AT DDW2016
SAN DIEGO (FRONTLINE MEDICAL NEWS) – A novel test distinguished patients with inflammatory bowel disease (IBD) who responded to vedolizumab from nonresponders, investigators reported at the annual Digestive Disease Week.
“If we can optimize and simplify this prescreening flow cytometry panel, it would allow nonresponding patients to avoid unnecessary side effects of treatment,” said lead author Sophia Diaz, a researcher at the University of Miami Health System.
Exactly how patients develop IBD remains unclear, but its pathogenesis involves chronic T-cell mediated inflammation and subsequent tissue damage, Ms. Diaz noted. Vedolizumab (Entyvio) is a monoclonal antibody – specifically, an alpha4-beta7 integrin blocker – that stops T cells from homing to lymphoid tissue in the gut, and is approved for treating IBD in the United States and Europe. The biologic offers specificity and efficacy across a range of patient types, and a good safety profile, but less than half of patients responded to it in the pivotal GEMINI trials, Ms. Diaz noted. “We wanted to find a biomarker that tracked with vedolizumab to enable physicians to prescribe it on a more informed basis, compared with other drugs,” she said.
The researchers therefore used flow cytometry to seek T-cell signatures that reliably discriminated between vedolizumab responders and nonresponders. They isolated peripheral leukocytes and lamina propria T cells from 14 active IBD patients before and about 16 weeks after starting vedolizumab and going to a maintenance dose. Next, the investigators used flow cytometry to probe the T cells for a number of cell surface antigens. They also tested T cells for chemokine receptors that are involved in gut homing and activation. They sorted the results based on response to vedolizumab maintenance therapy, defined as a 30% decrease in partial Mayo scores (for ulcerative colitis) or Harvey-Bradshaw index scores (for Crohn’s disease).
The study revealed several direct and inverse correlates of vedolizumab response, Ms. Diaz said. For example, compared with nonresponders, responders had a higher proportion of alpha4-beta7+MDR1+RO+ effector T cells, and lower percentages of effector T cells that were MDR1+RO-CD8a+ or CCR9+RO-CD8a+. Notably, the percentage of MDR1+RO-CD8a+ effector T cells was significantly higher among nonresponders than responders, both before (P = .048) and after (P = .005) treatment. “I thought that was interesting, because the difference is already significant at this small sample size,” Ms. Diaz said. “That’s a very powerful thing, because it indicates there is something within these patients that is stable that is telling us about their response.”
Taken together, the results suggest that the percentage of beta7+MDR1+ T cells directly predicts vedolizumab response, while MDR1+CD8a+ T cells and CCR9+CD8a+ T cells inversely correlate with response, Ms. Diaz said. The researchers plan to validate the panel in more patients, including multicenter cohorts of patients, both with ulcerative colitis and Crohn’s disease, she added.
The study was partially funded by Takeda. Ms. Diaz had no disclosures.
