Large-scale clustering of longitudinal faecal calprotectin and C-reactive protein profiles in inflammatory bowel disease

BackgroundCrohns disease (CD) and ulcerative colitis (UC) are highly heterogeneous, dynamic and unpredictable, with a marked disconnect between symptoms and intestinal inflammation. ObjectiveWe aimed to describe latent disease heterogeneity in IBD by identifying longitudinal faecal calprotectin (FC) and CRP patterns. DesignIn this longitudinal study, patient-level measurements of FC and CRP in two European cohorts were modelled. Latent class mixed models were used to cluster individuals with similar longitudinal profiles. Associations between cluster assignment and baseline characteristics were quantified using multinomial logistic regression. Differences in advanced therapy use across clusters were explored. Finally, we considered the overlap between FC and CRP clusters. ResultsWe included 1036 patients in the FC discovery analysis (Lothian) with a total of 10545 FC observations (median 9 per subject, IQR 6-13), and 7880 patients in the replication (Denmark). The CRP discovery analysis consisted of 1838 patients with 49364 measurements (median 20 per subject; IQR 10-36), with 10041 patients in the replication cohort. Eight distinct clusters of inflammatory behaviour over time were identified in the FC and CRP analysis. Similar patterns were observed in the replication cohort. The clusters included rapid remitters, delayed remitters, remitting-relapsing disease, and non-remitters The highest use of early advanced therapy was in the group with the lowest overall inflammation. There was broadly poor agreement between FC and CRP cluster assignment. ConclusionDistinct patterns of inflammatory behaviour over time are evident in patients with IBD. These data pave the way for a deeper understanding of disease heterogeneity in IBD.