Guselkumab Across Psoriatic Disease and Inflammatory Bowel Disease: A Structured Narrative Review of Its Mechanism, Clinical Evidence, and Therapeutic Positioning

Guselkumab is a human monoclonal antibody directed against the p19 subunit of interleukin-23. This structured narrative review evaluates its pharmacologic rationale, efficacy, safety, durability, and therapeutic role in plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. PubMed/MEDLINE and Europe PMC were searched from inception through 18 September 2026 using broad and disease-specific strategies; ClinicalTrials.gov was searched to link trial families and identify ongoing studies. Records were screened for directness, design, distinct contribution, and clinical relevance. The final synthesis included 64 PubMed-indexed articles and the current US prescribing information. In plaque psoriasis, guselkumab produces high and durable skin clearance rates and has demonstrated superiority over active comparators at prespecified time points. In psoriatic arthritis, it improves peripheral arthritis, skin disease, enthesitis, dactylitis, function, and patient-reported outcomes; long-term trials show low observed radiographic progression, whereas evidence for axial disease remains less definitive. In Crohn’s disease and ulcerative colitis, phase 3 programs demonstrate clinical and endoscopic efficacy with intravenous or fully subcutaneous induction and subcutaneous maintenance. Long-term trial data support a stable safety profile, although infection screening, tuberculosis assessment, vaccination review, and indication-specific liver monitoring remain important. Guselkumab may be clinically relevant when skin, joint, and bowel inflammation coexist, but treatment should remain domain based because efficacy cannot be assumed to be equivalent across manifestations. Direct within-class comparisons, validated response biomarkers, and dedicated axial and disease-modification studies remain priorities.