Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2019; 25(19): 2354-2364
Published online May 21, 2019. doi: 10.3748/wjg.v25.i19.2354
Combined evaluation of biomarkers as predictor of maintained remission in Crohn’s disease
Elisa Sollelis, Régine Minet Quinard, Guillaume Bouguen, Marion Goutte, Félix Goutorbe, Damien Bouvier, Bruno Pereira, Gilles Bommelaer, Anthony Buisson
Elisa Sollelis, Marion Goutte, Gilles Bommelaer, Anthony Buisson, Inserm 3iHP, CHU Clermont-Ferrand, Service d’Hépato-Gastro Entérologie, Université Clermont Auvergne, Clermont-Ferrand F-63000, France
Elisa Sollelis, Marion Goutte, Gilles Bommelaer, Anthony Buisson, Inserm U1071, M2iSH, USC-INRA 2018, Université Clermont Auvergne, Clermont-Ferrand F-63000, France
Régine Minet Quinard, Damien Bouvier, Biochemistry laboratory, University Hospital G. Montpied, Clermont-Ferrand F-63000, France
Guillaume Bouguen, CHU Rennes, Univ Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolisms and Cancer), Rennes F-35000, France
Félix Goutorbe, Gastroenterology Department, Hospital of Bayonne, Bayonne F-64100, France
Bruno Pereira, Biostatistics Unit, DRCI, University Hospital, Clermont-Ferrand F-63000, France
Author contributions: Buisson A is the guarantor of the article; Sollelis E and Buisson A contributed to study concept and design and writing of the article; Sollelis E, Bouguen G, Goutte M, Goutorbe F, Bouvier D, Pereira B, Bommelaer G and Buisson A contributed to substantial contribution to acquisition of data; Sollelis E, Quinard RM, Bouguen G, Goutte M, Goutorbe F, Bouvier D, Pereira B and Bommelaer G contributed to critical revision of the manuscript for important intellectual content; Sollelis E, Pereira B, Bommelaer G and Buisson A contributed to analysis and interpretation of data; Pereira B contributed to statistical analysis.
Institutional review board statement: The study was approved by local Ethics Committee (#2014/CE 72).
Informed consent statement: The study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice and applicable regulatory requirements. Informed consent was obtained from each patient included in the study.
Conflict-of-interest statement: Buisson A declares lecture fees for MSD, Abbvie, Ferring, Takeda, Vifor Pharma, Hospira and consulting fees for Abbvie, Takeda and Hospira. Bouguen G received lecture fees from Abbvie, Ferring, MSD, Takeda and Pfizer and consulting fees from Takeda and Janssen. The other authors declare no conflict of interest related to this work.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at a_buisson@hotmail.fr.
STROBE statement: The manuscript was prepared according to the STROBE Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Anthony Buisson, MD, PhD, Associate Professor, Senior Lecturer, Gastroenterology Department,
University Hospital Estaing, 1 place Aubrac, Clermont-Ferrand F-63100, France. a_buisson@hotmail.fr
Telephone: +33-473-750523 Fax: +33-473-750524
Received: March 7, 2019
Peer-review started: March 7, 2019
First decision: April 11, 2019
Revised: April 16, 2019
Accepted: April 19, 2019
Article in press: April 20, 2019
Published online: May 21, 2019
Research background

Crohn’s disease (CD) is a chronic and disabling disorder that can highly affect quality of life. Faecal calprotectin (Fcal) is a well-accepted monitoring tool and a surrogate marker of mucosal healing and could then be an alternative to endoscopy. Recently, the CALM trial compared two ways of monitoring patients with inflammatory bowel disease (IBD) treated with adalimumab. The authors reported that the group monitored using a tight control of inflammation with objective markers of disease activity and clinical symptoms to drive treatment decisions, achieved better endoscopic and clinical outcomes than conventional monitoring. In a post-hoc analysis of this study, the authors reported that most of the therapeutic intensification were related to increased level of Fcal in the tight control group. However, even though the conclusion of this landmark trial encourages IBD physicians to use Fcal testing in daily practice, the authors did not explore specifically the value of each marker, i.e., CD activity index (CDAI), C-reactive protein (CRP) and Fcal.

Research motivation

Understanding the value of each monitoring biomarker to guide physicians to manage patients with inflammatory bowel disease is a key point.

Research objectives

In this study, we aimed to investigate the performances of CDAI, CRP and Fcal variation, alone or combined, after 12 wk of anti-tumor necrosis factor (TNF) therapy to predict corticosteroids-free remission (CFREM) at one year, in CD patients treated with anti-TNF.

Research methods

It was a multicentre prospective observational study.

Research results

Among the 40 included patients, 13 patients (32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12 (P = 0.012), CRP level < 2.9 mg/L at W12 (P = 0.001) and Fcal improvement at W12 [Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal (<100 μg/g)] (P = 0.001) were predictive of CFREM at W52. Combined endpoint (CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with PPV = 100.0% (100.0-100.0) and NPV = 87.1% (75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio (OR) = 45.1 (2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3 (0.36-237.1); P = 0.145] and CRP < 2.9 mg/L (0.77-278.0; P = 0.073).

Research conclusions

The combined monitoring of CDAI, CRP and FCal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD. The most impactful biomarker was Fcal among these three biomarkers. Our results should lead IBD physicians to monitor patients with CD using a tight control strategy based on CDAI, CRP and Fcal in daily practice.

Research perspectives

Additional studies from independent cohorts should be conducted to confirm these data.