Defining biological remission in Crohn's disease: interest, challenges and future directions.

In Crohn's disease, the treat-to-target strategy has been highly encouraged and became a standard of care. In this context, defining the target (remission) constitutes a major stake which fuels the literature. Currently, clinical remission (symptoms control) is no longer the only objective of treatments since it does not allow to well control inflammation-induced tissue damage. The introduction of endoscopic remission as a therapeutic target was clearly a progress but this examination remains invasive, costly, not well accepted by patients and does not allow a tight control of disease activity. More fundamentally, morphological techniques (eg, endoscopy, histology, ultrasonography) are limited since they do not evaluate the biological activity of the disease but only its consequences. Besides, emerging evidence suggest that biological signs of disease activity could better guide treatment decisions than clinical parameters. In this context, we stress the necessity to define a novel treatment target: biological remission. Based on our previous work, we propose a conceptual definition of biological remission which goes beyond the classical normalisation of inflammatory markers (C-reactive protein and faecal calprotectin): absence of biological signs associated with the risk of short-term relapse and mid/long-term relapse. The risk of short-term relapse seems essentially characterised by a persistent inflammatory state while the risk of mid/long-term relapse implicates a more heterogeneous biology. We discuss the interest of our proposal (guiding treatment maintenance, escalation or de-escalation) but also the fact that its clinical implementation would require overcoming major challenges. Finally, future directions are proposed to better define biological remission.