Company: Biogen
Approval Status: Approved January 2003
Treatment for: Psoriasis
General Information
Amevive (alefacept) is an immunosuppressive dimeric fusion
protein that reduces lymphocyte counts (T-cells) thus treating the cause of
psoriasis. It is indicated in patients with moderate to severe chronic
plaque psoriasis who are candidates for systemic therapy or phototherapy
Amevive is available in either intramuscular injection
(15-mg alefacept) or intravenous injection (7.5-mg alefacept) formulations.
Amevive reduces immune cell counts which could increase the
chance of developing infection or malignancy.
Clinical Results
Amevive was evaluated in two randomized, double blind,
placebo-controlled studies in 726 adult subjects with chronic plaque
psoriasis. In both trials, Amevive or placebo was administered once a week
for 12 weeks. In total 77% of subjects had previously received systemic
therapy and/or phototherapy for psoriasis.
Response to treatment in both studies was defined as the
proportion of subjects with a reduction in score on the Psoriasis Area and
Severity Index (PASI)?of at least 75% from baseline at two weeks following
the 12-week treatment period. Other treatment responses included the
proportion of subjects who achieved a scoring of 'almost clear' or 'clear'
by Physician Global Assessment (PGA) and the proportion of subjects with a
reduction in PASI of at least 50% from baseline two weeks after the 12-week
treatment period.
In both studies, onset of response to Amevive treatment (at
least a 50% reduction of baseline PASI) began 60 days after the start of
therapy. In Study 1, the median duration of response (75% or greater
reduction in PASI) was 3.5 months for Amevive treated patients and 1 month
for placebo-treated patients. In Study 2, the median duration of response
was approximately 2 months for both groups. A majority of the subjects had
responded to either Amevive or placebo maintained a 50% or greater reduction
in PASI through the 3-month observation period. In both studies, an
additional 11% (42/367) and 7% (12/166) of subjects treated with Amevive,
respectively, achieved a 75% reduction from baseline PASI score at one or
more visits after the first 2 weeks of the follow-up period.
Side Effects
Adverse events associated with the use of Amevive may
include (but are not limited to) the following:
Mechanism of Action
Amevive (alefacept) is an immunosuppressive dimeric fusion
protein that consists of the extracellular CD2-binding portion of the human
leukocyte function antigen-3 (LFA-3) linked to the Fc (hinge, CH2 and CH3
domains) portion of human IgG1. Alefacept is produced by recombinant DNA
technology in a Chinese Hamster Ovary (CHO) mammalian cell expression
system.
Amevive interferes with lymphocyte activation by
specifically binding to the lymphocyte antigen, CD2, and inhibiting
LFA-3/CD2 interaction. Activation of T lymphocytes involving the interaction
between LFA-3 on antigen-presenting cells and CD2 on T lymphocytes plays a
role in the pathophysiology of chronic plaque psoriasis. The majority of T
lymphocytes in psoriatic lesions are of the memory effector phenotype
characterized by the presence of the CD45RO marker? express activation
markers (e.g., CD25, CD69) and release inflammatory cytokines, such as
interferon y.
Amevive also causes a reduction in subsets of CD2+ T
lymphocytes (primarily CD45RO+), presumably by bridging between CD2 on
target lymphocytes and immunoglobulin Fc receptors on cytotoxic cells, such
as natural killer cells. Treatment with Amevive results in a reduction in
circulating total CD4+ and CD8+ T lymphocyte counts. CD2 is also expressed
at low levels on the surface of natural killer cells and certain bone marrow
B-lymphocytes.
Literature References
Bos JD, Hagenaars C, Das PK, et al. Predominance of
'memory' T cells (CD4+, CDw29+) over 'na飗e' T cells (CD4+, CD45R+) in both
normal and diseased human skin. Arch Dermatol Res 1989; 281:24-30.
Ellis C, Krueger GG. Treatment of chronic plaque
psoriasis by selective targeting of memory effector T lymphocytes. N Engl
J Med 2001; 345:248-255.
Fredriksson T, Pettersson U. Severe psoriasis--oral
therapy with a new retinoid. Dermatologica 1978; 157:238-244.
Additional Information
For additional information regarding Amevive or psoriasis,
please contact The Amevive
Information Site
