Background: Cicatricial alopecias are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and Janus kinase dysregulation has shown involvement, providing rationale for this phase 2a trial with Tyrosine kinase 2/Janus kinase 1 inhibitor brepocitinib.
Methods: Randomized, placebo-controlled phase 2a trial spanning 52 weeks. Adults (≥18 years of age) with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia diagnosis were randomized 3:1 to brepocitinib 45 mg daily or placebo for 24 weeks, after which all patients received brepocitinib for another 24 weeks, with a safety follow up 4 weeks later. Lesional scalp biopsies were collected at baseline, week 24, and week 48. Coprimary endpoints were changes in lesional expression of C-C motif chemokine ligand (CCL5), changes in lesional expression of fibrosis-related markers, and safety at week 24.
Results: Patients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 (P = .004). Enrichment analysis of a subset of fibrosis markers showed trending upregulation in placebo patients (P < .1). Brepocitinib was well tolerated and improved clinical severity scores.
Limitations: Single-dose regimen, small placebo group.
Conclusion: Brepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting coprimary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile.
Keywords: IFNγ; JAK inhibitor; Th1; central centrifugal cicatricial alopecia; cicatricial alopecia; fibrosis; frontal fibrosing alopecia; lichen planopilaris; phase 2a trial; scarring alopecia; systemic treatment.
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