Immunopathogenetic mechanisms of action of ustekinumab, a new drug for the treatment of psoriatic arthritis and psoriasis

Abstract

The paper analyzes the data available in the literature on the mechanisms of action of ustekinumab (UST), a new medication to treat activepsoriatic arthritis (PsA) and psoriasis. UST is a human IgG1κ monoclonal antibody (mAb). The mechanism of action of the drug is described; UST is shown to effectively neutralize interleukin 12- (IL12) and IL-23-mediated responses in humans, but not to affect the immune response mediated by cytokines or cellular activity. The paper considers the results of clinical trials of UST used to treat psoriasis and psoriatic arthritis, among them there are PSUMMIT-1 and 2 which included 615 patients with active PsA. Long-term treatment with UST is noted to exhibit an increasing clinical efficacy. At week 52 of treatment, all the patients are shown to have 58% ACR20 responses, 34.2% ACR50 responses, 19.6% ACR70 responses, and 69% PASI75 responses. There is evidence that UST therapy slows down joint radiographic progression in patients with active PsA. Trends in the body mass index (BMI) of psoriatic patients treated with UST are comparatively analyzed; at this time the use of the drug contributes to a significantly smaller increase in BMI than that the other mAb-based drug infliximab, which is relevant in patients with PsA, whose obesity lowers the clinical effect of anticytokine therapy. It is concluded that the results of UST administration confirm successful targeted therapy with mAb-based drugs that effectively reduce the severity of clinical manifestations in psoriasis and psoriatic arthritis presumably through local changes in the expression of cytokines in the skin or synovium; however, but it is necessary to perform further fundamental studies and clinical trials of this class of drugs aimed at blocking the biological effects of certain cytokines.

Keywords

• псориатический артрит
• генно-инженерные биологические препараты
• устекинумаб