Systematic Reviews
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2024; 30(22): 2902-2919
Published online Jun 14, 2024. doi: 10.3748/wjg.v30.i22.2902
Approach to loss of response to advanced therapies in inflammatory bowel disease
Nikil Vootukuru, Abhinav Vasudevan
Nikil Vootukuru, Abhinav Vasudevan, Department of Gastroenterology and Hepatology, Eastern Health, Victoria, Box Hill 3128, Australia
Nikil Vootukuru, Abhinav Vasudevan, Eastern Health Clinical School, Monash University, Victoria, Box Hill 3128, Australia
Author contributions: Vasudevan A and Vootukuru N were involved in the conception and design of the manuscript, writing and editing of the manuscript and final approval of the version to be submitted.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abhinav Vasudevan, BMed, FRACP, Doctor, Department of Gastroenterology and Hepatology, Eastern Health, 8 Arnold St, Victoria, Box Hill 3128, Australia. abhinav.vasudevan@monash.edu
Received: February 27, 2024
Revised: May 6, 2024
Accepted: May 28, 2024
Published online: June 14, 2024
Abstract
BACKGROUND

Remarkable progress over the last decade has equipped clinicians with many options in the treatment of inflammatory bowel disease. Clinicians now have the unique opportunity to provide individualized treatment that can achieve and sustain remission in many patients. However, issues of primary non-response (PNR) and secondary loss of response (SLOR) to non-tumour necrosis factor inhibitor (TNFi) therapies remains a common problem. Specific issues include the choice of optimization of therapy, identifying when dose optimization will recapture response, establishing optimal dose for escalation and when to switch therapy.

AIM

To explores the issues of PNR and SLOR to non-TNFi therapies.

METHODS

This review explores the current evidence and literature to elucidate management options in cases of PNR/SLOR. It will also explore potential predictors for response following SLOR/PNR to therapies including the role of therapeutic drug monitoring (TDM).

RESULTS

In the setting of PNR and loss of response to alpha-beta7-integrin inhibitors and interleukin (IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response. For Janus kinase inhibitors dose optimization can be utilized to recapture response with loss of response.

CONCLUSION

The role of TDM in the setting of advanced non-TNFi therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future.

Keywords: Inflammatory bowel disease, Ulcerative colitis, Crohn, Biologics, Interleukin-12 and interleukin-23 inhibitors, Alpha-beta7-integrin inhibitors, Janus kinase inhibitors, Sphingosine-1-phosphate receptor modulators

Core Tip: In the setting of primary non-response (PNR) and loss of response (LOR) to alpha-beta7-integrin inhibitors and interleukin (IL)-12 and IL-23 inhibitors dose optimization is a reasonable option to capture response. For Janus kinase inhibitors dose optimization can be utilized to recapture response with LOR is less successful in the setting of PNR. The role of therapeutic drug monitoring in the setting of non-tumour necrosis factor inhibitor therapies to identify patients who require dose optimization and as a predictor for clinical remission is not yet established and this remains an area that should be addressed in the future research.