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 apoptosis, and suppression 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.
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 apoptosis, and suppression 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.
Authors: Frédéric Lebrun-Julien; Mathieu J Bertrand; Olivier De Backer; David Stellwagen; Carlos R Morales; Adriana Di Polo; Philip A Barker Journal: Proc Natl Acad Sci U S A Date: 2010-02-03 Impact factor: 11.205
Authors: A Kaczmarek; O Krysko; L Heyndrickx; T Løve Aaes; T Delvaeye; C Bachert; L Leybaert; P Vandenabeele; D V Krysko Journal: Cell Death Dis Date: 2013-12-12 Impact factor: 8.469
Authors: Lara Gibellini; Sara De Biasi; Elena Bianchini; Regina Bartolomeo; Antonella Fabiano; Marco Manfredini; Federica Ferrari; Giuseppe Albertini; Tommaso Trenti; Milena Nasi; Marcello Pinti; Anna Iannone; Carlo Salvarani; Andrea Cossarizza; Giovanni Pellacani Journal: PLoS One Date: 2016-12-09 Impact factor: 3.240