Recent Advances and Clinical Trials in Frontal Fibrosing Alopecia Research

Conclusions

• Genetic evidence suggests that FFA involves epistatic interactions between ERAP1 and specific MHC class I alleles, supporting an immune-mediated mechanism distinct from classic lichen planus.
• The ERAP1–MHC class I axis may be a future therapeutic target in FFA, although effective inhibitors are not yet available for clinical use.
• Eyebrow alopecia in FFA is often a scarring, inflammatory process rather than simple non-scarring shedding, and the degree of fibrosis appears to reflect more advanced disease with less chance of regrowth.
• Sebaceous glands are preserved in many eyebrow biopsies, indicating that adnexal destruction is incomplete in a substantial subset of patients.
• Forehead atrophy in FFA is characterized by follicular loss, dermal fibrosis, and reduced vascularity, which may help explain the visible facial veins seen in affected patients.
• Color Doppler ultrasound may become a useful non-invasive tool for assessing inflammation and atrophy in the forehead of patients with FFA.
• Male patients with FFA may have elevated serum leptin despite similar metabolic profiles to controls, suggesting leptin could serve as a biomarker or mechanistic clue.
• Topical delgocitinib produced modest but significant molecular improvement and reduced Th1-related biomarkers in FFA, indicating potential benefit despite short-term and small-sample limitations.
• Oral brepocitinib showed significant molecular and clinical improvement with acceptable tolerability across cicatricial alopecias, supporting the JAK/STAT pathway as a promising treatment target.
• Overall, current research points to FFA as an immune-driven, fibroinflammatory disease for which targeted anti-inflammatory and immunomodulatory therapies are increasingly promising but still need larger, longer trials.