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Fecal calprotectin is not a clinically useful marker for the prediction of the early nonresponse to exclusive enteral nutrition in pediatric patients with Crohn disease

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A Correction to this article was published on 02 October 2018

This article has been updated

Abstract

Exclusive enteral nutrition (EEN) has been recommended as the first-line therapy in children with active Crohn disease (CD). The primary aim of our study was to determine whether it is possible to use the difference between basal fecal calprotectin (F-CPT) and the value at week 2 of EEN to predict clinical response at week 6. We prospectively collected stool samples for F-CPT analysis and clinical and laboratory parameters during EEN from 38 pediatric patients (28 boys, median age 12.8 years) with newly diagnosed active luminal CD. The difference between F-CPT concentrations before EEN and at week 2 did not predict clinical non-response at week 6 (OR 0.9996 95% CI 0.9989–1.0002, p = 0.18); however, it predicted patients who did not achieve clinical remission at week 6 (OR 0.9993, 95% CI 00.9985–0.9998, p = 0.006) with sensitivity of 58%, and specificity of 92% for cut-off of F-CPT increase by 486 μg/g.

Conclusions: An early decrease in F-CPT levels in children with newly diagnosed active luminal CD did not predict clinical response at week 6 of EEN induction therapy, and clinical remission was predicted with low accuracy. Therefore, F-CPT cannot be used as a predictor to select the patients in whom EEN should be terminated.

What is Known:

• The fecal calprotectin (F-CPT) is an important marker of intestinal inflammation.

• Approximately 25% of pediatric patients with Crohn disease (CD) do not achieve clinical remission, and there is still no sufficient predictor of response to exclusive enteral nutrition (EEN) treatment.

What is New:

• The difference between the F-CPT concentrations before EEN treatment and at week 2 did not predict clinical response to treatment at week 6, even if it predicted clinical remission, however, with low accuracy. F-CPT is not a suitable predictor to select the patients for discontinuing of EEN induction therapy.

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Change history

  • 02 October 2018

    This article was originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above. The original article was corrected.

Abbreviations

AUC :

Area under the curve

AZA :

Azathioprine

CD :

Crohn disease

CI :

Confidence interval

CRP :

C-reactive protein

ECCO :

European Crohn and Colitis Organization

EEN :

Exclusive enteral nutrition

ELIA :

Fluorescence immunoassay

ESR :

Erythrocyte sedimentation rate

F-CPT :

Fecal calprotectin

IQR :

Interquartile ranges

OR :

Odds ratio

ROC :

Receiver operating characteristic

wPCDAI :

Weighted Pediatric Crohn Disease Activity Index

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Acknowledgments

The project was supported by the Grant Agency of Charles University in Prague, Project No. 136215, No. 364617, and No. 246216, and by the Czech Ministry of Health for the conceptual development of research organizations 00064203 (University Hospital Motol, Prague, Czech Republic).

Funding

Author Ivana Copova has received research grants from the Grant Agency of Charles University in Prague, Project No. 136215 and No. 246216. Author Tereza Lerchova has received a grant from the Grant Agency of Charles University in Prague, Project No. 364617. The project was supported by the Czech Ministry of Health for the conceptual development of research organizations 00064203 (University Hospital Motol, Prague, Czech Republic).

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Authors and Affiliations

  1. Department of Pediatrics, University Hospital Motol and Second Faculty of Medicine, Charles University in Prague, V Uvalu 84, 150 06, Prague 5, Czech Republic

    Ivana Copova, Ondrej Hradsky, Kristyna Zarubova, Lucie Gonsorcikova, Kristyna Potuznikova, Tereza Lerchova, Jiri Nevoral & Jiri Bronsky

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  1. Ivana Copova
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Contributions

Ivana Copova M.D. worked on the conception and design of the study as well as on background research, data collection, and its control and completion of the missing data, statistical analysis of data, and writing of this original article. She was responsible for financial planning and work efficiency within the budget of the study.

Ondrej Hradsky M.D., Assoc. Prof., Ph.D. worked on the conception and design of the study as well as on data collection and its control, statistical analysis of data, and revision of the original article. He critically revised the work for important intellectual content.

Kristyna Zarubova M.D. actively participated in data collection and its control in the context of the research, and revision of the original article.

Lucie Gonsorcikova M.D., Ph.D. participated in data collection and its control.

Kristyna Potuznikova M.D. participated in data collection and its control. She obtained the necessary documents from patients and their guardians, and revised the work.

Tereza Lerchova M.D. participated in data collection and its control. She obtained the necessary documents from patients and their guardians, and revised the work.

Jiri Nevoral M.D., Prof., Ph.D. worked on the conception and design of the study as well as on revision of the original article.

Jiri Bronsky M.D., Assoc. Prof., Ph.D. was responsible for leading the project team, he was involved in study scheduling, obtaining the necessary documents, highlighting potential problems, and proposing solutions. He critically revised the work critically for important intellectual content.

Corresponding author

Correspondence to Ivana Copova.

Ethics declarations

The study was approved by the Ethics Committee of the authors’ institution (the Ethics Committee Reference number is 1491/16).

Conflict of interest

The authors alone are responsible for the content and writing of the paper. There is no direct conflict of interest in relation to the topic of this study in any of the authors. Jiri Bronsky received honoraria/speaker’s fees/coverage of travel expenses from AbbVie, MSD, Nutricia, Nestle, Biocodex, Walmark, and Ferring. Ondrej Hradsky received honoraria/speaker’s fees/coverage of travel expenses from AbbVie, MSD, Nutricia, Nestle, Biocodex, Falk, and Ferring.

Informed consent

The patients’ guardians received written information on the study and signed a consent form.

Additional information

Communicated by Peter de Winter

The original version of this article was revised: This article was originally published with all author names incorrectly listed. All author names have now been transposed and appear correctly above.

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Fig. 3aFig. 3b

(PNG 86 kb)

(PNG 85 kb)

Prediction of the accuracy of the non-remission (a, b) based on the differences in the F-CPT levels between weeks 0 and 2. The non-remission was best predicted using an increase of fecal calprotectin (F-CPT) by 486 μg/g till week 2 and had a specificity of 92% and sensitivity of 58% (area under the curve (AUC) 0.753). Using cut-off of 1.47%, a specificity was 79% and sensitivity was 80% (AUC 0.788) to predict patient who did not achieve clinical remission at week 6 of exclusive enteral nutrition (EEN) treatment.

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Copova, I., Hradsky, O., Zarubova, K. et al. Fecal calprotectin is not a clinically useful marker for the prediction of the early nonresponse to exclusive enteral nutrition in pediatric patients with Crohn disease. Eur J Pediatr 177, 1685–1693 (2018). https://doi.org/10.1007/s00431-018-3228-5

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