Summary
A study in Nature Medicine grouped ulcerative colitis patients by how quickly their symptoms changed during treatment and linked vedolizumab nonresponse to SPP1-associated vascular inflammation. Retrospective cohorts also associated ACE inhibitor or ARB use with better outcomes for patients taking vedolizumab, a finding that needs prospective trial testing.
A study published in Nature Medicine on 9 November 2026 grouped people with ulcerative colitis by the course of their symptoms during treatment, rather than classifying them only as responders or nonresponders at a single time point. The researchers identified four response trajectories for vedolizumab and adalimumab, then linked vedolizumab nonresponse to a pattern of vascular inflammation involving SPP1-positive macrophages. In retrospective patient cohorts, use of ACE inhibitors or angiotensin-receptor blockers alongside vedolizumab was associated with fewer long-term complications.
Symptom trajectories separated treatment responses
The researchers analysed patient-reported rectal bleeding and stool frequency, combined in a measure called PRO-2. In the phase 3b VARSITY comparison, the analysis included 382 people treated with vedolizumab and 386 treated with adalimumab. For vedolizumab, the four modelled groups were labelled super-responders (45%), responders (11%), partial responders (26%) and nonresponders (18%). A second phase 3 vedolizumab trial, with 576 participants in the trajectory analysis, showed a similar four-group pattern.
The trajectory groups were associated with later clinical outcomes. In the validation cohort, the combined faster-response groups had a lower risk of hospitalization or colectomy over seven years than the partial-response and nonresponse groups (hazard ratio 0.56; 95% confidence interval 0.34–0.93). This suggests that the shape and speed of symptom improvement may help describe disease course beyond a single early assessment.
A vascular inflammation signal in vedolizumab nonresponse
To investigate why some patients did not respond, the team combined trajectory assignments with gene-expression, protein and single-cell data. Across trial datasets, vedolizumab nonresponse was associated with a vascular-inflammation signature. The protein SPP1, also known as osteopontin, stood out: higher baseline SPP1 was associated with a lower likelihood of week-52 clinical remission among vedolizumab-treated participants, while the same association was not observed for adalimumab.
Single-cell and spatial analyses connected this signature to SPP1-positive macrophages interacting with endothelial cells in intestinal tissue. Vedolizumab blocks the α4β7 integrin’s binding to MAdCAM-1, a route involved in immune-cell movement into the gut. The researchers propose that vascular inflammation could support alternative cell-trafficking routes that help sustain inflammation despite this blockade. The cell and spatial datasets were relatively small, so this proposed mechanism remains a research finding rather than a clinical test for choosing treatment.
Retrospective medication data point to a trial question
The team also examined two routine-care datasets of patients with ulcerative colitis and hypertension. In an electronic medical-record cohort, propensity-matched vedolizumab users taking an ACE inhibitor or ARB had higher treatment persistence and lower rates of hospitalization for ulcerative colitis flares and colectomy than matched patients not taking one. The study reported no similar outcome difference for these medicines alongside anti-TNF therapy or ustekinumab. In a separate claims cohort, concomitant ACE inhibitor or ARB use was associated with a lower one-year colectomy risk among vedolizumab users (adjusted hazard ratio 0.31; 95% CI 0.11–0.87).
These comparisons are observational: treatment was not randomly assigned, and differences between patients may influence outcomes despite statistical matching. The findings therefore support testing the proposed combination in prospective clinical trials; they do not establish that ACE inhibitors or ARBs improve ulcerative colitis when added to vedolizumab. The study’s broader proposal—that symptom trajectories could help guide adaptive treatment decisions—also needs validation in wider clinical populations.