Efalizumab: a review of events reported during clinical trials and side effects

Abstract

Efalizumab is a recombinant humanised IgG1 kappa isotype monoclonal antibody against the CD11a molecule. Efalizumab is approved for the treatment of moderate-to-severe psoriasis and is currently administered as a weekly subcutaneous injection. Throughout October 2005, 19,000 patients were treated with efalizumab. According to the package insert that is based on 2762 subjects, the most common adverse reactions associated with efalizumab are a first dose reaction complex that includes headache, chills, fever, nausea and myalgia within two days following the first two injections. These reactions are dose-level-related in incidence and severity and were largely mild-to-moderate in severity when a conditioning dose of 0.7 mg/kg was used as the first dose. Adverse events occurring at a rate between 1 and 2% greater in the efalizumab group compared with placebo were arthralgia, asthenia, peripheral oedema and psoriasis. Efalizumab is associated with a rebound flare reaction in approximately 5% of patients when therapy is ceased. Antiefalizumab antibodies develop in approximately 5% of the subjects who were treated with efalizumab, but the clinical significance of these antibodies is unclear. Efalizumab has rare but serious haematological side effects. Immune-mediated thrombocytopenia platelet counts at or below 52,000 cells/microl have been observed in 0.3% of cases and monitoring of platelet counts monthly for the first 3 months of use and each 3 months thereafter. Reports of four cases of haemolytic anaemia diagnosed four to six months after patients started on the monoclonal antibody exist. Infrequent new onset or recurrent severe arthritis events, including psoriatic arthritis events, have been reported in clinical trials and postmarketing surveillance. Symptoms associated with a hypersensitivity reaction (e.g., dyspnoea, asthma, urticaria, angioedema, maculopapular rash) were rarely noted in the first 12 weeks of the controlled clinical studies. The overall incidence of malignancies of any kind was 1.8 per 100 patient-years for efalizumab-treated patients compared with 1.6 per 100 patient-years for placebo-treated patients. One case each of the following serious adverse reactions was observed: transverse myelitis, bronchiolitis obliterans, aseptic meningitis, idiopathic hepatitis, sialedenitis and sensorineural hearing loss. In the complete safety data from both controlled and uncontrolled studies, the overall incidence of hospitalis ation for infections was 1.6 per 100 patient-years for efalizumab-treated patients compared with 1.2 per 100 patient-years for placebo-treated patients. The rate of infection was 26% in the control group and 29% in treated cases. The most common findings on laboratory assessments in patients using efalizumab were reversible increases in lymphocyte count and total white blood cell. Efalizumab is a safe, effective, but expensive treatment for psoriasis.