Psoriasis - ustekinumab
The chronic skin disorder psoriasis affects 2% of the population. Thick, scaly pink or red patches form on the skin, with the scalp, trunk, elbows and knees most commonly affected.
The chronic skin disorder psoriasis affects 2% of the population. Thick, scaly pink or red patches form on the skin, with the scalp, trunk, elbows and knees most commonly affected.
It frequently runs in families, and can occur in association with arthritis. Various drugs are available that provide symptomatic relief, including topical corticosteroids and vitamin D analogues such as calcipotriol. Systemic drugs such as cyclosporin, methotrexate and retinoids are given in particularly bad cases. However, none of these provides a cure.
The condition is believed to be caused by the activation of T cells in the immune system, and the interleukins IL-12 and IL-23 are implicated in the T cell response in psoriasis. One drug developed to treat psoriasis is Centocor's monoclonal antibody ustekinumab, which was created using Medarex's UltiMab technology.1 The humanised monoclonal antibody hits the IL-12p40 subunit that is present in both IL-12 and IL-23.
In a double blind, placebo-controlled, randomised Phase III trial, 766 patients with plaque psoriasis were given two subcutaneous doses of the antibody four weeks apart, of either 45 or 90mg, followed by the same doses every 12 weeks, or placebo.2 The placebo group was crossed over to the active group at weeks 12 and 16, and thereafter treated every 12 weeks. At week 40, those who responded to the drug were randomised to continue treatment or receive placebo.
After 12 weeks, two thirds of patients on both antibody treated groups had responded, with a 75% improvement on the psoriasis area and severity index, compared with just 3% of the placebo group. Efficacy was maintained through long-term therapy. The drug was generally well tolerated. Results after 76 weeks have also been reported; the good results were maintained over the longer term.3
Another randomised, double blind, placebo-controlled Phase III trial was carried out in 1,230 patients with moderate to severe plaque psoriasis.4 A similar dosing schedule was used, with 45 or 90mg of the drug being given subcutaneously at weeks 0, 4 and 12, followed by 12-weekly injection up to 52 weeks. Those showing a partial response had the dosing interval reduced to eight weeks. Again, the initial placebo group was crossed over to active at 12 weeks.
More than two thirds achieved a 75% PASI score improvement at 12 weeks, compared with 4% of the placebo group. The trial is being extended for responders to receive the drug for up to five years. Other Phase III trials are also underway, including one that compares its efficacy with that of etanercept.