New taxonomy for ulcerative colitis

Nov 10, 2026, 12:44:19 PM
Dr. rer. nat. Susanne Landis , PMI Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen

Joint Press release of the Excellence Cluster PMI – Precision Medicine in Chronic Inflammation and the Center for Human Immunobiology, Feinberg School of Medicine, Northwestern University, Chicago Kiel/Chicago, November 10, 2026: In the chronic inflammatory bowel disease ulcerative colitis, treatment success can for the first time be judged for each person individually after just a few weeks. The decisive yardstick is the individual speed of clinical improvement. This gives rise to a new taxonomy, that is, a way of classifying patients: A team from Kiel and Chicago shows in a newly published study in Nature Medicine that people with fast and slow response form biologically and clinically distinct groups. Patients who respond quickly are considerably more likely to achieve comprehensive disease control and have fewer complications in the long term. “You’re talking about teens or young adults who are suffering from uncontrollable diarrhea, bloody stool and an inability to function at school, work, or go out and have normal social interactions,” said study senior author Dr. Parambir Dulai, associate professor of medicine in the division of gastroenterology and hepatology at Northwestern University Feinberg School of Medicine. The team around Professor Stefan Schreiber of Kiel University (CAU), spokesperson of the Excellence Cluster “Precision Medicine in Chronic Inflammation” (PMI) and Director of the Department of Internal Medicine I at the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, analyzed the VARSITY trial together with the team from Chicago. In this large clinical head-to-head trial with 768 participants, two drugs were tested directly against each other: the integrin blocker vedolizumab and the TNF inhibitor adalimumab, which blocks an inflammatory messenger. For both drugs, the analysis revealed four trajectory groups. Independent data from 576 participants in Takeda’s vedolizumab approval program confirmed the classification. Faster improvement was associated with fewer hospital stays and fewer removals of the colon over seven years. “Simply distinguishing between responders and non-responders at the end of trials, as has been done so far, is like a car race in which all that counts is who crosses the finish line – and nobody looks at speed,” said Schreiber. High-resolution single-cell and spatial tissue analyses revealed a possible reason why vedolizumab does not work in some people: Activated immune scavenger cells (called SPP1-positive macrophages) are in close contact with the blood vessels of the intestinal lining. For adalimumab, the team found no comparable signal. These cells carry hardly any of the docking molecule (integrin) at which vedolizumab acts to slow the entry of immune cells into the tissue. They could use other routes: a bypass through which inflammation persists despite therapy. The renin-angiotensin system could play a role here, a signaling pathway best known for regulating blood pressure and one that can be inhibited with blood pressure medicines such as ACE inhibitors and angiotensin receptor blockers (ARBs). “This study shows how precision medicine in chronic inflammatory diseases can become concrete,” said Professor Philip Rosenstiel of Kiel University and Director of the Institute of Clinical Molecular Biology at UKSH. “The mechanism we uncovered opens up a targeted approach to making vedolizumab more effective. At the same time, we are creating the biological basis for determining which patients need such an addition and could benefit from it.” These findings are supported by analyses of the US databases TriNetX and Optum, covering a total of 8,835 people with ulcerative colitis and high blood pressure: Those who took an ACE inhibitor or an ARB in addition to vedolizumab had a better disease course with fewer complications. This association was not seen with TNF inhibitors such as adalimumab. Further studies must show whether the combination of vedolizumab with ACE inhibitors or ARBs actually works better. Patients should therefore not change their therapy on their own and should not take additional blood pressure medicines, but discuss any change with their treating physician. “This study is a breakthrough for precision medicine: The individual patient and their course of disease are now at the center,” said Schreiber. “It confirms the path of our Excellence Cluster and opens up the chance to boost vedolizumab in a targeted way. We now also know early on who might need this boost. This is reminiscent of the combination of anti-TNF therapy and azathioprine, but it follows a different mechanism and requires a prospective trial for further clinical work-up.” The next step is controlled clinical trials to test whether vedolizumab works better when combined with an ACE inhibitor or an ARB. For patients who often wait a long time for improvement after starting treatment, that would be an important advance. The collaboration of leading research from Kiel and Chicago shows where precision medicine is heading: knowing not only at the end of the race, but early on, which therapy helps whom – for every patient individually. Funding and disclosures: The study was funded, among others, by the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the European Union (Innovative Medicines Initiative 2), the German Research Foundation (Excellence Cluster PMI) and the German Federal Ministry of Research (iTREAT project). Takeda, the manufacturer of vedolizumab, is the sponsor of the study and provided data from the VARSITY and GEMINI 1 trials. Information on conflicts of interest can be found in the original publication.