Longitudinal transcriptomic analysis of mucosa in ulcerative colitis after anti-tumor necrosis factor withdrawal...

Monoclonal antibodies against tumor necrosis factor (anti-TNF) are effective agents in the treatment of moderate-to-severe ulcerative colitis (UC). It is unclear whether such treatment can safely be discontinued without relapse. This study aimed to identify biomarkers to predict which patients can successfully stop anti-TNF treatment, and to increase our understanding of the pathogenesis of relapse after withdrawal and flare on continued therapy.

We analyzed longitudinal bulk RNA-sequencing data derived from rectal mucosal biopsies from 163 patients in the BIOSTOP study collected at baseline, after 2 years (end of study), and at flares or relapse points.

In this cohort, pre-withdrawal transcriptomic profiles did not distinguish patients who later relapsed from those who remained in long-term remission. Longitudinal analysis of patients who relapsed or flared were both characterized by inflammatory gene expression profiles (eg, CXCL9, CXCL10, OSMR, SELE) and changes in cell-type composition typical for active UC (eg, monocytes/macrophages and THY1+ FAP+ PDPN+ activated fibroblasts). Both groups showed enrichment of T-cell-associated transcriptional signatures, including CD8 T-cell-related genes and IL-17-associated pathways. Additionally, both patient groups showed increased expression of targets of alternative therapeutic agents, suggesting potential treatment options for specific patient subgroups.

Our findings provide insights into the inflammatory mechanisms driving relapse after anti-TNF withdrawal and flare on continued treatment. The dataset offers a valuable resource for future research to improve personalized treatment strategies in UC.