skin CXCL10 levels also decreased significantly in lesional skin by week 12. These reductions correlated with improvements in T-VASI scores, demonstrating the cream's efficacy.

By week 24, significant mean percentage reductions in F-VASI (–32.9%) and T-VASI (–21.2%) were recorded. Adverse events were reported by 46.3% of patients using ruxolitinib cream, with common issues including COVID-19 (9.8%), application site acne (4.9%), and rash (4.9%), although none were serious.

In conclusion, the study supports the central role of the interferon-gamma:CXCL10 axis in vitiligo pathogenesis. Ruxolitinib cream significantly reduced CXCL10 levels, correlating with clinical improvements, and demonstrated good safety and tolerability over the study period.

Reference
Lebwohl M, Lynde C, Passeron T, Shayesteh M, et al. Vitiligo biomarker CXCL10 correlates with clinical response in the phase 2 randomized, double-blind, vehicle-controlled TRuE-V mechanism of action study. Poster presented at: Revolutionizing Atopic Dermatitis; June 8-10, 2024; Chicago, IL.