Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2018; 24(32): 3567-3582
Published online Aug 28, 2018. doi: 10.3748/wjg.v24.i32.3567
Positioning of old and new biologicals and small molecules in the treatment of inflammatory bowel diseases
Jason Reinglas, Lorant Gonczi, Zsuzsanna Kurt, Talat Bessissow, Peter L Lakatos
Jason Reinglas, Talat Bessissow, Peter L Lakatos, Department of Gastroenterology, McGill University Health Center, Montreal, Québec H4A 3J1, Canada
Lorant Gonczi, Zsuzsanna Kurt, Peter L Lakatos, First Department of Medicine, Semmelweis University, H-1083, Budapest, Koranyi S. 2A, Hungary
Author contributions: All the authors contributed to the writing of the manuscript.
Conflict-of-interest statement: Bessissow T has been a speaker and/or advisory board member for: AbbVie, Janssen, Takeda, Pfizer, Merck, Shire, Ferring and Pendopharm and has received unrestricted research grant from: AbbVie, Janssen, Pentax and Echosense; Lakatos PL has been a speaker and/or advisory board member: AbbVie, Celltrion, Falk Pharma GmbH, Ferring, Genetech, Jansen, Kyowa Hakko Kirin Pharma, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka Pharma, Pharmacosmos, Pfizer, Roche, Shire and Takeda and has received unrestricted research grant: AbbVie, MSD and Pfizer. There are no conflicts of interest to report from other authors
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:
Correspondence to: Peter L Lakatos, DSc, MD, PhD, Professor, Division of Gastroenterology, Montreal General Hospital C7-200, McGill University Health Center, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.
Telephone: +36-1-2100278 Fax: +36-1-3130250
Received: March 29, 2018
Peer-review started: March 29, 2018
First decision: April 26, 2018
Revised: May 9, 2018
Accepted: June 25, 2018
Article in press: June 25, 2018
Published online: August 28, 2018

The past decade has brought substantial advances in the management of inflammatory bowel diseases (IBD). The introduction of tumor necrosis factor (TNF) antagonists, evidence for the value of combination therapy, the recognition of targeting lymphocyte trafficking and activation as a viable treatment, and the need for early treatment of high-risk patients are all fundamental concepts for current modern IBD treatment algorithms. In this article, authors review the existing data on approved biologicals and small molecules as well as provide insight on the current positioning of approved therapies. Patient stratification for the selection of specific therapies, therapeutic targets and patient monitoring will be discussed as well. The therapeutic armamentarium for IBD is expanding as novel and more targeted therapies become available. In the absence of comparative trials, positioning these agents is becoming difficult. Emerging concepts for the future will include an emphasis on the development of algorithms which will facilitate a greater understanding of the positioning of novel biological drugs and small molecules in order to best tailor therapy to the patient. In the interim, anti-TNF therapy remains an important component of IBD therapy with the most real-life evidence and should be considered as first-line therapy in patients with complicated Crohn’s disease and in acute-severe ulcerative colitis. The safety and efficacy of these ‘older’ anti-TNF therapies can be optimized by adhering to therapeutic algorithms which combine clinical and objective markers of disease severity and response to therapy.

Keywords: Inflammatory bowel disease, Small molecule, Positioning, Biologic, Therapeutic

Core tip: Anti-tumor necrosis factor therapy should be considered as first-line therapy in patients with complicated Crohn’s disease and in acute-severe ulcerative colitis. Beyond these specific circumstances, the positioning of novel biologics and small molecules depends on the patient’s medical history, preference and disease phenotype. The efficacy and safety of using immunomodulatory therapy can be enhanced by adhering to therapeutic algorithms and using a ‘treat-to-target’ approach. The risks for adverse events due to poor disease control outweigh the risks associated with early aggressive therapy. In the setting of clinical and biochemical remission, following at least 6 mo of combined immunosuppressive therapy, consideration can be made to withdrawing thiopurine therapy in the correct patient with close follow-up.