Ilse A Pool, Ilse Volkerink, Mirthe Stavast, Jos G W Kosterink, Gerard Dijkstra, Paola Mian, Arno R Bourgonje
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The study included 259 patients (CD: n = 202; UC: n = 47; IBD-unclassified: n = 10) with 560 infliximab trough levels available for analysis. Higher hemoglobin was associated with lower infliximab levels (IBD: β = 0.668, p = 0.036; UC: β = 1.639, p = 0.018), as were albumin (IBD: β = 0.214, p = 0.002; CD: β = 0.345, p < 0.001) and AST (CD: β = 0.040, p = 0.019). Inverse associations were also found for ALT (UC: β = -0.100, p = 0.016), ALP (CD: β = -0.029, p = 0.021; UC: β = -0.018, p = 0.037) and GGT (IBD: β = -0.015, p = 0.028; UC: β = -0.034, p < 0.001). Endoscopic inflammation was positively associated with infliximab levels in CD (β = 3.402, p = 0.035). Systemic steroid use was associated with lower infliximab levels in UC (β = -4.263, p = 0.013). In conclusion, this study identified several clinical and biochemical variables, including albumin, hemoglobin and GGT across all patients, albumin, AST and ALP in CD, and hemoglobin, ALT, ALP and GGT in UC, that were associated with infliximab trough levels. Given the correlative nature of this study, these results should be interpreted cautiously. These findings merit validation and could inform model-informed precision dosing strategies in IBD clinical care.</p>","PeriodicalId":48908,"journal":{"name":"Journal of Clinical Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical and Biochemical Factors Associated With Infliximab Pharmacokinetics in Adult Patients With Inflammatory Bowel Disease.\",\"authors\":\"Ilse A Pool, Ilse Volkerink, Mirthe Stavast, Jos G W Kosterink, Gerard Dijkstra, Paola Mian, Arno R Bourgonje\",\"doi\":\"10.1002/jcph.70111\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Many patients with inflammatory bowel disease (IBD) do not adequately respond to infliximab, potentially due to individual differences in pharmacokinetics (PK). This study aimed to identify clinical and biochemical variables associated with infliximab PK. Adult IBD patients treated with infliximab and with registered infliximab trough levels between March 1, 2021 and November 22, 2023, were included. Univariable and multivariable linear mixed-effects models were used to evaluate associations between clinical and biochemical covariates and infliximab trough levels. A systematic literature review was conducted to contextualize findings. The study included 259 patients (CD: n = 202; UC: n = 47; IBD-unclassified: n = 10) with 560 infliximab trough levels available for analysis. Higher hemoglobin was associated with lower infliximab levels (IBD: β = 0.668, p = 0.036; UC: β = 1.639, p = 0.018), as were albumin (IBD: β = 0.214, p = 0.002; CD: β = 0.345, p < 0.001) and AST (CD: β = 0.040, p = 0.019). Inverse associations were also found for ALT (UC: β = -0.100, p = 0.016), ALP (CD: β = -0.029, p = 0.021; UC: β = -0.018, p = 0.037) and GGT (IBD: β = -0.015, p = 0.028; UC: β = -0.034, p < 0.001). Endoscopic inflammation was positively associated with infliximab levels in CD (β = 3.402, p = 0.035). Systemic steroid use was associated with lower infliximab levels in UC (β = -4.263, p = 0.013). In conclusion, this study identified several clinical and biochemical variables, including albumin, hemoglobin and GGT across all patients, albumin, AST and ALP in CD, and hemoglobin, ALT, ALP and GGT in UC, that were associated with infliximab trough levels. Given the correlative nature of this study, these results should be interpreted cautiously. 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引用次数: 0
摘要
许多炎症性肠病(IBD)患者对英夫利昔单抗没有充分的反应,可能是由于药代动力学(PK)的个体差异。该研究旨在确定与英夫利昔单抗PK相关的临床和生化变量。纳入了2021年3月1日至2023年11月22日期间接受英夫利昔单抗治疗和注册英夫利昔单抗谷底水平的成年IBD患者。单变量和多变量线性混合效应模型用于评估临床和生化协变量与英夫利昔单抗谷水平之间的关系。我们进行了系统的文献综述,以了解研究结果的背景。该研究包括259例患者(CD: n = 202; UC: n = 47; ibd未分类:n = 10),有560例英夫利昔单抗谷水平可用于分析。较高的血红蛋白与较低的英夫利昔单抗水平相关(IBD: β = 0.668, p = 0.036; UC: β = 1.639, p = 0.018),白蛋白(IBD: β = 0.214, p = 0.002; CD: β = 0.345, p < 0.001)和AST (CD: β = 0.040, p = 0.019)也是如此。ALT (UC: β = -0.100, p = 0.016)、ALP (CD: β = -0.029, p = 0.021; UC: β = -0.018, p = 0.037)和GGT (IBD: β = -0.015, p = 0.028; UC: β = -0.034, p = 0.016)均呈负相关
Clinical and Biochemical Factors Associated With Infliximab Pharmacokinetics in Adult Patients With Inflammatory Bowel Disease.
Many patients with inflammatory bowel disease (IBD) do not adequately respond to infliximab, potentially due to individual differences in pharmacokinetics (PK). This study aimed to identify clinical and biochemical variables associated with infliximab PK. Adult IBD patients treated with infliximab and with registered infliximab trough levels between March 1, 2021 and November 22, 2023, were included. Univariable and multivariable linear mixed-effects models were used to evaluate associations between clinical and biochemical covariates and infliximab trough levels. A systematic literature review was conducted to contextualize findings. The study included 259 patients (CD: n = 202; UC: n = 47; IBD-unclassified: n = 10) with 560 infliximab trough levels available for analysis. Higher hemoglobin was associated with lower infliximab levels (IBD: β = 0.668, p = 0.036; UC: β = 1.639, p = 0.018), as were albumin (IBD: β = 0.214, p = 0.002; CD: β = 0.345, p < 0.001) and AST (CD: β = 0.040, p = 0.019). Inverse associations were also found for ALT (UC: β = -0.100, p = 0.016), ALP (CD: β = -0.029, p = 0.021; UC: β = -0.018, p = 0.037) and GGT (IBD: β = -0.015, p = 0.028; UC: β = -0.034, p < 0.001). Endoscopic inflammation was positively associated with infliximab levels in CD (β = 3.402, p = 0.035). Systemic steroid use was associated with lower infliximab levels in UC (β = -4.263, p = 0.013). In conclusion, this study identified several clinical and biochemical variables, including albumin, hemoglobin and GGT across all patients, albumin, AST and ALP in CD, and hemoglobin, ALT, ALP and GGT in UC, that were associated with infliximab trough levels. Given the correlative nature of this study, these results should be interpreted cautiously. These findings merit validation and could inform model-informed precision dosing strategies in IBD clinical care.
期刊介绍:
The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.