Science to Clinical Practice: IL-23 Inhibition for the Treatment of Psoriasis. Latest Insights on the Selective Mode of Action of Risankizumab

Psoriasis affects 60 million people globally. It is an inflammatory skin condition that can significantly impact quality of life. Furthermore, comorbidities including psoriatic arthritis and cardiovascular disease are common, indicating wider immune system involvement. In recent years, the IL-23/Type 17 T cells (T17) axis of inflammation has been shown to play a key role in psoriasis pathogenesis, leading to the development and licensing of biologics that target IL-23- and IL-17-mediated inflammatory pathways. These advanced medications effectively disrupt the inflammatory cycle, resulting in sustained improvements in clinical disease. This article reviews newly available data that provide the latest insights into the molecular interactions and mode of action of IL-23 antagonists. It outlines evidence to demonstrate that IL-23 blockade with risankizumab selectively inhibits pathogenic T17 cell subsets in psoriasis skin lesions, while non-pathogenic or regulatory T17 subsets remain intact, as well as the potential clinical benefits. It also evaluates the alternative binding to CD64 and concludes that it is unlikely to affect the clinical efficacy or safety of licensed IL-23 antibodies. These new data provide clinically relevant insights into the durable efficacy and safety of anti-IL-23 biologics.