Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2023; 29(29): 4481-4498
Published online Aug 7, 2023. doi: 10.3748/wjg.v29.i29.4481
Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease: A literature review
Liang-Fang Wang, Ping-Run Chen, Si-Ke He, Shi-Hao Duan, Yan Zhang
Liang-Fang Wang, Ping-Run Chen, Shi-Hao Duan, Yan Zhang, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Liang-Fang Wang, Ping-Run Chen, Si-Ke He, Shi-Hao Duan, Yan Zhang, West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Wang LF and Zhang Y contributed to the study conception and design; Wang LF and Chen PR reviewed the literature and wrote the manuscript; He SK and Duan SH critically reviewed the manuscript; and all authors approved the final version of the manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Yan Zhang, MD, PhD, Chief Physician, Doctor, Professor, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, No. 37 Guoxue Street, Chengdu 610041, Sichuan Province, China.
Received: March 23, 2023
Peer-review started: March 23, 2023
First decision: June 17, 2023
Revised: June 28, 2023
Accepted: July 17, 2023
Article in press: July 17, 2023
Published online: August 7, 2023

Tumor necrosis factor-α (TNF-α) antagonists, the first biologics approved for treating patients with inflammatory bowel disease (IBD), are effective for the induction and maintenance of remission and significantly improving prognosis. However, up to one-third of treated patients show primary nonresponse (PNR) to anti-TNF-α therapies, and 23%-50% of IBD patients experience loss of response (LOR) to these biologics during subsequent treatment. There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs. This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients. Most predictors remain controversial, and only previous surgical history, disease manifestations, drug concentrations, antidrug antibodies, serum albumin, some biologic markers, and some genetic markers may be potentially predictive. In addition, we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists. Therapeutic drug monitoring plays an important role in treatment selection. Dose escalation, combination therapy, switching to a different anti-TNF drug, or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Keywords: Predictor, Management, Tumor necrosis factor antagonist, Primary nonresponse, Secondary nonresponse, Inflammatory bowel disease

Core Tip: Tumor necrosis factor-α (TNF-α) antagonists play an essential role in the management of inflammatory bowel disease (IBD). However, a significant number of patients experience primary or secondary nonresponse to these drugs. Here, we summarize relevant predictors of anti-TNF nonresponse in IBD and discuss the next steps for treating patients with primary or secondary nonresponse to anti-TNF agents.