Longitudinal Fecal Calprotectin Profiles Characterize Disease Course Heterogeneity in Crohn's Disease

BACKGROUND AND AIMS: The progressive nature of Crohn's disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There is therefore an urgent need to better characterize the heterogeneity of disease trajectories in Crohn's disease by utilizing objective markers of inflammation. We aimed to better understand this heterogeneity by clustering Crohn's disease patients with similar longitudinal fecal calprotectin profiles.METHODS: We performed a retrospective cohort study at the Edinburgh IBD Unit, a tertiary referral center, and used latent class mixed models to cluster Crohn's disease subjects using fecal calprotectin observed within five years of diagnosis. Information criteria, alluvial plots, and cluster trajectories were used to decide the optimal number of clusters. Chi-squared, Fisher's exact test, and ANOVA were used to test for associations with variables commonly assessed at diagnosis.RESULTS: Our study cohort comprised of 365 patients with newly diagnosed Crohn's disease and 2856 fecal calprotectin measurements taken within five years of diagnosis (median 7 per subject). Four distinct clusters were identified by characteristic calprotectin profiles: a cluster with consistently high fecal calprotectin and three clusters characterized by different downward longitudinal trends. Cluster membership was significantly associated with smoking (p = 0.015), upper gastrointestinal involvement (p < 0.001), and early biologic therapy (p < 0.001).CONCLUSIONS: Our analysis demonstrates a novel approach to characterizing the heterogeneity of Crohn's disease by using fecal calprotectin. The group profiles do not simply reflect different treatment regimens and do not mirror classical disease progression endpoints.