By Marilynn Larkin
NEW YORK (Reuters Health) - 13/5/2019
A 17-gene classifier can predict the course of inflammatory bowel disease (IBD) at diagnosis, helping to set the stage for personalized therapy, researchers in the UK say.
Dr. Kenneth Smith of the University of Cambridge told Reuters Health the test "is equally accurate and reliable in all IBD patients, provided they have evidence of active disease and are on minimal therapy. There are no other patient-related factors that we have found influence the effectiveness of the test."
Dr. Smith and colleagues had previously shown that a transcriptional signature in CD8 T cells could separate patients with IBD into two distinct subtypes, IBD1 (severe disease requiring repeated treatment) and IBD 2 (mild disease). The method used to distinguish the two was not practical for the clinic, so they embarked on the current study with the aim of developing a clinically useful, scalable test.
Working with a cohort of 69 Crohn's disease (CD) patients, they used a whole blood 17-gene qPCR assay and machine learning to identify genetic signatures that recreated the two subgroups from their earlier study. They then assessed the accuracy of the test in two validation cohorts consisting of 66 CD patients and 57 patients with ulcerative colitis (UC) recruited from four UK clinics.
As reported online April 27 in Gut, the qPCR test stratified patients into two distinct subgroups in both validation cohorts. Irrespective of the underlying diagnosis, patients deemed IBDhi (analogous to the original IBD1 subgroup) had significantly more aggressive disease than IBDlo (IBD2) patients. IBDhi patients in both cohorts needed earlier treatment escalation (hazard ratio = 2.65 for CD and 3.12 for UC) and more escalations over time.
The test's sensitivity for multiple escalations within 18 months was 72.7% for CD and 100% for UC, with negative predictive values of 90.9% and 100%, respectively.
"The test will be very easy to administer and interpret," Dr. Smith said. "(It) needs 2.5 ml of whole blood, which is processed in a reverse transcriptase polymerase chain reaction (RT-PCR) in a regional certified lab. This gives a result within 48 hours."
The test is already on the market in the UK and Ireland, and is expected to be available in the U.S. later in 2019, he added.
Dr. Jordan Axelrad, a gastroenterologist at NYU Langone's IBD Center in New York City, commented, "Applying personalized medicine to IBD is highly dependent on identifying meaningful disease subsets. A whole blood gene expression biomarker that can predict IBD prognosis provides a critical step towards precision medicine and personalized therapy in IBD."
"While the results are promising and validated, it's unlikely we will see this test in our clinical laboratories until data is available demonstrating the direct impact of this test on patient outcomes," he told Reuters Health by email. "As the authors state, an interventional study is underway to confirm that stratifying therapy using this biomarker would actually improve clinical outcomes."
"Clinicians should know that noninvasive biomarker technologies to assess prognosis and monitor disease activity in IBD are under study," he added. "Should the clinical utilization of these tests to guide treatment demonstrate improved IBD outcomes, they have the ability to transform the field towards a personalized approach to therapy."
Dr. Smith and four coauthors are coinventors on a patent covering the method of assessing prognosis in IBD. In addition, Dr. Smith and three coauthors are cofounders of and consultants to PredictImmune, a spinout company supported by the university's technology transfer arm, which funded the analytical validation experiments. Another coauthor is also a consultant to the company.