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 documents for information concerning other biologic disease-modifying antirheumatic drugs (DMARDs) that may be used for the treatment of chronic moderate to severe plaque psoriasis:

• DRUG.00002 Tumor Necrosis Factor Antagonists
• DRUG.00043 Ustekinumab (Stelara^®)

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

• Individual is 18 years of age or older with chronic moderate to severe plaque psoriasis (Ps) with either of the following:
  1. Plaque Ps involving greater than five percent body surface area (BSA); or
  2. Plaque Ps involving less than or equal to five percent BSA 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, treatment of an individual with any of the following:

1. Currently receiving other immunosuppressive therapy or phototherapy; or
2. Human immunodeficiency virus (HIV) positive status; or
3. CD4+ T lymphocyte count less than 250 cells per microliter; or
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 to rule out latent tuberculosis; or
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, 2011).

The efficacy of alefacept has been evaluated in a small multicenter, double-blind, randomized, placebo-controlled trial of individuals with severe alopecia areata (AA) (Strober, 2009). Forty-five participants with chronic and severe AA affecting 50% to 95% of the scalp hair and resistant to previous therapies received alefacept for 12 consecutive weeks with no statistically significant improvement when compared with a well-matched placebo-receiving group (p=.70). The investigators concluded that alefacept is ineffective for the treatment of severe AA.

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" (Menter, 2008). For individuals 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, Menter and colleagues state that the physician generally uses subjective qualitative assessment of the severity of an individual'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 individual'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, 2010), 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 individuals 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 DMARD for moderate to severe plaque psoriasis considers this definition of BSA surface involved with plaque psoriasis. In addition, for individuals 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 five percent 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 individual 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).

The following are warnings and precautions from the Product Information Label (2011): 

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 individuals with a CD4+ T lymphocyte count below normal. CD4+ T lymphocyte counts should be monitored every two weeks throughout the course of the 12-week dosing regimen. 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 individuals in the clinical studies of Amevive; some individuals required hospitalization. Urticaria was reported in less than one percent of Amevive-treated individuals. 
• 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 individuals 65 years of age and older.
• Alefacept is not indicated for children as the safety and efficacy has not been studied in this population.

Immunosuppressant drugs: A class of immunomodulatory drugs that reduce inflammation by affecting the immune system; includes 6-mercaptopurine (6-MP), azathioprine, cyclophosphamide, cyclosporine, methotrexate, and tacrolimus.

Interferon gamma (IFN- γ) release assay (IGRA): A test that aids in detecting Mycobacterium tuberculosis infection, both latent infection and infection manifesting as active tuberculosis that may be used for surveillance purposes and to identify persons likely to benefit from treatment. FDA-approved IGRAs include:

• QuantiFERON-TB Gold test (GFT-G)
• QuantiFERON-TB Gold In-Tube test (QFT-GIT)
• T-SPOT.TB test (T-Spot)

Plaque psoriasis: A skin disease in which red, scaly patches form on some areas of the body.

Peer-Reviewed Publications:

1. Brimhall 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(4):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(6):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. Patel RV, Clark LN, Lebwohl M, Weinberg JM. Treatments for psoriasis and the risk of malignancy. J Am Acad Dermatol. 2009; 60(6):1001-1017.
8. 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.
9. Roberts JL, Ortonne JP, Tan JK, et al. The safety profile and sustained remission associated with response to multiple courses of intramuscular alefacept for treatment of chronic plaque psoriasis. J Am Acad Dermatol. 2010; 62(6):968-978.
10. 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(2):273-280.
11. Strober BE, Menon K, McMichael A, et al. Alefacept for severe alopecia areata: a randomized, double-blind, placebo-controlled study. Arch Dermatol. 2009; 145(11):1262-1266.
12. 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). Sections 1.-5. Guidelines of care for management of psoriasis and psoriatic arthritis. Last updated January 2010. Available at: http://www.aad.org/education-and-quality-care/clinical-guidelines/current-and-upcoming-guidelines/current-guidelines-and-guidelines-in-development. Accessed on May 3, 2011.
2. Amevive [Product Information], Deerfield, IL. Astellas Pharma U.S., Inc.; May 2011. Available at: http://www.astellas.us/docs/amevive.pdf. Accessed on August 16, 2011.
3. Centers for Disease Control (CDC) and Prevention. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection - United States, 2010; 59(No. RR 5):1-28. Available at: http://www.cdc.gov/mmwr/pdf/rr/rr5905.pdf. Accessed on May 3, 2011.
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. 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 May 3, 2011. 

Alefacept (Amevive)
Plaque 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.