Multiomic characterisation of the clinical efficacy of guselkumab induction therapy in ulcerative colitis - PubMed
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- #guselkumab
- #ulcerative-colitis
- #multiomic-analysis
- Guselkumab, an IL-23p19 subunit antagonist, shows clinical efficacy in ulcerative colitis (UC).
- The QUASAR Phase IIb study involved 313 UC patients randomized to guselkumab (200/400 mg) or placebo.
- Molecular profiling included bulk RNA-seq, single-cell RNA-seq, flow cytometry, and serum proteomics.
- Guselkumab reduced pro-inflammatory serum proteins by week 4, with further decline by week 12.
- Transcriptional changes in pro-inflammatory and epithelial repair pathways were observed, especially in patients achieving histological-endoscopic mucosal improvement (HEMI).
- Single-cell analyses showed decreased pro-inflammatory cells and increased mucosal cell types post-treatment.
- The study links guselkumab's molecular changes to clinical outcomes like HEMI at week 12.