Amevive® (Alefacept) Introduction

• Alefacept is the first biologic to be approved for the treatment of chronic plaque psoriasis in Canada
• The biologics are proteins synthesized by recombinant DNA technology to mimic naturally occurring proteins
• Psoriasis is an immune disorder mediated by activated T cell lymphocytes which in turn lead to hyperproliferation of the epidermis
• Activated memory-effector T cells express higher levels of CD2 than resting (naïve) T cells

Disease-suppressing treatments relieve psoriasis symptoms for as long as treatment continues:

• Corticosteroids
• Methotrexate
• Cyclosporine
• Oral corticosteroids

Disease-remitting treatments produce changes in the pathology underlying psoriasis, resulting in effects that continue after treatment cessation

• Phototherapy
• Alefacept

Patient Survey

US National Psoriasis Foundation survey of 40,350 members (>17,000 respondents) found:

• Physicians underestimate disease severity
• Average of 26 minutes/ day to treat with topicals
• Severe psoriasis patients dissatisfied with treatment
  • 78% frustrated with lack of efficacy
  • 87% report treatment with topical agents

[Krueger GG et al. Arch Dermatol. 2001;137:280-284]

• As with small molecules, each biologic medication is very different in mechanism of action. Alefacept reduces memory-effector T cells, and prevents activation of T cells while other biologics reduce cytokines or prevent migration of lymphocytes into the periphery.
• Alefacept acts by preventing the binding of the CD2 on a T-cell to the LFA-3 receptor on an antigen presenting cell (APC)
• Alefacept also links memory-effector T cells to Natural Killer cells via its IgG domain which causes the granzyme mediated death of pathogenic T cells
• Alefacept works selectively on activated memory T cells inhibiting their activation and proliferation while leaving ‘Naïve T cell’, B cell and Natural Killer cell populations intact

Two hallmarks of Alefacept, in addition to it’s efficacy profile are:

• Its excellent safety profile
• Its ability to produce a long remission of chronic plaque type psoriasis

Dual Mechanism of Action of AMEVIVE^TM

Clinical Evidence & Clinical Experience
There are limitations for regulators, pharmaceutical companies and pharmaceutical sales representatives to present clinical evidence following development of product monograph and drug approval. The product monograph is the starting point for this A-Detail™. It also contains evidence-based decision making processes, current standards of practice and clinical experience to provide a practical approach to the treatment of this condition.

Disclaimer: This A-Detail™ is meant to be a practical guide and does not necessarily reflect all risks, side-effects or situations associated with this product.