Pharmacology Update: Efalizumab Injection — Raptiva
Efalizumab Injection—Raptiva
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
A second biological agent has been approved for the treatment of moderate-to-severe plaque psoriasis. Efalizumab is an anti-CD11a humanized IgG1 version of the murine monoclonal antibody. Similar to alefacept, efalizumab affects the activity of T lymphocytes. Genetech, Inc markets Efalizumab as Raptiva.
Indications
Efalizumab is indicated for the treatment of adults with chronic moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.1
Dosage
The recommended dose is a single 0.7 mg/kg subcutaneous dose followed by weekly doses of 1 mg/kg. The lower initial dose is to reduce the incidence and severity of adverse reactions associated with the initial dose.1
Potential Advantages
In contrast to alefacept, which requires intravenous or intramuscular injection, efalizumab is given subcutaneously and can be self-administered. Unlike alefacept, which decreases CD4+ lymphocyte counts, efalizumab actually increases lymphocyte counts.2
Potential Disadvantages
Efalizumab, like other immunosuppressives, may increase the risk of serious infections or malignancies. Thrombocytopenia has also been reported, although it is rare (0.3%). Platelet counts should be performed at baseline and periodically during therapy.1 Some subjects showed signs of serious worsening of psoriasis during discontinuation of therapy. Common side effects of efalizumab include headache (32% vs 22% for placebo), fever (7% vs 3%), chills (13% vs 4%), nausea (11% vs 7%), and myalgia (8% vs 5%). These commonly occur the day of or within 2 days of the first 2 injections.1,3 Efalizumab requires subcutaneous injections.
Comments
Efalizumab is humanized IgG1 monoclonal antibody to CD11a that is the subunit of lymphocyte function-associated antigen (LFA-1). The antibody interferes with the interaction of LFA-1 with intracellular adhesive molecule, thus inhibiting T-cell activation, cutaneous trafficking, and T-cell adhesion.4 The accumulation of activated T cells is a characteristic of psoriasis.5 The efficacy of efalizumab has been evaluated in 4 randomized, placebo-controlled, 12-week studies in patients with moderate-to-severe disease at a minimum of 10% body surface involvement.1 Efficacy end points were 75% or greater or 50% or greater reduction on the Psoriasis and Severity Index (PASI-75, PASI-50). The 72-point index is based on the percentage of body surface area affected, erythema, desquamation, and induration. In addition, subjects were evaluated on a static Physician Global Assessment (sPGA). This is a 6-point scale assessing severity with focus on plaque, scaling, and erythema. At 12 weeks, PASI-75 was 22-39% for 1 mg/kg of efalizumab (n = 1213) compared to 2-5% for placebo (n = 715).1,3 PASI-50 ranged from 52 -61% vs 14-16%. On the sPGA assessment, 19-32% of subjects treated with efalizumab showed the lesions to be minimal or clear compared to 3-4% for placebo.1 The onset of action is about 8 weeks. Unpublished data suggest that most responders (PASI > 75) may be maintained with once-weekly or once-every-other-week maintenance dosing. Weekly dosing may produce better results
in partial responders. The median time to relapse is 60-80 days after discontinuation of therapy. In some cases serious worsening of psoriasis may occur during or upon discontinuation of therapy.1 As with other immunosuppressive drugs, the risks of infection and malignancies may be increased. There are no published comparative studies between the 2 approved biological agents, efalizumab and alefacept. The wholesale cost for efalizumab is about $275 per week or about $14,000 per year. This is about 25% less than the cost of alefacept.
Clinical Implications
Efalizumab is the second biological agent for the treatment of mild-to-moderate plaque psoriasis in adults. While these drugs bind to different sites, they both target T-cell function. The primary advantage for efalizumab is that it can be self-administered and does not reduce lymphocyte counts.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are associate editors of Internal Medicine Alert.
References
1. Raptiva Product Information. Genetech, Inc. October 2003.
2. Amevive Product Information. Biogen, Inc. February 2003.
3. Leonardi CL. J Am Acad Dermatol. 2003;49:S98-S104.
4. Werther WA, et al. J Immunol. 1996;157:4986-4995.
5. Gottlieb AB, et al. Arch Dermatol. 2002;138:591-600.
A second biological agent has been approved for the treatment of moderate-to-severe plaque psoriasis.
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