Targeting tumor necrosis factor α in psoriasis and psoriatic arthritis

Background: Psoriasis is an immune-mediated chronic inflammatory disease triggered and maintained by inflammatory mediators, including TNF-alpha. Objective/methods: To summarize the role of anti-TNF-alpha agents psoriasis therapy, focusing on the mechanisms and biological pathways involved, by reviewing relevant literature. Results/conclusions: The three TNF-alpha antagonists currently available (etanercept, infliximab and adalimumab) are effective in the therapy of psoriasis and psoriatic arthritis. Certolizumab pegol and golimumab are TNF-alpha inhibitors not approved for therapy of psoriasis yet. In addition to neutralizing soluble TNF-alpha, TNF-alpha blockers bind to membrane TNF-alpha and change the behavior of TNF-alpha-expressing cells, resulting in hastened cell cycle arrest and apopotosis, and suppresion of cytokine production. TNF-alpha blockers may also affect adaptive immune responses by reducing T helper cell (Th)1 and Th17 responses, and favoring the development of T-regulatory cells. TNF-alpha antagonists can regulate differentiation and activation of osteoclasts, thus reducing bone destruction in psoriatic arthritis. Anti-TNF-alpha agents differ in their pharmacokinetics and pharmacodinamic properties, which is reflected in their therapeutic and safety profiles. The safety of TNF-alpha antagonists has been established, and patient selection and monitoring allow risk minimization.