Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Processing time: 74 Days and 22.2 Hours
BACKGROUND
The individual performances and the complementarity of Crohn’s disease (CD) activity index (CDAI), C-reactive protein (CRP) and faecal calprotectin (Fcal) to monitor patients with CD remain poorly investigated in the era of “tight control” and “treat to target” strategies.
AIM
To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk (W12) of anti-tumor necrosis factor (TNF) therapy to predict corticosteroids-free remission (CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 μg/g with no therapeutic intensification and no surgery) at W52.
METHODS
CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP > 2.9 mg/L or Fcal > 250 μg/g were prospectively enrolled.
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 positive predictive value = 100.0% (100.0-100.0) and negative predictive value = 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).
CONCLUSION
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.
Core tip: The CALM trial reported that a tight control of inflammation achieved better outcomes than conventional monitoring, but did not explore specifically the value of each biomarker. In this multicentre study, we investigated the performances of Crohn’s disease (CD) activity index (CDAI), C-reactive protein (CRP) and faecal calprotectin (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. We showed the complementarity of the variation of CDAI, CRP and Fcal after anti-TNF induction therapy, to predict CFREM at one year, and confirmed that Fcal was the most effective predictor among these three markers.
