Chaemsupaphan Thanaboon, Pudipeddi Aviv, Lin Hui-Yu, Paramsothy Sudarshan, Kariyawasam Viraj C, Kermeen Melissa, Leong Rupert W
Department of Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, New South Wales, Australia.
Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
World J Gastroenterol. 2025 Jan 14;31(2):101292. doi: 10.3748/wjg.v31.i2.101292.
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.
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.
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.
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.
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.
溃疡性结肠炎（UC）是一种慢性炎症性疾病，需要持续治疗和监测。关于维多珠单抗维持治疗期间的药代动力学数据有限，硫唑嘌呤对维多珠单抗谷浓度的影响尚不清楚。
探讨维多珠单抗的暴露-反应关系以及硫唑嘌呤撤药对在维持治疗期间已实现持续临床和内镜缓解的UC患者的影响。
这是一项对2018年至2022年澳大利亚8个中心的UC患者进行的前瞻性随机临床试验（VIEWS）的事后分析。临床和内镜缓解的患者在接受维多珠单抗治疗时被随机分为继续或停用硫唑嘌呤。我们评估了48周内维多珠单抗血清谷浓度、抗维多珠单抗抗体的存在情况以及临床结局，以评估暴露-反应关联和硫唑嘌呤撤药的影响。
有62名UC参与者，平均年龄43.4岁，42%为女性。所有参与者均接受维多珠单抗作为维持治疗，67.7%的患者停用了硫唑嘌呤。无论是否使用硫唑嘌呤，维多珠单抗血清谷浓度在48周内保持稳定，未检测到抗维多珠单抗抗体。临床缓解的患者在第48周时谷浓度较高。在四分位数分析中，>11.3μg/mL的阈值与持续临床缓解相关，敏感性为82.4%，特异性为60.0%，受试者操作特征曲线下面积为0.71（95%CI：0.49-0.93）。停用硫唑嘌呤的患者需要更高的维多珠单抗浓度才能实现缓解。
维多珠单抗谷浓度与UC结局之间存在正暴露-反应关系，提示监测药物水平可能有益。虽然硫唑嘌呤不影响维多珠单抗水平，但其撤药可能需要更高的维多珠单抗谷浓度以维持缓解。
