Latent Crohn's Disease Subgroups are Identified by Longitudinal Faecal Calprotectin Profiles

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackground and AimsC_ST_ABSThe progressive nature of Crohns disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There is therefore an urgent need to better characterise the heterogeneity of disease trajectories in Crohns disease by utilising objective markers of inflammation. We aimed to better understand this heterogeneity by clustering Crohns disease patients with similar longitudinal faecal calprotectin profiles. MethodsLatent class mixed models were used to model faecal calprotectin trajectories within five years of diagnosis and to cluster subjects. Information criteria, alluvial plots, and cluster trajectories were used to decide the optimal number of clusters. Chi-squared, Fishers exact test, and ANOVA were used to test for associations with variables commonly assessed at diagnosis. ResultsOur study cohort comprised of 365 patients with newly diagnosed Crohns disease and 2856 faecal 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 faecal calprotectin and three clusters characterised 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). ConclusionsOur analysis demonstrates a novel approach to characterising the heterogeneity of Crohns disease by using faecal calprotectin. The group profiles do not simply reflect different treatment regimes and do not mirror classical disease progression endpoints. We believe these profiles represent an entirely new way of classifying disease behaviour in Crohns disease.