Klervi Golhen PharmD, PhD, Tatjana Welzel MD, Andrew Atkinson PhD, Gilbert Koch PhD, Dominic Braem PhD, Johannes van den Anker MD, PhD, Andreas Woerner MD, Marc Pfister MD, Verena Gotta PhD
{"title":"Influence of Disease Type and Activity on Adalimumab Exposure in Children with Inflammatory Rheumatic Diseases","authors":"Klervi Golhen PharmD, PhD, Tatjana Welzel MD, Andrew Atkinson PhD, Gilbert Koch PhD, Dominic Braem PhD, Johannes van den Anker MD, PhD, Andreas Woerner MD, Marc Pfister MD, Verena Gotta PhD","doi":"10.1002/jcph.70045","DOIUrl":null,"url":null,"abstract":"<p>Understanding adalimumab pharmacokinetics (PK) in pediatric inflammatory rheumatic diseases (PIRD) could facilitate individualized treatment strategies. This pharmacometric (PMX) analysis, utilizing prospectively collected data, aimed to develop a PMX model investigating associations between disease-specific factors and adalimumab exposure in PIRD. PK data originating from a prospective two-center study including 36 children with PIRD (weight IQR: 33-55 kg) receiving subcutaneous adalimumab (IQR: 30-40 mg biweekly; n = 28 at steady state, n = 8 after first dose, i.e., treatment naïve) were analyzed. A total of 72 adalimumab concentrations were available for PMX analysis, measured at 1-9 days and 10-14 days post-dose. In addition to disease type (juvenile idiopathic arthritis [JIA] vs idiopathic uveitis) and disease activity (inactive/mild/minimal/moderate/severe), associations between methotrexate (MTX) co-administration and duration of adalimumab treatment with apparent clearance (CL/F) were investigated. A one-compartment model with standard allometric scaling adequately described adalimumab concentration–time data, with higher inter-individual variability in apparent clearance (63%). CL/F showed trends of association with disease type (52% higher in JIA vs idiopathic uveitis, <i>P</i> < .1), disease activity (12% higher in active vs inactive disease, <i>P</i> < .1), and duration of adalimumab (higher with longer duration, <i>P</i> < 0.1) but not MTX co-administration (n.s.). However, none of these factors could be incorporated into the model with sufficient precision, except for bodyweight. While this PMX analysis suggests disease-specific factors may influence adalimumab exposure in children with PIRD, additional prospective studies are warranted to further characterize influence of disease-specific factors on drug exposure and their effects on drug response with goal to facilitate implementation of personalized dosing strategies in pediatric rheumatology.</p><p>What is already known on this topic\n\n </p><p>What this study adds\n\n </p><p>How this study might affect research, practice, or policy\n\n </p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"65 10","pages":"1234-1245"},"PeriodicalIF":0.0000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Clinical Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://accp1.onlinelibrary.wiley.com/doi/10.1002/jcph.70045","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Understanding adalimumab pharmacokinetics (PK) in pediatric inflammatory rheumatic diseases (PIRD) could facilitate individualized treatment strategies. This pharmacometric (PMX) analysis, utilizing prospectively collected data, aimed to develop a PMX model investigating associations between disease-specific factors and adalimumab exposure in PIRD. PK data originating from a prospective two-center study including 36 children with PIRD (weight IQR: 33-55 kg) receiving subcutaneous adalimumab (IQR: 30-40 mg biweekly; n = 28 at steady state, n = 8 after first dose, i.e., treatment naïve) were analyzed. A total of 72 adalimumab concentrations were available for PMX analysis, measured at 1-9 days and 10-14 days post-dose. In addition to disease type (juvenile idiopathic arthritis [JIA] vs idiopathic uveitis) and disease activity (inactive/mild/minimal/moderate/severe), associations between methotrexate (MTX) co-administration and duration of adalimumab treatment with apparent clearance (CL/F) were investigated. A one-compartment model with standard allometric scaling adequately described adalimumab concentration–time data, with higher inter-individual variability in apparent clearance (63%). CL/F showed trends of association with disease type (52% higher in JIA vs idiopathic uveitis, P < .1), disease activity (12% higher in active vs inactive disease, P < .1), and duration of adalimumab (higher with longer duration, P < 0.1) but not MTX co-administration (n.s.). However, none of these factors could be incorporated into the model with sufficient precision, except for bodyweight. While this PMX analysis suggests disease-specific factors may influence adalimumab exposure in children with PIRD, additional prospective studies are warranted to further characterize influence of disease-specific factors on drug exposure and their effects on drug response with goal to facilitate implementation of personalized dosing strategies in pediatric rheumatology.
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