Blood Test Could Predict Which IBD Patients Benefit From Vedolizumab
Researchers identified a molecular signature—low interferon signaling in immune cells—that predicts which inflammatory bowel disease patients will respond to vedolizumab, a blockbuster therapy. The finding, validated across five patient cohorts, could help gastroenterologists avoid ineffective treatments and reduce trial-and-error prescribing that delays remission.
Originaltitel: DOWNREGULATED INTERFERON SIGNALLING IN T CELLS IS ASSOCIATED WITH RESPONSE TO VEDOLIZUMAB IN INFLAMMATORY BOWEL DISEASE
Background: Vedolizumab, a gut-selective anti-integrin therapy, is effective in IBD, but response rates remain variable. Conventional clinical and biochemical markers, including C-reactive protein and faecal calprotectin, have limited predictive value. Although recent transcriptomic studies have implicated T-cell-related signatures in predicting vedolizumab response, these findings lack validation across independent cohorts. Methods: We analyzed pre-treatment transcriptomic profiles from whole blood and T-cell subsets across five independent cohorts comprising 100 patients with UC and CD. The primary outcome was clinical response. Secondary outcomes included clinical and biochemical remission. Results: Among the 100 patients, 61 were responders and 39 non-responders, with no significant baseline clinical differences. Gene set enrichment analyses revealed downregulation of interferon alpha and gamma signalling in responders baseline blood samples, a finding validated across independent cohorts. Downregulated interferon signalling at baseline was also observed in patients who achieved clinical and biochemical remission. To build a predictive model, an adaptive elastic net logistic regression model was applied to baseline whole-blood RNA-sequencing data. The classifier achieved an AUC of 1.0 in training, 0.71-0.83 in UC validation cohorts, and 0.64-1.0 in CD cohorts. Reduced interferon signalling was observed across CD4 and CD8 T-cell subsets, including regulatory T cells, suggesting a broad immune signature rather than cell-type specificity. Conclusions: Downregulated interferon signalling in peripheral blood prior to treatment is a reproducible molecular signature predictive of vedolizumab response and biochemical remission. Whole-blood transcriptomics revealed a robust interferon-axis signal that predicted vedolizumab response across independent cohorts, with stronger performance in UC than CD. Given heterogeneous clinical endpoints and assessment windows, these data provide proof-of-concept that warrants validation with standardised, endoscopy-based outcomes.