Novel pharmacological approaches in the treatment of psoriasis

Abstract

Progress in the understanding of psoriasis as a T-cell mediated inflammatory disease has led to the development of new immunomodulatory therapies. Currently the main focus is on the so-called biologics (or biological agents), including fusion proteins, monoclonal antibodies, cytokines and selective receptors. They mainly target single steps in the complex cascade of humoral and cellular inflammatory immuno-mechanisms that finally lead to the accelerated growth of epidermal and vascular cells in the psoriatic lesions. The most promising and advanced biological agents are discussed along with their influence on the critical pathophysiological steps in psoriasis, including depletion of T cells, blockade of initial T-cell activation and T-cell receptor (TCR) stimulation, blockade of costimulatory signals and T-cell proliferative signals as well as restoration of the T helper type 1 (Th1)/Th2 balance by diminishing type 1 cytokines and administration of type 2 cytokines. In addition to the biological agents, further development of 'classical' dermatological therapies, such as retinoids, or the discovery of new indications for non-dermatological agents contribute to the novel pharmacological approaches in the treatment of psoriasis.

Psoriasis: crucial role of LXR-α RNomics

“…It has also been observed that selective skewing of T-helper 1 cells toward an interleukin-4 (IL-4)-producing (T-helper 2) phenotype can, in experimental animals, alleviate autoimmune disease without inducing general immunosuppression. 25,26 A decrease in the IFN-g expression and an increase in the IL-4 expression of T cells in psoriatic lesions after UVB irradiation lead to a decrease in local immunoreactivity. 27 The ability of LXR-a to modulate the expression of c-myc as in Figure 3 explains the mechanism by which LXR-a synthetic agonists inhibit the proliferation of keratinocytes in in vitro cultures.…”

Prevalence and factors associated with use of placebo control groups in randomized controlled trials in psoriasis: A cross-sectional study

“…28 Development of new systemic therapies for psoriasis has been the focus of much clinical research, including clinical trials, in the past 5 years. [29][30][31] In this study, we investigated the prevalence of and factors associated with use of placebo controls in randomized controlled trials published since 2001, when the first large-scale trial of one of the newer systemic agents-alefacept-was published. 32 We hypothesized (1) that pharmaceutical companye funded trials were more likely to have used placebo controls, which enable trials to be conducted more quickly and less expensively than active-controlled trials, 5,14,33 and (2) that trials conducted in the United States would have used placebo controls more often, since the FDA has historically favored placebo controls more explicitly than regulators in other countries.…”

Pimecrolimus 1% Cream in the Treatment of Facial Psoriasis: A 16-Week Open-Label Study

“…However, for chronic plaque-type psoriasis there are differing reports about the effectiveness of this treatment [25,26,27,28]. The lack of efficacy reported by some may be due to low absorption of the drug through thick psoriatic scales.…”