Prospective Monitoring of Calprotectin for Crohn’s Disease

A recent study (full text link: Wright EK, et al. Gastroenterol May 2015 Volume 148, Issue 5, Pages 938–947) shows that stool calprotectin levels can be useful to monitor Crohn’s disease (Links from AGA twitter feed).  This study measured levels as part of The Post-Operative Crohn’s Endoscopic Recurrence (POCER) study.

Here’s the abstract, followed by some comments:

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.

Some key points from the discussion:

  • 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. However, such endoscopic monitoring is invasive, expensive, cannot be repeated frequently, and, in some patients, will yield a normal result.” [De Cruz, P., Kamm, M.A., Hamilton, A.L. et al. Crohn’s disease management after intestinal resection: a randomised trial. Lancet2014; (Epub ahead of print)]
  • The POCER study had all postoperative patients receive 3 months of metronidazole.  High-risk patients also received thiopurine or adalimumab (if thiopurine intolerant) therapy.  High-risk was defined as patients who were smokers, patients with perforating disease, or patients with 1 or more previous resections.
  • “In our study we have shown that FC concentration is increased markedly before surgery and decreases substantially after resection of all macroscopic disease at 6 months”
  • The present study has shown that FC concentration is sufficiently sensitive to monitor for recurrence of Crohn’s disease, and has a high enough negative predictive value to be confident that few patients with recurrence will be missed.” The authors, though, recommend serial measurement rather than relying on a single assay.
  • Calprotectin: “At each time point in our study, a cut-off value of 100 μg/g had an NPV of 90% or greater, with the best combination of sensitivity and specificity.”
  • An important limitation of these findings is that patients had to have all macroscopic disease removed at the time of surgery.  Thus, these findings are not generalizable to patients with residual upper gastrointestinal disease.
  • “These results confirm the accuracy, utility and superiority of fecal calprotectin compared with CRP or CDAI as a monitoring tool and screening test for endoscopic recurrence of Crohn’s disease in the postoperative population.”

Additional summary of this information on AGA Journals blog:  Measurement of Fecal Calprotectin.  An excerpt:

In an editorial that accompanies the article, Alain M. Schoepfer and James D. Lewis explain that the role of fecal calprotectin in assessing post-operative recurrence has been debated because of inconsistent results in mainly small studies. The strengths of the study of Wright et al include its large size, prospective design, endoscopic validation, and longitudinal inter-individual measurements of fecal calprotectin.

Tests for biomarkers such as fecal calprotectin can be repeated more frequently than colonoscopies. This advantage could overcome the lower levels of sensitivity with which single measurements of biomarkers detect recurrence. Schoepfer and Lewis say that studies are needed to determine the optimal frequency for measuring fecal calprotectin.

However, they conclude that measurement of fecal calprotectin could have an important role in monitoring Crohn’s disease recurrence after intestinal resection; it is clearly superior to measurement of c-reactive protein or CDAI score.

Proposed algorithm for using calprotectin: In the editorial, they propose that patients with low or medium risk of “permanent bowel dysfunction as a consequence of post-operative recurrence” could use fecal calprotectin measurements every 3-6 months.  They propose a cut-off of 50 mcg/g in those with medium risk and a cut-off of 100 mcg/g in those with low risk.  Those who exceeded cut-off would need colonoscopy.  Among high risk patients, they recommend proceeding directly to colonoscopy every 6-12 months to assess for recurrence.  All patients who had recurrence of disease greater than i1 would need treatment for recurrence. (Related gutsandgrowth blog: Only One Chance to Make a First Impression).

This year’s 22Q at the zoo was on May 17th, 2015:

22Q at the Zoo.  More than 100 zoos across the world participate to improve awareness of 22Q deletion syndrome

22Q at the Zoo. More than 100 zoos across the world participate to improve awareness of 22Q deletion syndrome.  With Karlene Coleman, Nancy Morris, and Jennifer Hochman.

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3 thoughts on “Prospective Monitoring of Calprotectin for Crohn’s Disease

  1. Pingback: Value of Calprotectin | gutsandgrowth

  2. Pingback: Best Fecal Marker for Crohn’s Disease: Calprotectin | gutsandgrowth

  3. Pingback: Fecal Calprotectin Monitoring Helpful at Identifying Relapse in IBD | gutsandgrowth

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