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GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
A Journal on Dermatology and Sexually Transmitted Diseases
Official Journal of the Italian Society of Dermatology and Sexually Transmitted Diseases
Indexed/Abstracted in: EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,014
Giornale Italiano di Dermatologia e Venereologia 2004 February;139(1):3-13
New biologic therapies for the treatment of psoriasis
De Rie M. A., Bos J. D.
Department of Dermatology, Academic Medical Center University of Amsterdam, Amsterdam, The Netherlands
Psoriasis is a chronic immune-mediated disease that has a multifactorial genesis. It is generally believed that patients have a genetic predisposition and that by environmental assaults such as injury of the skin, infection, stress and medication psoriasis is triggered. The immune system is thought to be pivotal in the pathogenesis of psoriasis. Advances in the understanding of the immune basis of psoriasis have led to the development of therapies targeted at various steps in this process. In addition, new therapies are aimed at induction of long lasting remission and not just suppression as is true for most of presently used systemic therapies. Three distinct types of engineered proteins, so called “biological response modifiers” or “biologicals”, are under development to reach these goals: monoclonal antibodies, fusion proteins and cytokines. The primary target of these biologicals is to inhibit one or more steps in the immunopathogenesis of psoriasis: T-cell activation and T-cell interaction with antigen presenting cells, T-cell differentiation and proliferation, T-cell adhesion (“homing”) and migration, and effector actions (cytokine production) of T cells in the skin. The most extensively studied biologicals at this moment are the fusion protein alefacept and the humanized monoclonal antibody efalizumab that inhibit T cell-antigen presenting cell interaction and T-cell adhesion, respectively. Also the tumor necrosis factor (TNF) inhibitors infliximab and etanercept have demonstrated promising results. In general, several problems can be encountered when using biologicals: 1st-dose, cytokine release and hypersensitivity reactions, immunosuppression by (functional) depletion of immunocompetent cells, development of neutralizing antibodies and infrequent unpredictable adverse events discovered during introduction of these new drugs. In addition, caution is needed when patients have been treated in the past with potential carcinogenic therapies such as arsenic and abundant photochemotherapy. In this article an attempt is made to show an overview of this exciting new field of research with is the result of new protein engineering techniques and understanding of the immunobiology of psoriasis. Since the data on the outcome of clinical trials and new biologicals is constantly changing the reader is encouraged to check recent literature for up to date information.