Improving Initial Treatment Selection for Children with Crohn’s Disease
When a child is newly diagnosed with Crohn’s disease, physicians have only a few proven medications to offer and no practical way to tell which will achieve the most benefit. Researchers at Cincinnati Children’s hope to change that scenario by developing a novel, blood-based companion diagnostic to identify patients most likely to achieve mucosal healing with anti-tumor necrosis (anti-TNF) therapy.
The anti-TNF medications infliximab and adalimumab are the most commonly used first-line biologic agents for children with moderate to severe Crohn’s disease. Approximately 80% of pediatric Crohn’s disease patients respond well to anti-TNF therapy initially. But at the one-year mark, only about half of patients are in clinical remission, and only one-third to half are experiencing complete mucosal healing. Those who are not achieving this level of healing remain at high risk for strictures and fistula, which may require surgery.
Moving Toward a Precision Medicine Solution
Previous studies conducted elsewhere attempted to predict treatment response using clinical factors, serology or intestinal gene expression. The ENvISION study, a multicenter, prospective study led by Cincinnati Children’s, would be the first to develop a predictive blood biomarker.
“Now that the Food and Drug Administration has approved novel Crohn’s disease therapies, there is a critical need for us to develop a companion diagnostic for all biologics, including anti-TNFs, in order to improve initial treatment selection,” says Phillip Minar, MD, a pediatric gastroenterologist at Cincinnati Children’s and the lead principal investigator of the ENvISION study.
“Right now, we lack the tools to prioritize one therapy over another for children with Crohn’s,” he adds. “But with a reliable biomarker, you could identify patients who are unlikely to achieve mucosal healing with first-line medications. The priority would be to avoid anti-TNF therapy in patients with a ‘high-risk’ protein profile and prescribe a different therapy that targets their individual inflammatory signature. It amounts to precision medicine for these patients, and that would be a first.”
Targeting a Drug-Specific Inflammatory Profile
The ENvISION study is funded by a $1.5 million grant from The Leona M. and Harry B. Helmsley Charitable Trust. It will enroll about 70 patients (ages 6-22) at Cincinnati Children’s, Connecticut Children’s Medical Center, Medical College of Wisconsin and Nationwide Children’s Hospital. Study participants must be newly diagnosed and starting infliximab or adalimumab. They will be monitored for early treatment response with fecal calprotectin testing. At the one-year mark, they will have a colonoscopy to assess mucosal healing and a non-contrast abdominal magnetic resonance imaging study to assess transmural healing.
The research team will perform plasma proteomics multiple times during the first year, using a novel proteomic platform that measures 1,300 circulating proteins. Minar and others at Cincinnati Children’s developed the proteomic signature as part of a previous study that included patients on infliximab only. The goal is to utilize the protein signature to help identify a drug-specific inflammatory profile that can be used to personalize treatment selection and provide a minimally invasive assessment of endoscopic severity.
For more information, contact phillip.minar@cchmc.org.
(Published April 2020)
