Biological therapy of psoriasis

Abstract

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. These usually being well tolerated are being found useful in a growing number of immune-mediated diseases, psoriasis being just one example. The newest biologic, ustekinumab, is directed against the p40 subunit of the IL-12 and IL-23 cytokines. It has provided a new avenue of therapy for an array of T-cell-mediated diseases. Biologics are generally safe; however, there has been concern over the risk of lymphoma with use of these agents. All anti-TNF-alpha agents have been associated with a variety of serious and "routine" opportunistic infections.

Keywords: Adverse effects; biologics; psoriasis; therapy.

Figure 1

Biologics in psoriasis and their possible mechanisms. TNF- α secreted by antigen-presenting cells; Th-1 cells and keratinocytes can be neutralized by the anti-TNF biologics infliximab, etanercept, adalimumab, and golimumab. Adalimumab and golimumab are fully human antibodies directed against TNF-α. Infliximab was developed from a mouse anti-TNF antibody that was then partially humanized. Etanercept is a molecullarly engineered molecule formed by linking the TNF-α receptor to the Fc portion of an antibody. Ustekinumab and ABT-874 are directed against the p40 subunit of IL-12 and IL-23. IL-12 is needed for differentiation of naive cells into Th-1 cells and IL-23 is needed for the maintenance of IL-17-secreting Th17 cells. IFN-α secreted by Th-1 cells and IL-17 and IL-22 secreted by Th-17 cells activate keratinocytes, which in turn proliferate and secrete IL-12 and TNF-α.