An ulcerative colitis taxonomy defined by individual patient-reported response trajectories

A barrier to precision medicine for ulcerative colitis (UC) is the inability to predict and mechanistically explain treatment responses. Using patient-reported outcomes (PROs) from a phase 3b comparative trial of 768 participants, we identified four distinct patient response-trajectory groups for vedolizumab (anti-integrin) and adalimumab (antitumor necrosis factor). Validation in a second phase 3 trial of 576 participants linked PRO-defined vedolizumab trajectories to long-term disease complications. Bulk, single cell, and spatial transcriptomics and proteomics identified vascular inflammation as associated with vedolizumab nonresponse through interactions between SPP1 + macrophages and endothelial cells. In two separate real-world cohorts of 4,981 and 3,854 patients with UC, concomitant use of renin–angiotensin system inhibitors (modulators of vascular inflammation) was associated with reduced long-term complications for vedolizumab but not anticytokine therapies. These findings define a response-trajectory-based taxonomy that requires prospective validation for clinical utility and applications for selecting vedolizumab combination therapy in UC.