Pharmacology Update: Alefacept (Amevive) for Psoriasis Treatment
Pharmacology Update: Alefacept (Amevive) for Psoriasis Treatment
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Alefacept is a new biological agent for the treatment of moderate-to-severe plaque psoriasis. The drug, which targets T lymphocytes, is a fusion protein combining the binding site of lymphocyte function-associated antigen-3 and the Fc portion of human IgG1. Alefacept requires weekly administration by injection. It is marketed by Biogen, Inc, as "Amevive."
Indications
Alefacept is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.1
Dosage
The recommended dose is 7.5 mg given once weekly as an intravenous bolus or 15 mg given once weekly as an intramuscular injection. The recommended course of treatment is 12 weekly injections. Retreatment with an additional course may be initiated provided that CD4+ T lymphocytes counts are within normal range and at least 12 weeks has elapsed since the previous course.1
Alefacept is supplied as administration dose packs containing either 7.5 mg (IV) or 15 mg (IM) single-use vials with diluent, infusion set, or syringe and needles.
Potential Advantages
Patients with moderate-to-severe plaque psoriasis have shown improvement with alefacept therapy.1,2 In placebo-controlled studies, patients showed significant reduction in score on the Psoriasis and Severity Index (PASI) and physician global assessment for both intravenous route (7.5 mg) and intramuscular route (15 mg).
Potential Disadvantages
Alefacept requires parenteral administration. The most common adverse effects are chills, injection site reactions, and reduction in CD4+ T lymphocytes counts. Chills (6% vs 1% for placebo) generally occurred within 24 hours of the first few doses.1,2 Injection site reactions for intramuscular injection were 16% compared to 8% for placebo. The most common adverse event leading to discontinuation of treatment was CD4+ T lymphocyte levels below 250 cells/µL. Twenty eight percent of intramuscularly treated patients and 48% of patients treated intravenously had CD4+ T lymphocyte counts below normal.1 Lymphocyte counts should be monitored weekly throughout the 12-week dosing period and the drug should be discontinued if the counts are below 250 cells/µL for 1 month. Alefacept may increase the risk of malignancies or infections. In clinical trials, alefacept treated patients had a malignancy rate of 1.3% compared to 0.5% for placebo. The rate of infections involving hospitalization was 0.9% compared to 0.2% for placebo.1
Comments
Psoriasis, like other autoimmune diseases, appears to involve T lymphocyte activation.3 Alefacept is a recombinant protein that combines the lymphocyte-function-associated antigen type 3 (LFA-3) with IgG1. The LFA-3 portion binds to CD2 on T-lymphocytes. The LFA-2 CD2 interaction is an important part of activation of T lymphocytes.3,4 When alefacept binds to CD2 on memory effector T cells and with CD16 (Fc gamma receptor III) on natural killer cells and monocytes, apoptosis is facilitated leading to reduction of CD2+ cells.4,5 Efficacy data are based on 2 randomized, double-blind placebo-controlled studies in involving a total of 887 patients.1 These patients had chronic (1 year or longer) plaque psoriasis and a minimum body surface area involvement of 10% who were candidates for or who had previous systemic or phototherapy. In 1 study, the drug was given intravenously (7.5 mg weekly for 12 weeks) and the other intramuscularly (15 mg weekly for 12 weeks). Efficacy end points were 75% or 50% or greater reduction in PASI and physician global assessment (PGA) as almost clear’ or clear.’ PASI combined assessment on the percentage of body area affected, erythema, desquamation, and induration to produce a score ranging from 0 to 72. PGA was based on a 7-point scale.2 The onset of response is about 60 days. After one course of therapy, a 75% or greater reduction of PASI was achieved in 14% (vs 4% for placebo) for the IV route (7.5 mg) and 21% (vs 5%) for IM (15 mg). A 50% or greater reduction was seen in 38% (vs 10%) and 42% (vs 18%) respectively and for PGA almost care or clear,’ 11% (vs 4%) and 14% (vs 5%) respectively. After 1 course, the median duration of response was 3.5 months for the IV route (vs 1 month for placebo) and 2 months for the IM route and placebo.1 Improvement in PASI of 50% or more has been associated with better dermatology-specific quality-of-life scores.8 Additional benefit may be achieved with a second regimen if the patient’s psoriasis was less than clear and their CD4+ count was above the lower limit of normal.1 Adverse effects include suppression of lymphocyte counts, chills, and increased risk of infections or malignancies. There were no published comparative studies between alefacept and systemic or phototherapy. It is also not known whether patients who had or had not received systemic or phototherapy would respond differently. The cost for alefacept was not available at the time of this review.
Clinical Implications
Psoriasis is a skin disorder that affects about 2% of the population, and about 20% of these require systemic immunosuppressive therapy (eg, methotrexate, cyclosporine) or phototherapy.4,7 It is a condition that tends to relapse after cessation of therapy.8 Alefacept offers the first biological therapy for this chronic difficult-to-treat skin condition.
References
1. Amevive Product Information. Biogen, Inc. February 2003.
2. Kruegar GG, et al. J Am Acad Dermatol. 2002;47: 821-833.
3. Brottier P, et al. J Immunol. 1985;135:1624-1631.
4. Ellis CN, et al. N Engl J Med. 2001;345:248-255.
5 . Ellis CN, et al. Am J Clin Dermatol. 2003;4(2): 131-139.
6. Krueger JG. J Am Acad Dermatol. 2002;46:1-23.
7. Koo J, et al. J Am Acad Dermatol. 1999;41:51-59.
8. Greaves MW, et al. N Engl J Med. 1995;332:581-588.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente and Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager at Kaiser Permanente in Oakland, CA.
Alefacept is a new biological agent for the treatment of moderate-to-severe plaque psoriasis. The drug, which targets T lymphocytes, is a fusion protein combining the binding site of lymphocyte function-associated antigen-3 and the Fc portion of human IgG1.Subscribe Now for Access
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