Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study  

作　　者：Thanaboon Chaemsupaphan Aviv Pudipeddi Hui-Yu Lin Sudarshan Paramsothy Viraj C Kariyawasam Melissa Kermeen Rupert W Leong 

机构地区：[1]Department of Gastroenterology and Liver Services,Concord Repatriation General Hospital,Sydney 2139,New South Wales,Australia [2]Faculty of Medicine,Siriraj Hospital,Mahidol University,Bangkok 10700,Thailand [3]Faculty of Medicine and Health,University of Sydney,Sydney 2139,New South Wales,Australia [4]Department of Gastroenterology,Tan Tock Seng Hospital,Singapore 308433,Singapore [5]Faculty of Medicine and Health Sciences,Macquarie University,Sydney 2139,New South Wales,Australia [6]Department of Gastroenterology and Hepatology,Blacktown Hospital,Sydney 2148,New South Wales,Australia [7]Blacktown Clinical School,Western Sydney University,Sydney 2148,New South Wales,Australia

出　　处：《World Journal of Gastroenterology》2025年第2期102-112,共11页世界胃肠病学杂志（英文）

基　　金：Supported by Takeda Australia,No.IISR-2016-101883.

摘　　要：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 asso-ciation 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.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/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 with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.

关 键 词：PHARMACOKINETIC Vedolizumab THIOPURINE Ulcerative colitis Trough concentration Antibody Inflammatory bowel diseases 

分 类 号：R574.62[医药卫生—消化系统]