/publications/issue/2004/2004-09/2004-09-4517

RxPRODUCT NEWS: PROFILE: Raptiva (efalizumab)

Author: Claudio Faria, PharmD, RPh, and Carolyn Soo, PharmD, RPh

Background

Psoriasis is a condition that often presents symptoms such as erythema, raised demarcations, drying/cracking of the skin, and blistering. According to the FDA, the condition is prevalent in approximately 5% of the population in the United States, where a third of all cases are classified as a moderate-to-severe form of the disease.1 Though there are many types of psoriasis, plaque psoriasis is the most common form accounting for approximately 80% of adult cases.2 Though plaque psoriasis is a condition of the skin, it is an immune mediated disease involving hyperproliferation of T-lymphocytes. While there is no cure, the disease is treatable.3

Genentech Inc announced the FDA approval of Raptiva (efalizumab) in October 2003. Raptiva is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.4

Pharmacology

Raptiva is an immunosuppressive recombinant humanized IgG1 kappa isotype monoclonal antibody that binds to a subunit of the leukocyte function-associated antigen-1 (LFA-1), known as CD11a. Interaction between LFA-1 on lymphocytes and intercellular adhesion molecule-1 (ICAM-1) on antigen presenting cells contributes to the initiation and maintenance of activation of T-lymphocytes. This progresses to the adhesion of lymphocytes to endothelial cells and migration of Tlymphocytes to inflammatory sites. Raptiva impedes these processes responsible for plaque psoriasis by attaching to CD11a, resulting in a decrease in CD11a's cell surface expression, thereby preventing the interaction between LFA-1 and ICAM-1.2,4

Clinical Trials

Raptiva was studied in 4 randomized, double-blind, placebo-controlled trials. The studies included adult patients with chronic, stable, plaque psoriasis, with a minimum of 10% body surface area involvement. These patients also previously received, or were candidates for, systemic therapy or phototherapy. Patients were excluded if clinically significant flares were present or if the sole form of psoriasis was of guttate, erythrodermic, or postular form. Patients meeting these requirements were randomized to receive 1 mg/kg or 2 mg/kg of Raptiva or placebo subcutaneously (SC) once a week for 12 weeks. Patients assigned to either of the Raptiva groups were given an initial dose of 0.7 mg/kg as the first dose prior to receiving the entire 12-week regimen.4

Investigators utilized the Psoriasis Area and Severity Index (PASI) to evaluate efficacy. A median PASI score of 17 was observed at baseline for both treatment groups in all 4 studies. Additionally, both treatment groups in all 4 studies showed a median baseline body surface area involvement ranging between 22% to 28%. Results 1 week after the 12-week treatment phase in the Raptiva group showed at least a 75% reduction from baseline PASI scores when compared to placebo. The Raptiva 2 mg/kg group did not demonstrate superiority over Raptiva 1 mg/kg.4

Safety

Overall, Raptiva is well tolerated. The most common adverse events observed with Raptiva are headache, fever, nausea, chills, and myalgia within 48 hours of the first 2 injections. Less common but serious adverse events consist of infection, malignancy, thrombocytopenia, and worsening of psoriasis. Because Raptiva is an immunosuppressive agent, caution should be used when considering treatment in patients with current or future risk of serious infection or malignancy. In addition, monitoring platelets and signs of thrombocytopenia on a consistent basis is recommended. It is also recommended that patients taking Raptiva not receive vaccinations of any sort since its safety in this type of situation has not been examined.4

Outlook

Raptiva demonstrates admirable safety and efficacy profiles for the treatment of chronic moderate-to-severe plaque psoriasis. It has been approved as a single initial SC dose of 0.7 mg/kg followed by a weekly SC dose of 1 mg/kg but not to exceed 200 mg.4 Raptiva must be kept refrigerated at 2? to 8? C and protected from light until use.4 Raptiva gives health care practitioners another therapeutic option for the treatment of plaque psoriasis; however, future trials comparing Raptiva to other available products for the treatment of plaque psoriasis are warranted.

Dr. Faria is a senior research pharmacist for Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass, and a senior human research specialist at Partners HealthCare System. Dr. Soo is a senior research pharmacist for Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@mwc.com.