What ulcerative colitis biopsies reveal about healing

Endoscopic and histologic healing in ulcerative colitis may correspond with measurable molecular changes in the intestinal mucosa, according to a post hoc analysis of the phase 2b/3 SELECTION trial. Understanding whether these clinical endpoints reflect deeper biological healing has become an important question in ulcerative colitis management, particularly as treat-to-target frameworks such as STRIDE-II emphasize endoscopic healing as a key therapeutic goal.

The exploratory analysis examined whether commonly used trial outcomes — such as endoscopic improvement and histologic remission — correspond with measurable changes in gene expression within colonic tissue. Investigators found that patients achieving these outcomes showed gene-expression patterns consistent with reduced inflammation and epithelial recovery. The findings were published in the Journal of Crohn’s and Colitis.

Researchers analyzed patients with moderately to severely active ulcerative colitis enrolled in the SELECTION trial who received filgotinib 200 mg, filgotinib 100 mg, or placebo. Colonic biopsies collected at baseline and week 10 underwent RNA sequencing to evaluate gene-expression changes associated with treatment response.

Filgotinib is a selective Janus kinase 1 (JAK1) inhibitor approved for ulcerative colitis in several regions outside the United States, including Europe and Japan, but it has not received FDA approval for this indication.

Investigators assessed individual and composite endoscopic and histologic outcomes at week 10 and week 58. Patients receiving filgotinib 200 mg were more likely to achieve combined endoscopic and histologic remission compared with placebo.

Endo-histologic remission occurred in 6.7% of patients receiving filgotinib 200 mg versus 1.8% with placebo at week 10 (P = .0021). At week 58, remission occurred in 12.1% of patients receiving filgotinib 200 mg compared with 5.1% of patients receiving placebo (P = .0485). These results align with previously reported efficacy outcomes from the SELECTION program.

Investigators then evaluated whether these clinical endpoints corresponded with molecular changes in the colonic mucosa.

Patients who achieved endoscopic improvement or histologic remission showed gene-expression patterns moving in the opposite direction of those associated with active disease. Expression of genes involved in neutrophil activity and migration decreased significantly (P < .0001) among patients reaching these endpoints.

At the same time, gene signatures linked to epithelial repair and mitochondrial function increased. One example was increased expression of PADI2, a gene associated with epithelial processes, which demonstrated a log2 fold change of 2 (P < .0001) among patients achieving endoscopic or histologic outcomes.

Improvements seen on endoscopy and histology corresponded with broader molecular changes consistent with reduced inflammation and mucosal recovery.

For clinicians, however, these transcriptomic findings do not currently alter clinical management. The RNA sequencing analysis was exploratory and conducted on biopsy samples collected within the clinical trial. Although the analysis helps clarify biological mechanisms underlying treatment response, transcriptomic profiling is not currently used as a biomarker in routine care.

In practice, treatment targets in ulcerative colitis remain centered on symptom control, endoscopic improvement, and inflammatory biomarker trends.

The findings also contribute to ongoing discussion about histologic remission and composite endo-histologic endpoints in ulcerative colitis management. Current treat-to-target frameworks, including STRIDE-II recommendations, emphasize clinical remission and endoscopic healing as the primary treatment goals, while histologic remission is considered an additional marker of deeper disease control.

Previous studies suggest that patients achieving both endoscopic and histologic remission may experience lower relapse rates than those achieving endoscopic healing alone. The present analysis adds a molecular perspective by showing that patients reaching these combined endpoints demonstrate broader normalization of inflammatory gene pathways in the mucosa.

However, the study does not resolve whether histologic remission should become a formal treatment target or how composite endo-histologic endpoints should be incorporated into routine care. Those questions remain the subject of ongoing research.

Instead, the findings reinforce the concept that deeper mucosal healing corresponds with measurable biological changes within intestinal tissue.

Standard treat-to-target approaches — guided by symptoms, biomarkers, and endoscopic evaluation — remain the framework for clinical management. The transcriptomic analysis provides additional evidence that clinical endpoints used in ulcerative colitis trials reflect underlying shifts in inflammatory pathways within the mucosa.

Future studies may clarify whether molecular signatures could eventually help identify patients most likely to achieve durable remission.

Key Takeaways

• Endoscopic and histologic remission in ulcerative colitis corresponded with measurable molecular changes in colonic mucosa in an exploratory analysis of the SELECTION trial.

• Patients achieving endoscopic or histologic outcomes showed reduced expression of neutrophil-related inflammatory genes and increased signatures associated with epithelial repair.

• The findings provide biological validation of commonly used UC trial endpoints, suggesting these clinical measures reflect deeper mucosal recovery.

• Transcriptomic profiling remains a research tool, and the analysis does not currently support new biomarkers or changes to clinical management.

• Current treat-to-target strategies emphasizing symptom control and endoscopic healing remain unchanged, though the study adds molecular insight into mechanisms of mucosal healing.