Curr Opin Immunol. 2026 Jul 23;102:102820. doi: 10.1016/j.coi.2026.102820. Online ahead of print.
ABSTRACT
Once considered incurable, psoriasis is now being re-evaluated in light of sustained, drug-free remissions, prompting a redefinition of ‘cure’ as long-term/drug-free remission. Psoriatic disease is primarily driven by dysregulation of the interleukin-23 (IL-23)/IL-17 axis, and the survival of tissue-resident memory T cells (TRM), key mediators of lesion recurrence and chronicity. Targeting this axis early with high-dose IL-23 inhibitors has shown promise, as exemplified by the KNOCKOUT trial, where intensified induction dosing of risankizumab resulted in marked TRM cell depletion and durable remission. Early intervention appears crucial, with studies such as the GUIDE trial demonstrating that patients with early disease duration respond more to IL-23 inhibition with guselkumab, achieving higher rates of complete skin clearance. Beyond biologics, curative strategies encompass stem cell therapy, with case reports of long-lasting remission supporting their potential role in immune reprogramming. Cutting-edge interventions such as gene editing, chimeric antigen receptor-T cell therapy, and microRNA modulation are also under exploration.
PMID:42492164 | DOI:10.1016/j.coi.2026.102820