Selective Interleukin-23 p19 Inhibition: Another Game Changer in Psoriasis? Focus on Risankizumab

The history of psoriasis treatment has been marked by several milestones. Corticosteroids, cyclosporine, tumor necrosis factor alpha (TNF-α) inhibitors and, more recently, interleukin (IL)-17A inhibitors have revolutionized the treatment of psoriasis, each in its own way and time. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and selective IL-23p19 inhibition may bring several advantages with respect to IL-12/23p40 inhibition, or distal blockade of IL-17A or its receptor. In fact, IL-12 axis inhibition does not appear to be essential in psoriasis and IL-12 inhibition may even have a negative effect in the treatment of psoriasis and have potential risks in tumor immune surveillance and in host defense against intracellular pathogens. On the other hand, contrary to IL-17 inhibition, IL-23p19 blockade does not increase the risk of candida infection, nor is it associated with inflammatory bowel disease worsening. Several IL-23p19 inhibitors are currently being developed for the treatment of psoriasis, such as tildrakizumab, guselkumab, and risankizumab. Although clinical data on risankizumab is still scarce, it has shown characteristics that signify a major advance in the treatment of this disease, offering comparable or higher efficacy than IL-17 inhibitors, without the safety concerns of this therapeutic class, combined with the excellent dosing regimen of ustekinumab. Currently, only phase II trial data is available; thus, the results of the large phase III trials will be essential to establish the efficacy and safety profile of risankizumab and its value in the biological armamentarium for the treatment of psoriatic patients.