Gastroenterology

Gastroenterology

Volume 148, Issue 5, May 2015, Pages 938-947.e1
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Measurement of Fecal Calprotectin Improves Monitoring and Detection of Recurrence of Crohn's Disease After Surgery

https://doi.org/10.1053/j.gastro.2015.01.026Get rights and content

Background & Aims

Crohn’s disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa.

Methods

We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn’s disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn’s disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients.

Results

Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 μg/g before surgery to 166 μg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 μg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 μg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 μg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 μg/g at 6 months to 180 μg/g at 12 months and 109 μg/g at 18 months.

Conclusions

In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.

Section snippets

The Clinical Postoperative Recurrence Study

The POCER study was a prospective, randomized, controlled trial that aimed to assess the value of postoperative endoscopic assessment and treatment step-up for early mucosal recurrence.10 Patients were stratified according to risk of recurrence. Smokers, patients with perforating disease, or patients with 1 or more previous resections were classified as high risk; all others were classified as low risk. All patients underwent resection of all macroscopic disease.

Patients may have had previous

Results

Supplementary Figure 1 shows the study patient disposition. Demographic details of patients who provided stool samples are shown in Table 1.

Baseline patient demographics were similar for the 3 analysis groups. The number of patients and samples that contributed to each analysis and the rates of endoscopic recurrence are detailed in Table 2.

Discussion

The majority of patients with Crohn’s disease require a resection at some time, and most of these patients will require further surgery. The POCER study recently showed that postoperative endoscopic monitoring, together with treatment intensification for early recurrence, is superior to standard drug therapy alone in preventing disease recurrence, at least in the short term.10 However, such endoscopic monitoring is invasive, expensive, cannot be repeated frequently, and, in some patients, will

Acknowledgments

The authors thank J.I. Keenan, L. Burgess, and A. Ashcroft at the University of Otago (Christchurch, New Zealand) Gastroenterology Laboratory, who were responsible for the processing and testing of specimens and provided supervision and laboratory support to Emily Wright. The author are grateful to their colleagues and centers for their participation.

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      The sample size was limited, as this was a proof-of-concept study. We adopted a very stringent FC cutoff to define disease activity, which was lower than that generally used in clinical practice.41,42 The rationale for this decision was to increase the FC sensitivity to identify the highest number of patients with POR.

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    This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of this exam, successful learners will be able to integrate fecal calprotectin into a management algorithm for patients with Crohn's disease following surgical resection and interpret how these results reflect endoscopic disease recurrence.

    Conflicts of interest These authors disclose the following: Peter De Cruz has received travel grant support from Abbott and Schering-Plough; Michael Kamm has acted as an advisor to Abbott and Janssen, has received research support from Abbott, and has acted as a speaker at symposiums sponsored by Abbott and Janssen; Amy Hamilton has received an educational grant from Abbott; Danny Liew has served on advisory boards and received research grants from Abbott; Ian Lawrance has served on advisory boards for Abbott and Janssen, has acted as a speaker for Abbott and Janssen, and has received research and travel grants from Abbott and Janssen; Jane Andrews has been an advisory board member, spoken for, received research funds from, and received travel grants from Abbott and Janssen; Peter Bampton has served on advisory boards for and received travel sponsorship from Janssen and Abbott, and has received research funding from Abbott; Peter Gibson has received consulting fees from Abbott, Janssen, and Schering-Plough, research support from Abbott, and payments for lectures from Abbott and Janssen; Finlay Macrae has served on an advisory board for Janssen, has received travel grants from Abbott, and has received clinical research support from Janssen, Abbott, and MSD; Warwick Selby has served on an advisory board for Abbott; Sally Bell has received travel assistance from Abbott; Steven Brown has received travel support and speaker fees from both Abbott and Janssen; William Connell has served on an advisory board for Janssen and as a speaker for Abbott and Janssen; Andrew Day has served as an advisor to Janssen; and Richard Gearry has served on advisory boards for Abbott and Janssen, as a speaker for Abbott and Janssen, and has received research, educational, and travel grants from Abbott and Janssen. The remaining authors disclose no conflicts.

    Funding Research support was provided by the St Vincent’s Research Endowment Fund; Smart-Prep testing kits were provided by Bϋlhmann; and supported by the National Health and Medical Research Council (E.W., P.D.C., and M.A.K.).

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