An ulcerative colitis taxonomy defined by individual patient-reported response trajectories
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.
Authors
- Aakash Desai (ORCID: https://orcid.org/0000-0002-6604-7712)
- Cenfu Wei (ORCID: https://orcid.org/0000-0003-3368-4974)
- Parambir Singh Dulai (ORCID: https://orcid.org/0000-0002-9514-2321)
- Christian Agboton (ORCID: https://orcid.org/0000-0002-1178-2429)
- Philip C Rosenstiel (ORCID: https://orcid.org/0000-0002-9692-8828)
- Vijay Yajnik (ORCID: https://orcid.org/0000-0001-6767-1712)
- Stefan Schreiber (ORCID: https://orcid.org/0000-0003-2254-7771)
- Paresh Thakker (ORCID: https://orcid.org/0000-0003-3059-9133)
- Gursimran Singh Kochhar (ORCID: https://orcid.org/0000-0002-0597-2760)
- Ninfa M. Candela (ORCID: https://orcid.org/0000-0003-3469-6088)
- Saman Farahmand (ORCID: https://orcid.org/0000-0001-8999-2322)
- Pratik Panchal (ORCID: https://orcid.org/0000-0002-9048-0639)
- Maria D. Paraskevopoulou (ORCID: https://orcid.org/0000-0001-8527-5537)
- Banishree Saha (ORCID: https://orcid.org/0000-0003-3583-9837)
- Katherine H. Simpson
- Isabella Marie Peshek
- Alan Robinson (ORCID: https://orcid.org/0000-0003-2753-3133)
- Frida Chavez
- Libeth Rosas
- Franziska Kimmig (ORCID: https://orcid.org/0009-0004-1359-5258)
- Zitong Lin
- Joshua Brown
- Jie Cheng
Institutions
- Northwestern University (US)
- Northwell Health (US)
- Allegheny Health Network (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- University Hospital Schleswig-Holstein (DE)
- Takeda (Japan) (JP)
Publication Details
- Journal
- Nature Medicine
- Published
- 2026-11-09
- DOI
- https://doi.org/10.1038/s41591-026-04741-8
- Primary Topic
- Inflammatory Bowel Disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00