Alefacept (Amevive^®, Astellas Pharma U.S., Inc., Deerfield, IL) is an immunosuppressive fusion protein that prevents the activation of T lymphocytes involved in the development of psoriasis. This document addresses the U.S. Food and Drug Administration (FDA) approved indications for alefacept for the treatment of adults with chronic moderate to severe plaque psoriasis.

Note: Please refer to the following document for information concerning other biological agents for the treatment of chronic moderate to severe plaque psoriasis:

• DRUG.00002 Tumor Necrosis Factor Antagonists

Alefacept is considered medically necessary when the following criteria are met:

• Individual is ≥18 years of age with chronic moderate to severe plaque psoriasis (Ps) with either of the following:
  1. Greater than 5% of body surface area with plaque Ps; or
  2. Less than or equal to 5% body surface area with plaque Ps involving sensitive areas or areas that significantly impact daily function (e.g. palms, soles of feet, head/neck, or genitalia); and
• Individual has failed to respond to, is intolerant of, or has a medical contraindication to phototherapy or other systemic therapy (e.g. methotrexate).

Alefacept is considered not medically necessary for all other indications, including but not limited to, for individuals with any of the following:

1. Currently receiving other immunosuppressive therapy or phototherapy;
2. HIV positive status;
3. CD4+ T lymphocyte count < 250 cells per microliter;
4. History of recurrent infection, current chronic infection, clinically important infection, or positive tuberculin skin test (TST) or a positive Centers for Disease Control (CDC)-recommended equivalent test;
5. History of systemic malignancy within the last five years.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

Alefacept (Amevive) is a biological agent approved by the FDA for the treatment of adults with chronic moderate to severe plaque psoriasis (greater than one year). The safety and efficacy of alefacept was evaluated in two randomized, double-blind, placebo-controlled studies (Krueger, 2002; Lebwohl, 2003). The study data is available on the current FDA-approved label (Amevive product information, 2009).

Psoriasis is a multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. The major manifestation of psoriasis is chronic inflammation of the skin, characterized by "disfiguring, scaling, and erythematous plaques that may be painful or often severely pruritic and may cause significant quality of life issues" (Mentor, 2008). For patients with chronic plaque psoriasis, key metrics for outcome assessment include improvement in the Psoriasis Area and Severity Index (PASI) as well as objective assessment of disease via the Physician Global Assessment (PGA). The PASI is a measure of overall psoriasis severity and coverage that assesses body surface area (BSA) and erythema, induration, and scaling. PASI is the metric commonly used in the clinical trials for psoriasis treatments, but is rarely used in clinical practice. Therefore, Mentor and colleagues state that the physician generally uses subjective qualitative assessment of the severity of a patient's psoriasis by combining objective assessment of the BSA involvement, disease location, thickness, and symptoms, presence or absence of psoriatic arthritis with the subjective assessment of the physical, financial, and emotional impact of the diseases on the patient's life.

The American Academy of Dermatology (AAD) has approved a set of evidence-based guidelines, Guidelines of Care for the Management of Psoriasis and Psoriatic Arthritis (AAD, 2008), intended to assist physicians in managing the complexities of the treatment of individuals with psoriasis and psoriatic arthritis. In the guideline section titled Overview of Psoriasis and Guidelines of Care for the Treatment of Psoriasis with Biologics (Menter, 2008), the work group states that approximately 80% of patients affected with psoriasis have mild to moderate disease, with 20% having moderate to severe psoriasis, defining the extent of BSA involvement as "affecting more than 5% of the BSA or affecting crucial body areas such as the hands, feet, face, or genitals." "The areas of involvement and types of psoriasis should be considered in evaluating severity of disease because the impact of these types of psoriasis may be quite substantial." Treatment planning for use of an FDA-approved biologic agent for moderate to severe plaque psoriasis considers this definition of BSA surface involved with plaque psoriasis. In addition, for patients with plaque psoriasis involving sensitive areas or areas that would significantly impact daily function (e.g. palms, soles of feet, head/neck, or genitalia), less than or equal to 5% of BSA involvement is considered as moderate to severe disease.

The AAD has recommended that biological agents, including alefacept, should not be initiated or resumed in the presence of active bacterial infection (or a bacterial infection currently requiring antibiotic therapy), active TB (or latent TB infection prior to starting preventive therapy), active herpes zoster infection, or active life-threatening fungal infections. In addition, the use of all biologic agents is not recommended when severe upper respiratory tract infections (bacterial or viral) or nonhealed infected skin ulcers are present. If the patient develops a serious infection while being treated with a biologic agent, "it is prudent to hold the biologic until the infection has resolved" (Menter/AAD, 2008).

Medical Management Information (Amevive Product Information, 2009)

FDA Boxed Warning: Lymphopenia
Amevive induces dose-dependent reductions in circulation CD4+ and CD8+ T lymphocyte counts. A course of Amevive should not be initiated in patients with a CD4+ T lymphocyte count below normal. CD4+ T lymphocyte counts should be monitored at initiation of therapy and every two weeks throughout the 12-week course. If CD4+ T lymphocyte counts are below 250 cells/uL, Amevive dosing should be withheld and weekly monitoring instituted. Amevive should be discontinued if the counts remain below 250 cells/uL for one month.

Precautions and Warnings with the Use of Amevive

• The most serious adverse reactions with Amevive were lymphopenia, malignancies, serious infections requiring hospitalization, and hypersensitivity reactions:
  • Amevive should not be administered to individuals with a history of systemic malignancy. Caution should be exercised when considering use in individuals at high risk for malignancy.
  • Caution should be exercised when considering the use of alefacept in individuals with chronic infections or a history of recurrent infection. Monitored for signs and symptoms of infection during or after a course of alefacept. New infections should be closely monitored. If an individual develops a serious infection, alefacept should be discontinued.
  • Angioedema was experienced in 0.2% of patients in the clinical studies of Amevive; some patients required hospitalization. Urticaria was reported in <1% of Amevive-treated patients. 
• There are no adequate and well-controlled studies evaluating the use of Amevive in pregnant women. Amevive should be used during pregnancy only if clearly needed. If pregnancy occurs while taking Amevive, continued use of the drug should be assessed. It is unknown whether Amevive is excreted in human milk, therefore, a decision should be made whether to discontinue nursing while taking Amevive or discontinue taking the drug, taking into account the importance of the drug to the mother.
• Evaluate individuals with signs or symptoms of hepatic injury during treatment. Amevive should be discontinued in individuals with clinical signs of liver injury.
• Live virus or live-attenuated vaccines should not be administered concurrently with Amevive
• Caution should be used when treating patients 65 years of age and older.
• Alefacept is not indicated for pediatric patients as the safety and efficacy has not been studied in this population.

Peer-Reviewed Publications:

1. Brinhall AK, King LN, Licciardone JC, et al. Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials. Br J Dermatol. 2008; 159(2):274-285.
2. Carey W, Glazer S, Gottlieb AB, et al. Relapse, rebound, and psoriasis adverse events: an advisory group report. J Am Acad Dermatol. 2006; 54(Suppl):5171-5181.
3. Krueger GG, Ellis CN. Alefacept therapy produces remission for patients with chronic plaque psoriasis. Br J Dermatol. 2003; 148:784-788.
4. Krueger GG, Gottlieb AB, Sterry W, et al. A multicenter, open-label study of repeat courses of intramuscular alefacept in combination with other psoriasis therapies in patients with chronic plaque psoriasis. J Dermatolog Treat. 2008; 19(3):146-155.
5. Krueger GG, Papp KA, Stough DB, et al. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of two courses of alefacept in patients with chronic plaque psoriasis. J Am Acad Dermatol. 2002; 47:821-833.
6. Lebwohl M, Christophers E, Langley R, 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(6):719-727.
7. Ortonne JP. Clinical response to alefacept: results of a phase 3 study of intramuscular administration of alefacept in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol. 2003; 17 Suppl 2:12-16.
8. Saini T, Tutrone WD, Weinberg JM, et al. Advances in therapy for psoriasis: an overview of infliximab, etanercept, efalizumab, alefacept, adalimumab, tazarotene, and pimecrolimus. Curr Pharm Design 2005; 11:273-280.
9. Winterfield L, Menter A, Gordon K, et al. Psoriasis treatment: current and emerging therapies. Ann Rheum Dis 2005; 64(Suppl II):ii87-ii90.

Government Agency, Medical Society, and other Authoritative Publications:

1. American Academy of Dermatology (AAD). American Academy of Dermatology Association (AADA). Guidelines of care for management of psoriasis and psoriatic arthritis. May 2008. Available at: http://www.aad.org/. Accessed on June 25, 2009.
2. Amevive [Product Information], Deerfield, IL. Astellas Pharma U.S., Inc.; March 1, 2009. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory Accessed on June 25, 2009.
3. Centers for Disease Control (CDC). MMWR™. Guidelines for using the QuantiFERON™-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. 2005 Dec 16; 54(No. RR-15):49-55. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm. Accessed on June 25, 2009. 
4. Gottlieb AB, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008; 58(5):851-864.
5. Hayes Inc. Hayes Medical Technology Directory. Alefacept for Psoriasis and Psoriatic Arthritis. Lansdale, PA: Hayes, Inc.; March 6, 2007. Search updated March 27, 2009.
6. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008; 58(5):826-850.

1. National Psoriasis Foundation (NPF). Psoriasis treatment. Available at: http://www.psoriasis.org/treatment/psoriasis/. Accessed on June 25, 2009. 

Alefacept (Amevive)
Psoriasis

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.