Exploring infliximab serum level variability in inflammatory bowel disease: Comprehensive analysis of patient subgroups and treatment outcomes.

IF 1.9 4区 医学 Q3 GASTROENTEROLOGY & HEPATOLOGY
Carles Iniesta-Navalón, Lorena Rentero-Redondo, Rosa Gómez-Espín, Manuel Ríos Saorín, Isabel Nicolás de Prado, Juan José Gascón-Cánovas
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Abstract

Background and aims: Inflammatory bowel disease (IBD) features diverse clinical presentations and progressions, impacting IFX exposure. Understanding IFX serum concentration changes is crucial for tailored monitoring in specific patient groups. The main objective of this study was to analyze ITL trajectories in patients with IBD to identify distinct groups and subgroups, revealing heterogeneity in treatment responses.

Methods: A retrospective cohort study was conducted involving IBD patients treated with infliximab in a regional reference hospital in Spain. Latent class linear mixed models were applied to identify subgroups based on serum infliximab measurements over time. To analyze the factors associated with IFX discontinuation, we employed both logistic regression and Cox regression models.

Results: The study included 165 IBD patients, and a total of 799 ITL samples were analyzed. The selected model included three clusters, with a random intercept and a random effect on both time and natural cubic spline time in the linear mixed model. Cluster 1 (20.6%) had lower IFX exposure, with 93.9% experiencing treatment discontinuation, compared to 45.1% in Cluster 2 (43.0%) and 43.3% in Cluster 3 (36.4%) (p<0.001). Treatment discontinuation was observed in 91 individuals (55.2%) out of the total patients. In the multivariate analysis, the presence of cluster 1 was a significant predictor (OR: 7.25, 95% CI: 1.45-36.12). Bayesian dose adjustment was found to significantly reduce the risk of IFX discontinuation (OR: 0.19, 95% CI: 0.46-1.96).

Conclusions: The lack of TDM during induction and a lower proportion of adjustments made through Bayesian methods were associated with a subgroup demonstrating suboptimal pharmacokinetic profiles and reduced drug persistence. These findings highlight the clinical relevance of model-informed TDM in optimizing IFX exposure and minimizing treatment discontinuation in IBD.

探讨炎症性肠病中英夫利昔单抗血清水平变异性:对患者亚组和治疗结果的综合分析“炎症性肠病中英夫利昔单抗水平变异性”。
背景和目的:炎症性肠病(IBD)具有不同的临床表现和进展,影响IFX暴露。了解IFX血清浓度变化对于特定患者群体的量身定制监测至关重要。本研究的主要目的是分析IBD患者的ITL轨迹,以确定不同的组和亚组,揭示治疗反应的异质性。方法:对西班牙一家地区参考医院接受英夫利昔单抗治疗的IBD患者进行回顾性队列研究。潜伏类线性混合模型用于根据血清英夫利昔单抗随时间的测量来确定亚组。为了分析与IFX停药相关的因素,我们采用了logistic回归和Cox回归模型。结果:本研究纳入165例IBD患者,共分析ITL样本799份。所选择的模型包括三个簇,在线性混合模型中具有随机截距和对时间和自然三次样条时间的随机效应。第1组(20.6%)有较低的IFX暴露,93.9%经历了治疗中断,而第2组(43.0%)和第3组(36.4%)的这一比例分别为45.1%和43.3%。结论:诱导过程中缺乏TDM和通过贝叶斯方法进行调整的比例较低与亚组表现出次优的药代动力学特征和药物持久性降低有关。这些发现强调了模型知情TDM在优化IFX暴露和最小化IBD治疗中断方面的临床相关性。
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来源期刊
Gastroenterologia y hepatologia
Gastroenterologia y hepatologia GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
1.50
自引率
10.50%
发文量
147
审稿时长
48 days
期刊介绍: Gastroenterology and Hepatology is the first journal to cover the latest advances in pathology of the gastrointestinal tract, liver, pancreas, and bile ducts, making it an indispensable tool for gastroenterologists, hepatologists, internists and general practitioners.
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