Amevive (alefacept)
Company: Biogen
Approval Status: Approved January 2003
Treatment for: Psoriasis
Areas: Dermatology/Plastic Surgery; Immunology/Infectious Diseases
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
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)³ 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:- Serious Infections
- Malignancies
- Lymphopenia
- Sore throat
- Dizziness
- Cough
- Nausea
- Itching
- Muscle Aches
- Chills
- Injection Site Pain
- Injection Site Inflammation
- Accidental injury
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 marker¹, 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 'naïve' 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 SiteThe FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
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