Alefacept

(BAN, USAN, rINN)
Synonyms: Aléfacept; Alefaceptum; BG9273; BG-9712; LFA3TIP; Recombinant Human LFA-3/1gG 1 Fusion Protein. A dimer of 1-92 antigen LFA-3 (human) fusion protein with human immunoglobulin G1 (hinge-C H 2-C H 3 γ1-chain).
Cyrillic synonym: Алефацепт.

💊 Chemical information

CAS — 222535-22-0.
ATC — L04AA15.
ATC Vet — QL04AA15.

💊 Adverse Effects and Precautions

Chills are common on intravenous dosage of alefacept. Other adverse effects are cough, dizziness, headache, injection site pain and inflammation, myalgia, nausea, pharyngitis, and pruritus. More serious adverse reactions are cardiovascular events (including coronary artery disorder and myocardial infarction), hypersensitivity reactions, lymphopenia, and serious infections requiring hospitalisation. Cases of hepatotoxicity including asymptomatic transaminase elevation, fatty infiltration of the liver, hepatitis, and acute liver failure have occurred. Like other drugs with immunosuppressant actions, alefacept may increase the risk of malignancies, particularly basal or squamous cell cancers of the skin. It should not be given to patients with a history of malignancy. Alefacept should also not be given to patients with pre-existing serious infections, and should be stopped if these develop. Its use should be considered carefully in patients with chronic infections or a history of recurrent infection. Alefacept induces a dose-dependent reduction in circulating CD4+ and CD8+ T-lymphocyte counts. It is therefore also contra-indicated in patients with HIV infection as the reduction in CD4+ T-lymphocytes could accelerate disease progression or increase complications of HIV infection. CD4+ T-lymphocyte counts should be monitored before starting alefacept therapy and then every 2 weeks during the 12-week treatment period. Treatment should not be started in patients with a CD4+ T-lymphocyte count below normal. Doses should be withheld and weekly monitoring started if the counts fall below 250 cells/microlitre, and treatment stopped if the counts remain below this level for one month. Therapy should be stopped immediately, and appropriate treatment given, in patients who experience anaphylaxis or serious hypersensitivity; it should not be restarted.
1. Goffe B, et al. An integrated analysis of thirteen trials summarizing the long-term safety of alefacept in psoriasis patients who have received up to nine courses of therapy. Clin Ther 2005; 27: 1912–21.

💊 Pharmacokinetics

Alefacept has a bioavailability of about 63% after intramuscular injection. After an intravenous dose it has an elimination half-life of about 11 to 12 days.
1. Vaishnaw AK, TenHoor CN. Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. J Pharmacokinet Pharmacodyn 2002; 29: 415–26.

💊 Uses and Administration

Alefacept is a recombinant human fusion protein that binds to CD2 on memory T-lymphocytes, preventing their activation and reducing their number. It is used in the management of moderate to severe chronic plaque psoriasis and is given in a dose of 7.5 mg once weekly by intravenous injection, or 15 mg once weekly by intramuscular injection, for 12 weeks. A second 12week course may be given if necessary, starting not less than 12 weeks after the completion of the first.
1. Ellis CN, Krueger GG. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 2001; 345: 248–55
2. Krueger GG, et al. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol 2002; 47: 821–33
3. Krueger GG, Ellis CN. Alefacept therapy produces remission for patients with chronic plaque psoriasis. Br J Dermatol 2003; 148: 784–8.
4. Lebwohl M, et al. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol 2003; 139: 719–27
5. Korman NJ, Moul DK. Alefacept for the treatment of psoriasis: a review of the current literature and practical suggestions for everyday clinical use. Semin Cutan Med Surg 2005; 24: 10–18
6. Ortonne JP, et al. An open-label study of alefacept plus ultraviolet B light as combination therapy for chronic plaque psoriasis. J Eur Acad Dermatol Venereol 2005; 19: 556–63
7. Mease PJ, et al. Alefacept in Psoriatic Arthritis Study Group. Alefacept in combination with methotrexate for the treatment of psoriatic arthritis: results of a randomized, double-blind, placebo-controlled study. Arthritis Rheum 2006; 54: 1638–45.

💊 Preparations

Proprietary Preparations

Arg.: Amevive; Canad.: Amevive; Israel: Amevive; Switz.: Amevive; USA: Amevive.
Published October 20, 2018.