Psoriasis - efalizumab
Psoriasis is a chronic condition in which thick, scaly pink or red patches are formed on the skin, particularly the scalp, trunk, elbows and knees. It frequently runs in families, and can occur in association with arthritis. Drug treatments include topical corticosteroids and vitamin D analogues such as calcipotriol, and systemic drugs, including methotrexate, retinoids and cyclosporin, are given in very bad cases. While these provide symptomatic relief, they do not cure the condition.
Psoriasis is believed to be caused by the activation of T cells in the immune system. A potential cure has been developed by Genentech, and is being commercialised in conjunction with Serono. Efalizumab is a recombinant humanised monoclonal antibody that has been designed to inhibit the adhesion of T lymphocytes to other cell types.
A placebo-controlled trial has been carried out in 556 patients with moderate to severe plaque psoriasis.1 After 12 weeks of therapy with efalizumab or placebo, 27% of those given the active demonstrated an improvement in psoriasis area and severity index (PASI) score in excess of 75%, compared with just 8% of those given placebo. A total of 59% had a 50% or greater improvement, compared with 14% of those given placebo.
A further study has been carried out to see whether subcutaneous delivery of the monoclonal antibody was as effective as when it is administered by the normal intravenous route.2 In the open label single and multiple dose, escalating dose study, subjects received a single dose of efalizumab (0.3mg/kg a week) or escalating multiple doses of 0.5 to 2.0mg/kg a week. On assessment by PASI, target lesion assessment and physician's global assessment, an improvement of 40-60% in signs and symptoms of plaque psoriasis was seen after eight weeks. Furthermore, mean PASI scores were still declining at this time, indicating that longer duration of treatment should be beneficial. In the six-week follow-up period, patients maintained their treatment benefit. There were considerably fewer adverse events than were seen when the antibody was administered intravenously. So not only does subcutaneous administration appear to improve the overall tolerability and safety of the treatment, it also is a more convenient delivery method, so patients are more likely to comply with their treatment.