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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2015; 21(44): 12519-12543
Published online Nov 28, 2015. doi: 10.3748/wjg.v21.i44.12519
Update on pathogenesis and predictors of response of therapeutic strategies used in inflammatory bowel disease
Emilio G Quetglas, Zlatan Mujagic, Simone Wigge, Daniel Keszthelyi, Sebastian Wachten, Ad Masclee, Walter Reinisch
Emilio G Quetglas, Project Strategy and Science, Grünenthal GmbH, 52078 Aachen, Germany
Zlatan Mujagic, Daniel Keszthelyi, Ad Masclee, Internal Medicine, University of Maastricht Medical Center, 6229 Maastricht, The Netherlands
Simone Wigge, Translational Science, Grünenthal GmbH, 52078 Aachen, Germany
Sebastian Wachten, Molecular Pharmacology, Grünenthal GmbH, 52078 Aachen, Germany
Walter Reinisch, Internal Medicine. McMaster University, Hamilton 8LS 4L8, Canada
Author contributions: All authors made contributions to this manuscript.
Conflict-of-interest statement: Emilio G Quetglas, Simone Wigge and Sebastian Wachten are currently Grünenthal Employees. Zlatan Mujagic and Daniel Keszthelyi declare no conflict of interest. Ad Masclee has received research funding from Grünenthal, Ferring Pharmaceuticals, Falk Medical and DSM. Walter Reinisch Walter Reinisch has served as a speaker, consultant, and/or advisory board member for Abbott Laboratories, AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria, Elan, Ferring, Galapagos, Genentech, Grünenthal, Johnson and Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter and Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, Austria, and 4SC.
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/
Correspondence to: Emilio G Quetglas, MD, PhD, Project Strategy and Science, Grünenthal GmbH, 52078 Aachen, Germany. emilio.quetglas@grunenthal.com
Telephone: +34-913-017809 Fax: +34-913-017809
Received: February 6, 2015
Peer-review started: February 7, 2015
First decision: May 18, 2015
Revised: August 5, 2015
Accepted: September 13, 2015
Article in press: September 14, 2015
Published online: November 28, 2015
Abstract

The search for biomarkers that characterize specific aspects of inflammatory bowel disease (IBD), has received substantial interest in the past years and is moving forward rapidly with the help of modern technologies. Nevertheless, there is a direct demand to identify adequate biomarkers for predicting and evaluating therapeutic response to different therapies. In this subset, pharmacogenetics deserves more attention as part of the endeavor to provide personalized medicine. The ultimate goal in this area is the adjustment of medication for a patient’s specific genetic background and thereby to improve drug efficacy and safety rates. The aim of the following review is to utilize the latest knowledge on immunopathogenesis of IBD and update the findings on the field of Immunology and Genetics, to evaluate the response to the different therapies. In the present article, more than 400 publications were reviewed but finally 287 included based on design, reproducibility (or expectancy to be reproducible and translationable into humans) or already measured in humans. A few tests have shown clinical applicability. Other, i.e., genetic associations for the different therapies in IBD have not yet shown consistent or robust results. In the close future it is anticipated that this, cellular and genetic material, as well as the determination of biomarkers will be implemented in an integrated molecular diagnostic and prognostic approach to manage IBD patients.

Keywords: Mucosal immunology, Biomarkers, Pharmacology, Mode of action, Therapeutic drug monitoring

Core tip: The following article is an update on the latest findings on the pathogenesis of inflammatory bowel disease (IBD) and its correlation with genetic and non-genetic predictors of the efficacy of the different strategies of treatment. Although many therapies have been used for decades, this is a completely new approach that has become even more complicated with new therapies like biologics. While most of these strategies are still in a very early stage, and have not been validated in clinical practice, they have begun suggesting the direction in which physicians should start looking to establish the most adequate therapeutic strategy for each individual patient.