Ustekinumab (Stelara®): A Comprehensive Monograph on a First-in-Class IL-12/23 Inhibitor

Executive Summary

Ustekinumab is a first-in-class, fully human IgG1κ monoclonal antibody that represents a significant milestone in the treatment of immune-mediated inflammatory diseases. Marketed under the brand name Stelara® and now available as multiple biosimilars, it functions as a dual inhibitor, uniquely targeting the shared p40 protein subunit of two critical cytokines: Interleukin-12 (IL-12) and Interleukin-23 (IL-23).[1] This targeted mechanism of action allows Ustekinumab to potently downregulate the Th1 and Th17 inflammatory pathways, which are central to the pathophysiology of several autoimmune conditions.[1]

The therapeutic utility of Ustekinumab has been firmly established through a robust clinical development program, leading to regulatory approvals for a range of indications. These include the treatment of moderate-to-severe plaque psoriasis (PsO), active psoriatic arthritis (PsA), moderately to severely active Crohn's disease (CD), and moderately to severely active ulcerative colitis (UC).[1] Its approval extends to pediatric populations for both plaque psoriasis and psoriatic arthritis, underscoring its well-characterized efficacy and safety profile across different age groups.[7] Clinical trials have consistently demonstrated that Ustekinumab can achieve significant clinical endpoints, including skin clearance in psoriasis, joint symptom improvement in psoriatic arthritis, and clinical and endoscopic remission in inflammatory bowel diseases.[9]