Efficacy and Safety of Secukinumab in Chronic Plaque Psoriasis and Psoriatic Arthritis Therapy

摘要

Psoriasis is a chronic inflammatory skin disease affecting about 1–3% of the general population. Moderate-to-severe psoriasis is commonly associated with various comorbidities, including psoriatic arthritis (PsA) and cardio-metabolic disorders such as obesity, hypertension, diabetes, and metabolic syndrome. There is increasing recognition that systemic inflammation accompanies severe skin disease. Abnormal innate and adaptive immune responses in the skin are involved in pathogenesis. The cytokine interleukin (IL)-17A is produced by T helper 17 (Th17) cells, neutrophils, mast cells, and T cytotoxic 17 cells. IL-17 plays a key role in host defense against extracellular bacteria and fungi. IL-17A acts on keratinocytes to increase expression of chemokines involved in recruiting myeloid dendritic cells, Th17 cells, and neutrophils to the lesion site. IL-17A also induces the production of antimicrobial peptides and pro-inflammatory cytokines that, in turn, may amplify and sustain immune responses in the skin. Blocking IL-17A improved psoriasis-like pathology in experimental models, and reduction in IL-17 signaling is part of the mechanism of action of tumor necrosis factor-α blockers. Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or antagonizing its receptor (i.e., brodalumab) are currently being tested for efficacy and safety in the treatment of plaque psoriasis and PsA. Secukinumab is a fully human IgG1 monoclonal antibody that selectively binds and neutralizes IL-17A whose efficacy in the therapy of chronic plaque psoriasis has been demonstrated in different phase II clinical trial. No new safety signals have emerged so far.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-014-0042-5) contains supplementary material, which is available to authorized users.