Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
vials containing 125 mg lyopholised powder for reconstitution
Approved indication: psoriasis
Australian Medicines Handbook section 8.6.1
The recognition of psoriasis as an autoimmune disorder has prompted research into the role of T-lymphocytes. The activation of these lymphocytes involves leukocyte-function associated antigen type 1 (LFA-1). By binding to LFA-1 efalizumab reduces inflammation by inhibiting the adhesion of T-lymphocytes to other cells.
Efalizumab is a monoclonal antibody produced by genetic engineering. Although it is produced using Chinese hamster ovary cells, the molecule is humanised. Efalizumab has to be given by weekly subcutaneous injections.
A placebo-controlled trial of efalizumab enrolled 556 patients with chronic plaque psoriasis covering at least 10% of their bodies. After 12 weeks 27% of the patients given efalizumab (1 mg/kg) had at least a 75% improvement in their psoriasis area and severity index (PASI). Only 4% of the patients given a placebo had a similar response.1
Another placebo-controlled trial treated 597 patients weekly for 12 weeks then re-randomised patients who had responded to efalizumab to continue treatment for another 12 weeks, reduce to fortnightly injections, or switch to placebo. Patients whose PASI had not improved were re-randomised to take a higher dose or a placebo for another 12 weeks. After the first 12 weeks there was a 75% improvement in the PASI in 5% of the patients given weekly injections of placebo. This outcome was achieved by 22% of the patients given efalizumab 1 mg/kg and 28% of those given 2 mg/kg. The improvement was sustained in most of the patients who responded and were re-randomised to continue treatment. The response was only maintained by 20% of the responders who were switched to a placebo. Only 13% of the patients who did not initially respond achieved a PASI improvement of 75% when treated with a higher dose.2 Although a dose of at least 2 mg/kg was used in the patients who continued treatment after 12 weeks, the recommended weekly dose in Australia is 1 mg/kg with a maximum single dose of 200 mg.
As efalizumab affects the immune system there is a potential for serious adverse effects such as malignancy and lymphoproliferative disorders. Patients should have their blood counts checked as lymphocytosis and thrombocytopenia can occur. Flu-like symptoms such as headache, fever and chills are significantly more common with efalizumab than with placebo. As adverse reactions may be more frequent early in treatment an initial dose of 0.7 mg/kg is recommended. Efalizumab is potentially immunogenic. Approximately 8% of patients will have an allergic reaction and some will develop anti-efalizumab antibodies. Information about the long-term safety of efalizumab is limited, but there is a risk of the psoriasis getting worse if the drug is stopped abruptly.
In Europe efalizumab is restricted to patients who have failed to respond to treatments such as cyclosporin, methotrexate or phototherapy. This restriction does not apply in Australia, but there is a need to investigate if efalizumab is more effective than other systemic therapies for chronic plaque psoriasis.
- Efalizumab for patients with moderate to severe plaque psoriasis. JAMA 2003;290: 3073-80. .
- Efalizumab Study Group. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003;349:2004-13. .