Efalizumab in the treatment of psoriasis

Abstract

The humanized antibody efalizumab is currently the only T-cell directed biologic approved for the treatment of moderate-to-severe psoriasis by both American and European authorities. Binding to and blocking the function of the adhesion molecule leukocyte function associated antigen 1 (LFA-1), it is believed to interfere with T-cell activation in the lymph node, migration through the circulation into the skin, and re-activation in-loco, all of these representing central steps in the pathogenesis of psoriasis. A comprehensive clinical development program provided large and consistent evidence that efalizumab induces a major clinical benefit in psoriasis. Efalizumab rapidly and substantially improves psoriatic skin symptoms and leads to profound gain in quality of life. It allows safe and effective long-term control of psoriasis. Therefore, evidence-based treatment guidelines recommend its use in moderate to severe plaque-type psoriasis.

Keywords: T-cell; T-cell activation; biologics; efalizumab; psoriasis; recirculation.

Figure 1

Mode of action of efalizumab in psoriasis: According to a widely accepted working hypothesis, antigen-presenting dendritic cells of the epidermis transport yet unknown antigens to regional lymph nodes and present them to naïve T-cells. These respond by activation, proliferation, and maturation into effector T-cells, which patrol the body and leave circulation at the site of antigen contact. Subsequently, these cells migrate toward the epidermis and upon re-activation, release effector molecules, namely pro-inflammatory cytokines. Efalizumab interferes with this process at the LFA-1 dependent stages, namely activation of T-cells in lymph nodes (A), extravazation of circulating T-cells in inflammatory skin (B), and T-cell re-activation in the skin (C).