Guselkumab (Tremfya®): A Comprehensive Monograph on a Selective Interleukin-23 Inhibitor for Immune-Mediated Inflammatory Diseases

Executive Summary

Guselkumab, marketed under the brand name Tremfya®, is a first-in-class, fully human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that has emerged as a cornerstone therapy for a range of immune-mediated inflammatory diseases (IMIDs).[1] It functions through the highly selective inhibition of the p19 subunit of interleukin-23 (IL-23), a key cytokine implicated in the pathogenesis of chronic inflammation. This targeted mechanism disrupts the IL-23/T helper 17 (Th17) axis, a critical pathway that drives the inflammatory cascade in conditions such as psoriasis and inflammatory bowel disease.[1]

Initially approved for the treatment of adult patients with moderate-to-severe plaque psoriasis (PsO), Guselkumab's therapeutic applications have expanded significantly based on a robust and ambitious clinical development program. It is now also established for the treatment of active psoriatic arthritis (PsA) and has made a transformative entry into gastroenterology with approvals for moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD).[1]

The evidence base for Guselkumab is distinguished by data from large-scale, pivotal Phase 3 clinical trial programs, including VOYAGE for PsO, DISCOVER for PsA, QUASAR for UC, and GALAXI for CD. A defining feature of this evidence is the inclusion of active comparators in head-to-head trials, which have demonstrated Guselkumab's superiority over established standards of care. Notably, Guselkumab has shown superior efficacy compared to the tumor necrosis factor-alpha (TNF-α) inhibitor adalimumab in plaque psoriasis and, in a landmark finding for the IL-23 inhibitor class, superiority over the IL-12/23 inhibitor ustekinumab for achieving endoscopic endpoints in Crohn's disease.[2]