Secukinumab Reverses Disease-Defining Psoriasis Histopathology While Retaining Full T-cell Activation Potential

Secukinumabis an anti-IL-17A fully human monoclonal antibody with clinical efficacy in psoriasis. The effects of secukinumabon skin pathology and T cell activation were investigated. In a randomized double-blinded placebo controlled study, subjects with chronic plaque-type psoriasis received 300 mg s.c. secukinumab(n=24) or placebo(n=12) at Weeks 0, 1, 2, 3 and 4, then every 4 weeks until Week 12. Biopsies of lesional and non-lesional skin were assessed for epidermal growth, differentiation / maturation, mitotic rate, infiltrating T-cells, macrophages, and dendritic cell (DC) subsets. The primary endpoint was histological disease reversal at Week 12. Circulating T-cells were evaluated by flow cytometry for the activation marker CD69. 14/23 secukinumab-treated (61%) and 0/12 (0%) placebo-treated subjects attained histologic disease reversal at Week 12 (p<0.001; secukinumabvs. placebo). 14/24 (58.3%) secukinumab-treated and 0/12 (0%) placebo-treated subjects had a PASI90 response at Week 12. Histologic...