维多利祖马布
医学
内科学
炎症性肠病
胃肠病学
治疗药物监测
槽水位
硫嘌呤甲基转移酶
溃疡性结肠炎
相伴的
维持疗法
曲线下面积
药代动力学
克罗恩病
药品
疾病
药理学
化疗
移植
他克莫司
作者
Casper Steenholdt,Ruben Due Lorentsen,Pernille Nørgaard Petersen,Ella S. K. Widigson,Charlotte Kloft,Rolf Anton Klaasen,Jørn Brynskov
摘要
Abstract Background Therapeutic drug monitoring is effective for optimizing anti‐tumor necrosis factor therapies in inflammatory bowel disease, but for vedolizumab, a gut‐selective leucocyte migration inhibitor, data are scarce. Methods Observational cohort study including 116 bio‐experienced inflammatory bowel disease patients treated with vedolizumab for active luminal disease. Biobanked trough blood samples ( n = 676) covering 96% of patients were analyzed using a drug‐binding immunofluorometric assay. Steroid‐free treatment outcomes were classified by clinical disease activity indices and objective findings, primarily endoscopy. Results Patients with clinical remission to vedolizumab induction therapy (37%) had significantly higher trough levels than those without at weeks 6 (mean 34.1 vs 28.0 μg/mL, P = 0.03) and 10 (34.8 vs 27.5 μg/mL, P = 0.01). Optimal thresholds for discrimination were 32.4 μg/mL (AUC ROC 0.66, P = 0.04) and 23.5 (AUC ROC 0.67, P = 0.01), respectively. This positive association persisted during maintenance phase with 11.9 μg/mL (AUC ROC 0.69, P < 0.01) associated with clinical remission (37%) and 15.3 (AUC ROC 0.74, P < 0.001) for objective remission (46%). Stratification by temporal evolution of treatment effects revealed higher induction and maintenance vedolizumab levels in persistent and slow responders as compared to secondary or persistent failures. Pharmacokinetics was influenced by rare formation of anti‐vedolizumab antibodies (2%), and to a lesser extent gender and albumin during induction, but not disease severity, concomitant steroids, or thiopurine metabolites. Switching to subcutaneous administrations resulted in 2.3‐fold increase in steady‐state trough levels. Conclusion Our study supports maintaining adequate drug exposure being essential for sustained positive outcomes of vedolizumab and emphasizes individualized, therapeutic drug monitoring‐based treatment regimens. Controlled trials and pharmacokinetic modeling are, however, needed.
科研通智能强力驱动
Strongly Powered by AbleSci AI