Novel blood protein panel may predict TNF antagonist treatment failure in Crohn’s
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SAN DIEGO — A novel blood protein panel correlated with tumor necrosis factor antagonist treatment failure had modest predictive capacity among patients newly diagnosed with Crohn’s disease, according to research.
“Tumor necrosis factor antagonists are a frequent first-line biologic treatment for Crohn’s disease,” Ryan C. Ungaro, MD, associate professor of gastroenterology at the Icahn School of Medicine at Mount Sinai, said in a presentation at Digestive Disease Week 2022. “However, many patients do not respond to TNF antagonists, with up to 30% not responding to initial treatment and another 23-46% of patients losing response over time.”
Seeking to validate blood protein biomarkers of TNF antagonist response in recently diagnosed CD patients, Ungaro and colleagues assessed bio-naive patients from two groups: a discovery cohort of 384 patients from the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s disease (RISK) study (mean age, 12 years; 65.6% boys) and a validation cohort, which included 163 patients from the Ocean State Crohns and Colitis Area Registry (OSCCAR; mean age, 29 years; 43% men).
Investigators used a proximity extension assay (Olink Proteomics Inflammation Panel) to analyze candidate protein biomarkers in baseline plasma samples and defined TNF antagonist treatment failure as stricturing/penetrating complications, CD-related surgery, CD-related hospitalization or stopping TNF antagonist. They selected 10 baseline blood proteins as predictors of TNF antagonist treatment failure, as well as time from diagnosis to TNF antagonist start.
By 3 years from baseline, 223 patients in the RISK cohort had a TNF antagonist failure event, compared with 92 patients in the OSCCAR cohort. Patients in the RISK cohort with a score above cut-off point at 3 years were more likely to have TNF antagonist treatment failure compared with those below (86.8% vs. 43.5%; OR = 8.5; 95% CI, 4.9-15.4). Results at 3 years were similar in the OSCCAR cohort, with patients above the cut-off point having higher TNF antagonist failure (79.2% vs. 42.3%; OR = 5.1; 95% CI, 2.6-10.5).
In both cohorts, the selected score cut-off point had similar sensitivity and specificity for TNF antagonist failure at 3 years (RISK sensitivity 50.2%, specificity 89.4%; OSCCAR sensitivity 56%, specificity 80%).
“Precision medicine approaches are needed to provide rational selection and positioning of medications in IBD and our research demonstrates the potential and promise of blood-based panels to improve treatment selection,” Ungaro, told Healio.
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Ungaro RC, et al. Abstract 102. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego (hybrid meeting).
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