Study: Brepocitinib Reduces Inflammatory Markers in Cicatricial Alopecia

A recent phase 2a clinical trial showed brepocitinib was associated with a significant reduction in C-C motif chemokine ligand 5 (CCL5) expression and improved clinical severity scores in patients with cicatricial alopecia (CA).

Researchers on the double-blind study followed 51 patients (50 of whom completed the study) who were diagnosed with lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), or central centrifugal cicatricial alopecia (CCCA). Participants were randomized (3:1) to receive either 45 mg of brepocitinib daily or a placebo for 24 weeks, followed by an open-label phase where all patients received brepocitinib for an additional 24 weeks. The researchers collected lesional scalp biopsies at baseline, week 24, and week 48 to assess changes in biomarker expression.

According to the study data, patients treated with brepocitinib exhibited a significant downregulation in CCL5 expression (P = 0.004) at week 24. There was no significant reduction in fibrosis-related markers, although enrichment analysis showed a trend toward upregulation in the placebo group. 

Clinical efficacy varied among CA subtypes. LPP patients receiving brepocitinib had a 51.0% mean percent reduction in the Lichen Planopilaris Activity Index (LPPAI) at week 24 (P < 0.001), which improved to 79.2% by week 48. FFA patients saw a 33.6% decrease in the Frontal Fibrosing Alopecia Severity Index (FFASI) at week 24 (P = 0.02), improving to 39.0% by week 48. CCCA patients showed an 11.9% reduction in the Central Hair Loss Grade (CHLG) at week 16, with continued improvement to 43.5% by week 48 (P < 0.001).

The safety profile of brepocitinib was favorable. Adverse events were consistent with previous research.

"This study demonstrates that brepocitinib effectively decreases inflammatory biomarker expression and improves clinical severity measures at 24 and 48 weeks while also maintaining a favorable safety profile through 52 week follow up period," the authors concluded. "Larger scale studies utilizing brepocitinib for the treatment of CA are warranted to move towards formal approval."

Source: David E, et al. Journal of the American Academy of Dermatology. 2025. Doi:10.1016/j.jaad.2024.09.073

Disclosures: Dr Meariman is a consultant for Abbvie. Dr Ungar is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Incyte, Rapt Therapeutics, and Pfizer. He is also a consultant for Arcutis Biotherapeutics, Bristol Myers Squib, Castle Biosciences, Fresenius Kabi, Galderma, Janssen, Lilly, Pfizer, Primus Pharmaceuticals, Sanofi, and UCB. Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from: Abbvie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, UCB. They are also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, Abbvie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. Drs Oemar, Mahling, and Peeva are Pfizer employees and own stock and stock option. Authors David, Shokrian, Hawkins, Sikand, Singer, Estrada, Bose, and Pulsinelli, and Drs Duca, Dubin, Andrews, and Da Rosa have no conflicts of interest to declare.