Ustekinumab

Abstract

Ustekinumab is a fully human monoclonal antibody that binds with high specificity and affinity to the cytokines interleukin (IL)-12 and IL-23, thereby suppressing IL-12- and IL-23-mediated inflammation associated with psoriasis. In two large, phase III trials in patients with moderate to severe plaque psoriasis, significantly more subcutaneous ustekinumab 45 or 90 mg recipients (administered as two injections 4 weeks apart) than placebo recipients achieved a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) score at 12 weeks. Other efficacy measures, including the physician's global assessment of clinical response at week 12, also favored ustekinumab over placebo. Psoriatic symptom control was maintained during ustekinumab maintenance therapy (administered once every 12 weeks) for up to 76 weeks. In a phase II trial in patients with active plaque psoriasis and psoriatic arthritis, signs and symptoms of arthritis and psoriatic symptom control were improved to a greater extent with ustekinumab than with placebo at 12 weeks, based on the proportion of patients achieving a 20% improvement in American College of Rheumatology response criteria (arthritis) or PASI 75 (skin symptoms). Health-related quality of life, assessed using the Dermatology Life Quality Index and the Health Assessment Questionnaire disability index, was improved to a significantly greater extent with ustekinumab than with placebo at week 12. Subcutaneous ustekinumab was generally well tolerated in clinical trials, with most treatment-emergent adverse events being of mild severity.