An open-label study to evaluate the transition of patients with chronic plaque psoriasis from cyclosporine to alefacept.

Eleven patients with well-controlled psoriasis on cyclosporine (Physician's Global Assessment [PGA] of "mild" or better) participated in an open-label study that evaluated a strategy for transition to alefacept. Using this transition strategy, 7 of 11 patients (64%) maintained PGA scores. Quality of life improved or was maintained in all patients. Adverse events and reductions in CD4+ T cell counts were consistent with those seen during alefacept monotherapy.

A randomized, double-blind, vehicle-controlled, bilateral comparison trial of bexarotene gel 1% versus vehicle gel in combination with narrowband UVB phototherapy for moderate to severe psoriasis vulgaris.

We report results of a randomized, vehicle-controlled, bilateral comparison pilot study of bexarotene gel 1% with narrowband UVB (NBUVB) phototherapy for moderate to severe psoriasis. In all, 9 patients applied drug or vehicle gel to comparable target lesions up to twice daily for 10 weeks. NBUVB was initiated 2 weeks after topical therapy began. Limitations include small sample size and interim analysis. Based on analysis of target lesion scores, bexarotene gel 1%/NBUVB was significantly more effective than placebo/NBUVB.

Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of responding patients.

BACKGROUND: Etanercept is a tumor necrosis factor-alpha binding fusion protein that demonstrates efficacy in the treatment of psoriasis, which is accompanied by decreased plaque infiltration of T cells and myeloid dendritic cells. We hypothesized that etanercept decreases inflammatory cell infiltration by inducing apoptosis. OBJECTIVE: We sought to investigate the effect of etanercept on circulating and plaque leukocyte apoptosis in psoriasis. METHODS: Blood and plaque specimens were obtained from 10 patients with psoriasis treated with etanercept (25 mg subcutaneously twice weekly) for 24 weeks. Apoptosis was determined in tissue samples using immunohistochemistry and flow cytometry. RESULTS: Etanercept selectively induced apoptosis in dermal dendritic cells in plaques of responding patients at 1 month, before most of the clinical and histologic response was achieved. No apoptosis was detected in plaque or circulating T cells or in circulating monocytes. LIMITATIONS: Addition of multiple time points earlier than 1 month would be valuable to establish the time point of maximum induction in cell apoptosis. CONCLUSION: Etanercept selectively induces apoptosis of pathogenic dermal dendritic cells in responding patients early in the course of treatment.

Induction of lesional and circulating leukocyte apoptosis by infliximab in a patient with moderate to severe psoriasis.

Infliximab demonstrates high efficacy in treating psoriasis in a high proportion of patients. In this report we demonstrate induction of plaque (T cells, dendritic cells) and peripheral blood (T cells, monocytes) leukocyte apoptosis following a single infliximab infusion in a psoriasis patient.

Emerging drugs for moderate-to-severe psoriasis.

Psoriasis is a chronic, incurable, disabling skin disease characterised by red, scaly plaques. Approximately 23% of psoriasis patients also have an accompanying arthritis that can become debilitating. Psoriasis has a stigmatising effect on its victims, who often feel socially isolated. Although the exact aetiology of psoriasis is still unknown, it is clearly an immune-mediated disease. Traditional therapies for psoriasis include topical drugs, such as corticosteroids, retinoids and vitamin D3 analogues; systemic drugs, such as methotrexate, ciclosporin and retinoids; and phototherapy. These mainstays of treatment are efficacious for the treatment of severe disease; however, most are associated with toxicities or are inconvenient. Recent advances in biotechnology have produced new pharmaceuticals that interfere with immune responses thought to be involved in the pathogenesis of psoriasis and other inflammatory diseases. The immunobiologicals, one new family of drugs, consist of monoclonal antibodies and fusion proteins. Many have demonstrated efficacy in treating psoriasis. Some appear to offer safety benefits over traditional therapies; further monitoring and surveillance of these agents is required to adequately establish safety profiles. This article discusses existing and emerging treatments for moderate-to-severe psoriasis.

Etanercept therapy for patients with psoriatic arthritis and concurrent hepatitis C virus infection: report of 3 cases.

Psoriasis and psoriatic arthritis are exacerbated by interferon alfa and other treatments for hepatitis C virus infection. Immunosuppressants and hepatotoxic drugs are relatively contraindicated in hepatitis C. Data in the literature suggest that etanercept is a safe option in the treatment of patients with rheumatoid arthritis and concurrent hepatitis C. We present three cases in which we have successfully used etanercept to treat psoriatic arthritis/psoriasis in patients with hepatitis C without worsening their hepatitis or interfering with their hepatitis treatment. With close monitoring of viral load and hepatic enzymes, etanercept may be a safe option for treating psoriatic arthritis/psoriasis in patients who also have hepatitis C.

TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques.

The mechanisms of action of marketed TNF-blocking drugs in lesional tissues are still incompletely understood. Because psoriasis plaques are accessible to repeat biopsy, the effect of TNF/lymphotoxin blockade with etanercept (soluble TNFR) was studied in ten psoriasis patients treated for 6 months. Histological response, inflammatory gene expression, and cellular infiltration in psoriasis plaques were evaluated. There was a rapid and complete reduction of IL-1 and IL-8 (immediate/early genes), followed by progressive reductions in many other inflammation-related genes, and finally somewhat slower reductions in infiltrating myeloid cells (CD11c+ cells) and T lymphocytes. The observed decreases in IL-8, IFN-gamma-inducible protein-10 (CXCL10), and MIP-3alpha (CCL20) mRNA expression may account for decreased infiltration of neutrophils, T cells, and dendritic cells (DCs), respectively. DCs may be less activated with therapy, as suggested by decreased IL-23 mRNA and inducible NO synthase mRNA and protein. Decreases in T cell-inflammatory gene expression (IFN-gamma, STAT-1, granzyme B) and T cell numbers may be due to a reduction in DC-mediated T cell activation. Thus, etanercept-induced TNF/lymphotoxin blockade may break the potentially self-sustaining cycle of DC activation and maturation, subsequent T cell activation, and cytokine, growth factor, and chemokine production by multiple cell types including lymphocytes, neutrophils, DCs, and keratinocytes. This results in reversal of the epidermal hyperplasia and cutaneous inflammation characteristic of psoriatic plaques.