Psoriasis: Alefacept recommendations

IMPORTANT NOTICE: This drug has been voluntary discontinued as of December 15, 2011.

  • Indication: moderate to severe psoriasis
  • Dosing: 15 mg every wk given as an intramuscular injection for 12 wk, with a 12-wk follow-up nontreatment period
  • Short-term results:
    • 21% of patients achieved a PASI-75 at wk 14
  • Long-term results:
    • Associated with long remissions in a subset of responders
    • Prior response to alefacept is a likely marker of future treatment response; thus, patients responding to the first course of therapy may be treated long-term with repeated 12-wk courses of alefacepte at a minimum of 24-wk intervals
  • Toxicity: excellent safety profile in clinical trials
  • Baseline monitoring: CD4 count
  • Ongoing monitoring: biweekly CD4 count required; hold dose for counts <250
  • Pregnancy category: B
  • Contraindications: HIV infection
Level of Evidence: I Strength of Recommendation: A

Read more on Alefacept

Efficacy

Alefacept is a recombinant dimeric fusion protein that consists of the extracellular CD2-binding portion of lymphocyte function associated antigen-3 linked to the Fc portion of human IgG1.91-93 Alefacept binds to CD2 on memory-effector T lymphocytes, thereby inhibiting the activation and reducing the number of these cells. The effects of alefacept in inducing in vitro apoptosis and selectively decreasing circulating CD45RO cells suggest disease-remitting properties of this agent.91,94  Alefacept is approved for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic agents or phototherapy. Alefacept does not interfere with the primary and secondary responses to a newly encountered antigen and acquired immune response to recall antigen.79  In the pivotal phase III trials of alefacept given intramuscularly and dosed at 15 mg per week, 21% of patients achieved a PASI 75 at week 14, 2 weeks after cessation of the 12 week alefacept dosing period.  Patients treated with alefacept who achieve at least a 50% improvement in their PASI score also demonstrate a statistically significant improvement in their DLQI compared to placebo.61,91,92,95-100  Although the primary endpoint for the alefacept studies was specified as 14 weeks, 2 weeks after the 12 week course of therapy, the maximum response to alefacept generally occurred 6-8 weeks after the last intramuscular shot of the 12 week course.97,98,100  Although some patients do not respond to this medication, patients who do respond to alefacept can achieve additional benefit from successive 12-week treatment courses.  A proportion of patients who respond to alefacept by achieving a 75% or greater reduction from baseline PASI maintained a 50% or greater reduction in PASI for a median duration of 10 months.91

Currently, there is no way to predict which patients will improve significantly with alefacept although investigation looking for predictive markers is ongoing.101  A baseline CD4 lymphocyte count should be performed before treatment and according to label repeated every other week.102  Dosing of alefacept should be withheld whenever the CD4 count falls below 250 cells/ml and dosing should be discontinued if the CD4 count remains below 250 cells/ml for four consecutive weeks.102

Safety

Alefacept therapy is not indicated for patients with a CD4 T lymphocyte count below normal or in those who are infected with the human immunodeficiency virus because of the potential for acceleration of disease progression due to CD4 T lymphocyte count reduction induced by alefacept.  Caution should be exercised in patients who are at risk for or have a history of malignancy or infection, especially clinically significant infections.  Alefacept is pregnancy category B.102

Navigate section 1 of the psoriasis guideline: Biologics

Citation note

When referencing this guideline in a publication, please use the following citation: Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB,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 May;58(5):826-50. 



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