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Guselkumab + golimumab + JNJ-78934804 is an investigational triple combination therapy being developed by Janssen for the treatment of moderately to severely active ulcerative colitis. This regimen, evaluated in the Phase 2 TRIO study, combines three distinct mechanisms of action: guselkumab (an IL-23p19 inhibitor), golimumab (a TNF-alpha inhibitor), and JNJ-78934804 (an IL-22 Fc fusion protein acting as an IL-22 agonist). The therapeutic rationale is based on the DUET study findings, which suggested that dual pathway inhibition (TNF and IL-23) provides superior efficacy over monotherapy. By adding an IL-22 agonist, the triple therapy aims to not only suppress multiple inflammatory cascades but also actively promote mucosal healing and epithelial barrier restoration, potentially offering a higher ceiling for clinical and endoscopic remission in refractory patients.
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