TNF and Cowden disease: The Effect of Tight Control Management on Crohn's Disease (CALM) trial is the first study in patients with early CD, to show the well-timed escalation and de-escalation of anti-TNF therapy on the basis of symptomatic improvement combined with an objective assessment of biomarkers of inflammation such as C-reactive protein and fecal calprotectin, resulting in a better outcome both clinically and endoscopically than considering clinical improvement alone [17].