Advances in Therapy for Psoriasis: An Overview of Infliximab, Etanercept, Efalizumab, Alefacept, Adalimumab, Tazarotene, and Pimecrolimus

Abstract

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to review the progress of the biologic agents which are available, or under investigation for clinical use: infliximab, etanercept, efalizumab, alefacept, and adalimumab. In addition, two other investigational therapies, oral tazarotene and oral pimecrolimus will be discussed. Clinical data for these agents, including the most recent phase II and/or III study results, will be discussed, as well as the most recent safety data.

Successful Treatment of Severe Atopic Dermatitis in a Child and an Adult With the T-Cell Modulator Efalizumab

“…The interaction between LFA-1 on T cells and ICAM-1 (intercellular adhesion molecule 1) on antigenpresenting cells is an important costimulatory signal resulting in T-cell activation. 1 Located on endothelial cells, ICAM-1 also interacts with LFA-1 on circulating T cells, a necessary interaction for migration of T cells into inflamed skin. Efalizumab can therefore treat psoriasis by blocking T-cell migration into the skin and by preventing T-cell activation.…”

“…3,[6][7][8] There have been no opportunistic infections, no clinical signs of immunosuppression, and no hepatotoxic effects or nephrotoxic effects associated with the use of efalizumab in study subjects treated for up to 3 years (unpublished data, Genentech Inc, South San Francisco, Calif, February 2005). 1 This lack of endorgan toxic effect and lack of demonstrated risk of immunosuppression differentiates efalizumab from cyclosporine and makes it an appealing long-term option for patients with severe atopic dermatitis.…”

Comano's (Trentino) thermal water interferes with tumour necrosis factor-α expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: Yet other mechanisms of its anti-psoriatic action

“…Clinical improvements of psoriasis associate with a fall in lesional skin and serum TNF-· levels (36,56,57), whereas clinical aggravations of psoriatic area severity index (PASI) scores concur with surges in serum and lesional skin TNF-· concentrations (40,60). Neutralisation of TNF-· by infliximab, an anti-TNF-·-specific chimerical monoclonal antibody, or by etanercept, a soluble p75 TNF receptor fusion protein that binds both TNF and lymphotoxin (LT), is known to cause a rapid and complete remission of psoriasis even in its recalcitrant von Zumbusch form (39)(40)(41) and, when associated with methotrexate, of psoriatic arthritis (58)(59)(60)(61).…”

“…Resident dermal cells (fibroblasts, mast-cells) and infiltrated antigen-presenting cells (APCs), macrophages, and T lymphocytes also express TNF-· (38). The early-occurring TNF-· overproduction and hyper-secretion in psoriasis vulgaris, and in its recalcitrant generalised pustular (von Zumbusch) form (39)(40)(41) favours the cellular infiltration of epidermal and dermal layers by eliciting the expression of intercellular adhesion molecules such as ICAM-1, V-CAM-1, and E-selectin by the keratinocytes and endothelial cells (42). In synergism with IFN-Á and IL-1, TNF-· acts as a proinflammatory agent by up-regulating cytokines and chemokines such as IL-8 (19,20,43), IL-6, IL-1, leukemia inhibitory factor (LIF), GM-CSF (43), and TGF-· (19).…”

Benefit-risk analysis of adalimumab versus methotrexate and placebo in the treatment of moderate to severe psoriasis: Comparison of adverse event–free response days in the CHAMPION trial

“…Potential safety concerns regarding the use of such tumor necrosis factor antagonists include reactivation of tuberculosis, development of other opportunistic infections, malignancies, demyelinating diseases, and congestive heart failure. 2,11 Adalimumab (ADA), a fully human monoclonal antibody against tumor necrosis factor, has demonstrated efficacy and tolerability in treating patients with psoriasis across several randomized trials. 5,12 In 2008, the FDA approved the use of ADA for treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and when other systemic therapies are medically less appropriate.…”