Ustekinumab for the treatment of psoriasis: review of three multicenter clinical trials

Abstract

Ustekinumab, a fully human monoclonal antibody that binds to the p40 subunit of IL-12 and IL-23, has been recently approved in Europe and the U.S. for the treatment of moderate to severe plaque psoriasis. The efficacy and safety of ustekinumab have been demonstrated in three randomized phase III clinical trials, which are reviewed herein. In the PHOENIX 1 and 2 trials, significantly more patients achieved a PASI 75 response at week 12 on ustekinumab 45 mg (67.1% and 66.7%, respectively) or 90 mg (66.4% and 75.7%, respectively) than on placebo (3.1% and 3.7%, respectively; P < 0.0001 for each comparison versus placebo, in both trials). In the ACCEPT trial, PASI 75 was achieved at week 12 by 67.5% of patients on ustekinumab 45 mg, 73.8% on ustekinumab 90 mg and 56.8% on etanercept (comparison versus etanercept: P = 0.01 and P < 0.001, respectively). Injection-site reactions were significantly more common on etanercept than on ustekinumab. These results show that ustekinumab is significantly more effective than placebo and etanercept in the short-term treatment of moderate to severe psoriasis. Its safety has also been demonstrated during 76 weeks in patients without active infection or malignancy. Long-term safety data should be provided by the ongoing follow-up of the PHOENIX 1 and 2 cohorts.