Early At-Home Measurement of Adalimumab Concentrations to Guide Anti-TNF Precision Dosing: A Pilot Study.

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Paul A G de Klaver, Ron J Keizer, Rob Ter Heine, Lisa Smits, Paul J Boekema, Inge Kuntzel, Tiny Schaap, Annick de Vries, Karien Bloem, Theo Rispens, Frank Hoentjen, Luc J J Derijks
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引用次数: 1

Abstract

Background and objective: Underdosing of adalimumab can result in non-response and poor disease control in patients with rheumatic disease or inflammatory bowel disease. In this pilot study we aimed to predict adalimumab concentrations with population pharmacokinetic model-based Bayesian forecasting early in therapy.

Methods: Adalimumab pharmacokinetic models were identified with a literature search. A fit-for-purpose evaluation of the model was performed for rheumatologic and inflammatory bowel disease (IBD) patients with adalimumab peak (first dose) and trough samples (first and seventh dose) obtained by a volumetric absorptive microsampling technique. Steady state adalimumab concentrations were predicted after the first adalimumab administration. Predictive performance was calculated with mean prediction error (MPE) and normalised root mean square error (RMSE).

Results: Thirty-six patients (22 rheumatologic and 14 IBD) were analysed in our study. After stratification for absence of anti-adalimumab antibodies, the calculated MPE was -2.6% and normalised RMSE 24.0%. Concordance between predicted and measured adalimumab serum concentrations falling within or outside the therapeutic window was 75%. Three patients (8.3%) developed detectable concentrations of anti-adalimumab antibodies.

Conclusion: This prospective study demonstrates that adalimumab concentrations at steady state can be predicted from early samples during the induction phase.

Clinical trial registration: The trial was registered in the Netherlands Trial Register with trial registry number NTR 7692 ( www.trialregister.nl ).

Abstract Image

早期在家测量阿达木单抗浓度以指导抗tnf精确给药:一项试点研究。
背景和目的:阿达木单抗剂量不足可导致风湿性疾病或炎症性肠病患者无反应和疾病控制不良。在这项初步研究中,我们旨在通过基于群体药代动力学模型的贝叶斯预测在治疗早期预测阿达木单抗浓度。方法:通过文献检索确定阿达木单抗药代动力学模型。对风湿病和炎症性肠病(IBD)患者通过体积吸收微采样技术获得阿达木单抗峰(第一次剂量)和谷(第一次和第七次剂量),对该模型进行了适合目的的评估。第一次阿达木单抗给药后预测稳态阿达木单抗浓度。用平均预测误差(MPE)和归一化均方根误差(RMSE)计算预测性能。结果:本研究共分析了36例患者(风湿病22例,IBD 14例)。分层后无抗阿达木单抗,计算的MPE为-2.6%,归一化RMSE为24.0%。预测和测量的阿达木单抗血清浓度在治疗窗内或治疗窗外的一致性为75%。3名患者(8.3%)出现可检测到的抗阿达木单抗抗体浓度。结论:这项前瞻性研究表明,在诱导阶段的早期样品中可以预测稳态下的阿达木单抗浓度。临床试验注册:该试验已在荷兰试验注册中心注册,试验注册号为NTR 7692 (www.trialregister.nl)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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