Targeting T-cell subsets to achieve remission.
Patients with psoriasis have an increase in pathogenic CD45RO+ memory-effector T cells during active disease. The genetically engineered fully human fusion protein alefacept has been developed to selectively target this subset of T cells. Alefacept binds to memory-effector CD45RO+ T cells, inhibiting their activation and inducing T-cell apoptosis. The selectivity of alefacept for memory-effector CD45RO+ T cells was evaluated in 229 patients with chronic psoriasis in a randomized, placebo-controlled, double-blind study conducted at 22 centres in the USA. Patients received alefacept intravenously at doses of 0.025 mg/kg, 0.075 mg/kg, or 0.150 mg/kg, or placebo once weekly for 12 weeks. Two weeks after completing treatment, patients receiving alefacept showed significant improvement in the Psoriasis Area and Severity Index (PASI) compared with those receiving placebo. Mean reductions in the PASI score were up to 53% lower than baseline scores in the alefacept treatment group, compared with a 21% decline from baseline in the placebo group (P < 0.001). In addition to the significant improvement in psoriasis, treatment with alefacept produced long-term remission in some patients. Twelve weeks after completion of therapy, 28 patients became clear or almost clear. The therapy was well tolerated and nonimmunogenic. Importantly, during treatment, there was a correlation between improvement in psoriasis and a dose-dependent reduction in peripheral blood CD45RO+ memory-effector T cells, but not in CD45RA+ naive T cells. This correlation indicates a relationship between a specific T-cell subset reduction (CD45RO+) and clinical outcome in psoriasis.
Christophers
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Department of Dermatology, University of Kiel, Kiel, Germany. e.christophers@web.de
D000293:Adolescent; D000328:Adult; D000368:Aged; D000077944:Alefacept; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome
D011993:Recombinant Fusion Proteins; D000077944:Alefacept