Prospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2019; 25(14): 1764-1774
Published online Apr 14, 2019. doi: 10.3748/wjg.v25.i14.1764
Endoscopic response to tumor necrosis factor inhibitors predicts long term benefits in Crohn’s disease
Ignacio Alfaro, Maria Carme Masamunt, Nuria Planell, Alicia López-García, Jesús Castro, Marta Gallego, Rebeca Barastegui, Angel Giner, Alejandro Vara, Azucena Salas, Elena Ricart, Julián Panés, Ingrid Ordás
Ignacio Alfaro, Maria Carme Masamunt, Alicia López-García, Jesús Castro, Marta Gallego, Rebeca Barastegui, Angel Giner, Alejandro Vara, Elena Ricart, Julián Panés, Ingrid Ordás, Gastroenterology Department, Hospital Clínic de Barcelona, Barcelona 08036, Spain
Nuria Planell, Azucena Salas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona 08036, Spain
Author contributions: Alfaro I, Salas A, Ricart E, Panés J and Ordás I contributed to study conception and design; Masamunt MC, López-García A, Castro J, Gallego M, Barastegui R, Giner A and Vara A contributed to patients recruitment and data acquisition; Planell N contributed to data analysis and interpretation; Alfaro I contributed to writing of article; Panés J and Ordás I contributed to editing and reviewing; all authros approve the final versión of the article.
Supported by the Leona M. and Harry B Helmsley Charitable Trust, No. 2015PG-IBD005.
Institutional review board statement: The study was reviewed and approved by the Hospital Clinic of Barcelona Institutional Review Board.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: All available data can be obtained by contacting the corresponding author
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/
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Corresponding author: Ingrid Ordás, MD, PhD, Staff Physician, Gastroenterology Department, Hospital Clínic de Barcelona, Villarroel 170, Barcelona 08036, Spain. iordas@clinic.cat
Telephone: +34-932275418 Fax: +34-932275454
Received: November 9, 2018
Peer-review started: November 12, 2018
First decision: January 30, 2019
Revised: February 26, 2019
Accepted: March 1, 2019
Article in press: March 1, 2019
Published online: April 14, 2019
Processing time: 155 Days and 5.5 Hours
Abstract
BACKGROUND

Identifying predictors of therapeutic response is the cornerstone of personalized medicine.

AIM

To identify predictors of long-term mucosal healing (MH) in patients with Crohn’s disease (CD) treated with tumor necrosis factor α (TNF-α) inhibitors.

METHODS

Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity (CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response (ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments.

RESULTS

Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment (53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52% and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46 (59% sensitivity and 91% specificity; area under the curve = 0.778).

CONCLUSION

Clinical and biomarker data are not useful predictors of response to TNF-α inhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-α therapy.

Keywords: Crohn’s disease; Endoscopy; Mucosal healing; Crohn’s Disease Endoscopic Index of Severity; Tumor necrosis factor

Core tip: In our study we report that endoscopic response after completion of induction treatment with a tumor necrosis factor inhibitor predicts mucosal healing at long term in patients with Crohn’s disease, and that endoscopic evaluation at this time point may be considered in clinical practice to predict long term outcomes and could contribute to perform treatment adjustments.