Study co-author Frida Chavez conducting research in Dr. Parambir Dulai's lab at Northwestern University Feinberg School of Medicine in Chicago. Credit: Northwestern University / Ben Schamisso
Tracking Symptoms Over Time May Predict Colitis Surgery Years Ahead
In A Nutshell
- Colitis patients with high blood pressure who took a common blood pressure medicine alongside vedolizumab needed colon-removal surgery roughly half as often as similar patients who did not.
- The link showed up only with vedolizumab among the colitis drugs tested, and not with other types of blood pressure medicine.
- Tracking how quickly symptoms improved sorted patients into four groups that predicted hospitalization and surgery years later.
- Medical-records findings cannot prove cause and effect, so randomized trials must test whether the pills actually help.
Uncontrolled ulcerative colitis, an inflammatory bowel disease, can end in surgery to remove the colon, but a common blood pressure medicine may lower those odds. In a new Nature Medicine study, colitis patients with high blood pressure who took that medicine alongside the drug vedolizumab needed colon-removal surgery roughly half as often as similar patients who did not. The pattern showed up only with vedolizumab among the drugs tested.
Medical records, not a randomized trial where chance assigns treatments, produced that result, so the pills may not be the cause. The lead emerged from a hunt for why vedolizumab, a drug that blocks immune cells from entering the gut, leaves a sizable share of patients with little improvement.
Researchers first tracked how patients’ symptoms changed over time instead of judging them at a single checkup, and then studied gut immune cells from patients who did and did not improve.
Symptom Patterns Predict Long-Term Ulcerative Colitis Outcomes
Rectal bleeding and bathroom trips are hallmark colitis symptoms, and researchers used daily reports of both from 768 patients with moderately to severely active disease, about 58 percent of them men. All had joined a trial pitting vedolizumab against adalimumab, a drug that calms inflammatory signals body-wide. Mapping each person’s reports across a year showed a pattern no single checkup would.
Among the 382 vedolizumab patients, four groups emerged: fast, lasting improvers (45 percent), other good responders (11 percent), partial improvers whose progress stalled (26 percent), and nonresponders whose symptoms barely budged (18 percent). Adalimumab patients sorted into similar groups, though far fewer landed in the top group: about 7 percent, versus 45 percent on vedolizumab.
A second trial of 576 patients, about 59 percent men, reproduced the vedolizumab groups. In a seven-year follow-up of 450 patients from that trial, faster improvers had roughly 44 percent lower risk of hospitalization or colon removal. A standard six-week scope exam of the gut lining, which regulators use to judge early success, did not forecast those outcomes reliably.
One Immune Cell Tied to Vedolizumab Treatment Failure
Nonresponders showed signs of inflammation involving blood vessels in the gut. Single-cell mapping, which reads the activity of individual cells, spotted a likely culprit: macrophages, the immune system’s cleanup crew, carrying a marker called SPP1. These cells had fewer of the docking proteins vedolizumab is built to latch onto. One possible explanation is that they slip in through a side door the drug does not guard, then keep inflammation going by interacting with blood vessel cells. Gut biopsies placed these macrophages next to blood vessel cells in nonresponders.
Those tissue analyses involved small groups, sometimes as few as five patients. Blood tests offered backup: among roughly 280 vedolizumab patients, higher starting SPP1 levels went with a lower chance of remission after a year, with no clear link for adalimumab.
Blood Pressure Pills Linked to Fewer Ulcerative Colitis Surgeries
SPP1 cells appeared to operate alongside the renin-angiotensin system, a hormone chain best known for controlling blood pressure. Two drug families, ACE inhibitors and ARBs, quiet that system, so researchers checked whether patients already taking them fared better on vedolizumab. They mined two U.S. databases covering nearly 9,000 colitis patients with high blood pressure, one of health records and one of insurance claims.
In the health records, 325 vedolizumab patients taking an ACE inhibitor or ARB were matched with 325 patients who were not, alike in age, sex, and other health factors. The pill takers were less likely to switch drugs, land in the hospital, or lose their colons, with colon removal about half as common. Claims data covering 490 matched pairs showed an even bigger gap after one year, roughly 69 percent lower. Both estimates are imprecise, so the true benefit could be smaller or larger.
Beta blockers and calcium channel blockers, two other blood pressure drug types, showed no such effect with vedolizumab. Neither did ACE inhibitors or ARBs paired with adalimumab and similar drugs, or with ustekinumab, another colitis drug. That fits the idea that this particular drug-and-pill pairing matters, not blood pressure control alone, though nobody has tested that.
Observational Data Cannot Yet Prove the Pills Work
Authors call the blood pressure results hypothesis generating, meaning a promising lead rather than a tested treatment. Doctors chose who took the pills, so differences nobody measured could explain part of the gap. Randomized trials have to settle it.
If trials confirm the link, an already approved class of medicine could become an add-on that helps vedolizumab work for more patients. Early symptom trends could help doctors decide when to switch drugs or add a second one, an idea the authors say still needs testing. All patients in the databases had high blood pressure, so nothing here speaks to colitis patients without it. Nobody should start one of these medicines for colitis on this evidence alone. For now, the pills remain a lead worth a real trial, and the sturdier takeaway is that watching how fast a patient improves may flag trouble years before surgery.
Disclaimer: This article summarizes a published research study for general information only and is not medical advice. Anyone with ulcerative colitis or high blood pressure should talk with a doctor before changing any treatment.
Paper Notes
Limitations
Several parts of the study are preliminary, by the authors’ own account. The single-cell and spatial tissue analyses behind the SPP1 macrophage explanation used small patient groups, and the authors describe those findings and the blood pressure results as hypothesis generating. The medication analyses drew on electronic health records and insurance claims in which physicians and patients, not chance, chose treatments, leaving room for unmeasured factors to skew results. Clinical trial participants meet strict enrollment criteria and may differ from everyday patients with ulcerative colitis, and the real-world databases were limited to patients with high blood pressure. The authors could not identify a clear molecular signature of nonresponse for adalimumab, so the proposed explanation applies to vedolizumab only. Earlier studies of these blood pressure drugs in bowel disease were conflicting. The symptom-trajectory approach also needs prospective validation before clinical use, and the authors say further evaluation in Crohn’s disease is needed. Confirming that these drugs boost vedolizumab will require dedicated randomized clinical trials.
Funding and Disclosures
Takeda, the study sponsor, provided access to data from the VARSITY and GEMINI 1 trials and supported the study, including medical writing assistance from Envision Medical Communications. Parambir S. Dulai received partial funding from the National Institute of Diabetes and Digestive and Kidney Diseases. Stefan Schreiber and Philip Rosenstiel received funding from the Innovative Medicines Initiative 2 Joint Undertaking, which is supported by the European Union’s Horizon 2020 program and the European Federation of Pharmaceutical Industries and Associations. Additional funding came from the DFG Excellence Cluster Precision Medicine in Inflammation and the BMBF iTREAT program, and Kiel University covered open access fees. Ten authors are Takeda employees who hold company stock or stock options. Schreiber, Dulai, and Gursimran Singh Kochhar reported consulting fees, research support, or advisory and speaking roles with multiple pharmaceutical companies, and the remaining authors declared no competing interests.
Publication Details
The study, titled “An ulcerative colitis taxonomy defined by individual patient-reported response trajectories,” was published online November 9, 2026, in Nature Medicine as an open access article (DOI: https://doi.org/10.1038/s41591-026-04741-8). The lead and corresponding author is Stefan Schreiber of the Department Medicine I and Institute of Clinical Molecular Biology at Kiel University and University Hospital Schleswig-Holstein in Kiel, Germany. Vijay Yajnik, Paresh Thakker, and Parambir S. Dulai contributed equally. Co-authors include 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, and Philip Rosenstiel, with affiliations including Takeda, Northwestern University Feinberg School of Medicine, Northwell Health, Allegheny Health Network, and Kiel University.
