Crohn's Disease Activity Index in the era of obesity: time to abandon it?

Obesity and metabolic syndrome are now common among patients with Crohn's disease, with prevalence rates approaching those of the general population. Yet the Crohn's Disease Activity Index (CDAI), which still underpins the design and interpretation of many phase 3 trials, was developed in an era dominated by undernutrition and only weakly reflects intestinal inflammation. In this Viewpoint, we revisit the construction of the CDAI and argue that its weight component is particularly ill-adapted to contemporary Crohn's disease populations. Because the index rewards weight gain and penalizes weight loss relative to an "ideal" or pre-illness body weight, increasing body mass index can drive CDAI scores down, even when symptoms and inflammatory burden are unchanged. Using simple numerical examples, we show how obese patients with the same clinical activity as normal-weight individuals may be reclassified from moderate-severe disease into apparent clinical remission due solely to the weight term. We discuss the implications of this bias for trial eligibility, endpoint assessment, and therapeutic strategies that modify body weight, and outline pragmatic options to modernize disease activity assessment in the era of obesity.