Background: Treatment options for frontal fibrosing alopecia (FFA) are limited. A better knoledment of the immunopathogeny of this primary lymphocytic scarring alopecia. Objective: To assess safety and efficacy of ustekinumab in moderate-to-severe AD. Methods: In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n¼16) or placebo (n¼17), with subsequent crossover at 16wks, and last dose at 32wks. Background therapy (mild topical steroids) was allowed to increase compliance. Study endpoints included clinical (SCORAD50) and biopsy-based measures of tissue structure and inflammation, using protein and gene expression studies. Results: The ustekinumab group achieved higher SCORAD50 responses at 12, 16 (primary endpoint), and 20wks than placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 40wks, only in the initial ustekinumab-group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen only after 4wks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-g, elafin/PI3, CXCL1, CCL17; p7; p7; p