Researchers identify biomarkers for infliximab response in pediatric patients with CD
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Researchers identified novel candidate biomarkers for infliximab response after unsupervised plasma proteomic analysis in pediatric patients with Crohn’s disease, according to a presentation at Digestive Disease Week.
“For pediatric inflammatory bowel disease, precision medicine is selecting the right drug for the right patient and providing the right dose at the right time. ... As you know, the anti-TNFs are the only FDA approved biologic for pediatric IBD; the clinical response rate is high, yet the rates of endoscopic and deep remission are low,” Phillip Minar, MD, MS, Cincinnati Children’s Hospital Medical Center, said. “To achieve optimal durability, drug selection is vital, right drug to the right patient, as is the development of pharmacodynamic biomarkers in order to non-invasively monitor drug response.”
In a multicenter, observational study, researchers enrolled 51 anti-TNF naive pediatric patients with CD (mean age 13 years; 67% boys; 92% white) beginning infliximab therapy. Patients provided longitudinal biospecimens over 2-years; researchers detected plasma protein abundance using aptamer-based SOMAscan (1,305 protein analytes) at baseline (BL), prior to first maintenance dose (week 14, n = 39) and at week 52 (n = 15); they further applied weighted gene co-expression analysis (WGCNA) framework at each time point.
According to study results, researchers identified six BL modules by WGCNA; BL module three (BL-M3) and BL module six (BL-M6) correlated with subsequent clinical and biochemical traits. Specifically, negative correlations between BL-M3 (158 proteins) and week 14 fecal calprotectin, C-reactive protein and wPCDAI as well as positive correlations between BL-M3 and week 14 albumin suggested a response signature. Further, positive correlations between the BL-M6 and week 14 fecal calprotectin, C-reactive protein and neutrophil CD64 as well as a negative correlation with albumin suggested a non-response signature. Researchers noted enrichment analysis was in line with pathways previously shown to be associated with anti-TNF response.
Researchers reduced the number of proteins using generated pairwise heatmaps and reported BL-M3, week 14 M6 and week 52 M1 shared 60 common proteins with four hub proteins; baseline hub protein EPHB2 plasma abundance was higher in infliximab remitters compared with infliximab non-remitters.
“We have shown with an unsupervised plasma proteomic analysis we were able to identify novel candidate biomarkers of infliximab outcomes, including response and non-response. We also filtered a set of 34 proteins with a high area under the curve to a set of 10 candidate proteins for biochemical remission,” Minar concluded. “We want to validate our findings in a larger cohort that is using endoscopic healing as the primary outcome. We also want to validate the protein expression as detected by the SOMAscan with other assays. Finally, we want to evaluate the relationship of the peripheral blood proteins abundance to the intestinal tissue expression to see how they correlate with that.”
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Minar P, et al. Abstract 728. Presented at: Digestive Disease Week; May 21-23 (virtual meeting).
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