{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T18:09:25Z","timestamp":1772993365216,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\u2010specific factors and adalimumab exposure in PIRD. PK data originating from a prospective two\u2010center study including 36 children with PIRD (weight IQR: 33\u201055 kg) receiving subcutaneous adalimumab (IQR: 30\u201040 mg biweekly; n = 28 at steady state, n = 8 after first dose, i.e., treatment na\u00efve) were analyzed. A total of 72 adalimumab concentrations were available for PMX analysis, measured at 1\u20109 days and 10\u201014 days post\u2010dose. 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\u2010administration and duration of adalimumab treatment with apparent clearance (CL\/F) were investigated. A one\u2010compartment model with standard allometric scaling adequately described adalimumab concentration\u2013time data, with higher inter\u2010individual variability in apparent clearance (63%). CL\/F showed trends of association with disease type (52% higher in JIA vs idiopathic uveitis,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; \u00a0.1), disease activity (12% higher in active vs inactive disease,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; \u00a0.1), and duration of adalimumab (higher with longer duration,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.1) but not MTX co\u2010administration (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\u2010specific factors may influence adalimumab exposure in children with PIRD, additional prospective studies are warranted to further characterize influence of disease\u2010specific factors on drug exposure and their effects on drug response with goal to facilitate implementation of personalized dosing strategies in pediatric rheumatology.\n                  <\/jats:p>\n                  <jats:p>\n                    What is already known on this topic\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Adalimumab is a monoclonal antibody directed against tumor necrosis factor alpha (TNF\u03b1), used for treatment of various inflammatory diseases, including pediatric inflammatory rheumatic diseases (PIRD).<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Data on adalimumab PK in children with PIRD is limited, indicating the need for further clinical research to support development and implementation of personalized treatment in pediatric clinical practice.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    What this study adds\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Applying standard weight\u2010based allometric scaling, a one\u2010compartment model with first\u2010order absorption and elimination adequately described available prospectively collected adalimumab concentration\u2013time data in patients with PIRD.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Higher CL\/F was seen (i) in children with JIA versus those with idiopathic uveitis, (ii) in children with active disease, and (iii) with prolonged duration of adalimumab treatment.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    How this study might affect research, practice, or policy\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Disease\u2010specific factors can influence adalimumab exposure in children with PIRD, but (a priori) dose individualization based on these factors is not directly supported by our investigation (high remaining inter\u2010individual variability).<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>A posteriori dose individualization based on adalimumab exposure (e.g., by PMX\u2010based therapeutic drug monitoring) may be promising to avoid adalimumab over\u2010 and underexposure, particularly after achievement of remission\/inactive disease in children with PIRD.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Together with increasing knowledge on exposure\u2013response relationships in PIRD, the developed PMX model may be applied to optimize and personalize tapering or dose escalation in PIRD patients.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>This research identified disease\u2010specific factors that can influence adalimumab exposure, which in turn can inform design and set\u2010up of larger prospective clinical studies.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  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