Key findings
One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.
The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.
“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.
A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.
“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
Promising start
“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.
“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.
Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.
The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.
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A version of this article first appeared on Medscape.com.
