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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study
Thanaboon Chaemsupaphan, Aviv Pudipeddi, Hui-Yu Lin, Sudarshan Paramsothy, Viraj C Kariyawasam, Melissa Kermeen, Rupert W Leong
Thanaboon Chaemsupaphan, Aviv Pudipeddi, Hui-Yu Lin, Sudarshan Paramsothy, Melissa Kermeen, Rupert W Leong, Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, New South Wales, Australia
Thanaboon Chaemsupaphan, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Aviv Pudipeddi, Sudarshan Paramsothy, Rupert W Leong, Faculty of Medicine and Health, University of Sydney, Sydney 2139, New South Wales, Australia
Hui-Yu Lin, Department of Gastroenterology, Tan Tock Seng Hospital, Singapore 308433, Singapore
Sudarshan Paramsothy, Rupert W Leong, Faculty of Medicine and Health Sciences, Macquarie University, Sydney 2139, New South Wales, Australia
Viraj C Kariyawasam, Department of Gastroenterology and Hepatology, Blacktown Hospital, Sydney 2148, New South Wales, Australia
Viraj C Kariyawasam, Blacktown Clinical School, Western Sydney University, Sydney 2148, New South Wales, Australia
Author contributions: Leong RW designed and supervised the study; Chaemsupaphan T, Pudipeddi A, Paramsothy S, Leong RW were involved in methodology; Chaemsupaphan T, Pudipeddi A, Kermeen M, and Kariyawasam VC conducted the investigation; Chaemsupaphan T, Pudipeddi A, and Lin HY performed data analysis; Chaemsupaphan T and Leong RW wrote the original draft. All authors have edited and approved the final manuscript.
Supported by Takeda Australia, No. IISR-2016-101883.
Institutional review board statement: The study was reviewed and approved by the Sydney Local Health District Human Research Ethics Committee (Approval No. HREC/17/CRGH/22).
Clinical trial registration statement: This study is registered at Australian New Zealand Clinical trials registry website (
https://www.anzctr.org.au/). The registration identification number is ACTRN12618000812291.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data, analytic methods, and study materials are available to other researchers upon request to the corresponding author.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
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: Rupert W Leong, AGAF, FRACP, MBBS, MD, Professor, Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Hospital Road, Sydney 2139, New South Wales, Australia.
rupert.leong@health.nsw.gov.au
Received: September 12, 2024
Revised: October 22, 2024
Accepted: November 18, 2024
Published online: January 14, 2025
Processing time: 96 Days and 19.2 Hours
BACKGROUND
Ulcerative colitis (UC) is a chronic inflammatory condition requiring continuous treatment and monitoring. There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.
AIM
To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.
METHODS
This is a post-hoc analysis of prospective randomized clinical trial (VIEWS) involving UC patients across 8 centers in Australia from 2018 to 2022. Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab. We evaluated vedolizumab serum trough concentrations, presence of anti-vedolizumab antibodies, and clinical outcomes over 48 weeks to assess exposure-response association and impact of thiopurine withdrawal.
RESULTS
There were 62 UC participants with mean age of 43.4 years and 42% were females. All participants received vedolizumab as maintenance therapy with 67.7% withdrew thiopurine. Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use, with no anti-vedolizumab antibodies detected. Patients with clinical remission had higher trough concentrations at week 48. In quartile analysis, a threshold of > 11.3 μg/mL was associated with sustained clinical remission, showing a sensitivity of 82.4%, specificity of 60.0%, and an area of receiver operating characteristic of 0.71 (95%CI: 0.49-0.93). Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.
CONCLUSION
A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial. While thiopurine did not influence vedolizumab levels, its withdrawal may necessitate higher vedolizumab trough concentrations to maintain remission.
Core Tip: This prospective study investigated the pharmacokinetic relationship between vedolizumab trough concentrations and clinical outcomes in ulcerative colitis patients who had achieved clinical remission, on vedolizumab with or without thiopurine. Vedolizumab levels remained stable over 48 weeks, regardless of thiopurine withdrawal. Significant associations between vedolizumab trough concentrations and endoscopic, histologic, and histo-endoscopic remission at week 48 suggest that monitoring vedolizumab levels could be beneficial, with a threshold of > 11.3 µg/mL linked to sustained clinical remission. Although thiopurine withdrawal did not affect vedolizumab levels, it may necessitate higher vedolizumab trough concentrations to maintain remission.
