Randomized Controlled Trial of the Topical JAK Inhibitor Delgocitinib Cream in Patients with Frontal Fibrosing Alopecia.

Abstract

Background: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia with generally poor prognosis if untreated, and no approved treatment options.

Objective: To evaluate changes in the molecular signature of FFA lesions after application of delgocitinib cream. Safety, tolerability and efficacy were also investigated.

Methods: This was a phase 2a, randomized, double-blind, exploratory trial of delgocitinib cream 20 mg/g (2%) versus cream vehicle in patients with FFA.

Results: A total of 30 adult females with FFA were randomized to delgocitinib cream (n=15) or cream vehicle (n=15). After 12 weeks, expression of the T helper 1-related biomarker CXCL9 was significantly downregulated (-3.10; p<0.05) while there were non-significant reductions in CXCL10 (-2.60; p<0.1), and interferon-γ (-1.49; p=0.22) in lesions treated with delgocitinib cream but not cream vehicle. Delgocitinib-treated lesions had a small but significant mean improvement in transcriptomic profile (4%; p<0.001) whereas lesions treated with cream vehicle worsened (33%). Delgocitinib cream was well tolerated and associated with improvements in exploratory clinical severity endpoints.

Limitations: Limitations of the trial include small sample size, biomarker analyses only being conducted to week 12, and the exploratory nature of efficacy endpoints.

Conclusion: Delgocitinib cream resulted in an improvement in the transcriptomic profile of lesions and may have potential as a topical treatment for FFA.