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

Abstract

Background High faecal calprotectin is associated with poor outcomes in Crohn's disease. Monitoring of faecal calprotectin trajectories could characterise disease progression before severe complications occur. Aims We undertook an unbiased assessment of a retrospective incident Crohn's disease cohort to assess for inter-individual variability in faecal calprotectin levels over time. We aimed to explore whether latent classes of such profiles are associated with a composite endpoint consisting of surgery, hospitalisation, or Montreal behaviour progression and other clinical information. Methods Latent class mixed models were used to model faecal calprotectin trajectories within five years of diagnosis. Akaike information criterion, Bayesian information criterion, alluvial plots, and class-specific trajectories were used to decide the optimal number of classes. Log-rank tests of Kaplan-Meier estimators were used to test for associations between class membership and outcomes. Results Our study cohort comprised 365 subjects and 2856 faecal calprotectin measurements (median 7 per subject). Four latent classes were found and broadly described as a class with consistently high faecal calprotectin and three classes characterised by downward trends for calprotectin. Class membership was significantly associated with the composite endpoint, and separately, hospitalisation and Montreal disease progression, but not surgery. Early biologic therapy was strongly associated with class membership. Conclusions Our analysis provides a novel stratification approach for Crohn's disease patients based on faecal calprotectin trajectories. Characterising this heterogeneity helps to better understand different patterns of disease progression and to identify those with a higher risk of worse outcomes. Ultimately, this information will assist the design of more targeted interventions.

Competing Interest Statement

NC-C: none declared; KM-G: none declared; NP has received consultancy fees from Takeda, speaker fees and/or travel support from Abbvie, Takeda, Norgine; LAAPD has received consultancy fees from Sandoz, speaking fees from Janssen; BG has received consultancy fees from Abbvie ; REM: has received a speaker fee from Illumina, is a scientific advisor to the Epigenetic Clock Development Foundation, and is a scientific consultant to Optima Partners; CWL has received research support from Abbvie and Gilead, consultancy fees from Abbvie, Pfizer, Janssen, Gilead, Celltrion, Pharmacosmos, Takeda, Vifor, Iterative Scopes and Trellus Health; speaker fees and/or travel support from Janssen, Abbvie, Pfizer, Dr Falk, Ferring, Hospira, and Takeda; CAV: none declared.

Funding Statement

This work has been supported by the Medical Research Council & University of Edinburgh Precision Medicine PhD studentship (MR/N013166/1, to NC-C) and the UKRI Future Leaders Fellowship (MR/S034919/1, to CWL. KM-G was supported by an MRC University Unit grant to the MRC Human Genetics Unit.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

As this study was considered a retrospective audit due to all data having been collected as part of routine clinical care, no ethical approval or consent was required as per UK Health Research Authority guidance. Caldicott guardian approval (NHS Lothian) was granted (Project ID: 18002).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Data Availability

The data used in this study is not publicly available as it originates from patients who have not given consent for the data to be publicly shared. For access to the data, please contact CWL.

https://vallejosgroup.github.io/lcmm-site/

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