An ulcerative colitis taxonomy defined by individual patient-reported response trajectories
Year: 2026
Type: article
Abstract: 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.
Source: Nature Medicine
Authors: Stefan Schreiber, Vijay Yajnik, Cenfu Wei, Maria D. Paraskevopoulou, Saman Farahmand, Jie Cheng, Katherine Simpson, Zitong Lin, Christian Agboton, Pratik Panchal, Banishree Saha, Ninfa Candela, Joshua Brown, Isabella Peshek, Frida Chavez, Libeth Rosas, Alan Robinson, Gursimran Singh Kochhar, Aakash Desai, Franziska Kimmig, Philip Rosenstiel, Paresh Thakker, Parambir S. Dulai
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7225658750