Treatment of plaque psoriasis.
Alefacept (Amevive) is a fully human lymphocyte function–associated antigen 3/immunoglobulin 1 (LFA-3/IgG1) fusion protein. It binds to CD2 on T cells, inhibiting T-cell activation and producing selective T-cell apoptosis. Alefacept is FDA approved as a 12-week course of 15 mg weekly intramuscular injections. Long remissions can be seen in responders. Peripheral CD4 counts should be followed and doses withheld if counts drop below 250 cells/μL. Therapy should be discontinued if the CD4 count remains below 250 cells/μL for >4 weeks. A second course lengthens the period of remission without additional toxicities.
This recombinant immunosuppressive protein (FW = 51800 g/mol; CAS
222535-22-0), marketed under the trade name Amevive?, reduces the
number of psoriasis-associated T lymphocytes, thereby alleviating an
underlying cause of the disorder. Alefacept is indicated in patients with
moderate to severe chronic plaque psoriasis. The dimeric fusion protein
consists of the extracellular CD2-binding portion of the human Leukocyte
Function Antigen-3 (or LFA-3) linked to the Fc (hinge, CH2 and CH3
domains) portion of human IgG1. Amevive is a fully humanized toxin
that binds to CD2 and blocks costimulatory signaling, selectively inducing
apoptosis of activated memory T cells involved in the pathogenesis of
psoriasis. Alefacept has a slow onset of action, peaking approximately 18
weeks after the first injection of a 12-week course. Because psoriasis is
a chronic disorder, patients require lifelong access to injectable biologic
agents targeting specific immune mediators, raising concerns about their
longterm safety. Alefacept is only effective in a small proportion of
patients, and its maximal efficacy is not achieved until 4-6 weeks after a
treatment course.
