Highlights from

ECCO 2019

European Crohn's and Colitis Organisation's 14th congress

Copenhagen 6-9 March 2019

Gene expression signature predicts non-response

The molecular profile score (MPS) consistently predicted non-responders to therapy in 4 independent trials of TNF-antagonists in inflammatory bowel disease (IBD) and an anti-IL-12/23 trial in Crohn’s disease [1]. This ability was regardless of ethnicity or whether the therapy targeted TNF or IL-12/23 pathways. Clinical parameters and inflammatory markers by themselves lack the granularity to identify this subset of non-responder patients.

The MPS consisted of a colonic 13-gene expression panel. It accurately predicted non-responders, as defined by lack of mucosal improvement, to TNF-antagonist therapy in UC in all 4 independent clinical trials. There was a high negative predictive value of 0.78 in the ACT1 trial, 0.79 in PURSUIT-SC, 0.89 in PROgECT, and 0.73 in PURSUIT-J. In addition, the MPS could predict non-responders, as defined by lack of endoscopic response, to anti-IL-12/23 therapy in the UNITI trial, with a negative predictive value of 0.85. Non-responders, as predicted by MPS, did not differ from predicted responders in baseline disease severity, nor in baseline inflammatory markers including C-reactive protein, faecal calprotectin, or faecal lactoferrin levels. Transcriptomics and microbiome analysis revealed potential ways to treat these predicted non-responders, as they had 268 differentially expressed genes enriched in inflammatory pathways and demonstrated significant microbial dysbiosis. The MPS is now the first prospectively validated predictive biomarker that can accurately identify a discrete subset of non-responder patients to 2 different anti-inflammatory therapies. It may be valuable in identifying subsets of patients in need of treatment with alternative therapies or for patient stratification in clinical trials.

Keywords: Crohn’s disease, interleukin

  1. Sato T, et al. ECCO 2019, OP36.

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