Description
Alefacept is a recombinant human LFA3-Ig-G1 fusion protein that blocks the T-cell CD2
receptor preventing T-cell proliferation, a key mechanism in psoriasis. It was launched
in the US for the treatment of chronic plaque psoriasis. It is a dimeric fusion protein
consisting of the LFA-3 (leukocyte function antigen-3) and Fc (hinge, CH2 and CH3)
portion of human IgG1 and has been produced in Chinese hamster ovary (CHO) and NS-
0 myeloma cell lines. In transgenic mice expressing human CD2, alefacept demonstrated
efficacy in inhibiting antigen and mitogen-induced T-cell response. In the baboon
cardiac-graft survival model alefacept, dosed 3 mpk intravenously for 12 days and
treatment initiated two days before graft surgery, increased the mean survival of the
transplanted hearts from 10.6 days (placebo) to 18.0 days (treatment group). In all clinical
trials, improvement in PASI scores were noted and a long-lasting effect was noted. Thus
this agent does not require chronic, maintenance dosing in all patients. Clinical studies for
repeat courses (second twelve weeks) showed additional improvement. It has a half-life
of 12 days, is dosed once weekly by injection either subcutaneously or intramuscularly
and is approved for 12-week regimen. Side effects limit the use of current treatments such
as phototherapy, cyclosporin, and methotrexate. Thus far, alefacept has been well
tolerated.
Indications
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.
