Blood pressure meds may improve therapy for most common IBD

• Most ulcerative colitis patients don’t get better with available drugs
• Study linked poor response to one of those drugs to a mechanism driving vascular inflammation
• That mechanism, the study found, is targeted by inexpensive blood pressure meds, ACE inhibitors and ARBs
• Further analysis found the blood pressure meds were tied to fewer complications in ulcerative colitis patients

CHICAGO — A class of blood pressure medications may improve a widely used treatment for ulcerative colitis, the most common type of inflammatory bowel disease, suggests a new study, led by Northwestern Medicine and Kiel University in Germany, of thousands of patients with the disease.

The study found that those taking the blood pressure meds for hypertension alongside the ulcerative colitis drug vedolizumab (brand name Entyvio) were less likely to experience serious complications resulting in hospitalization and surgery to remove the colon.

The findings were published on Nov. 9 in Nature Medicine

Ulcerative colitis, a chronic condition that causes inflammation and sores in the colon, affects over 1 million people in the U.S. and often begins in adolescence or young adulthood. Despite the emergence of advanced and expensive therapies, such as vedolizumab, most patients with ulcerative colitis do not achieve lasting remission with available treatments.

“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.

“And the psychosocial and physical impact of the disease is substantial, to the point where it may be on par with cancer in terms of the impact,” Dulai added. “Finding a new pathway where we have the potential to repurpose an inexpensive, generic, readily available medication could offer a tremendous reprieve for a lot of these young adults who are suffering on a daily basis.”

How the study was conducted

Dulai, Dr. Stefan Schreiber of Kiel University and their colleagues analyzed data from more than 1,300 patients enrolled in two clinical trials of vedolizumab for ulcerative colitis. By tracking how symptoms (stool frequency and rectal bleeding) changed over time in the trial participants, the scientists were able to identify different patterns of response to the drug.

Next, to understand the biology behind treatment resistance, the research team analyzed tissue biopsies and blood samples to measure gene and protein activity — and made two key discoveries. First, they found that poor response to vedolizumab was linked to a form of inflammation involving blood vessels in the colon. Second, they discovered that this inflammation was linked to a biological pathway that is already targeted by common blood pressure drugs known as ACE inhibitors and angiotensin receptor blockers, or ARBs.

Finally, to explore whether the blood pressure drugs could enhance the effectiveness of vedolizumab, the scientists analyzed healthcare data from nearly 9,000 ulcerative colitis patients who also had high blood pressure (hypertension). Among patients on vedolizumab, those taking ACE inhibitors or ARBs were less likely to be hospitalized or require surgery. Other blood pressure drug classes examined did not show the same association. The benefits were also specific to vedolizumab as patients taking ACE inhibitors or ARBs alongside other ulcerative colitis medications saw no difference.

Next steps

The study authors say clinical trials are now needed to confirm their findings and to understand how they might be applied to patients who have normal blood pressure.

“We don’t know yet if you can use anti-hypertensive medications in normal-tensive patients. People who have normal blood pressure, you don’t want to give them a medicine to drop their blood pressure,” said Dulai who also is a Northwestern Medicine physician and a member of the Center for Human Immunobiology at Feinberg. “There may be other ways to target that same pathway without the other effects that are present from blood pressure medications.”

“In other words, our study offers a rationale to start thinking about developing drugs specifically for this,” Dulai said.

Dulai said his team is also working on developing a diagnostic test based on the biological markers they discovered in those who didn’t respond to vedolizumab. Such a test could allow clinicians to identify, ahead of time, patients who are either likely to respond well to treatment or who would be better suited for alternatives.

That level of foresight could be crucial for “many patients who are starting these medications and are suffering from ongoing symptoms for months before they get any reprieve from finding a medication that works for them,” Dulai said.

Other Northwestern study co-authors are Cenfu Wei, Katherine Simpson, Zitong Lin, Isabella Peshek, Frida Chavez, Libeth Rosas and Alan Robinson.

The study is called “An ulcerative colitis taxonomy defined by individual patient-reported response trajectories.” It was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants R01DK135620 and U01DK134321), the European Union’s Innovative Medicines Initiative 2 (3TR and ImmUniverse projects), the German Research Foundation (DFG) and the German Federal Ministry of Education and Research (BMBF). Takeda, which manufactures vedolizumab, provided access to clinical trial data and supported the study.