ISSN:
1468-3083
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background Recognition of psoriasis as a T-cell-mediated immune disease has led to the development of various therapeutic approaches directed against the pathogenic T cells. Alefacept, a novel and selective biological recombinant protein, binds CD2 on T cells to block T-cell activation and proliferation and interacts with FcγRIII receptors on accessory cells to produce selective T-cell apoptosis.Objective To demonstrate the efficacy and safety of once-weekly alefacept IM compared with placebo given for 12 weeks to patients with chronic plaque psoriasis.Methods Multicentre (63 sites in Europe, the USA, and Canada), randomized, double-blind, parallel-group study comparing 10 mg and 15 mg of alefacept and placebo administered IM once weekly for 12 weeks. Patients were followed for an additional 12 weeks after cessation of therapy. Patients were eligible for enrolment if they were ≥ 18 years of age, had chronic plaque psoriasis for ≥ 12 months involving ≥ 10% body surface area, and had CD4+ T-cell counts at or above the lower limit of normal.Results 507 patients were enrolled into three treatment groups, which were well balanced for demographic, baseline disease characteristics, and treatment history. A significantly greater percentage of patients treated with alefacept 15 mg IM achieved ≥ 75% PASI reduction from baseline 2 weeks after the last dose compared with placebo (21% vs. 5%, P 〈 0.001); 12% of patients treated with alefacept 10 mg IM reached this level of improvement (P = NS vs. placebo). Alefacept was well tolerated, with adverse events similar to that of placebo.Conclusions Treatment with alefacept 15 mg IM provided highly significant improvements in all measures of psoriasis disease activity compared with placebo. Pharmacodynamic data confirmed that alefacept is a selective biological agent that reduces memory-effector T cells (CD4+CD45RO+ and CD8+CD45RO+), the source of the pathogenic mediators of psoriasis, while having relatively no effect on naive T-cell populations.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1468-3083.17.s2.3.x
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