Serum CXCL10 Levels Decreased With Use of Ruxolitinib Cream In Patients With Vitiligo

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After treatment with topical ruxolitinib cream (Opzelura; Incyte), C-X-C motif chemokine ligand 10 (CXCL10) biomarker levels in patients with vitiligo were significantly reduced, according to data presented in a poster at the 2024 Revolutionizing Alopecia Areata, Vitiligo, and Eczema (RAVE) Conference in Chicago, Illinois.¹

The poster examined data from the phase 2 sTRuE-V mechanism of action study (NCT04896385).²

Conducted on adult patients with vitiligo covering less than or equal to 50% of their body surface area, the randomized, double-blind, vehicle-controlled trial examined ruxolitinib cream’s efficacy and safety profile while also taking changes in local and systemic immune biomarkers, such as CXCL10, into account.

The study enrolled 60 adult participants, randomly assigned in a 2:1 ratio to receive either 1.5% ruxolitinib cream or a vehicle cream, applied twice daily for 24 weeks. After this period, all patients were allowed to use ruxolitinib cream until week 52.

Researchers utilized the Olink Explore platform to evaluate the expression of over 3000 serum protein analytes. They further confirmed absolute serum CXCL10 levels using a validated Meso Scale Discovery assay. Quantitative polymerase chain reaction from isolated biopsy samples helped determine the relative expression of CXCL10. Punch biopsies from lesional and nonlesional skin were taken at baseline and from lesional skin at weeks 12, 24, and 40.

Efficacy was primarily measured using the percentage change from baseline in facial and total Vitiligo Area Scoring Index (F-VASI and T-VASI, respectively). Safety evaluations considered the frequency and severity of adverse events throughout the study duration.

The study revealed several key findings:

1. CXCL10 reduction: Serum CXCL10 levels saw a significant reduction as early as week 12 in patients treated with ruxolitinib cream. Skin CXCL10 levels, initially similar in lesional and nonlesional skin at baseline, also significantly decreased in lesional skin by week 12.
2. Protein expression: Olink Explore identified few differentially expressed proteins in patient sera, including CXCL10, SH2D1A, and granzyme B, with a significant adjusted p-value (<0.05) and a log2 fold change >1.25.
3. Clinical improvements: Patients using ruxolitinib cream experienced substantial mean percentage reductions in F-VASI and T-VASI scores, showing improvements of -32.9% (SD 33.6) at week 12 for F-VASI and -21.2% (SD 18.5) at week 24 for T-VASI. Furthermore, changes in serum CXCL10 levels correlated significantly with improvements in T-VASI scores.
4. Adverse events: By week 24, 46.3% of the ruxolitinib cream group reported treatment-emergent adverse events, with none classified as serious. The most frequent events were COVID-19 (9.8%), application site acne (4.9%), and application site rash (4.9%).

Authors of the poster concluded that the TRuE-V study supports the hypothesis that the interferon-gamma axis is a central mediator in the pathogenesis of vitiligo.

Reference

1. Passeron T, Lebwohl M, Lynde C, 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: 2024 Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference; June 8-10, 2024; Chicago, IL.
2. National Institutes of Health. A study to evaluate the mechanism of action of ruxolitinib cream in subjects with vitiligo (TRuE-V MOA). ClinicalTrials.gov. https://www.clinicaltrials.gov/study/NCT04896385. May 2, 2024. Accessed June 7, 2024.