Misinterpretation and misapplication of biomarkers in inflammatory bowel disease: how do we avoid this?

INTRODUCTION: The management of inflammatory bowel disease (IBD) has evolved substantially over the past decade, with the emergence of new advanced therapies presenting unprecedented challenges in clinical decision-making. While these therapies provide patients with more opportunities to get better, biomarkers to guide their use remain elusive. AREAS COVERED: This article highlights the challenges associated with biomarker discovery, interpretation, and application in IBD - based on literature review, first-hand experience of biomarker discovery, and personal opinion. We highlight problems including the misinterpretation of predictive capabilities, lack of independent validation, and reverse causation in retrospective studies, and explain why associations with clinical parameters or seropositivity to microbial antigens often fail to meet the rigorous performance metrics required for clinical utility. The relative need for different biomarkers is also discussed - particularly in light of recent evidence from the PROFILE trial, which emphasizes the considerably greater risk posed by uncontrolled disease than by the potential side-effects of medications. EXPERT OPINION: Despite multiple challenges, the potential of biomarkers for precision medicine in IBD remains promising, particularly in combination with other clinical and biochemical parameters. Further research into combinatorial biomarker approaches is needed, but must be combined with learning how to communicate results that are inherently uncertain.