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
{"title":"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。","authors":"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","doi":"10.1007/s13318-023-00835-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>This prospective study demonstrates that adalimumab concentrations at steady state can be predicted from early samples during the induction phase.</p><p><strong>Clinical trial registration: </strong>The trial was registered in the Netherlands Trial Register with trial registry number NTR 7692 ( www.trialregister.nl ).</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":"48 4","pages":"377-385"},"PeriodicalIF":1.9000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Early At-Home Measurement of Adalimumab Concentrations to Guide Anti-TNF Precision Dosing: A Pilot Study.\",\"authors\":\"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\",\"doi\":\"10.1007/s13318-023-00835-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Underdosing of adalimumab can result in non-response and poor disease control in patients with rheumatic disease or inflammatory bowel disease. 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Early At-Home Measurement of Adalimumab Concentrations to Guide Anti-TNF Precision Dosing: A Pilot Study.
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 ).
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.