Full Prescribing Information
Raptiva (PML) Dear Healthcare Provider Letter (122K/PDF)
Raptiva (Label Update) Dear Healthcare Provider Letter (68K/PDF)
Raptiva (PML 2nd Case) Dear Healthcare Provider Letter (145K/PDF)

Raptiva® (efalizumab) is a humanized therapeutic antibody designed to selectively and reversibly block the activation, reactivation and trafficking of T-cells that lead to the development of psoriasis.

Status The U.S. Food and Drug Administration (FDA) approved Raptiva in October 2003.

Raptiva is approved for the treatment of chronic moderate-to-severe plaque psoriasis in adults 18 years or older who are candidates for systemic therapy or phototherapy. Between 5.8 and 7.5 million Americans have psoriasis and of these between 1.5 and 1.9 million are considered to have moderate-to-severe disease. In clinical studies, Raptiva demonstrated a rapid onset of action, in some patients by four weeks, in the reduction of symptoms associated with psoriasis. Raptiva is administered once-weekly via subcutaneous injection and can be self-administered by patients at home.

Raptiva was approved on the basis of efficacy and safety seen in 4 pivotal trials which showed sustained improvement in psoriasis symptoms over 6 months. Genentech presented final results from a long-term study at the American Association of Dermatology Academy 2005 meeting that showed sustained improvement in psoriasis symptoms throughout three years of continuous treatment.

Safety

WARNING: RISK OF SERIOUS INFECTIONS Infections, including serious infections leading to hospitalizations or death, have been observed in patients treated with Raptiva (see WARNINGS and ADVERSE REACTIONS). These infections have included bacterial sepsis, viral meningitis, invasive fungal disease and other opportunistic infections. Patients should be educated about the symptoms of infection and be closely monitored for signs and symptoms of infection during and after treatment with Raptiva. If a patient develops a serious infection, Raptiva should be discontinued and appropriate therapy instituted. Progressive Multifocal Leukoencephalopathy (PML) resulting from JC virus infection has occurred during therapy with Raptiva (see WARNINGS).

Raptiva should not be administered to patients with known hypersensitivity to Raptiva or any of its components.

The most serious adverse reactions observed during treatment with Raptiva are serious infections including PML, malignancies, thrombocytopenia, hemolytic anemia, psoriasis worsening and variants, and neurologic events.

Raptiva is an immunosuppressive agent. Many immunosuppressive agents have the potential to increase the risk of infection, reactivate latent, chronic infections, or increase the risk of malignancy. Patients receiving other immunosuppressive agents should not receive concurrent therapy with Raptiva.

Serious infections requiring hospitalization occurred in 0.3% of Raptiva patients during clinical trials. Additional serious infections have been reported during postmarketing surveillance, including JC virus infection resulting in PML. Some of these infections have been fatal. Raptiva should not be administered to patients with clinically important infections. New infections developing during Raptiva treatment should be monitored closely. If a patient develops a serious infection, Raptiva should be discontinued.

PML has been reported in the post-marketing setting. Raptiva likely increases the risk for PML. Based on the clinical characteristics of reported cases of PML in Raptiva patients, prolonged exposure to Raptiva and older age may further increase this risk. Physicians should consider PML in any patient with new-onset neurologic manifestations. Patients being treated with Raptiva should be instructed to report any new neurological signs or symptoms to their physician. Raptiva should be discontinued in patients who develop PML.

The role of Raptiva in the development of malignancy is not known. In clinical trials, the overall incidence of malignancies was 1.8 per 100 patient-years for Raptiva-treated patients vs 1.6 per 100 patient-years for placebo-treated patients. Caution should be exercised when considering the use of Raptiva in patients at high risk for malignancy or with a history of malignancy. If a patient develops a malignancy, Raptiva should be discontinued.

Immune-mediated thrombocytopenia was observed in 0.3% of Raptiva-treated patients during clinical trials and reports of severe thrombocytopenia have been received postmarketing; therefore, platelet monitoring is recommended. Physicians should follow patients for signs and symptoms of thrombocytopenia, and Raptiva should be discontinued if thrombocytopenia develops.

Reports of immune mediated hemolytic anemia, some serious, diagnosed 4-6 months after the start of Raptiva treatment have been received. Raptiva should be discontinued if hemolytic anemia occurs.

Worsening of psoriasis can occur during or after treatment with Raptiva. During clinical studies, 19 of 2589 (0.7 %) Raptiva-treated patients had serious worsening of psoriasis during treatment (n = 5, 0.2 %) or after discontinuation of Raptiva (n = 14, 0.5 %). Some patients required hospitalization (n = 17). Patients, including those not responding to Raptiva treatment, should be closely observed following discontinuation of Raptiva and appropriate psoriasis treatment instituted as necessary.

Neurological events have been observed in patients receiving Raptiva, including cases of Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, facial palsy, and transverse myelitis. Patients should be instructed to report any new neurological signs or symptoms to their physician. Physicians treating patients with Raptiva should consider PML in any patient with new-onset neurological manifestations. Prescribers should exercise caution in considering the use of Raptiva in patients with significant existing or new onset nervous system adverse events.

Infrequent new onset or recurrent severe arthritis events, including psoriatic arthritis events, have been reported in clinical trials and postmarketing. These arthritis events began while on treatment or following discontinuation of Raptiva and were uncommonly associated with flare of psoriasis. Patients improved after discontinuation of Raptiva with or without anti-arthritis therapy.

Prior to initiating therapy with Raptiva, psoriatic patients should receive all immunizations appropriate for age as recommended by current immunization guidelines. Patients on treatment with Raptiva should not receive live (including live-attenuated) vaccines. Vaccinations that are not live, which are received during a course of Raptiva, may not elicit an immune response sufficient to prevent disease. Patients receiving Raptiva should be cautioned if household contacts receive live vaccines, because of the potential risk for shedding and transmission.

Raptiva should not be prescribed in pediatric patients because of the potential risk of non-recoverable suppression of humoral immunity based on juvenile animal studies.

The most common adverse reactions associated with Raptiva are a symptom complex that includes headache, chills, fever, nausea, and myalgia within 48 hours following the first 2 injections. In clinical trials, these events were largely mild to moderate when a first dose of 0.7 mg/kg was given. Less than 1% of patients discontinued Raptiva treatment because of these adverse events.

Pregnancy Registry
Female patients should also be advised to notify their physicians if they become pregnant while taking Raptiva (or within 6 weeks of discontinuing Raptiva) and be advised of the existence of and encouraged to enroll in the Raptiva Pregnancy Registry by calling 1-877-Raptiva (1-877-727-8482).

Mechanism of Action In psoriasis, special immune cells called T-cells become overactive. This activity sets off a whole series of events that eventually makes skin cells multiply so fast, they simply pile up on the surface of the skin. As cells multiply faster and faster, they form red, scaly patches called plaques.

Raptiva prevents T-cells from becoming activated and entering the skin. This, in turn, inhibits the process that leads to plaque formation. As Raptiva starts working in the body and plaque formation is slowed, psoriasis symptoms start to clear.

For more information, see the Raptiva Proposed Mechanism of Action.