Medication Review: Describe the Dual Mechanism of Action of Guselkumab

In this video, Audrey Gibson, PA-C, a rheumatology physician assistant with nearly two decades of clinical experience, breaks down the unique dual mechanism of action of guselkumab and its role in targeting IL-23–driven inflammation. The discussion explores how this fully human monoclonal antibody selectively binds the IL-23 p19 subunit to inhibit downstream inflammatory signaling, while also engaging CD64 on inflammatory monocytes through its Fc region, addressing IL-23 at its source. Designed to clarify the science behind dual-acting IL-23 inhibition, this overview provides practical insight for clinicians managing immune-mediated rheumatic diseases and highlights emerging therapeutic strategies in modern rheumatology care.