Large-Scale Clustering of Longitudinal Fecal Calprotectin and C-Reactive Protein Profiles in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis are highly heterogeneous, dynamic, and unpredictable, with a marked disconnect between symptoms and intestinal inflammation. We aimed to describe latent disease heterogeneity in inflammatory bowel disease (IBD) by identifying longitudinal fecal calprotectin (FC) and C-reactive protein (CRP) patterns.

METHODS

In this longitudinal study, patient-level measurements of FC and CRP in 2 European cohorts were modeled. 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.

RESULTS

We included 1036 patients in the FC discovery analysis (Lothian) with a total of 10,545 FC observations (median, 9 per subject; interquartile range, 6-13), and 7880 patients in the replication (Denmark). The CRP discovery analysis consisted of 1838 patients with 49,364 measurements (median, 20 per subject; interquartile range, 10-36), with 10,041 patients in the replication cohort. Eight distinct clusters of inflammatory behavior 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.

CONCLUSIONS

Distinct patterns of inflammatory behavior over time are evident in patients with IBD. These data pave the way for a deeper understanding of disease heterogeneity in IBD.