Briakinumab for the treatment of plaque psoriasis

摘要

Psoriasis is a chronic inflammatory skin disorder affecting approximately 2 of individuals worldwide. An improved understanding of the pathogenesis of psoriasis has led to the development of targeted biologic therapies. Briakinumab (ABT-874) is a recombinant human antibody that blocks the biological activity of the cytokines interleukin (IL)-12 and IL-23 through their shared subunit p40. IL-12 and IL-23 are key mediators in T-cell differentiation and have been shown to play a significant role in maintaining inflammation and abnormal keratinocyte function in psoriasis patients through development and stimulation of Th1 and Th17 subsets, respectively. In one phase II and four phase III studies (including two 52-week trials), the Psoriasis Area and Severity Index (PASI)-75 score at weeks 12 and 52 was achieved by at least 80.6 and 66.2 (p<0.001) of patients receiving more than one dose of briakinumab every 4 weeks, respectively, with high proportions of patients achieving PASI-90 and PASI-100 scores (at least 55.4 and 28.8, respectively; p<0.001). These studies indicate safety and tolerance of briakinumab therapy for patients with moderate-to-severe chronic plaque psoriasis. In one clinical trial, therapy was associated with increased incidence of major cardiac events. Available results from two briakinumab trials show its positive impact on health-related quality of life. However, the manufacturer has now withdrawn the application in the EU and US.